摘要:ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease (DKD), and to explore its renal protective effects and underlying mechanisms.MethodsEight db/m mice were assigned to the normal group, and forty db/db mice were randomly divided into a model group, low-, medium-, and high-dose Danggui Shaoyaosan groups (8.39, 16.77, 33.54 g·kg-1), and an irbesartan group (0.025 g·kg-1). All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention, 24-h urine samples were collected using metabolic cages, after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein (GSP), serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), and triglycerides (TG). The urinary albumin-to-creatinine ratio (UACR) was measured. Renal pathological changes were observed using hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and Masson staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and monocyte chemoattractant protein-1 (MCP-1) levels. Immunofluorescence (IF) was performed to detect F4/80 expression in renal tissue, and immunohistochemistry (IHC) was used to assess CD206 expression. Real-time quantitative polymerase chain reaction (Real-time PCR) was employed to measure the mRNA expression of TNF-α, IL-10, inducible nitric oxide synthase (iNOS), and arginase-1 (Arg-1). Western blot analysis was used to detect the protein expression of iNOS, Arg-1, CD86, and CD206 in renal tissue.ResultsCompared with the normal group, the model group showed increased levels of GSP, UACR, SCr, BUN, TC, and TG, elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1, and decreased IL-10 levels (P<0.01). Pathological examination revealed glomerular hypertrophy, mesangial cell proliferation with marked mesangial expansion, inflammatory cell infiltration, vacuolar degeneration of renal tubular epithelial cells, prominent glycogen deposition, and increased collagen fiber deposition. In addition, relative F4/80 fluorescence intensity was enhanced, CD206 expression in the glomeruli and renal interstitium was reduced, and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased, iNOS and CD86 protein expression was increased, and Arg-1 and CD206 protein expression was decreased (P<0.05, P<0.01). Compared with the model group, the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP, UACR, SCr, BUN, TC, and TG, reduced serum TNF-α and MCP-1 levels, and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced, CD206 expression in the glomeruli and renal interstitium was increased, and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased, iNOS and CD86 protein expression was reduced, and Arg-1 and CD206 protein expression was increased (P<0.05, P<0.01).ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization, promoting M2 anti-inflammatory macrophage polarization, reducing inflammatory responses, delaying the progression of renal fibrosis, improving renal pathological injury, and thereby exerting renal protective effects.
摘要:ObjectiveTo investigate the potential mechanism of Danggui Shaoyaosan (DSS) in ameliorating renal injury in db/db mice.MethodsThirty 8-week-old specific pathogen-free (SPF)-grade male db/db mice and six db/m mice were acclimated for one week. Urinary microalbumin and blood glucose levels were measured weekly in both db/db and db/m mice. Successful modeling was determined by significantly higher microalbuminuria in db/db mice compared to db/m mice and a fasting blood glucose ≥16.7 mmol·L-1. The 30 db/db mice were randomly divided into five groups: the model group, the irbesartan (IBN) group, and three DSS dose groups (low-, medium-, and high-dose DSS groups, administered at 16.77, 33.54, 67.08 g·kg-1·d-1, respectively). Additionally, the six db/m mice served as the normal control group. The IBN group received irbesartan at 0.025 g·kg-1·d-1 by gavage, while the three DSS groups received DSS at 16.77, 33.54, and 67.08 g·kg-1·d-1 by gavage, respectively. The normal and model groups were administered with an equivalent volume of normal saline by gavage. All interventions lasted for 8 consecutive weeks. After intervention, serum creatinine (SCr), blood urea nitrogen (BUN), urinary total protein (UTP), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were measured to evaluate the therapeutic efficacy of the treatments. Renal histopathological changes were observed with hematoxylin-eosin (HE) staining. Western blot was used to detect the protein expression of silencing information regulator 1 (SIRT1), hypoxia-inducible factor-1α (HIF-1α), very low-density lipoprotein receptor (VLDLr), and cluster of differentiation 31 (CD31). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA levels of HIF-1α and VLDLr. Immunohistochemistry was used to observe the expression and distribution of HIF-1α and Caspase-3.ResultsCompared to the normal group, the model group showed significantly increased SCr, BUN, UTP, TG, and LDL-C. HE staining revealed glomerulosclerosis, mesangial matrix hyperplasia, capillary loop distortion and thickening, with extensive inflammatory cell infiltration. Protein expression of SIRT1 and CD31 significantly decreased (P<0.05), while HIF-1α and VLDLr protein and mRNA levels increased (P<0.05). Immunohistochemistry showed increased expression of HIF-1α and Caspase-3 (P<0.05), indicating hypoxia and apoptosis in renal cells. In all treatment groups, SCr, BUN, TG, and LDL-C were significantly reduced compared to the model group (P<0.05), and UTP was significantly improved in the medium-dose DSS group (P<0.05). Renal tissue structure and morphology were improved, inflammatory cells were reduced, and no vascular hyaline degeneration was observed. SIRT1 and CD31 protein expression was elevated to varying degrees compared to the model group (P<0.05), while HIF-1α and VLDLr protein and mRNA levels decreased (P<0.05). Immunohistochemistry showed reduced expression of HIF-1α and Caspase-3 in all treatment groups (P<0.05), with the most significant improvement observed in the IBN group and medium-dose DSS group (P<0.05).ConclusionDSS can effectively ameliorate glomerulosclerosis and lipid deposition in db/db mice, and its mechanism may involve the SIRT1/HIF-1α/VLDLr signaling pathway.
