Issue Ebookcover storyIssue CoverIssue Contents
Latest Issue
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Scan Code To Listen
Online FirstList of IssuesDocument Types
Liuwei Dihuangwan Reduces Valproic Acid-induced ASD-like Behaviors in Rats by Modulating mTOR-mediated Synaptic Plasticity in Prefrontal Cortex-hippocampus Circuit Enhanced Publication AI Introduction
Abstract：ObjectiveTo investigate the effects of Liuwei Dihuangwan on mammalian target of rapamycin （mTOR）-mediated synaptic plasticity in the prefrontal cortex-hippocampus circuit in the rat model of valproic acid （VPA）-induced autism spectrum disorder （ASD） and to explore its potential mechanism for reducing behavioral abnormalities in ASD rats.MethodsThirteen SD pregnant rats were randomized into the VPA group （10 rats） and the control group （3 rats）. On gestational day 13， the VPA group was intraperitoneally injected with VPA solution （600 mg·kg-1）， while the control group was injected with an equal volume of normal saline. Male pups of 21 days old from both groups underwent behavioral tests to screen the ASD model rats （32 rats）. These rats were then randomly assigned to the model （distilled water）， vitamin D （1 480 U·kg-1）， low-dose （0.75 g·kg-1） Liuwei Dihuangwan， and high-dose （1.5 g·kg-1） Liuwei Dihuangwan groups， and normal male pups were selected as the blank group （distilled water）， with 8 rats in each group. Each group was treated with the corresponding drug or an equal volume of distilled water via gavage daily. After drug administration， behavioral tests were conducted again， followed by anesthesia and tissue collection. Nissl staining was carried out to observe the morphological changes of neurons in the prefrontal cortex and hippocampus. Transmission electron microscopy was used to observe changes in hippocampal synaptic structure. Immunohistochemistry and Western blot were employed to determine the expression of mTOR， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the prefrontal cortex， as well as synaptophysin-1 （SYP-1）， postsynaptic density 95 （PSD95）， and N-methyl-D-aspartate receptors （NMDARs） in the hippocampus.ResultsCompared with the control group， the model group exhibited severe growth retardation and developmental deformities， with abnormal behavioral performance and pathological damage to neurons and synapses in the prefrontal cortex and hippocampus. Compared with the model group， all treatment groups showed reduced behavioral abnormalities and pathological damage to neurons and synapses in the prefrontal cortex and hippocampus， with the most significant effects in the high-dose Liuwei Dihuangwan group. Immunohistochemistry and Western blotting results showed that compared with the control group， the model group exhibited significantly increased protein levels and phosphorylation ratios of p-mTOR， p-Akt， and p-PI3K in the prefrontal cortex （P<0.05， P<0.01）， and decreased protein levels of SYP-1 and PSD95 and increased protein level of NMDARs in the hippocampus （P<0.01）. Compared with those in the model group， the protein levels of p-mTOR， p-Akt， and p-PI3K in the prefrontal cortex decreased in the vitamin D and high-dose Liuwei Dihuangwan groups （P<0.05）， and the p-mTOR/mTOR， p-Akt/Akt， and p-PI3K/PI3K ratios in the prefrontal cortex declined in the vitamin D group （P<0.05）. The high-dose Liuwei Dihuangwan group showed a reduction in p-PI3K/PI3K ratio （P<0.05）. The protein level of SYP-1 and PSD95 in the hippocampus increased in the vitamin D， low-dose Liuwei Dihuangwan， and high-dose Liuwei Dihuangwan groups （P<0.05， P<0.01）， while the protein level of NMDARs decreased in the vitamin D and high-dose Liuwei Dihuangwan groups （P<0.01）.ConclusionLiuwei Dihuangwan significantly reduces VPA-induced ASD-like behaviors and enhances the regeneration and repair of neurons in the prefrontal cortex and synaptic structures in the hippocampus by downregulating of PI3K/Akt/mTOR expression in the prefrontal cortex， upregulating SYP-1 and PSD95 expression in the hippocampus， and inhibiting NMDARs expression.Keywords：Liuwei Dihuangwan;autism spectrum disorder;mammalian target of rapamycin （mTOR） signaling pathway;synaptic plasticity63|12|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Mechanism of Wendan Tang Against Atherosclerosis by Regulating Ferroptosis Based on JAK2/STAT3 Signaling Pathway AI Introduction
Abstract：ObjectiveTo investigate the mechanism through which Wendan Tang ameliorates atherosclerosis （AS） in mice by regulating ferroptosis via the Janus kinase 2（JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway.MethodsTwelve 8-week-old male C57BL/6J mice of SPF grade were selected as the blank control group and fed a standard diet. Additionally， sixty age-matched male apolipoprotein E knockout （ApoE-/-） mice of the same strain and SPF grade were selected and assigned through a random number table into the following groups （n=12 per group）： a model group， a low-dose （3.9 g·kg-1·d-1） Wendan Tang group， a medium-dose （7.8 g·kg-1·d-1） Wendan Tang group， a high-dose （15.6 g·kg-1·d-1） Wendan Tang group， and an atorvastatin calcium （0.01 g·kg-1·d-1） group. All ApoE-/- mice were fed a high-fat diet for the modeling of AS. Starting from week 9， the blank and model groups were administrated with an equal volume of normal saline by gavage， and the remaining groups with corresponding agents by gavage. After 8 weeks of intervention， samples were collected for analysis. Oil red O staining and Masson staining were used to observe lipid deposition in the aorta， and hematoxylin-eosin （HE） staining was employed to examine AS plaque formation. The serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by an automatic biochemical analyzer. The serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， malondialdehyde （MDA）， and reduced glutathione （GSH） were determined by enzyme-linked immunosorbent assay （ELISA）. The level of Fe2+ in the aortic tissue was measured by ELISA. Western blot was performed to determine the protein levels of JAK2， phosphorylated JAK2 （p-JAK2）， STAT3， phosphorylated STAT3 （p-STAT3）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to measure the mRNA levels of JAK2， STAT3， SLC7A11， and GPX4 in the aortic tissue.ResultsCompared with the blank control group， the model group exhibited increased aortic plaque number and area， enhanced lipid deposition， elevated serum levels of TC， TG， LDL-C， TNF-α， IL-6， and MDA （P<0.05， P<0.01）， declined serum levels of HDL-C， SOD， and GSH， and downregulated protein levels of SLC7A11 and GPX4 in the aortic tissue （P<0.05， P<0.01）. The aortic tissue of the model group exhibited an elevated Fe2+ level and upregulated protein levels of p-JAK2 and p-STAT3 and mRNA levels of JAK2 and STAT3 （P<0.05， P<0.01）. Compared with the model group， low-， medium-， and high-dose Wendan Tang， as well as atorvastatin calcium， significantly attenuated these pathological alterations. Specifically， the treatments decreased aortic plaque burden and lipid deposition and lowered serum TC， TG， LDL-C， TNF-α， and MDA levels （P<0.05， P<0.01）. Concurrently， these interventions raised serum HDL-C， SOD， and GSH levels， upregulated the protein levels of SLC7A11 and GPX4 in the aortic tissue （P<0.05， P<0.01）， reduced the Fe2+ level， and downregulated the protein levels of p-JAK2 and p-STAT3 and the mRNA levels of JAK2 and STAT3 in the aortic tissue （P<0.05， P<0.01）.ConclusionWendan Tang ameliorates aortic lesions， dyslipidemia， and oxidative stress， decreased the phosphorylation levels of JAK2/STAT3， and increased the expression of SLC7A11 and GPX4 in the mouse model of AS. The results suggest that the anti-AS effect of Wendan Tang may be associated with the modulation of the JAK2/STAT3 signaling pathway and inhibition of ferroptosis.Keywords：Wendan Tang;atherosclerosis;ferroptosis;Janus kinase 2/signal transducer and activator of transcription 3（JAK2/STAT3） signaling pathway56|11|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Lianpo Yin Ameliorates Bile Reflux Gastritis in Rats by Regulating TLR4/NF-κB Signaling Pathway AI Introduction
Abstract：ObjectiveTo investigate the ameliorative effect of Lianpo Yin on gastric mucosal injury in the rat model of bile reflux gastritis （BRG） and decipher the underlying mechanism based on the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway.MethodsThirty-six SPF-grade male Sprague-Dawley （SD） rats were randomized into blank， model， hydrotalcite （positive control drug， 0.20 g·kg-1）， NF-κB inhibitor （BAY11-7082， 5.00 mg·kg-1）， low-dose Lianpo Yin （LPY-L， 9.77 g·kg-1）， and high-dose Lianpo Yin （LPY-H， 19.54 g·kg-1） groups （n=6）. Except that the blank group was administrated with distilled water by gavage， the rats in the other groups were induced for the modeling of BRG by gavage with reflux fluid for 35 consecutive days. From the 2nd week of modeling， each treatment group was administrated with the corresponding drugs by gavage 6 h after the end of daily reflux fluid gavage. The BAY11-7082 group received intraperitoneal injection. Meanwhile， the blank group and model group received an equal volume of distilled water by gavage. All interventions were performed for 28 consecutive days. During the experiment period， the general status of rats was observed and body mass changes were recorded， and the stomach index was calculated after the last administration. The histopathological changes of the gastric mucosa were observed under the light microscope after hematoxylin-eosin （HE） staining. The serum levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） were quantified by enzyme-linked immunosorbent assay （ELISA）. The protein levels of TLR4， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65） and IL-6 in the gastric mucosal tissue were determined by Western blot. The nuclear translocation of NF-κB p65 was observed by immunofluorescence （IF） staining.ResultsCompared with the blank group， the model group showed mental depression， retarded body weight gain （P<0.05， P<0.01）， an increased stomach index （P<0.01）， severely damaged gastric mucosal structure with massive inflammatory cell infiltration and intestinal metaplasia （P<0.01）， elevated serum levels of TNF-α and IL-6 （P<0.01）， up-regulated protein levels of TLR4， p-NF-κB p65/NF-κB p65， and IL-6 in the gastric tissue （P<0.01）， and evident nuclear translocation of NF-κB p65 （P<0.01）. Compared with the model group， all drug intervention groups showed improved general status of rats. The body mass of rats in the hydrotalcite group， LPY-L， and LPY-H groups increased （P<0.05）， while the average body mass of rats in the BAY11-7082 group was slightly higher than that in the model group at each time point. All drug intervention groups showed decreased stomach index （P<0.05， P<0.01）， alleviated pathological damage of gastric mucosa with reduced inflammatory cell infiltration （P<0.05， P<0.01）， and declined serum levels of TNF-α and IL-6 （P<0.01）. Hydrotalcite and LPY-L reduced the levels of TLR4 and IL-6 （P<0.05）， but had no significant effect on p-NF-κB p65. LPY-H down-regulated the protein levels of TLR4， p-NF-κB p65/NF-κB p65， and IL-6 and inhibited the nuclear translocation of NF-κB p65 （P<0.01）， with its effect equivalent to that of BAY11-7082 and superior to that of hydrotalcite and LPY-L.ConclusionLianpo Yin can effectively ameliorate gastric mucosal inflammatory injury in BRG rats by inhibiting the activation of the TLR4/NF-κB signaling pathway， reducing the release of downstream pro-inflammatory cytokines， and suppressing the nuclear translocation of NF-κB p65.Keywords：Lianpo Yin;bile reflux gastritis;Toll-like receptor 4/nuclear factor-κB （TLR4/NF-κB） signaling pathway;inflammatory response;gastric mucosal injury49|9|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Chaihu Jia Longgu Muli Tang Inhibits Microglial Activation to Protect Neuro-2A Neurons AI Introduction