关键词:diabetic kidney disease;db/db mice;Danggui Shaoyaosan;glucose and lipid metabolism
摘要:ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 (TLR4/NF-κB p65/NLRP3) signaling pathway in the renal tissues of db/db mice with spontaneous diabetes, and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease (DKD).MethodsThirty db/db mice were divided into five groups: A model group, Danggui Shaoyaosan low- (16.77 g·kg-1·d-1), medium- (33.54 g·kg-1·d-1), and high-dose (67.08 g·kg-1·d-1) intervention groups, as well as an irbesartan group (0.025 g·kg-1·d-1) by the random number table method, with 6 mice in each group. Additionally, 6 db/m mice were assigned to the normal group. After 8 weeks of intervention, the following parameters were determined by corresponding methods: body weight, fasting blood glucose (FBG), 24-hour urinary protein (24 h-UTP), and serum creatinine (SCr) levels, renal histopathological analysis by hematoxylin-eosin (HE) staining, Masson staining, and periodic acid-Schiff (PAS) staining, the protein and mRNA expression levels of TLR4, NF-κB p65, NLRP3, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-18 (IL-18) by Western blot and Real-time quantitative polymerase chain reaction (Real-time PCR), as well as TLR4, NF-κB p65, and NLRP3 protein expression in renal tissues by immunohistochemistry (IHC).ResultsCompared with the normal group, the model group exhibited increased body weight, FBG, 24 h-UTP, and SCr levels (P<0.05); disordered renal structure, thickened basement membrane, and interstitial inflammatory cell infiltration, elevated TLR4, NF-κB p65, NLRP3, TNF-α, IL-1β, IL-6, and IL-18 expression; as well as decreased IL-10 expression (P<0.05). Compared with the model group, these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees (P<0.05).ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.
关键词:diabetic kidney disease;Danggui Shaoyaosan;inflammatory response;Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 (TLR4/NF-κB p65/NLRP3) signaling pathway;db/db mice
摘要:ObjectiveTo investigate the therapeutic efficacy of Danggui Shaoyaosan (DSS) on renal injury in db/db mice and its impact on endoplasmic reticulum stress (ERS) in renal tissues.MethodsThirty 8-week-old male db/db mice and six db/m mice were acclimated for one week, after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease (DKD) model. The model mice were randomly divided into a model group, an irbesartan group, and three DSS treatment groups with different doses (16.77, 33.54, and 67.08 g·kg-1·d-1). A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention, general conditions were observed. Serum cystatin C (Cys-C), 24-hour urinary total protein (24 h-UTP), 24-hour urinary microalbumin (24 h-UMA), urinary creatinine (Ucr), and urea nitrogen (UUN) were measured. Transmission electron microscopy (TEM) was used to observe glomerular basement membrane (GBM) and ultrastructural changes of the endoplasmic reticulum (ER) in glomerular endothelial cells. Western blot, real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78, CHOP, and related markers.ResultsCompared with the normal group, the mice in the model group showed curled posture, sluggish response, poor fur condition, increased levels of Cys-C, 24 h-UTP, 24 h-UMA, and UUN (P<0.05), while Ucr decreased (P<0.05). The GBM was significantly thickened, with podocyte and foot process fusion. The protein expressions of GRP78, CHOP, and ATF6 were significantly upregulated (P<0.05), the mRNA levels of GRP78 and CHOP increased (P<0.05), and immunohistochemistry showed an enhanced GRP78 signal (P<0.05). After treatment, the mice exhibited improved behavior, normalized GBM and podocyte structure, improved ER morphology and markedly better biochemical indicators. Western blot, Real-time PCR, and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups (P<0.05), suggesting alleviated ERS and improved renal function.ConclusionDSS can effectively ameliorate renal pathological damage in db/db mice, possibly by regulating ERS in glomerular endothelial cells, although the underlying signaling mechanisms require further investigation.
摘要:ObjectiveTo investigate the effects of Anmeidan (AMD) on protein expression of the ephrin type-A receptor 4 (EphA4)/ephrinA3 signaling pathway and synaptic structural function in an aged sleep deprivation model.MethodsSeventy-two 18-month-old aged mice were randomly divided into a blank group, a model group, AMD high-, medium-, and low-dose groups (26.26, 13.13, 6.565 g·kg-1·d-1, respectively), and a melatonin group (1.3 mg·kg-1·d-1), with 12 mice in each group. Cognitive function was assessed using the novel object recognition test. Hematoxylin-eosin (HE) staining was used to observe cell number and morphology in hippocampal tissues, and Nissl staining was performed to examine cellular structure and quantify Nissl bodies. Transmission electron microscopy was used to observe synaptic ultrastructure, with emphasis on changes in synaptic morphology and structure. Western blot was employed to detect the expression levels of EphA4, ephrinA3, brain-derived neurotrophic factor (BDNF), glutamate aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), growth-associated protein 43 (GAP43), postsynaptic density protein 95 (PSD95), and synaptophysin (SYN) in hippocampal tissues. Immunofluorescence double labeling was performed to co-stain EphA4 and ephrinA3 with glial fibrillary acidic protein (GFAP) and neuronal nuclei antigen (NeuN), respectively, to observe the colocalization of target proteins with neurons and astrocytes.ResultsCompared with the blank group, the model group exhibited increased exploration time of familiar objects (P<0.01), while exploration time of novel objects and the recognition index were decreased (P<0.01). The number of neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus was reduced, Nissl bodies were decreased, and synaptic structures were damaged. Protein expression levels of BDNF, GLAST, GLT-1, GAP43, PSD95, and SYN in hippocampal tissues were decreased, whereas the expression levels of EphA4, ephrinA3, and GFAP were increased. Compared with the model group, the AMD low-, medium-, and high-dose groups and the melatonin group showed increased exploration time of novel objects and higher novel object recognition indices (P<0.01), along with significantly reduced exploration time of familiar objects (P<0.01). Neuronal damage in the CA1 and DG regions was ameliorated, the number of Nissl bodies in the CA1 region was increased, and organelle and synaptic structural damage was alleviated. Protein expression levels of BDNF, GLAST, GLT-1, GAP43, PSD95, and SYN were increased, and protein expression levels of EphA4, ephrinA3, and GFAP were decreased (P<0.05,P<0.01).ConclusionAMD can regulate protein expression of the EphA4/ephrinA3 signaling pathway in an aged sleep deprivation model, enhance synaptic protein expression, and improve neuronal synaptic damage.
摘要:ObjectiveTo investigate the mechanisms by which Renshentang treats atherosclerosis (AS) in mice, focusing on the regulation of endothelial inflammatory responses mediated by transient receptor potential vanilloid subtype 1 (TRPV1).MethodsAn AS model was established in apolipoprotein E knockout (ApoE-/-) mice fed a high-fat diet. The mice were randomly divided into a simvastatin group (0.02 g·kg-1·d-1) and low-, medium-, and high-dose Renshentang groups (1.77, 3.54, 7.08 g·kg-1·d-1), with 12 mice in each group. ApoE-/- mice were fed a high-fat diet and treated simultaneously. C57BL/6J mice fed a normal diet served as the normal group (n=9). After continuous administration for 12 weeks, mice were anesthetized and the aortas were collected. Oil Red O staining was used to observe lipid plaque formation in the aorta. Hematoxylin-eosin (HE) staining was performed to examine pathological changes in the aortic root. Immunohistochemistry was used to analyze the levels of pro-inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), as well as the expression of TRPV1, phosphorylated phosphoinositide 3-kinase (p-PI3K), and phosphorylated protein kinase B (p-Akt) in the aortic root. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect endothelial nitric oxide synthase (eNOS) mRNA expression in the aorta, and Western blot was used to detect TRPV1 protein expression.ResultsCompared with the normal group, the model group showed a significant increase in aortic plaque formation (P<0.01) and significantly elevated levels of TNF-α and IL-1β in the aortic root (P<0.01). The expression levels of TRPV1, p-PI3K, and p-Akt were decreased (P<0.05, P<0.01), and eNOS mRNA expression was reduced (P<0.05, P<0.01). Compared with the model group, all Renshentang groups significantly reduced aortic plaque formation (P<0.01), significantly decreased TNF-α and IL-1β levels (P<0.01), and markedly increased the expression levels of TRPV1, p-PI3K, p-Akt, and eNOS mRNA (P<0.05, P<0.01).ConclusionRenshentang may inhibit endothelial inflammation and suppress the formation of AS by increasing TRPV1 protein expression and up-regulating the PI3K/Akt/eNOS signaling pathway, which may be one of the molecular mechanisms underlying its therapeutic effect against AS.
摘要:ObjectiveThis study aims to elucidate the potential mechanism of Zuojinwan in improving liver fibrosis through hepatic tissue metabolomics analysis.MethodsTwenty-four mice were randomly allocated into normal group, model group , positive drug group (silymarin, 100 mg·kg-1), and Zuojinwan group (Zuojinwan solution, 2.5 g·kg-1), with per group six mice. Liver fibrosis model was induced via intraperitoneal injection of olive oil solution with 10% carbon tetrachloride (CCl4) (0.5 μL·g-1, three times weekly for 8 weeks) in all groups except the normal group. During the final 4 weeks, the silymarin group received silymarin (100 mg·kg-1) by gavage thrice weekly, while the Zuojinwan group was administered Zuojinwan solution (2.5 g·kg-1) under the same regimen. After the last administration, the levels of liver fibrosis indicators and liver injury markers in serum were detected. The pathological morphological changes of the liver tissues were observed. The levels of liver fibrosis markers α-smooth muscle actin (α-SMA) and Collagen Ⅰ(ColⅠ) were detected. Metabolomics was analyzed on mice's liver tissues. The mice's serum was collected for metabolomics analysis.ResultsCompared with the model group, Zuojinwan significantly improved indicators related to liver fibrosis and liver injury. Compared with the normal group, the model group showed significantly elevated levels of fibrosis markers such as laminin (LN), hyaluronic acid (HA), procollagen typeⅢ (PC-Ⅲ), and type Ⅳ Collagen (Ⅳ-C), while liver injury indicators such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and total bilirubin (TBIL), exhibited a marked upward trend (P<0.05). Compared with the model group, the silymarin group showed a significant decrease in the aforementioned indicators (P<0.05). Notably, compared with the model group, the Zuojinwan group exhibited a significant reduction in all these indicators (P<0.05), with efficacy comparable to that of the silymarin group. Zuojinwan reduced mRNA and protein levels of α-SMA and ColⅠ in the liver tissue. Metabolomics results revealed that compared with the model group, Zuojiinwan significantly reduced levels of glucose metabolism-related metabolites such as D-fructose 1,6-bisphosphate (FBP), nicotinamide adenine dinucleotide phosphate (NADPH), sodium beta-D-fructose 6-phosphate (F6P), dihydroxyacetone phosphate (DHAP), fumaric acid, and D-glucose 6-phosphate (G6P) (P<0.05). Serum enzyme-linked immunosorbent assay (ELISA) was used to detect glucose metabolism indicators and further validate the regulatory effect of Zuojinwan on glucose metabolism.ConclusionThese results suggest that Zuojinwan may improve liver fibrosis by regulating the dysregulated levels of glucose metabolism during the progression of liver fibrosis.