Abstract：ObjectiveTo examine the effects of Chaihu Jia Longgu Muli Tang （CLMT）-containing serum on Neuro-2A cell damage when exposed to conditioned medium from lipopolysaccharide （LPS）-stimulated microglia （BV-2） and explore the underlying mechanism.MethodsBV-2 cells were activated by LPS at a concentration of 1 mg·L-1 to generate conditioned medium. Concurrently， a blank control group， a model group and groups treated with varying concentrations of CLMT （5%， 10%， and 15%）， dexamethasone （2.5 μmol·L-1）， stimulator of interferon genes （STING） agonist （MSA-2， 10 μmol·L-1）， and STING inhibitor （STING-IN-4， 4 μmol·L-1） were established. Neuro-2A cells were subsequently cultured in the conditioned medium from each treatment group. The viability of BV-2 cells following interventions was assessed by the cell counting kit-8 （CCK-8） assay. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the supernatant of Neuro-2A cells from each group were measured through enzyme linked immunosorbent assay （ELISA）. Additionally， the expression of tyrosine hydroxylase （TH） in Neuro-2A cells was evaluated through immunohistochemistry （IHC）， while the expression of phosphorylated alpha-synuclein （p-α-Syn） was assessed by immunofluorescence （IF） assay. The expression levels of STING， interferon regulatory factor 3 （IRF3）， phosphorylated interferon regulatory factor 3 （p-IRF3）， nuclear transcription factor-kappa B p65 （NF-κB p65）， and phosphorylated nuclear transcription factor-kappa B p65 （p-NF-κB p65） in Neuro-2A cells were determined by Western blot.ResultsIn comparison to the control group， both the model group and the MSA-2 group exhibited reduced viability of Neuro-2A cells （P<0.01）， elevated concentrations of TNF-α， IL-1β， and IL-6 in the cell supernatant （P<0.01）， reduced expression of TH （P<0.01）， increased expression of p-α-Syn （P<0.01）， and upregulated relative protein levels of STING， p-IRF3， and p-NF-κB p65 （P<0.01）. Compared with the model group， medium- and high-dose CLMT enhanced the viability of Neuro-2A cells （P<0.01）， lowered the levels of TNF-α， IL-1β， and IL-6 （P<0.01）， promoted TH expression， and suppressed p-α-Syn expression （P<0.01）. In the dexamethasone group， the levels of IL-6， TNF-α， and IL-1β were reduced （P<0.05， P<0.01）. In the STING-IN-4 group， the levels of TNF-α and IL-1β were decreased （P<0.01）. The expression of TH was increased in both the dexamethasone group and the STING-IN-4 group （P<0.01）， while the expression of p-α-Syn was reduced （P<0.01）. The relative protein levels of p-IRF3， STING， and p-NF-κB p65 were reduced in medium- and high-dose CLMT groups （P<0.05， P<0.01）. Similarly， the dexamethasone group exhibited decreases in the expression levels of STING， p-IRF3， and p-NF-κB p65 （P<0.01）. In the STING-IN-4 group， the expression levels of p-NF-κB p65， STING， and p-IRF3 were also diminished （P<0.05， P<0.01）. However， no statistically significant differences were observed in the expression of IRF3 or NF-κB p65 across the groups.ConclusionCLMT has the potential to suppress the activation of BV-2 microglial cells， consequently mitigating the inflammatory response induced by LPS and further preventing inflammation-mediated damage to Neuro-2A cells. The underlying mechanism is likely associated with the modulation of the STING/NF-κB signaling pathway， which results in reduced inflammation and confers neuroprotective effects.Keywords：Parkinson's disease;neuroinflammation;Chaihu Jia Longgu Muli Tang;lipopolysaccharide （LPS）;neuroprotective effect37|8|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Ditantang Ameliorates MAFLD in Rats Through UDPG-S1P-SREBP Axis-mediated Glycogen Synthesis AI Introduction
Abstract：ObjectiveTo investigate the effects of Ditantang on metabolic dysfunction-associated fatty liver disease （MAFLD） in rats by focusing on the regulation of glycogen synthesis mediated by the uridine diphosphate glucose （UDPG）-site-1-protease （S1P）-sterol regulatory element-binding protein （SREBP） axis.MethodsMAFLD was modeled in SD rats by feeding a high-fat diet for 12 weeks. Rats were randomized into a control group， a model group， low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg-1·d-1， respectively） Ditantang groups， and a positive control （Yishanfu， 0.18 g·kg-1·d-1） group. Starting from week 9 of modeling， each treatment group received corresponding drug interventions via gavage. After the experiment， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured. The levels of TG， non-esterified fatty acids （NEFA）， glycogen， glucose-6-phosphate （G6P）， glucose-1-phosphate （G1P）， and UDPG in the liver tissue samples were measured by biochemical assay kits. Liver pathological morphology and lipid/glycogen deposition were observed via hematoxylin-eosin （HE） staining， oil red O staining， and Periodic acid-Schiff （PAS） staining. Immunofluorescence assay was conducted to detect the expression and localization of phosphoglucomutase-1 （Pgm1） and UDP-glucose pyrophosphorylase 2 （Ugp2） in the rat liver. Real-time PCR and Western blot were employed to quantify mRNA and protein levels， respectively， of key glycogen synthesis enzymes （Pgm1 and Ugp2）， key lipogenesis-related transcription factor SREBP and its target genes ［acetyl-CoA carboxylase （ACC）， fatty acid synthetase （FASN）， and stearoyl-CoA desaturase （SCD1）］， as well as S1P.ResultsCompared with the control group， the model group exhibited elevated levels of TC， TG， LDL-C in the serum and TG and NEFA in the liver， decreased serum HDL-C level （P<0.01）， reduced hepatic levels of G1P， G6P， UDPG， and glycogen （P<0.01）， appearance of fat vacuoles of varying sizes and abundant red lipid droplets， with prominent lipid deposition and reduced areas of deep glycogen staining in the liver tissue， upregulated mRNA and protein levels of SREBP1， S1P， ACC， FASN， and SCD1 （P<0.01）， and downregulated mRNA and protein levels of Pgm1 and Ugp2 （P<0.01）. Compared with the model group， all doses of Ditantang reduced the levels of TC and TG in the serum and TG and NEFA in the liver， while elevating the serum HDL-C level. Additionally， medium- and high-dose Ditantang reducted the LDL-C level （P<0.05）. Ditantang at all doses increased the hepatic levels of G1P， G6P， UDPG， and glycogen， alleviated hepatic steatosis and lipid deposition， enhanced glycogen storage， downregulated the mRNA and protein levels of SREBP1， S1P， ACC， FASN， and SCD1 （P<0.05）， while upregulating the expression of Pgm1 and Ugp2 （P<0.01）. Immunofluorescence analysis revealed decreased fluorescence intensity of S1P and enhanced fluorescence intensity of Ugp2 （P<0.01）.ConclusionDitantang can regulate glycogen synthesis through the UDPG-S1P-SREBP axis to prevent and treat MAFLD.Keywords：Ditantang;metabolic dysfunction-associated fatty liver disease;the uridine diphosphate glucose （UDPG）-site-1-protease （S1P）-sterol regulatory element-binding protein （SREBP） axis;glycogen synthesis;lipid metabolism45|7|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Youguiwan Promotes Localization and Differentiation of Embryonic Stem Cells in Mouse Ovaries via Akt/mTOR/4EBP1/P70S6K Signaling Pathway AI Introduction
Abstract：ObjectiveTo observe the effects of Youguiwan on the localization and differentiation of embryonic stem cells transplanted into ovaries，and to preliminarily explore whether its mechanism is related to the protein kinase B （Akt）/mammalian target of rapamycin （mTOR）/4E-binding protein 1 （4EBP1）/p70S6 kinase （P70S6K） signaling pathway.MethodsA total of 81 healthy adult female C57BL/6 mice that had received ovarian transplantation of GFP-labeled embryonic stem cells were randomly allocated into a control group，a Youguiwan group，and a positive control group. The control group received normal saline via gavage，the Youguiwan group was administered Youguiwan decoction at a clinical equivalent dose of 17.1 g·kg-1，and the positive control group received human menopausal gonadotropin （HMG） injections every 48 h. Ovarian tissue samples were collected on days 7，14，and 21 post-administration. Frozen sections were prepared to observe stem cell localization. The immunofluorescence assay was used to detect growth differentiation factor 9 （GDF9） and mTOR expression. real time polymerase chain reaction（Real-time PCR） was performed to measure the mRNA levels of follicle-stimulating hormone receptor （FSHR） and luteinizing hormone receptor （LHR）. Western blotting was conducted to assess the expression and phosphorylation levels of Akt，mTOR，4EBP1，and P70S6K.ResultsFluorescence microscopy revealed that the transplanted embryonic stem cells were predominantly localized within the granular cell layer，the cell layer of the follicular structure，and the stroma. After 14 days of drug intervention，compared with the control group，the Youguiwan group showed upregulated mRNA levels of FSHR and LHR in the ovarian tissue （P<0.01），as well as elevated phosphorylation/protein ratios of Akt，mTOR，4EBP1，and P70S6K （P<0.05）. After 21 days of drug intervention，compared with the control group，the Youguiwan group exhibited enhanced expression of GDF9 and mTOR in the ovarian tissue as detected by immunofluorescence （P<0.05），along with elevated mRNA levels of FSHR and LHR （P<0.01） and phosphorylation/protein ratios of Akt and 4EBP1 （P<0.05）.ConclusionYouguiwan can promote the localization and differentiation of mouse embryonic stem cells within the ovary and enhance the expression of GDF9，FSHR，and LHR mRNA in the ovarian tissue by influencing the Akt/mTOR/4EBP1/P70S6K pathway.Keywords：Youguiwan;embryonic stem cells;protein kinase B （Akt）/mammalian target of rapamycin （mTOR）/4E-binding protein 1 （4EBP1）/p70S6 kinase （P70S6K） signaling pathway;localization;differentiation10|4|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16- Abstract：ObjectiveTo investigate the mechanism of Hei Xiaoyaosan （HXS） in ameliorating cognitive impairment in the rat model of Alzheimer's disease （AD） by regulating the adenosine 5'-monophosphate-activated protein kinase （AMPK）/sterol regulatory element-binding protein 2 （SREBP2）/proprotein convertase subtilisin/kexin type 9 （PCSK9）/low-density lipoprotein receptor-related protein 1 （LRP-1） signaling pathway to clear amyloid-β （Aβ） from the peripheral circulation.MethodsNinety 8-week-old specific pathogen-free （SPF）-grade male Sprague-Dawley （SD） rats were acclimatized for 1 week. After acclimatization， 10 rats were randomly selected as the blank control group， and the remaining 80 rats were prepared for surgical modeling. Among the 80 rats for modeling， 70 were anesthetized and injected with 1 μL of amyloid-β1-42 （Aβ1-42） solution into the bilateral hippocampal CA1 region for the modeling of AD， and the remaining 10 were assigned to the sham operation group， which received an injection of 1 μL normal saline at the same anatomical site. The successfully modeled rats were randomly assigned into 6 groups （n=10 per group）： a model group， a donepezil hydrochloride group， an acadesine （AICAR， an AMPK agonist） group， and high-， medium-， and low-dose HXS groups. After 42 consecutive days of administration intervention， the Morris water maze test and T-maze test were performed to evaluate the learning and memory abilities of rats. Fluoro-Jade B （FJB） staining was conducted to observe pathological changes of neurons in the rat hippocampus， and thioflavin S staining to quantify the area of Aβ deposition in the hippocampal region. Immunofluorescence double staining （IF-DS） was performed to detect the expression of LRP-1 and Aβ signals in the liver tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of Aβ1-42 and soluble LRP-1 （sLRP-1） in the serum. Western blot was performed to determine the protein levels of AMPK， phosphorylated AMPK （p-AMPK）， SREBP2， PCSK9， and LRP-1 in the liver tissue. Real time polymerase chain reaction（Real-time PCR） was adopted to assess the mRNA levels of AMPK， SREBP2， PCSK9， and LRP-1 in the liver tissue.ResultsCompared with the blank control group， the model group showed increased total swimming distance on day 6 and path length in the target quadrant on day 7 （P<0.01）， a decreased correct alternation rate in the T-maze test （P<0.01）， disarrangement of hippocampal neurons， increased FJB-positive cells （P<0.01）， enlarged area of Aβ deposition （P<0.01）. reduced LRP-1 fluorescence signals and enhanced Aβ fluorescence signals in the liver tissue （P<0.01）， elevated serum level of Aβ1-42， declined serum level of sLRP-1 （P<0.01）， downregulated protein levels of p-AMPK and LRP-1 as well as mRNA levels of AMPK and LRP-1， and upregulated protein and mRNA levels of SREBP2 and PCSK9 in the liver tissue （P<0.01）. Compared with the model group， the high-dose HXS group， donepezil hydrochloride group， and AICAR group exhibited reduced total swimming distance and target quadrant path length （P<0.05， P<0.01）， an increased correct alternation rate in the T-maze test （P<0.05）， decreased FJB-positive cells （P<0.01）， reduced Aβ deposition （P<0.01） in the hippocampal tissue， enhanced LRP-1 signals and weakened Aβ signals in the liver tissue （P<0.01）， a declined serum level of Aβ1-42 and an elevated serum level of sLRP-1 （P<0.01）， upregulated protein levels of p-AMPK and LRP-1 as well as mRNA levels of AMPK and LRP-1， and downregulated protein and mRNA levels of SREBP2 and PCSK9 in the liver tissue （P<0.01）.ConclusionHei Xiaoyaosan can regulate the AMPK/SREBP2/PCSK9/LRP-1 signaling pathway to enhance the clearance of peripheral Aβ by the liver tissue and reduce Aβ deposition in the brain， thereby improving the learning and memory abilities of AD rats.Keywords：Alzheimer's disease;Hei Xiaoyaosan;peripheral amyloid-β （Aβ） clearance;adenosine 5'-monophosphate-activated protein kinase （AMPK）/sterol regulatory element-binding protein 2 （SREBP2）/proprotein convertase subtilisin/kexin type 9 （PCSK9）/low-density lipoprotein receptor-related protein 1 （LRP-1） signaling pathway22|3|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16