摘要:ObjectiveTo explore the mechanism of Xianfang Huomingyin (XFHMY) in the treatment of type Ⅲ prostatitis (CP/CPPS) through network pharmacology, molecular docking, and animal experiments.MethodsThe traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Swiss Target Prediction database were used to screen and sort out the active ingredients and corresponding targets of XFHMY. The potential therapeutic targets of CP/CPPS were collected from online databases, such as the Online Mendelian Inheritance in Man (OMIM), GeneCards, and DisGeNET. The potential core targets of XFHMY for treating CP/CPPS were further screened by constructing a protein-protein interaction (PPI) network and performing topological analysis. Meanwhile, the DAVID database was chosen to perform enrichment analysis on the intersection targets. On this basis, the AutoDock software was used for molecular docking, and the data was subsequently imported into the GraphPad Prism 8 software to generate a heat map. SD rats were divided into seven groups: A blank group, a sham operation group, a model group, low-, medium-, and high-dose XFHMY groups (3.645, 7.29, 14.58 g·kg-1), and a tamsulosin hydrochloride group (0.018 mg·kg-1). Hematoxylin-eosin (HE) staining was used to evaluate the pathological changes in prostate tissue. The inflammatory factor indicators of rats in each group were detected via enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative reverse transcription polymerase chain reaction (Real-time PCR) and Western blot were used to evaluate the mRNA and protein expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and nuclear transcription factor-κB (NF-κB) p65 in prostate tissue.ResultsThe HE staining showed no significant signs of inflammatory cell infiltration in the prostate of the sham operation group compared to the blank group, while the model group had significantly inflammatory cell infiltration. The ELISA results showed that compared to the blank group, TNF-α, IL-1β, and COX-2 in the sham operation group had no significant differences. However, they were significantly higher in the model group (P<0.01), indicating successful CP/CPPS modeling in rats. Compared with the model group, the low-,medium-and high-dose XFHMY group and the tamsulosin hydrochloride group showed significant decreases in TNF-α, IL-1β, and COX-2 (P<0.05,P<0.01). The Real-time PCR analysis revealed that compared to the model group, the low-dose XFHMY group had reduced Akt and NF-κB p65 mRNA expression(P<0.05,P<0.01). In the medium-and high-dose XFHMY group and tamsulosin hydrochloride group, PI3K, Akt, and NF-κB p65 mRNA levels decreased significantly(P<0.05,P<0.01). Western blot analysis showed that compared to the model group, the low-dose XFHMY group had lower p-NF-κB p65/NF-κB p65 (P<0.05). The medium- and high-dose XFHMY group and the tamsulosin hydrochloride group showed significant decreases in p-PI3K/PI3K, p-Akt-ser473/Akt, p-Akt-thr308/Akt, and p-NF-κB p65/NF-κB p65 (P<0.01).ConclusionXFHMY may exert therapeutic efficacy on CP/CPPS by inhibiting the PI3K/Akt/NF-κB signaling pathway and reducing inflammatory responses. Additionally, NF-κB activation may be related to the activation of ser473 and thr308 sites.