- Abstract：ObjectiveTo investigate the role and mechanism of Hei Xiaoyaosan in regulating asparaginyl endopeptidase （AEP） to inhibit tau protein （tau） phosphorylation， amyloid-beta protein （Aβ） deposition， and neuroinflammation in the prevention and treatment of Alzheimer's disease （AD）.MethodsNinety SPF-grade SD male rats of 8 weeks old were selected and randomly grouped as follows： 10 rats in the blank group， 10 rats in the sham group （bilateral hippocampus injected with 1 μL normal saline）， and 70 rats in the modeling group （bilateral hippocampus injected with 1 μL Aβ1-42 solution for the modeling of AD）. Fifty successfully modeled rats were selected and randomly assigned into the model， donepezil hydrochloride （positive control， 0.45 mg·kg-1）， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg-1， respectively） Hei Xiaoyaosan groups. Rats were administrated with corresponding agents by gavage once a day for 42 days. Morris water maze and Y maze tests were carried out to assess the cognitive abilities of rats. Hematoxylin-eosin （HE） staining was employed to observe morphological changes in hippocampal neurons， and immunohistochemistry （IHC） was employed to assess phosphorylation （p）-tau and Aβ expression in the hippocampal tissue of rats. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-1 beta （IL-1β）， interleukin-18 （IL-18）， and Aβ1-42 in the hippocampal tissue. Western blot was employed to determine the protein levels of AEP， tau， phosphorylated tau （p-tau）， α-Syn （α-Syn）， phosphorylated α-Syn （p-α-Syn）， Toll-like receptor 2 （TLR2）， and NOD-like receptor thermal protein domain associated protein 3 （NLRP3）. Real time polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of AEP， tau， α-Syn， TLR2， and NLRP3.ResultsCompared with the blank group， the model group showed prolonged escape latency， a decreased percentage of time spent in the platform quadrant， and a decreased alternation rate （P<0.01）， a reduced number， shrinkage， and increased vacuoles of hippocampal neurons， increased expression of p-tau and Aβ in the hippocampus （P<0.01）， elevated levels of IL-1β， IL-18， and Aβ1-42， up-regulated protein and mRNA levels of AEP， tau， α-Syn， TLR2， and NLRP3， and up-regulated protein levels of p-tau and p-α-Syn （P<0.01）. Compared with the model group， the positive control group and the high-dose Hei Xiaoyaosan group exhibited shortened escape latency （P<0.01）， an increased percentage of retention time in the target quadrant， an increased alternation response rate （P<0.05， P<0.01）， alleviated neuronal shrinkage， regular morphology and arrangement of neurons in the hippocampal tissue， lowered levels of p-tau and Aβ in the hippocampal tissue （P<0.05， P<0.01）， declined levels of IL-1β， IL-18， and Aβ1-42， downregulated mRNA and protein levels of AEP， tau， α-Syn， TLR2， and NLRP3， and downregulated protein levels of p-tau and p-α-Syn （P<0.05， P<0.01）.ConclusionHei Xiaoyaosan can protect hippocampal neurons and ameliorate cognitive impairment in the rat model of AD. Specifically， it may inhibit AEP to regulate tau phosphorylation， Aβ deposition， and neuroinflammation.Keywords：Alzheimer's disease;Hei Xiaoyaosan;asparaginyl endopeptidase （AEP）33|5|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16
Hei Xiaoyaosan Reduces Neuroinflammation in APP/PS1 Mice via CX3CL1-CX3CR1 Signaling Axis Enhanced Publication AI Introduction
Abstract：ObjectiveTo investigate the effects of Hei Xiaoyaosan on neuroinflammation in APP/PS1 mice and decipher the mechanism based on the C-X3-C chemokine ligand 1 （CX3CL1）-CX3CL1 receptor 1 （CX3CR1） signaling axis.MethodsSixty 16-week-old male APP/PS1 mice were selected and acclimatized for one week， and they were then randomly allocated into a model group， a CX3CL1 group （bilateral hippocampal injection of CX3CL1 at 0.5 g·L-1）， and high-， medium-， and low-dose （22.10， 11.05， and 5.53 g·kg-1， respectively） Hei Xiaoyaosan groups， with 12 mice in each group. Twelve age-matched male C57BL/6J mice served as the blank group （bilateral hippocampal injection of an equal volume of PBS）. The high-， medium-， and low-dose Hei Xiaoyaosan groups received corresponding drugs via gavage， while the blank group received an equal volume of normal saline， with an intervention period of 90 days. Morris water maze was used to assess learning and memory abilities. Nissl staining was performed to observe the pathological changes in neurons of the hippocampal CA1 region. Immunohistochemistry was adopted to detect amyloid-β1-42 （Aβ1-42） deposition in the hippocampal CA1 region. The immunofluorescence assay was employed to detect the expression of M1 and M2 microglial markers， including cluster of differentiation 86 （CD86）/ionized calcium-binding adapter molecule 1 （Iba-1） and arginase-1 （Arg1）/Iba1. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-8 （IL-8） and interleukin-13 （IL-13） in the hippocampal tissue. Western blot was employed to determine the protein levels of CX3CL1， CX3CR1， CREB-binding protein （CBP）， cyclic AMP response element-binding protein （CREB）， phosphorylated （p）-CREB， and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue.ResultsCompared with the blank group， the model group exhibited prolonged escape latency on day 5 and a reduced swimming distance in the target quadrant （P<0.01）， disarrangement of hippocampal neurons， with a reduced number of cells and uneven Nissl body staining， increased CD86/Iba1 expression， decreased Arg1/Iba1 expression （P<0.01）， enhanced Aβ expression （P<0.01）， an elevated IL-8 level and a declined IL-13 level （P<0.01）， and downregulated protein levels of CX3CL1， CX3CR1， CBP， p-CREB， and BDNF （P<0.01）. Compared with the model group， all treatment groups showed shortened escape latency on day 5 and an increased swimming distance in the target quadrant （P<0.05， P<0.01）， regular arrangement of neurons with an increased number and increased Nissl bodies， reduced CD86/Iba1 expression， increased Arg1/Iba1 and decreased Aβ expression （P<0.01）， and a declined IL-8 level and an elevated IL-13 level （P<0.05， P<0.01）. In the CX3CL1 group and the high- and medium-dose Hei Xiaoyaosan groups， the relative expression levels of CX3CL1， CX3CR1， CBP， and p-CREB were upregulated （P<0.01）. In the low-dose Hei Xiaoyaosan group， the relative expression levels of CX3CL1， CX3CR1， CBP， p-CREB/CREB， and BDNF were upregulated （P<0.05， P<0.01）.ConclusionHei Xiaoyaosan can improve learning and cognitive abilities in APP/PS1 mice. Specifically， it may regulate the CX3CL1/CX3CR1 signaling axis to activate the CREB/BDNF signaling pathway for the subsequent release of BDNF， modulation of microglial polarization， reduction of inflammatory cytokine levels， and attenuation of Aβ deposition.Keywords：Alzheimer's disease;Hei Xiaoyaosan;C-X3-C chemokine ligand 1 （CX3CL1）-CX3CL1 receptor 1 （CX3CR1） signaling axis;cyclic AMP response element-binding protein （CREB）/brain-derived neurotrophic factor （BDNF） signaling pathway;neuroinflammation26|5|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Hei Xiaoyaosan Ameliorates Cognitive Impairment in Rat Model of Alzheimer's Disease by Activating Autophagy Through Regulating AMPK/ULK1 Signaling Pathway Enhanced Publication AI Introduction
Abstract：ObjectiveTo investigate the effect and mechanism of Hei Xiaoyaosan in preventing and treating Alzheimer's disease （AD） by activating autophagy through regulating the adenosine monophosphate-activated protein kinase （AMPK）/UNC-51 like autophagy activating kinase 1 （ULK1） signaling pathway.MethodsNinety 8-week-old male SPF-grade SD rats were selected and randomized into two groups： a blank control group （n=10） and a modeling group （n=80）. From the modeling group， 10 rats were randomly assigned as a sham group （bilateral hippocampal injection of 1 μL normal saline）， while the remaining 70 rats were injected with 1 μL Aβ1-42 solution bilaterally into the hippocampus to replicate the AD model. The Morris water maze test was conducted to screen the successfully modeled rats， which were then randomly allocated to the model， donepezil hydrochloride， 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside （AICAR， an AMPK agonist）， and high-， medium-， and low-dose Hei Xiaoyaosan groups， with 10 rats per group. After 42 days of drug intervention， the Morris water maze and open field tests were conducted to assess learning and memory abilities and motor function. Pathological changes in the hippocampal tissue were observed by Nissl staining， and autophagy-related pathological damage was examined via transmission electron microscopy （TEM）. The expression of LC3 in the hippocampus was observed by immunofluorescence staining. The protein levels of AMPK， phosphorylate （p）-AMPK， ULK1， p-ULK1， p62， and autophagy related 7 （Atg7） were determined by Western blot， while the mRNA levels of AMPK and ULK1 were measured by Real-time polymerase chain reaction （Real-time PCR）.ResultsCompared with the blank control group， the model group showed increased escape latency （P<0.01） and decreased platform crossings （P<0.01） on day 6 in the water maze test， reduced total distance traveled and average speed in the open field test （P<0.01）， disarranged neurons with Nissl body loss and evident autophagic damage， weakened LC3 fluorescence signal （P<0.01）， downregulated protein levels of p-AMPK， p-ULK1， and Atg7 and mRNA levels of AMPK and ULK1 in the hippocampus （P<0.01）， and upregulated protein level of p62 （P<0.01）. Compared with the model group， the positive drug group， high-dose Hei Xiaoyaosan group， and AICAR group showed decreased escape latency （P<0.05， P<0.01） and increased platform crossings （P<0.01） on day 6， and increased total distance traveled and average speed in the open field test （P<0.05）. The positive drug group， high- and medium-dose Hei Xiaoyaosan groups， and the AICAR group showed alleviated cellular structural damage， regular neuronal arrangement， increased Nissl bodies， and orderly distribution of autophagosomes. Furthermore， the LC3 fluorescence intensity was enhanced in the positive drug group， high- and medium-dose Hei Xiaoyaosan groups， and the AICAR group （P<0.01）. The positive drug group， high-dose Hei Xiaoyaosan group， and the AICAR group exhibited upregulated protein and mRNA levels of p-AMPK and p-ULK1 （P<0.05， P<0.01）， upregulated protein level of Atg7 （P<0.05， P<0.01）， and downregulated protein level of p62 （P<0.01）.ConclusionHei Xiaoyaosan can improve learning and memory abilities and alleviate pathological status in the rat model of AD by regulating the AMPK/ULK1 signaling pathway， enhancing cellular autophagy， and repairing damaged nerve cells.Keywords：Alzheimer's disease;Hei Xiaoyaosan;autophagy;adenosine monophosphate-activated protein kinase （AMPK）/UNC-51 like autophagy activating kinase 1 （ULK1） signaling pathway38|5|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Dysregulated Cholesterol Homeostasis Drives T Cell-mediated Neuroinflammation in Alzheimer's Disease and Its Modulation by Traditional Chinese Medicine Enhanced Publication AI Introduction
Abstract：Alzheimer's disease （AD） is a neurodegenerative disorder characterized by amyloid-β （Aβ） plaque deposition， neurofibrillary tangle （NFT） formation， and chronic neuroinflammation. Its global incidence and mortality continue to rise， yet effective curative therapies remain unavailable. In recent years， dysregulated cholesterol metabolism and immune-inflammatory responses have been increasingly recognized as key drivers of AD pathological progression. Both clinical and experimental studies have shown that patients with AD exhibit disrupted cholesterol homeostasis and aberrant T-cell function， with a significant correlation between these alterations， suggesting that cholesterol metabolic disturbances may participate in and amplify neuroinflammatory responses by modulating T-cell differentiation and activation states. This review systematically delineates the coupling relationship among cholesterol homeostasis imbalance， T-cell abnormalities， AD neuroinflammation， and related pathological injury. Specifically， we summarize the immunometabolic pathological links spanning the peripheral and central compartments， ranging from the effects of peripheral cholesterol metabolic disturbances on T-cell activation， differentiation， and blood-brain barrier permeability to the regulatory role of impaired brain cholesterol homeostasis in infiltrating T-cell inflammatory responses， glial activation， and neural microenvironment remodeling. We further highlight how abnormalities in cholesterol synthesis， transport， efflux， and oxidative product accumulation promote Th17/Treg imbalance， enhanced CD8+ T-cell effector activity， increased inflammatory cytokine release， as well as Aβ deposition， blood-brain barrier disruption， glial activation， and neuronal injury. In addition， we review recent progress in natural herbal formulas and bioactive phytochemicals that alleviate T-cell abnormalities and neuroinflammation through restoration of cholesterol homeostasis. Taken together， current evidence suggests that cholesterol homeostasis imbalance is not only a fundamental metabolic abnormality in AD， but may also construct and amplify AD neuroinflammation and related pathological injury by reshaping T-cell immunophenotypes. Therefore， immunometabolic intervention strategies aimed at restoring cholesterol homeostasis may provide a new theoretical basis for mechanistic studies and multi-target prevention and treatment of AD.Keywords：Alzheimer's disease;cholesterol homeostasis imbalance;T-cell abnormalities;neuroinflammation;cholesterol synthesis;cholesterol efflux35|7|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Effect of Schisanlactone E on Neuroinflammation and Synaptic Damage in APP/PS1 Mice and Their Relationship with Th17/Treg Immune Balance Enhanced Publication AI Introduction