摘要:ObjectiveTaking classical herbal pair compatibility research as the entry point, this study aimed to deeply investigate the material basis and compatibility rules underlying the antidepressant effects of the traditional Chinese medicine (TCM) formula Zhizi Houpotang, and to elucidate its antidepressant mechanism, with a particular focus on its regulation of neuroinflammatory responses mediated by the NOD-like receptor protein 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway and the consequent improvement of neuronal synaptic plasticity.MethodsC57BL/6J mice were randomly divided into a blank control group, a chronic unpredictable mild stress (CUMS) depression model group, a Zhizi Houpotang full-formula group (6 g·kg-1·d-1), a Magnoliae Officinalis Cortex (MOC)-Aurantii Fructus Immaturus (AFI) herbal pair group (4.2 g·kg-1·d-1), a Gardeniae Fructus (GF)-MOC herbal pair group (4.2 g·kg-1·d-1), a GF-AFI herbal pair group (3.6 g·kg-1·d-1), and a positive drug group (fluoxetine, 12 mg·kg-1·d-1). Depressive-like behaviors in mice were evaluated using behavioral tests. Immunofluorescence staining was used to label and quantify the expression of the microglial marker ionized calcium-binding adaptor molecule 1 (Ibal) and the purinergic receptor P2X ligand-gated ion channel 7 (P2RX7) in the prefrontal cortex (PFC). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) in serum and PFC tissues. Western blot was employed to determine the expression of pannexin 1 (Panx1), P2RX7, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, GSDMD, postsynaptic density protein 95 (PSD95), and the presynaptic protein Synapsin 1 in PFC tissues. Golgi staining was used to assess dendritic spine density of neurons in the PFC.ResultsCompared with the blank control group, the depression model group exhibited significant depressive-like behaviors. In addition, the immunofluorescence areas of Ibal and P2RX7 in the PFC were significantly increased (P<0.01), the levels of IL-1β and IL-18 in serum and the PFC were significantly elevated (P<0.01), and the protein expression levels of Panx1, P2RX7, NLRP3, ASC, Caspase-1, and GSDMD in the PFC were significantly upregulated (P<0.01). In contrast, the protein expression levels of PSD95 and Synapsin 1 were significantly downregulated (P<0.01), and neuronal dendritic spine density was significantly reduced (P<0.01). Compared with the model group, the Zhizi Houpotang full-formula group and the GF-MOC herbal pair group showed significant improvement in all the above indicators (P<0.01). The GF-AFI herbal pair group improved all the above indicators except P2RX7, Caspase-1, GSDMD, and PSD95 (P<0.05, P<0.01). In contrast, the MOC-AFI herbal pair group showed no statistically significant improvement in any of the above indicators compared with the model group.ConclusionZhizi Houpotang and its key herbal pair, GF-MOC, can effectively ameliorate CUMS-induced depressive-like behaviors in mice. Its core antidepressant mechanism may involve inhibition of P2RX7/Panx1 signaling, thereby blocking the NLRP3/GSDMD-mediated pyroptosis pathway and significantly reducing the release of inflammatory cytokines IL-1β and IL-18. Simultaneously, it upregulates the expression of synapse-related proteins PSD95 and Synapsin 1 and increases dendritic spine density, promoting the recovery of synaptic plasticity. These results suggest that GF plays a key role in the antidepressant effects of this formula, and that the compatibility of GF with MOC may represent the principal herbal pair combination responsible for its core therapeutic action.
关键词:depression;Zhizi Houpotang;herbal pair;NOD-like receptor protein 3 (NLRP3) inflammasome;gasdermin D (GSDMD)
摘要:ObjectiveTo establish a mouse model of rheumatoid arthritis with interstitial lung disease (RA-ILD) in DBA/1 mice using Porphyromonas gingivalis (Pg) infection combined with collagen-induced arthritis (CIA), and to comprehensively evaluate pathological characteristics in joints, lungs, and serum.MethodsForty DBA/1 mice were randomly divided into four groups, i.e., Control, Pg infection (Pg), CIA, and Pg infection combined with CIA (Pg+CIA), with 10 mice in each group. Arthritis clinical symptoms were evaluated by recording arthritis incidence and clinical scores. Micro-CT scanning was used to assess knee joint pathology. Histopathological changes and collagen deposition in knee joints and lung tissues were analyzed using hematoxylin-eosin (HE) and Masson staining. Immunohistochemistry was performed to detect protein expression of α-smooth muscle actin (α-SMA), typeⅠ collagen (ColⅠ), and fibronectin (FN) in lung tissues. Real-time quantitative polymerase chain reaction(Real-time PCR)was used to measure mRNA expression levels of α-SMA, ColⅠ, FN, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β in lung tissues. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of Pg, cyclic citrullinated peptide (CCP), and immunoglobulin G (IgG).ResultsJoint lesions: The CIA and Pg+CIA groups showed 100% arthritis incidence, with evident joint redness, swelling, and deformity. The number of affected limbs was 27 and 28, and clinical scores were 68 and 70, respectively. No obvious clinical symptoms were observed in the Pg group. Histopathological and imaging analyses showed severe joint lesions in the CIA and Pg+CIA groups, with significantly increased histopathological scores, bone mineral density, bone volume fraction, trabecular thickness, and trabecular number compared to the Control group (P<0.01). No obvious joint pathology was observed in the Pg group. Lung lesions: The Pg+CIA group exhibited marked alveolar inflammation, interstitial inflammatory cell infiltration, and alveolar wall thickening, with pronounced blue staining of collagen fibers. Histopathological scores and collagen area ratios were significantly higher than those of the Control, Pg, and CIA groups (P<0.05). Lung protein and mRNA expression levels of α-SMA, ColⅠ, and FN were markedly increased, and mRNA levels of IL-6, TNF-α, and IL-1β were significantly elevated compared to the Control group (P<0.05). Serology: The Pg+CIA group showed significantly higher levels of CCP, Pg, and IgG compared with the Control, Pg, and CIA groups (P<0.05).ConclusionDBA/1 mice subjected to Pg infection combined with CIA exhibited pronounced symptoms and pathological features of RA-ILD, along with elevated serum anti-CCP antibody levels. This model represents a novel RA-ILD mouse model, providing a valuable experimental tool for investigating RA-ILD pathogenesis and developing new therapeutics, and serves as a basis for establishing anti-cyclic citrullinated peptide antibody (ACPA)-positive RA-ILD animal models.