Abstract：ObjectiveTo investigate the effect of schisanlactone E in ameliorating neuroinflammation and synaptic injury in APP/PS1 mice and to elucidate whether its mechanism is related to the regulation of helper T cell 17 （Th17）/regulatory T cell （Treg） immune balance.MethodsAPP/PS1 transgenic mice were assigned into model， low- and high-dose （2 mg·kg-1·d-1 and 4 mg·kg-1·d-1， respectively） schisanlactone E， and donepezil （1 mg·kg-1·d-1） groups. C57BL/6J mice were used as the control group. Each group received the corresponding drug by gavage for 30 days. Learning and memory abilities were assessed by the Morris water maze and novel object recognition tests. The percentages of Th17 and Treg cells in the peripheral blood were analyzed by flow cytometry. The mRNA levels of retinoid-related orphan receptor γt （RORγt）， interleukin （IL）-17A， forkhead box protein 3 （FoxP3）， and IL-4 in the hippocampus were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The synaptic ultrastructure in the hippocampus was observed by transmission electron microscopy. The protein levels of synapsin Ⅰ and postsynaptic density protein 95 （PSD95） in the hippocampus were measured by Western blot. Aβ aggregation and microglial activation in the hippocampus were observed by immunofluorescence staining. The mRNA levels of tumor necrosis factor （TNF）-α， IL-6， and IL-1β in the hippocampus were determined by Real-time PCR.ResultsCompared with the control group， the model group showed prolonged escape latency （P<0.05）， decreased time spent in the target quadrant， platform crossings， novel object exploration time， and percentage of novel object contact frequency （P<0.05， P<0.01）， increased Aβ aggregation in the hippocampal tissue （P<0.01）， an increased proportion of Th17 cells （P<0.05）， a decreased proportion of Treg cells （P<0.05）， and an increased Th17/Treg ratio （P<0.01） in the peripheral blood. Furthermore， the hippocampal tissue in the model group exhibited upregulated mRNA levels of RORγt and IL-17A （P<0.05， P<0.01）， downregulated mRNA levels of FoxP3 and IL-4 （P<0.01）， decreased synapses （P<0.05）， decreased PSD density， synaptic interface curvature， and active zone length （P<0.05， P<0.01）， and increased synaptic cleft width （P<0.05）， downregulated protein levels of Synapsin Ⅰ and PSD95 （P<0.01）， increased microglial activation （P<0.01）， and upregulated mRNA levels of TNF-α， IL-6， and IL-1β （P<0.05）. Compared with the model group， the high-dose schisanlactone E group and the donepezil group exhibited shortened escape latency and increased time in the target quadrant and platform crossings （P<0.05， P<0.01）. The schisanlactone E groups and the donepezil group showed increased novel object exploration time （P<0.05， P<0.01） and percentage of novel object contact frequency （P<0.05， P<0.01）， and reduced hippocampal Aβ aggregation （P<0.05， P<0.01）. The schisanlactone E groups showed a decreased proportion of Th17 cells （P<0.05） and an increased proportion of Treg cells （P<0.05） in the peripheral blood， and all treatment groups showed a decreased Th17/Treg ratio （P<0.05， P<0.01）. The high-dose schisanlactone E group showed a downregulated mRNA level of RORγt in the hippocampal tissue （P<0.05）， and all treatment groups showed a downregulated mRNA level of IL-17A （P<0.05， P<0.01）， and upregulated mRNA levels of FoxP3 and IL-4 （P<0.05， P<0.01）. The schisanlactone E groups and the donepezil group showed increased synapses， active zone length， synaptic interface curvature， and PSD density， decreased synaptic cleft width （P<0.05， P<0.01）， and upregulated protein levels of synapsin Ⅰ and PSD95 （P<0.05， P<0.01）. The high-dose schisanlactone E group and the donepezil group showed decreased microglial activation in the hippocampus （P<0.01）. The schisanlactone E groups and the donepezil group showed downregulated mRNA levels of TNF-α， IL-6， and IL-1β in the hippocampal tissue （P<0.05， P<0.01）.ConclusionSchisanlactone E significantly improves the cognitive function in APP/PS1 mice by regulating the Th17/Treg immune balance， inhibiting neuroinflammation， and ameliorating synaptic injury.Keywords：schisanlactone E;Alzheimer's disease;synapses;helper T cell 17 （Th17）;regulatory T cell （Treg）;neuroinflammation29|5|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Aspirin Curcumin Ester Inhibits High Glucose/Aβ1-42-induced Microglial Inflammatory Response by Regulating Glucose Metabolism Reprogramming Enhanced Publication AI Introduction
Abstract：ObjectiveTo observe the effect of aspirin curcumin ester （CA） on the activation and glucose metabolism reprogramming of the mouse microglia （BV2） model of inflammation induced by high glucose/β-amyloid （Aβ）1-42， and to explore the potential mechanism of CA in reducing neuroinflammatory response in the brain.MethodsThe BV2 activation model was constructed by high glucose combined with Aβ1-42 oligomers. BV2 cells were treated with Aβ1-42 oligomers （10 μmol·L-1） in a high glucose （50 mmol·L-1） environment and allocated into normal， high glucose， Aβ， and high glucose + Aβ groups. The cell morphology of each group was observed under a bright field. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to assess the mRNA levels of inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） as well as glycolysis-related glucose transporter type 1 （GLUT1）， hexokinase 2 （HK2）， phospofructokinase-2/fructose-2，6-bisphosphatase 3 （PFKFB3）， and pyruvate kinase M2 （PKM2）. To reveal the effects of CA on inflammatory response and glucose metabolism in BV2 cells exposed to high glucose/Aβ1-42， this study established the BV2 cell model of inflammatory activation by high glucose and Aβ1-42 oligomer intervention. The cells were allocated into normal， model （50 mmol·L-1 glucose + 10 μmol·L-1 Aβ1-42）， CA （10 μmol·L-1）， 2DG （0.2 mmol·L-1）， and DADA （1 mmol·L-1） groups. Cell counting kit-8 （CCK-8） was used to detect cell survival rate. The cell morphology of each group was observed under a bright field. The expression of inflammatory factors TNF-α， IL-6， and IL-1β and glycolysis-related key enzymes GLUT1， HK2， PFKFB3， and PKM2 at the mRNA level in each group was measured by real-time PCR. The protein levels of GLUT1， HK2， PFKFB3， and PKM2 were determined by Western blot. The glycolysis rate in each group was measured by seahorse. LC-MS was employed to identify the glucose metabolism intermediates. The morphology of mitochondria in cells was observed by electron microscopy.ResultsConstruction of the BV2 cell model： Compared with the normal group， the Aβ group and the high glucose + Aβ group showed more amoeboid-shaped cells and cell aggregation. The high glucose + Aβ group exhibited increased the mRNA levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， as well as those of key glycolytic enzymes GLUT1， HK2， PFKFB3， and PKM2 （P<0.01）. The Aβ group also showed significantly increased mRNA levels of PKM2 and PFKFB3 （P<0.01）. Effects of CA on the inflammatory response and glucose metabolism in BV2 cells exposed to high glucose/Aβ1-42： Compared with the normal group， the model group exhibited amoeboid-shaped cells and cell aggregation， upregulated mRNA levels of TNF-α， IL-1β， IL-6， iNOS， GLUT1， HK2， PFKFB3， and PKM2 （P<0.01） and protein levels of GLUT1， HK2， and PFKFB3 （P<0.05， P<0.01）， an increased basal glycolysis rate （P<0.01）， a decreased compensatory glycolysis rate （P<0.01）， increased glycolytic intermediates and reduced TCA cycle intermediates. In addition， the mitochondria in the model group exhibited a decreased number （P<0.05）， impaired crista integrity （P<0.01）， an increased proportion of vacuolization （P<0.01）， and abnormal mitochondrial morphology. Compared with those in the model group， the number of amoeboid-shaped BV2 cells reduced in the CA and 2DG groups， while most BV2 cells in the DADA group became elongated spindle-shaped. All the three treatment groups showed downregulated mRNA levels of TNF-α， IL-1β， IL-6， GLUT1， HK2， PFKFB3， and PKM2 （P<0.05， P<0.01）， downregulated protein levels of GLUT1， HK2， and PFKFB3 （P<0.05， P<0.01）， and slow compensatory glycolysis and basal glycolysis （P<0.05， P<0.01）. Glycolytic intermediates were decreased and TCA cycle intermediates were increased in the CA and 2DG groups. Mitochondrial morphology largely returned to the normal level in all the three treatment groups， with an increase in mitochondrial number （P<0.05）， improved crista integrity （P<0.05， P<0.01）， and a decreased proportion of vacuolization （P<0.05）.ConclusionAβ1-42 oligomers can activate BV2 cells and enhance glycolytic activity in the high glucose environment. CA can reduce the expression of inflammatory factors and inhibit the activation of BV2 cells by regulating the glucose metabolism reprogramming in BV2 cells.Keywords：microglia;glycolysis;aspirin curcumin ester;Alzheimer's disease;neuroinflammation40|7|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Paeoniflorin Ameliorates Neuroinflammation and Cognitive Impairment in Rat Model of Alzheimer's Disease via JAK2/STAT3 Signaling Pathway Enhanced Publication AI Introduction
Abstract：ObjectiveTo investigate the effects of paeoniflorin （PF） on neuroinflammation and cognitive impairment in the rat model of Alzheimer's disease （AD） and to clarify whether its mechanism is associated with regulation of the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway.MethodsGlycosides related to AD-associated neuroinflammation were screened through bibliometric analysis， and the potential targets of PF were predicted through network pharmacology and molecular docking. A rat model of AD was established by intraperitoneal injection of D-galactose （100 mg·kg-1·d-1）. Rats were assigned into a control group， a model group， a PF （200 mg·kg-1） group， and a donepezil （0.5 mg·kg-1·d-1） group， and drugs were administered by gavage for 21 days. The learning and memory abilities were evaluated by the Morris water maze （MWM）. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe hippocampal neuronal morphology. The mRNA levels of inflammatory factors were determined by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of molecules in the JAK2/STAT3 signaling pathway were determined by Western blot.ResultsCompared with the control group， the model group showed prolonged escape latency and decreased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， accompanied by increased expression of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as elevated ratios of phosphorylated （p）-JAK2/JAK2 and p-STAT3/STAT3 （P<0.01）. Compared with the model group， the PF group and donepezil group exhibited shortened escape latency and increased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， decreased expression levels of IL-1β and TNF-α， upregulated mRNA levels of interleukin-4 （IL-4） and interleukin-10 （IL-10）， and reduced ratios of p-JAK2/JAK2 and p-STAT3/STAT3 （P<0.05， P<0.01）.ConclusionPaeoniflorin can alleviate cognitive impairment and neuroinflammation in the rat model of AD by inhibiting the JAK2/STAT3 signaling pathway.Keywords：paeoniflorin;Alzheimer's disease;neuroinflammation;Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway;cognitive impairment29|10|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16- Abstract：ObjectiveTo explore the potential mechanism by which Huoxue Wentong prescription （HXWT） ameliorates post-myocardial infarction （MI） ventricular remodeling by regulating endothelial-to-mesenchymal transition （EndMT） via the hypoxia-inducible factor-1α （HIF-1α）/transforming growth factor-β1 （TGF-β1）/periostin （POSTN） signaling pathway.MethodsEighty SPF-grade male Sprague-Dawley rats were randomly assigned to a sham-operated group （n=10） and a modeling group （n=70）. The MI model was established by left anterior descending coronary artery ligation. Successfully modeled rats were further randomized into a model group， a sacubitril/valsartan （Entresto， 0.021 g·kg-1） group， and low， medium， and high-dose （4.15， 8.30， and 16.60 g·kg-1， respectively） HXWTF groups （n=10 per group）. From postoperative day 2， rats received HXWTF or sacubitril/valsartan by gavage once daily for 4 weeks， and those in sham and model groups received an equal volume of normal saline. After intervention， general conditions were assessed. Echocardiography was performed to measure the left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end diastolic diameter （LVEDD）， and left ventricular end systolic diameter （LVESD）. Hematoxylin and eosin （HE） staining was employed to evaluate myocardial histopathology， and Masson's trichrome staining to assess myocardial fibrosis. Serum levels of B-type natriuretic peptide （BNP）， interleukin （IL）-6， IL-10， and matrix metalloproteinase-9 （MMP-9） were determined by enzyme-linked immunosorbent assay （ELISA）. Collagen type Ⅰ （ColⅠ） expression was assessed by immunohistochemistry. Immunofluorescence double staining was adopted to detect the expression of platelet endothelial cell adhesion molecule-1 （CD31） and α-smooth muscle actin （α-SMA）. Western blot was performed to quantify the expression of collagen type Ⅰ α2 （Col1A2）， VE-cadherin， CD31， α-SMA， HIF-1α， TGF-β1， and POSTN.ResultsCompared with the sham group， the model group exhibited thinning and collapse of the left ventricular wall， decreased LVEF and LVFS and increased LVEDD and LVESD （P<0.01）， disrupted myocardial fibers with marked inflammatory cell infiltration， increased collagen deposition， enhanced ColⅠ immunoreactivity， elevate serum BNP， IL-6， and MMP-9 levels， a reduced IL-10 level （P<0.01）， downregulated expression of CD31 and VE-cadherin， and upregulated expression of α-SMA， Col1A2， HIF-1α， TGF-β1， and POSTN （P<0.05，P<0.01）， accompanied by increased CD31/α-SMA co-localization. Compared with the model group， the sacubitril/valsartan group and all HXWTF groups showed improved ventricular wall structure， increased LVEF and LVFS， decreased LVEDD and LVESD， attenuated myocardial injury with reduced inflammatory infiltration and collagen deposition， declined serum BNP， IL-6， and MMP-9 levels， an elevated serum IL-10 level， upregulated expression of CD31 and VE-cadherin， downregulated expression of α-SMA， Col1A2， HIF-1α， TGF-β1， and POSTN， and reduced CD31/α-SMA co-localization （P<0.05，P<0.01）. No significant differences were observed between the sacubitril/valsartan group and the medium- and high-dose HXWTF groups.ConclusionHXWTF may regulate the HIF-1α/TGF-β1/POSTN pathway to inhibit EndMT， thereby ameliorating post-MI ventricular remodeling.Keywords：Huoxue Wentong prescription;myocardial infarction;ventricular remodeling;endothelial-to-mesenchymal transition （EndMT）;hypoxia-inducible factor-1α （HIF-1α）/transforming growth factor-β1 （TGF-β1）/periostin （POSTN） signaling pathway31|5|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16
Mechanism of Shenji Guben Prescription in Treating Chronic Obstructive Pulmonary Disease in Mice Enhanced Publication AI Introduction
Abstract：ObjectiveTo evaluate the therapeutic effect of Shenji Guben prescription （SJGB） on chronic obstructive pulmonary disease （COPD） in mice and to explore its potential therapeutic mechanism via transcriptomics.MethodsA mouse model of COPD was established by combined exposure to lipopolysaccharide （LPS） and cigarette smoke. C57BL/6J mice were randomly allocated into a control group， a model group， an acetylcysteine （78 mg·kg-1·d-1） group， and low- （7.5 g·kg-1·d-1）， medium- （15 g·kg-1·d-1）， and high-dose （30 g·kg-1·d-1） SJGB groups. After 13 weeks of modeling， oral administration was initiated and continued for 28 days. The therapeutic effects of SJGB were assessed based on body weight， lung function， lung tissue pathology， and inflammatory factors in bronchoalveolar lavage fluid （BALF）. Ultra-high performance liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS） was employed to identify the active ingredients in SJGB. Transcriptomic profiling of lung tissue was performed by RNA-seq to identify differentially expressed genes （DEGs）， followed by gene ontology （GO） enrichment analysis， Kyotoencyclopedia of Genes and Genomes （KEGG） enrichment analysis， Gene Set Enrichment Analysis （GSEA）， and protein-protein interaction （PPI） network construction. Key genes were further validated by Western blot and Real‑time polymerase chain reaction （Real-time PCR）.ResultsAfter drug intervention， the final body weights of mice in medium- and high-dose SJGB groups were higher than those in the model group （P<0.05）. Compared with the model group， SJGB groups demonstrated a significant decrease in expiratory time （Te）， along with increases in peak expiratory flow （PEF）， 50% expiratory flow （EF50）， tidal volume （TV）， and expiratory volume （EV） （P<0.05）. High-dose SJGB ameliorated pathological changes in the lung tissue， reduced peribronchial inflammation scores， and decreased mean linear intercept （MLI） （P<0.01）. Compared with the model group， medium- and high-dose SJGB groups showed reductions in interleukin-6 （IL-6） and interleukin-1β （IL-1β） levels （P<0.01）. UHPLC-MS/MS revealed that the five most abundant components in SJGB were （S）-actinidine， ephedrine， pyroglutamic acid， methylephedrine， and coumarin. Transcriptomic analysis revealed 219 DEGs regulated by SJGB， suggesting that the anti-COPD effects of SJGB may be mediated through key genes such as cluster of differentiation 68 （CD68）， integrin subunit alpha X （ITGAX）， and cathepsin S （CTSS）， primarily involved in the lysosomal pathway. Western blot and Real-time PCR results confirmed that SJGB inhibited the expression of CD68， ITGAX， and CTSS compared with the model group （P<0.05）.ConclusionSJGB effectively improved the lung function and attenuated lung tissue inflammation in the mouse model of COPD by modulating the lysosomal pathway and related genes including CD68， ITGAX， and CTSS.Keywords：Shenji Guben prescription;chronic obstructive pulmonary disease （COPD）;transcriptomics;lysosomal pathway;therapeutic mechanism33|5|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Exploration on Mechanism of Shengjiang Pingchuan Zhike Pills Against Cough Variant Asthma by Modulating AMPK/mTOR/ULK1 Signaling Pathway Based on Transcriptomics Enhanced Publication AI Introduction
Abstract：ObjectiveTo investigate the mechanism by which Shengjiang Pingchuan Zhike pills （SPZP） alleviate airway injury in the rat model of cough variant asthma （CVA） via regulating autophagy through activating the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/Unc-51-like autophagy activating kinase 1 （ULK1） signaling pathway based on transcriptomics， thus providing experimental evidence for the clinical application of SPZP.MethodsForty SPF-grade SD rats were enrolled in the present study and randomly via the random number table method assigned into four groups： a blank group， a model group， a SPZP （2 160 mg·kg-1·d-1） group， and a positive drug （montelukast sodium， MTL， 0.9 mg·kg-1·d-1）group， with 10 rats in each group. After one week of adaptive feeding， the rat model of cough variant asthma （CVA） was established by two-week sensitization with ovalbumin （OVA） and aluminium hydroxide， followed by capsaicin atomization challenge. Rats in the blank group received an equal volume of normal saline during modeling. Upon successful modeling， rats in the SPZP group and positive drug group were administrated with SPZP suspension and MTL solution， respectively， while those in the blank and model groups received the same dose of normal saline by gavage. The whole intervention lasted for 21 consecutive days. After the intervention， general behaviors of rats in each group were observed. Pulmonary function indicators were subsequently detected. Hematoxylin-eosin （HE） staining was performed to visualize the pathological morphology of the lung tissue， and periodic acid-Schiff （PAS） staining was adopted to evaluate airway mucus secretion. Transcriptomic sequencing was conducted to screen differentially expressed genes in the lung tissue across groups. The levels of inflammatory cytokines including interleukin （IL）-4， IL-5， immunoglobulin E （IgE）， and interferon-γ （IFN-γ） in the bronchoalveolar lavage fluid （BALF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence staining was used for detecting the co-localization of autophagy-related protein Beclin-1 and phosphorylated mammalian target of rapamycin （p-mTOR）. Transmission electron microscopy was employed to count autophagosomes and observe mitochondrial morphological changes in the lung tissue. Western blot assay was utilized to measure the expression levels of AMPK/mTOR/ULK1 axis-related proteins， including AMPK， phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， mTOR， phosphorylated mammalian target of rapamycin （p-mTOR）， ULK1， and phosphorylated Unc-51-like autophagy activating kinase 1 （p-ULK1） as well as the autophagy biomarkers Beclin-1 and selective autophagy adaptor protein p62 in lung specimens.ResultsCompared with the blank group， the model group exhibited markedly elevated cough frequency accompanied by wheezing and stridor， dull fur， poor mental activity， diminished motor activity， accelerated respiratory rate， and weakened sensory response and mobility to external stimuli， accompanied by a declining tendency of body mass. Meanwhile， the model group exhibited decreased dynamic lung compliance， increased airway resistance （P<0.01）， severe pathological damage and excessive mucus secretion in the lung tissue （P<0.01）， and elevated levels of IL-4， IL-5， and IgE and declined level of IFN-γ in the BALF （P<0.01）. Ultrastructural observation revealed damaged mitochondrial morphology and a sharp reduction in the number of autophagosomes in the lung tissue. In addition， the expression of p-AMPK， p-ULK1， and Beclin-1 were downregulated， whereas p-mTOR and p62 were highly expressed （P<0.05， P<0.01） in the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses demonstrated significant enrichment of AMPK， mTOR， and autophagy-related pathways. Compared with the model group， both the positive drug group and SPZP group obtained visible improvements in general behavioral manifestations and obvious recovery of pulmonary function indicators （P<0.05）， alleviated pulmonary pathological lesions and suppressed excessive airway mucus secretion （P<0.05）， recovered levels of inflammatory cytokines in the BALF （P<0.05）， restored mitochondrial morphology， increased autophagosomes， upregulated expression levels of p-AMPK， p-ULK1， and Beclin-1， and downregulated expression levels of p-mTOR and p62 （P<0.05）.ConclusionSPZP can effectively ameliorate airway inflammation and improve the pulmonary function in the rat model of CVA by activating the AMPK/mTOR/ULK1 signaling pathway， enhancing autophagy in the lung tissue， and inhibiting excessive airway mucus secretion and immune inflammatory imbalance.Keywords：Shengjiang Pingchuan Zhike pills;cough variant asthma;autophagy;adenosine monophosphate-activated protein kinase/mammalian target of rapamycin/Unc-51-like autophagy activating kinase 1 （AMPK/mTOR/ULK1） signaling pathway;transcriptomics;autophagosome38|6|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Investigating Therapeutic Effect and Mechanism of Zhengqi Prescription on Cancer-related Fatigue by UPLC-MS and Network Pharmacology Enhanced Publication AI Introduction
Abstract：ObjectiveTo characterize the systemically absorbed components of Zhengqi prescription （ZQP） and investigate its therapeutic effects and mechanisms against cancer-related fatigue （CRF） through an integrated approach of network pharmacology and animal experiments.MethodsThe systemically absorbed components of ZQP were identified by ultra-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry （UPLC-Q-Exactive Orbitrap MS）. Network pharmacology was employed to predict the potential targets and signaling pathways involved in the anti-CRF effects of ZQP. A mouse model of paclitaxel-induced CRF， mimicking breast cancer-related fatigue， was established. Mice were administered different doses of ZQP extract. The therapeutic efficacy was evaluated based on fatigue-related indicators， behavioral test results， and energy metabolism parameters. Western blot analysis was conducted to validate the regulation of core signaling pathways.ResultsA total of 48 systemically absorbed components were identified. Network pharmacology analysis revealed 124 intersecting targets （including Akt1） and implicated signaling pathways such as phosphatidylinositol 3-kinase/protein kinase （PI3K/Akt）. Pharmacodynamic studies with the established CRF model demonstrated that ZQP alleviated fatigue symptoms. Specifically， ZQP-treated mice exhibited increased exhaustive swimming time （P<0.05）， prolonged struggling time in the tail suspension test， and enhanced movement duration and distance in the open field test （P<0.05， P<0.01）. Furthermore， ZQP treatment decreased serum lactate and blood urea nitrogen levels （P<0.05， P<0.01）， increased liver and muscle glycogen content （P<0.05， P<0.01）， and upregulated the expression of phosphorylated （p）-Akt and p-PI3K in the gastrocnemius muscle （P<0.05， P<0.01）.ConclusionZQP exerts significant therapeutic effects on paclitaxel-induced breast cancer-related fatigue by regulating the PI3K/Akt signaling pathway. Furthermore， this study provides a preliminary foundation for subsequent quality control of the formula and further investigation into its mechanism against CRF.Keywords：Zhengqi prescription;cancer-related fatigue;ultra-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry （UPLC-Q-Exactive Orbitrap MS）;network pharmacology;phosphatidylinositol 3-kinase/protein kinase （PI3K/Akt） signaling pathway37|5|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Clinical Efficacy of Modified Zhishi Daozhi Decoction on Metabolic Associated Fatty Liver Disease Due to Dampness-heat and Stasis Obstruction Enhanced Publication AI Introduction