摘要:ObjectiveAbnormal lipids in neurons can cause the accumulation of α-synuclein(α-syn). This study aimed to explore the mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract (ASH) in treating Parkinson's disease (PD) mice using lipidomics combined with network pharmacology.MethodsMice were divided into the blank group, model group and ASH (45.5 mg·kg-1) group. Motor ability was evaluated by pole climbing time and autonomous activity count; The oxidative stress indicators were detected by enzyme-linked immunosorbent assay (ELISA). Lipid biomarkers in brain tissues were screened and identified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and metabolic pathway analysis was conducted. The key targets of ASH for PD treatment were explored using network pharmacology. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for pathway enrichment analysis, and the "compound-reaction-enzyme-gene" network was constructed using the MetScape plugin. The protein expression levels of glutathione S-transferase P1 (GSTP1), glutathione S-transferase Mu 2 (GSTM2), prostaglandin peroxide synthase 1 (PTGS1), prostaglandin peroxide synthase 2 (PTGS2), and prostaglandin E synthase (PTGES) were validated by Western blot.ResultsCompared with the blank group, the model group showed significantly prolonged pole climbing time and reduced autonomous activity count (P<0.01). Compared with the model group, the ASH group demonstrated significantly faster pole climbing and increased autonomous activity count (P<0.01). The model group exhibited significantly decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, and increased malondialdehyde (MDA) level in brain tissues compared with the blank group (P<0.01). The ASH group showed increased SOD and GSH-Px levels and decreased MDA level compared with the model group (P<0.05, P<0.01). Lipidomics analysis identified 10 differential metabolites and 8 differential metabolic pathways. Network pharmacological analysis revealed 213 intersection targets between ASH components and PD, with KEGG enrichment involving the sphingolipid signaling pathway, lipid arteriosclerosis, phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, and hypoxia inducible factor-1(HIF-1) signaling pathway. Integrated lipidomics and network pharmacology analysis highlighted the central role of the arachidonic acid metabolic pathway. The Western blot results showed that ASH effectively up-regulated GSTP1, GSTM2, and PTGS1 protein expression, and down-regulated PTGS2 and PTGES protein expression.ConclusionASH can ameliorate behavioral deficits, exert antioxidant effects, regulate lipid differential metabolites and the arachidonic acid metabolic pathway, thereby exerting therapeutic effects in PD model mice.
关键词:Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract;Parkinson's disease;lipidomics;network pharmacology
摘要:ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease (CKD) through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway.MethodsSeventy specific pathogen-free (SPF) Sprague-Dawley (SD) rats were randomly divided into a control group (n=15) and a modeling group (n=55). Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg-1·d-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group, an irbesartan group (20.25 mg·kg-1·d-1), and Bushen Tongluo Jiangzhuo prescription low-, medium-, and high-dose groups (5.82, 11.64, and 23.28 g·kg-1·d-1, respectively), with 10 rats in each group. Each group was administered an equal volume of physiological saline, the corresponding concentration of irbesartan, or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine (SCr), blood urea nitrogen (BUN), urine albumin-to-creatinine ratio (ACR), 24-hour urinary total protein (24 hUTP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin (HE) and Masson staining. Immunohistochemistry (IHC) was used to detect the expression of PI3K, Akt, phosphorylated Akt (p-Akt), and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K, p-Akt, Akt, phosphorylated mTOR (p-mTOR), and mTOR in renal tissues. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to determine the mRNA expression levels of PI3K, Akt, and mTOR in renal tissues.ResultsCompared with the model group, rats in the irbesartan group and the low-, medium-, and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr, BUN, ACR, 24 hUTP, IL-1β, IL-6, and TNF-α (P<0.01). AST levels were significantly increased (P<0.01), while no significant difference was observed in ALT levels. Histopathological examination revealed that, compared with the model group, renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated, inflammatory cell infiltration was reduced, and interstitial and glomerular fibrosis was markedly improved in all treatment groups, with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K, Akt, and mTOR were significantly downregulated in the high-dose group (P<0.01). IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group (P<0.01). Western blot analysis further confirmed that the expression levels of PI3K, p-Akt/Akt, and p-mTOR/mTOR were significantly reduced in the high-dose group (P<0.01).ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats, reduces collagen deposition in renal tissues, and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway, thereby alleviating renal fibrosis.