Abstract：ObjectiveTo evaluate the clinical efficacy of modified Zhishi Daozhi decoction in treating patients with metabolic associated fatty liver disease （MAFLD） due to dampness-heat and stasis obstruction.MethodsA randomized controlled trial design was adopted， with patients diagnosed with MAFLD due to dampness-heat and stasis obstruction treated in the Department of Endocrinology， Metabolism， and Gastroenterology at the Third Affiliated Hospital of Changchun University of Chinese Medicine between November 2023 and November 2024 as the study subjects. A total of 126 patients who met the inclusion criteria were randomized into an observation group and a control group， with 63 patients in each group. The observation group was administered the granule preparation of modified Zhishi Daozhi decoction， while the control group received Xuezhikang capsules orally. Both groups underwent a 12-week treatment course. The two groups before and after treatment were compared in terms of obesity indicators ［body weight， body mass index （BMI）， waist circumference （WC）， weight-adjusted waist circumference index （WWI）， and waist-to-hip ratio （WHR）］， lipid indicators ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C）］， liver function indicators ［alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and gamma-glutamyl transpeptidase （GGT）］， liver ultrasound imaging， traditional Chinese medicine （TCM） symptom scores， and Patient-Reported Outcome （PRO） scale scores at follow-up.Results① After treatment， the body weight， BMI， and levels of TC， TG， and LDL-C declined in both groups （P<0.05， P<0.01）， and the observation group demonstrated larger reductions in BMI， WC， LDL-C （P<0.05）， and WHR （P<0.01）. The levels of ALT， AST， and GGT declined in the observation group after treatment （P<0.05）， whereas no statistically significant differences in the three indicators were observed in the control group before and after treatment. Subgroup analysis based on normal vs. abnormal liver function revealed intergroup differences only in the abnormal liver function cohort. After treatment， the observation group demonstrated greater reductions in ALT （P<0.01） and AST （P<0.05） than the control group. ② The total response rate of liver ultrasound imaging was 79.24% （42/53） in the observation group and 62% （31/50） in the control group. Post-treatment comparison showed that the observation group （χ2=21.311， P<0.01） achieved greater alleviation of fatty liver disease severity. ③ The total response rate of TCM syndrome was 94.34% （50/53） in the observation group and 66% （33/50） in the control group， with the observation group demonstrating superior efficacy （χ2=26.78， P<0.01）. Compared with the control group post-treatment， the observation group showed enhanced reductions in the total TCM symptom score （P<0.01） and individual symptom scores of rib distension and pain， sticky and unsmooth stools， obesity with abdominal distension， sticky sensation in the mouth， and yellowish-red urine （P<0.01）. ④ After treatment， the PRO score improved in both groups （P<0.01）， and the increase was larger in the observation group （P<0.01）， primarily reflected in the physiological dimension （P<0.01）.ConclusionModified Zhishi Daozhi decoction shows definite efficacy in treating MAFLD patients with the syndrome of dampness-heat and stasis obstruction， with effects of alleviating abdominal obesity and regulating blood lipids. Additionally， it positively impacts patients quality of life， as evidenced by the changes in TCM symptom and PRO scores.Keywords：modified Zhishi Daozhi decoction;metabolic associated fatty liver disease;syndrome of dampness-heat and stasis obstruction;clinical efficacy;resolving food stagnation， promoting digestion， and dredging collaterals27|5|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16- Abstract：ObjectiveTo observe the clinical efficacy and safety of Shenshuai Guanchang prescription in improving the intestinal barrier function，reducing non-indole uremic toxins，ameliorating micro-inflammatory state，and delaying renal function progression in non-dialysis patients with chronic kidney disease （CKD） stage 4-5.MethodsA total of 80 patients with CKD stage 4-5 who did not receive dialysis replacement therapy and were diagnosed with the syndrome of spleen and kidney deficiency，blood stasis and dampness turbidity were randomly assigned into a control group and a treatment group，with 40 patients in each group. The control group received conventional basic treatment and Western medicine symptomatic treatment，while the treatment group received combined intervention with Shenshuai Guanchang prescription through retention enema in addition to the treatment of the control group. Both groups had a treatment course of 4 weeks. The two groups were compared regarding the changes in urine toxin indicators ［p-cresyl sulfate （PCS） and trimethylamine oxide （TMAO）］，intestinal barrier indicators ［D-lactic acid （D-LA），lipopolysaccharide （LPS），and intestinal fatty acid-binding protein （I-FABP）］，renal function indicators ［serum creatinine （SCr），blood urea nitrogen （BUN），and estimated glomerular filtration rate （eGFR）］，and micro-inflammatory state indicators ［interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），and neutrophil-to-lymphocyte ratio （NLR）］ before and after treatment. The therapeutic effects were evaluated from three aspects：The efficacy regarding traditional Chinese medicine （TCM） symptom scores，the efficacy regarding laboratory indicators，and comprehensive efficacy. The safety of the clinical research drugs used by both groups of patients was also observed.ResultsA total of 37 cases in the treatment group and 38 cases in the control group completed the observation. After treatment，the treatment group showed declined levels of PCS，TMAO，D-LA，SCr，TNF-α，and NLR，spleen and kidney deficiency symptom score，blood stasis and dampness symptom score，and total symptom score （P<0.05），and increased eGFR （P<0.05）. Moreover，the treatment group had lower levels of PCS，TMAO，D-LA，I-FABP，IL-6，and TNF-α，spleen and kidney deficiency symptom score，blood stasis and dampness symptom score，and total symptom score （P<0.05），higher response rate regarding TCM symptoms （χ2=6.68，P<0.05），and higher comprehensive efficacy （χ2=4.08，P<0.05） than the control group. No significant abnormalities were observed in the safety indicators of the two groups of patients. During the treatment period，adverse reactions were reduced after symptomatic treatment，and no serious adverse reactions occurred.ConclusionShenshuai Guanchang prescription can alleviate the clinical symptoms，improve the intestinal barrier function，reduce non-indole-type uremic toxins，alleviate the micro-inflammatory state，and has good clinical application safety of non-dialysis patients with CKD stage 4-5.Keywords：chronic kidney disease;Shenshuai Guanchang prescription;randomized controlled trial;external treatment of traditional Chinese medicine8|2|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16
Compilation Explanation for Expert Consensus on Clinical Application of Ruyi Zhenbao Pills AI Introduction
Abstract：The compilation explanation for the Expert Consensus on Clinical Application of Ruyi Zhenbao pills systematically expounds the formulation methods and evidence-based basis of this consensus. In response to the weak clinical application evidence and ambiguous indications of Ruyi Zhenbao pills， the Institute of Basic Research in Clinical Medicine of China Academy of Chinese Medical Sciences， Wangjing Hospital of China Academy of Chinese Medical Sciences， and Dongzhimen Hospital of Beijing University of Chinese Medicine invited 39 experts from 31 medical institutions across China to complete the compilation through multi-disciplinary collaboration. The compilation strictly adheres to the World Health Organization （WHO） guidelines for guideline development and the GRADE evidence grading system. The work process covered the construction of clinical questions （a total of 30 clinical questions were determined based on expert voting results）， evidence retrieval （covering Chinese and English databases and gray literature）， safety assessment （integrating drug monitoring data and clinical research）， and the formation of recommendation opinions and consensus suggestions （18 recommendation opinions were reached through the GRADE grid method， and 22 consensus suggestions were reached through majority voting rules）. The results show that the consensus clearly states that this medicine is suitable for knee osteoarthritis， gouty arthritis， rheumatoid arthritis， neuropathic pain， and sequelae of stroke. In terms of safety， the adverse reactions are mainly gastrointestinal reactions such as nausea， vomiting， and abdominal pain. Pregnant women and those allergic to the ingredients of this medicine are contraindicated. The compilation process underwent three rounds of expert reviews and adopted methods such as nominal group technique and Delphi method to ensure the rigor of the consensus compilation process. It provides a paradigm for the formulation of expert consensus on clinical application of Tibetan medicine through the academic promotion and dynamic revision.Keywords：Ruyi Zhenbao pills;clinical application;expert consensus;compilation explanation;Tibetan medicine9|2|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Outcome Indicators in Randomized Controlled Trials of Traditional Chinese Medicine Intervention in Chronic Kidney Disease Enhanced Publication AI Introduction
Abstract：ObjectiveTo systematically collate the randomized controlled trials （RCTs） on the intervention of traditional Chinese medicine （TCM） in chronic kidney disease （CKD） and analyze the characteristics of clinical trials and the current situation of outcome indicators， thus providing references for constructing a core outcome set （COS） for CKD.MethodsThe RCTs on the intervention of TCM in CKD were retrieved from CNKI， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science with the time interval from January 2022 to December 2024. The risk of bias was evaluated， and the outcome indicators were qualitatively analyzed.ResultsA total of 242 RCTs were included， which reported 238 outcome indicators， with the cumulative frequency of 2 724 times. These outcome indicators can be classified into seven domains： TCM syndromes and diseases （270 times， accounting for 9.90%）， symptoms and signs （218 times， 8.00%）， physical and chemical examinations （1 609 times， 59.07%）， quality of life （29 times， 1.06%）， long-term prognosis （6 times， 0.22%）， economic evaluation （0 times）， and safety events （535 times， 19.64%）. The results demonstrated that the RCTs of TCM intervention for CKD had several shortcomings such as the lack of a basis for sample size estimation， lack of standardization in TCM syndrome differentiation and classification， room for improvement in methodological quality， flaws in the design of the timing of efficacy measurement， absence of long-term prognosis evaluation， imbalance in the selection of surrogate and endpoint indicators， disconnection between overall evaluation and individualized assessment， lack of TCM characteristic indicators， and insufficient reporting of safety indicators.ConclusionAt present， the design of outcome indicators in the RCTs for TCM intervention in CKD is still not standardized. It is recommended that future research endeavors to enhance methodological quality， establish a standardized COS for TCM intervention in CKD， and thereby propel the high-quality development of TCM.Keywords：chronic kidney disease;traditional Chinese medicine;randomized controlled trials;outcome indicators;core set of indicators46|5|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Exploring Clinical Application and Mechanism of Huangqi Guizhi Wuwutang Based on Theory of Treating Different Diseases with Same Method Enhanced Publication AI Introduction
Abstract：Huangqi Guizhi Wuwutang was first documented in ZHANG Zhongjing's Synopsis of the Golden Chamber in the Eastern Han Dynasty as the principal formula for treating blood obstruction syndrome. It is composed of Astragali Radix， Cinnamomi Ramulus， Paeoniae Radix Alba， Zingiberis Rhizoma Recens， and Jujubae Fructus. This formula exhibits the effects of replenishing Qi， warming meridians， harmonizing blood， and relieving obstruction， being primarily indicated for blood obstruction syndrome characterized by diminished Yin and Yang functions with external manifestations of bodily numbness. Traditional Chinese medicine （TCM） emphasizes strict adherence to pathogenesis while applying tailored therapies， employing consistent treatment approaches for conditions with diverse clinical presentations but shared pathogenesis， which embodies the principle of treating different diseases with the same method. In modern clinical practice， Huangqi Guizhi Wuwutang is widely applied in multisystem disorders presenting with symptoms such as cutaneous numbness， cold-induced pain and stiffness， and soreness and weakness， including diabetic peripheral neuropathy， cervical radiculopathy， rheumatoid arthritis， coronary heart disease， pediatric spastic cerebral palsy， and recovery phases of cerebral infarction， demonstrating proven efficacy. Modern pharmacological studies confirm its anti-inflammatory， antioxidant-stress， hemorheological-improving， immunomodulatory， and neuroprotective effects by regulating multiple signaling pathways such as nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3） and nuclear factor erythroid 2-related factor 2 （Nrf2）-antioxidant response element （ARE）， thereby addressing common pathological processes including inflammation， hypercoagulability， oxidative stress， immune dysregulation， and neural injury， highlighting the integrated regulatory advantages of TCM formulas with multi-target， multi-level， multi-component， and multi-pathway mechanisms. According to the theory of treating different diseases with the same method and focusing on three core syndromes of blood obstruction， this article systematically reviews and elucidates the clinical extensions and shared mechanisms of this formula， aiming to provide evidence-based insights for the modern adaptation and precise application of this classical formula in orthopedic and related disciplines for chronic musculoskeletal disorders.Keywords：treating different diseases with the same method;Huangqi Guizhi Wuwutang;blood obstruction syndrome;clinical application;mechanism60|14|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Mechanism of Mitochondrial Dynamics in Chronic Heart Failure and Treatment from Perspective of Yin at Peace and Yang Being Compact AI Introduction
Abstract：Chronic heart failure is the terminal stage of various cardiovascular diseases， and its occurrence and progression are closely associated with impaired myocardial energy metabolism and mitochondrial dysfunction. Mitochondrial dynamics maintain cardiomyocyte energy homeostasis through fusion， fission， and quality control. Disruption of mitochondrial dynamics may lead to mitochondrial network fragmentation， insufficient adenosine triphosphate （ATP） production， enhanced oxidative stress， and activation of ferroptosis. The theory of Yin at peace and Yang being compact originates from the Chapter Discussion on Interrelationship between Life and Nature in the Plain Questions， and emphasizes that the dynamic balance between Yin and Yang is fundamental to normal life activities. According to this theory and mitochondrial dynamics， this paper explores the pathogenic connotations of Yang failing to remain compact and Yin failing to remain at peace in chronic heart failure. In traditional Chinese medicine （TCM）， chronic heart failure is characterized by deficiency in origin and excess in manifestation. Deficiency of heart Qi and Yang is the root， often accompanied by Yang deficiency or Yin deficiency， while blood stasis， phlegm turbidity， and water retention constitute the manifestations. When Yang fails to remain compact， cardiac propulsion becomes weakened and Qi transformation is impaired. When Yin fails to remain at peace， Yin pathogens are generated and Yin essence is consumed. At the microscopic level， imbalance of mitochondrial dynamics is manifested as insufficient mitochondrial fusion， excessive fission， reduced energy production， excessive ROS generation， expansion of the labile iron pool， and accumulation of lipid peroxidation products， which contribute to Yin-Yang imbalance in chronic heart failure. Furthermore， by integrating formula-pattern correspondence and the approach of inferring patterns from formula effects， this paper summarizes the possible molecular phenotypes corresponding to different syndrome elements and syndrome patterns. It further proposes keeping Yang compact and keeping Yin at peace as therapeutic principle for chronic heart failure， aiming to restore energy metabolism homeostasis by regulating mitochondrial dynamics with TCM and to provide new perspectives and ideas for the treatment of chronic heart failure.Keywords：chronic heart failure;Yin at peace and Yang being compact;mitochondrial dynamics;"keeping Yang compact";"keeping Yin at peace"35|5|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Current Status of Prediction Models of Traditional Chinese Medicine for Emerging Acute Infectious Diseases Enhanced Publication AI Introduction
Abstract：ObjectiveTo analyze the current status of traditional Chinese medicine （TCM） prediction model research for emerging acute infectious diseases， in order to provide reference for subsequent model construction and optimization.MethodsEight databases， including PubMed， Cochrane Library， and Embase， were systematically searched to comprehensively collect Chinese and English literature on TCM prediction models for emerging acute infectious diseases. The search period ranged from database inception to July 5， 2024. Reporting quality compliance was evaluated using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis—Traditional Chinese Medicine （TRIPOD-TCM） guideline. Risk of bias and applicability were assessed using the Prediction Model Risk of Bias Assessment Tool （PROBAST）.ResultsA total of 21 studies were included， comprising 11 early warning model studies， 5 diagnostic model studies， 3 prognostic model studies， and 2 prescription prediction model studies， involving 84 models in total. The diseases involved were mainly viral infectious diseases such as coronavirus disease 2019 （COVID-19） and hepatitis B. The most frequently applied TCM theory was the "five movements and six climates" theory. The most commonly used modeling method was neural network-based approaches. The most frequently reported predictive factors were meteorological variables， including daily mean temperature， wind speed， precipitation， relative humidity， and vapor pressure. In terms of reporting quality， the included studies showed poor item-level compliance， with only 13 sub-items achieving compliance rates above 50%. Overall compliance ranged from 27% to 59% across studies. Although the included studies showed relatively good applicability， all were assessed as having a high risk of bias. The main sources of bias included inappropriate handling of missing data， absence of calibration methods， and unreasonable validation strategies， indicating deficiencies across multiple stages of model development.ConclusionCurrent research on TCM prediction models for emerging acute infectious diseases exhibits distinctive modeling characteristics. These models are based on traditional TCM theories such as the "five movements and six climates"， incorporate TCM-specific features as predictive variables， and use TCM syndromes as outcomes. However， they generally suffer from low reporting compliance and a high risk of bias. Future studies should systematically design model development and validation processes， adhere to TRIPOD-TCM reporting standards， and apply PROBAST or develop dedicated bias risk assessment tools for TCM prediction models to improve methodological quality and promote their translation into clinical practice.Keywords：emerging acute infectious diseases;traditional Chinese medicine;prediction model research;methodological quality;current analysis43|6|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Chinese Medicine in Treatment of Colorectal Cancer by Regulating Hedgehog Signaling Pathway： A Review Enhanced Publication AI Introduction
Abstract：Colorectal cancer （CRC）， as a highly prevalent malignant tumor worldwide， continues to rank among the leading malignancies in both incidence and mortality. At present， the clinical treatment of CRC mainly relies on surgery， radiotherapy， chemotherapy， and drug therapy. However， due to individual differences among patients and the emergence of drug resistance in cancer cells， the postoperative recurrence rate remains high， significantly affecting patient prognosis. In recent years， traditional Chinese medicine （TCM） has attracted extensive attention in the field of tumor prevention and treatment because of its therapeutic advantages of multi-component， multi-target， multi-pathway， and holistic regulation. Aberrant activation of the Hedgehog signaling pathway is closely associated with the occurrence of various cancers. Studies have shown that the Hedgehog signaling pathway plays a key regulatory role in the occurrence and development of CRC. This pathway regulates the expression of downstream target genes through glioma-associated oncogene homolog （GLI） transcription factors and participates in biological processes such as tumor cell proliferation， apoptosis， invasion， and metastasis. It exerts anti- CRC effects through mechanisms including inducing apoptosis of CRC cells， inhibiting cancer cell proliferation， reversing drug resistance， and suppressing epithelial-mesenchymal transition （EMT）， thereby influencing the progression of CRC. This article systematically reviews the latest research progress in China and abroad and comprehensively discusses the molecular regulatory mechanisms of the Hedgehog signaling pathway in CRC. It particularly focuses on the specific mechanisms by which active components of Chinese medicine， such as alkaloids and terpenoids， and Chinese medicine compound formulas， such as Baitouwengtang and Zhizhenfang， exert anti-CRC effects by interfering with the Hedgehog-GLI signaling axis. By integrating and analyzing the molecular relationship between the Hedgehog signaling pathway and the pathological progression of CRC， and combining the TCM theories of "holistic concept" and "syndrome differentiation and treatment"， this article explores new TCM therapeutic strategies based on the Hedgehog signaling pathway， with the aim of providing innovative theoretical foundations and practical guidance for the prevention and treatment of CRC with TCM.Keywords：colorectal cancer;Hedgehog signaling pathway;active ingredients of Chinese medicine;Chinese herbal compound prescription;research progress48|7|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Traditional Chinese Medicine Manages Lung Cancer Based on Epigenetic Regulation： A Review Enhanced Publication AI Introduction
Abstract：Lung cancer is the malignant tumor with the highest morbidity and mortality worldwide. The number of cases and deaths in China also remains at a high level， posing a severe threat to human health. In recent years， although early diagnostic and therapeutic strategies for lung cancer have been continuously optimized， with clinical interventions mainly consisting of surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy， the patient prognosis remains unsatisfactory. The core reason is that the mechanisms underlying lung cancer development and progression have not yet been fully elucidated. Therefore， delving into the molecular mechanisms and key regulatory nodes is of great significance for improving diagnostic and therapeutic outcomes. In recent years， traditional Chinese medicine （TCM） and its active components have demonstrated unique advantages and potential in the prevention and treatment of lung cancer through epigenetic regulation. Studies have confirmed that single herbs， compound formulas， and active components of TCM can exert anti-tumor effects by modulating epigenetic pathways such as DNA methylation， histone modification， and non-coding RNAs. These effects include inhibiting tumor cell proliferation， inducing apoptosis， reducing invasive and metastatic capacity， regulating the cell cycle， and modulating the tumor microenvironment， thereby blocking the initiation and progression of lung cancer. Furthermore， TCM shows significant advantages in enhancing the anti-tumor efficacy of chemotherapeutic agents and alleviating treatment-related adverse effects. However， the current research on TCM-based epigenetic regulation of lung cancer remains at a preliminary exploratory stage. Common limitations include the complexity of targets， a predominant focus on crude herbal extracts or single epigenetic modifications， and a lack of systematic elucidation of the synergistic effects among multiple epigenetic modifications and the regulatory networks involving multicellular interactions. This article reviews the epigenetic mechanisms involved in the development and progression of lung cancer and summarizes the basic and clinical research progress in TCM interventions， aiming to offer insights for further elucidating lung cancer pathogenesis and exploring TCM-based therapeutic strategies.Keywords：epigenetics;lung cancer;traditional Chinese medicine;DNA methylation;histone modification;non-coding RNA51|5|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Traditional Chinese Medicine and Its Active Components Treat Pancreatic Cancer via Regulation of Programmed Cell Death： A Review Enhanced Publication AI Introduction