关键词:chronic kidney disease;Bushen Tongluo Jiangzhuo prescription;renal fibrosis;phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) signaling pathway
摘要:ObjectiveTo investigate the mechanism of Xiaozhi Qinggan decoction (XQD) in preventing and treating metabolic dysfunction-associated steatotic liver disease (MASLD) by regulating ferroptosis, network pharmacology, in vitro and in vivo experiments.MethodsIn the in vivo experiment, mouse MASLD models were established by high-fat diet (HFD) induction. The model mice were randomly assigned to a positive control group (silybin, 50 mg·kg-1), low-, medium- and high-dose XQD groups (4.725, 9.45, 18.9 g·kg-1), with a normal control group. After 4 weeks of modeling, mice except the normal group were administered intragastrically for 8 consecutive weeks. Liver function, serum lipid levels, hepatic histopathology, as well as the levels of malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) and oxidized glutathione (GSSG) and Fe2+ were detected. The mRNA and protein expression of p53, SLC7A11 and GPX4 were determined by quantitative Real-time quantitative polymerase chain reaction(Real-time PCR) and Western blot. In the network pharmacology analysis, active components and potential targets of XQD for MASLD were screened, followed by functional and pathway enrichment analyses, and molecular docking was performed to verify the target binding activity. In the in vitro experiment, the optimal concentration of XQD-containing serum was screened by cytotoxicity assay. HepG2 cells were transfected with ov-NC or ov-p53 plasmid, and a lipid accumulation model was induced by free fatty acid (FFA, 1.0 mmol·L-1). Cells were divided into a normal group, FFA model group, ov-NC+XQD (15%) group and ov-p53+XQD (15%) group. Intracellular Fe2+ level and lipid accumulation were evaluated, and the protein expression of p53, SLC7A11 and GPX4 was measured by Western blot.ResultsCompared with the normal group, the model group exhibited markedly elevated body weight, liver weight, liver index, fasting blood glucose, AUC of glucose tolerance test, serum liver function and blood lipid levels at week 12 (P<0.01). Hepatic steatosis and inflammatory infiltration were observed by pathological staining. Additionally, hepatic levels of MDA, SOD and Fe2+ were increased (P<0.01), while GSH, GSSG and the GSH/GSSG ratio were decreased (P<0.01). The mRNA and protein expression of hepatic p53 was upregulated (P<0.01), whereas the expression of SLC7A11 and GPX4 was downregulated (P<0.01). Compared with the model group, the low- and medium-dose XQD groups showed significantly decreased body weight at week 12 (P<0.05). The silybin group, together with the medium- and high-dose XQD groups, presented reduced liver weight and liver index (P<0.05). Fasting blood glucose and the AUC of glucose tolerance test were lowered in all four treatment groups (P<0.05, P<0.01). Pathological staining revealed alleviated hepatic steatosis and inflammation, accompanied by decreased serum liver function and blood lipid levels (P<0.05, P<0.01). Moreover, hepatic MDA and SOD levels were markedly reduced, while GSH, GSSG and the GSH/GSSG ratio were significantly elevated (P<0.05, P<0.01). Hepatic Fe2+ level was decreased (P<0.01). The mRNA and protein expression of hepatic p53 was downregulated, and the expression of SLC7A11 and GPX4 was upregulated (P<0.05, P<0.01). Network pharmacology analysis identified quercetin, kaempferol, luteolin, tanshinone IIA and isorhamnetin as the core active components of XQD, with p53 serving as the key target. Stable binding was verified between these active components and the p53 protein. The optimal concentration of XQD-containing serum in vitro was determined to be 15%. Compared with the normal group, the model group showed increased intracellular Fe2+ and lipid accumulation, significantly upregulated p53 protein expression (P<0.01), and markedly downregulated SLC7A11 and GPX4 protein expression (P<0.01). Compared with the model group, the ov-NC group exhibited reduced Fe2+ and lipid accumulation, downregulated p53 expression, and upregulated SLC7A11 and GPX4 expression. In the ov-p53 group, p53 expression was upregulated (P<0.01), while SLC7A11 and GPX4 expression was downregulated (P<0.01).ConclusionXQD inhibits ferroptosis by downregulating p53 and upregulating SLC7A11 and GPX4, thereby alleviating oxidative stress and lipid peroxidation in hepatocytes and improving MASLD.
关键词:Xiaozhi Qinggan decoction;metabolic dysfunction-associated steatotic liver disease;ferroptosis;tumor suppressor protein 53 (p53)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway;network pharmacology
摘要:ObjectiveTo explore the effect and mechanism of Jianpi Xiaoai prescription (JPXA) in ameliorating the 5-fluorouracil (5-FU) resistance of colon cancer.MethodsA HCT116/5-FU resistant cell line was established. Different concentrations (10%, 15%, 20%) of JPXA-containing serum and drug-free serum were used for intervention, and 10% fetal bovine serum (10% FBS), fibroblast growth factor receptor (FGFR) inhibitor (AZD4547), and recombinant fibroblast growth factor 2 (FGF2) were set as the control groups. Sensitive HCT116 cells were used in the FGF2 group, while HCT116/5-FU cells were used in other groups. Drug resistance, the level of FGF2 in the cell culture medium, the mRNA level of FGF2 in cells, and the protein levels of FGF2/FGFR and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) were determined. The drug-resistant cells were transplanted into the axilla of nude mice to establish a tumor model. The modeled mice were allocated into model, JPXA (15 g·kg-1), 5-FU (0.02 g·kg-1), JPXA+5-FU (15 g·kg-1+0.02 g·kg-1), AZD4547 (0.012 5 g·kg-1), and AZD4547+5-FU (0.012 5 g·kg-1+0.02 g·kg-1) groups. The tumor growth and the protein levels of FGF/FGFR and PI3K/Akt in each group were observed.ResultsThe survival rate of HCT116/5-FU cells decreased in all the JPXA groups with different concentrations. The cell survival rate was decreased most obviously in the 20% JPXA group. The level of FGF2 in the cell culture medium and the mRNA level of FGF2 in cells of each JXPA group decreased, and the decrease was the most significant in the 20% group (P<0.01). HCT116/5-FU cells showed up-regulated protein levels of FGF2 and phosphorylated fibroblast growth factor receptor 1 (p-FGFR1), but down-regulated protein level of FGFR1 (P<0.01). JPXA down-regulated the expression of FGF2 and p-FGFR1 and up-regulated the expression of FGFR1 (P<0.05). In addition, JPXA down-regulated the expression levels of phosphorylated protein kinase B (p-Akt) and phosphorylated mammalian target of rapamycin (p-mTOR), while up-regulating the expression levels of Akt and Bcl-2-asociated death promoter (Bad) (P<0.05). Animal experiments showed that the JPXA combined with 5-FU significantly inhibited the growth of drug-resistant tumors, reduced the protein levels of FGF2, p-FGFR1, phosphorylated phosphatidylinositol-3-kinase (p-PI3K), p-Akt, and p-mTOR, and increased the expression of Bad. It indicated that JPXA can inhibit the FGF2/FGFR1 signaling in colon cancer and regulate PI3K/Akt and downstream signaling pathways.ConclusionJPXA can ameliorate the chemotherapy resistance of colon cancer through down-regulating FGF2 expression and inhibiting the activation of the PI3K/Akt signaling pathway.