Abstract：Pancreatic cancer （PC）， a highly malignant tumor of the digestive system， is characterized by extremely high incidence and mortality rates， imposing a severe burden on the healthcare system. Despite significant advancements in comprehensive therapeutic strategies for PC， clinical benefits for patients remain limited due to the high heterogeneity and unique microenvironment of the tumor. Therefore， further elucidating the molecular mechanisms underlying PC progression and developing novel， effective therapeutic strategies have become an urgent necessity in the current research. Programmed cell death （PCD） is a genetically orchestrated process of autonomous cell demise that is crucial for maintaining cellular homeostasis. Recent studies have demonstrated that tumor cells can remodel the tumor microenvironment by modulating various PCD pathways—including apoptosis， autophagy， pyroptosis， and ferroptosis—thereby driving tumor proliferation， invasion， and drug resistance. Traditional Chinese medicine （TCM） possesses unique advantages in anti-tumor therapy， characterized by multi-component， multi-target， and multi-pathway regulation. Accumulating evidence suggests that TCM formulas and their natural active compounds can effectively delay the malignant progression of PC by modulating PCD in tumor cells. This article systematically summarizes the molecular mechanisms of PCD in PC progression and reviews the mechanisms by which TCM formulas and natural active compounds intervene in PC through PCD modulation. This review aims to provide theoretical support and future research directions for the prevention and treatment of PC with TCM.Keywords：pancreatic cancer;programmed cell death;traditional Chinese medicine;molecular mechanisms;research progress43|6|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Traditional Chinese Medicine Treats Coronary Heart Disease by Intervening in Cardiovascular Cell Apoptosis： A Review Enhanced Publication AI Introduction
Abstract：Coronary heart disease （CHD）， as a globally prevalent disease with high mortality， is closely associated with cardiovascular cell apoptosis in its pathogenesis. Although current therapies such as percutaneous coronary intervention （PCI） can alleviate local stenosis and significantly improve revascularization， challenges such as postoperative reperfusion injury and microcirculation dysfunction persist. Due to the limitations of single-target therapy in modern medicine， traditional Chinese medicine （TCM） has attracted increasing attention for its multi-component and multi-target interventions. Modern medical research indicates that cardiovascular cell apoptosis contributes to CHD progression through multiple pathways， including the mitochondrial pathway， death receptor pathway， and endoplasmic reticulum stress pathway. In TCM theory， CHD falls under the categories of chest obstruction， heart pain， and real heart pain. The Synopsis of the Golden Chamber （Jin Gui Yao Lue） proposes the pathogenesis theory of Yang deficiency and Yin excess， emphasizing the therapeutic principles of activating blood， regulating Qi movement， resolving stasis， and unblocking collaterals. TCM demonstrates unique advantages in ameliorating myocardial ischemia and combating atherosclerosis. However， existing studies are largely confined to clinical observations， lacking in-depth exploration of TCM mechanisms in inhibiting cardiovascular cell apoptosis. This article systematically reviews the regulatory mechanisms of cardiovascular cell apoptosis in CHD and TCM intervention strategies， aiming to provide a theoretical basis for elucidating the scientific rationale behind TCM's role in suppressing apoptosis and improving cardiac function， while offering insights for developing innovative treatment approaches combining TCM and modern medicine. Future studies should leverage modern molecular biological technologies to further uncover the scientific essence of TCM regulation of apoptotic pathways. Integrating TCM's holistic regulation and multi-target intervention strengths with modern medicine's targeted therapies can advance both fundamental research and clinical translation， ultimately providing superior strategies for the prevention and treatment of CHD.Keywords：coronary heart disease;endogenous apoptosis;exogenous apoptosis;endoplasmic reticulum stress （ERS） pathway;traditional Chinese medicine46|9|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Exploring Biological Mechanism and Potential Targets of "Heat-toxin Stagnation in Collaterals" in AECOPD Based on Neutrophil Extracellular Traps Enhanced Publication AI Introduction
Abstract：Acute exacerbation of chronic obstructive pulmonary disease （AECOPD） belongs to the pulmonary collateral disease of traditional Chinese medicine， and its pathogenesis is always lung deficiency and blood stasis， heat and toxin stagnation. Lung deficiency and blood stasis are the pathological basis of COPD， and heat and toxin stagnation lead to acute exacerbation of the disease. Currently， there are few direct studies on the intervention of traditional Chinese medicine regulating NETs in AECOPD， but based on the idea of treating similar diseases differently， exploring NETs as a biological target for "heat toxin blocking the meridians" can provide modern theoretical support for the traditional Chinese medicine treatment method of clearing heat and regulating meridians for AECOPD， and provide new ideas for the mechanism research and new drug development of AECOPD. Studies have shown that the overproduction of neutrophil extracellular traps （NETs） can mediate lung inflammation and damage lung epithelial and endothelial cells， which is intrinsically consistent with the pathogenesis of this traditional Chinese medicine. Based on the theory of collateral disease， this paper combs the relevant generation pathways of NETs and the modern scientific mechanism of NETs involved in the pathogenesis of AECOPD， analyzes the correlation between the pathogenesis of AECOPD "heat and toxin stagnation" and the biological effects of NETs， and summarizes the potential targets of traditional Chinese medicine to regulate nets in the prevention and treatment of AECOPD. NETs can damage the airway epithelium and alveolar microvascular endothelium through cytotoxic effects， activate multiple inflammatory signaling pathways to release a large number of pro-inflammatory factors， induce mucus hypersecretion and promote thrombosis， and mediate the occurrence and development of AECOPD. This pathological process corresponded to the pathogenesis of heat and poison burning the qi collaterals of the lung， consuming the blood collaterals， and brewing phlegm and blood stasis over time. Existing studies have shown that traditional Chinese medicine monomers， compounds and acupuncture and moxibustion can inhibit the Peptidylarginine deiminase 4（PAD4）， nicotinamide adenine dinucleotide phosphate（NADPH） oxidase 2（NOX2）， nuclear factor-κB（NF-κB）， Toll like protein（TLR） and other signaling pathways， reduce the excessive release of NETs， play a role in clearing heat and dredging collateral， detoxification and blood stasis， and reduce lung tissue damage. At present， there are few direct studies on the regulation of NETs by traditional Chinese medicine in AECOPD. However， relying on the idea of treating different diseases together， mining NETs as the biological target of "heat and toxin stagnation" can provide modern theoretical support for the treatment of AECOPD with traditional Chinese medicine to clear heat and clear collaterality， and provide new ideas for the mechanism research and new drug research and development of AECOPD.Keywords：acute exacerbation of chronic obstructive pulmonary disease （AECOPD）;collateral disease;neutrophil extracellular traps （NETs）;heat-toxin stagnation in collaterals;target13|3|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Application of Germ-free Animal Models in Sepsis and Traditional Chinese Medicine Research：A Review AI Introduction
Abstract：Sepsis remains a challenge in critical care worldwide，with intestinal microbiome dysbiosis implicated in its onset，progression，and organ dysfunction. Germ-free （GF） and human microbiota-colonized animals，by eliminating confounding from resident microbiota and combining induction methods such as CLP/LPS/live-bacterial challenge with fecal microbiota transplantation （FMT） and mono- or combined colonization，enable causal tests and dissection of microbiota-host interactions and drug mechanisms. This review summarizes the application of GF and related models in sepsis research. At the immune level，TLR-related signaling and pathogen community-induced suppression of IRF3-dependent defense affect innate immunity and pathogen clearance. At the barrier level，reprogramming of tight junction proteins and increased permeability drive gut-derived amplification. At the metabolic level，short-chain fatty acids and bile acids function as metabolic valves influencing GPR/HDAC signaling. At the epigenetic level，EZH2 and histone deacetylation emerge as druggable targets. We further synthesize anti-sepsis evidence for traditional Chinese medicine （TCM），mainly from conventional animals and clinical studies，discussing how formulae （e.g.，Xuebijing，Shenfu，and Huanglian Jiedu Tang） and active constituents （e.g.，berberine，luteolin，ginsenosides，and resveratrol） may act through microbiota-related and direct host pathways，with FMT/metabolite replenishment enabling further causal testing. Finally，we propose a closed-loop GF-humanized-clinical stratification paradigm for integrated evaluation of microecology，epigenetics，immunity，and organ outcomes，providing a translational path for precision prevention and treatment based on TCM and the microbiome.Keywords：germ-free animals;humanized germ-free;sepsis;gut microbiota;traditional Chinese medicine14|3|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16Therapeutic Mechanisms of Active Components and Compound Formulas of Astragali Radix for Ischemic Stroke： A Review AI Introduction
Abstract：Ischemic stroke （IS） is characterized by a high incidence， a high disability rate， and a high mortality rate. Its pathological mechanism is complex， involving oxidative stress， neuroinflammation， glutamate excitotoxicity， blood-brain barrier （BBB） disruption， abnormal autophagy and apoptosis， energy metabolism disorder， ferroptosis， and cuproptosis. Long-term use of conventional clinical drugs is associated with certain adverse reactions. As a classic Chinese herbal medicine for replenishing Qi， Astragali Radix is widely used in the prevention and treatment of IS. Modern research has confirmed that it contains various active components， including total astragalosides， total polysaccharides， and total flavonoids， which exert cerebroprotective effects by regulating signaling pathways such as nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， nuclear factor-κB （NF-κB）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， adenosine monophosphate-activated protein kinase/mammalian target of rapamycin （AMPK/mTOR）. These effects include anti-oxidation， anti-inflammation， inhibition of excitotoxicity， protection of BBB， regulation of autophagy and apoptosis， suppression of ferroptosis， and improvement of energy metabolism. This article systematically reviews the core pathological links of IS， summarizes the cerebroprotective effects of the main active components， classic herb pairs， and representative compound formulas of Astragali Radix， and analyzes their synergistic intervention patterns against the above pathological mechanisms. Furthermore， this paper discusses the current research limitations in clinical translation， material basis， and emerging cell death modalities， along with future perspectives， aiming to provide a theoretical reference for the clinical application of Astragali Radix and its combinations in treating IS and for the development of new drugs.Keywords：Astragali Radix;active components;compound formulas;ischemic stroke;mechanism of action60|7|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-10-16