关键词:Jianpi Xiaoai prescription;colorectal cancer;chemotherapy resistance;fibroblast growth factor;phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt)
摘要:ObjectiveTo investigate whether Shenmai injection (SMI) improves cisplatin resistance in non-small cell lung cancer (NSCLC) by modulating lipid metabolism and inducing ferroptosis.MethodsHuman lung adenocarcinoma cisplatin-resistant A549/DDP cells were divided into the following groups: Blank group, cisplatin group (23.3 μmol·L-1 cisplatin), SMI group (20 g·L-1 SMI), cisplatin combined with SMI group (23.3 μmol·L-1 cisplatin + 20 g·L-1 SMI), cisplatin combined with ferroptosis inhibitor/inducer Ferrostatin-1/Erastin group (23.3 μmol·L-1 cisplatin + 10 μmol·L-1 Ferrostatin-1/5 μmol·L-1 Erastin), and cisplatin combined with SMI and Ferrostatin-1/Erastin group (23.3 μmol·L-1 cisplatin + 20 g·L-1 SMI + 10 μmol·L-1 Ferrostatin-1/5 μmol·L-1 Erastin). Network pharmacology, transcriptomics and metabolomics, Cell Counting Kit-8 (CCK-8) assay, transmission electron microscopy (TEM), colorimetric assays, and Western blot analysis were employed to evaluate the effects of these treatments on A549/DDP cell viability, lipid droplet formation, lipid metabolite levels, mitochondrial function, lipid peroxidation, glutathione (GSH) content, total and ferrous iron content, and effects on ferroptiosis and autophagy related protein expression levels.ResultsSMI improved cisplatin resistance in NSCLC mainly by targeting lipid metabolism-related pathways in A549/DDP cells, affecting tumor cell lipid metabolism via autophagy, ferroptosis, and glycerophospholipid metabolism pathways. Compared with the cisplatin group, the cisplatin combined with SMI group showed significantly decreased cell viability (P<0.01), increased lipid droplet accumulation (P<0.01), and reduced mitochondrial maximal respiration, basal respiration, mitochondrial membrane potential, GSH content, total iron, and ferrous iron (all P<0.01). Mitochondrial reactive oxygen species (ROS) was significantly elevated(P<0.01), and lipid peroxidation levels were significantly increased. Protein expression analysis showed significant downregulation of solute carrier family 7 member 11 (SLC7A11) and p62 (P<0.05,P<0.01) and upregulation of ferritin heavy chain (FTH) and microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ) (P<0.05,P<0.01). Compared with the cisplatin combined with SMI group, addition of Ferrostatin-1 significantly increased cell viability (P<0.05), decreased mitochondrial ROS levels (P<0.05), alleviated mitochondrial shrinkage, and reduced lipid peroxidation. Conversely, addition of Erastin further decreased cell viability (P<0.01).ConclusionSMI improves cisplatin resistance in NSCLC by inducing oxidative stress, which may trigger ferroptosis through upregulation of lipophagy.
摘要:ObjectiveTo construct a risk prediction model for frequent acute exacerbations of chronic obstructive pulmonary disease (COPD) under disease-syndrome combination, thus providing decision support for precise clinical intervention.MethodsA total of 2 029 patients with acute exacerbations of COPD admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2020 to August 2024 were retrospectively included. These patients were classified into groups of frequent acute exacerbations (≥2 times/year) and infrequent acute exacerbations (<2 times/year) according to the hospitalization times per year. Risk factors were screened by LASSO regression combined with logistic regression, and a nomogram model was constructed. The model performance was assessed based on the area under the curve (AUC), calibration curves, and decision curve analysis (DCA).ResultsThe differences in baseline characteristics between the frequent acute exacerbations group (1 196 cases) and infrequent acute exacerbations group (833 cases) were not statistically significant. LASSO regression combined with multivariate logistic regression screened the following independent risk factors: body mass index (BMI), hospitalization days, number of smoking years, place of residence, use of noninvasive ventilators, oxygen-demanding therapy, liver cirrhosis, use of systemic glucocorticosteroids, and traditional Chinese medicine syndrome (phlegm and stasis obstructing the lung). The nomogram model showed good discrimination and calibration in both the training set (AUC=0.748) and validation set (AUC=0.774).ConclusionThe risk prediction model for frequent acute exacerbations of COPD, integrating traditional Chinese medicine syndrome, constructed in this study has high accuracy. It can provide a scientific basis for early clinical identification of high-risk patients and individualized intervention.
摘要:The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines (hereinafter referred to as the Guidelines) is first specialized in the field of drug safety for oral Chinese patent medicines (OCPMs) in China. Rooted in China's healthcare context, the Guidelines address the unique usage patterns and risk characteristics of OCPMs, filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines, and to promote the standardized development of pharmacovigilance practices for OCPMs, this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting, the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment, the Guidelines were examined from three dimensions of formulation components, medication behaviors, and population to address complex safety issues arising from medicinal constituents, irrational use, and individual susceptibility. In the area of risk control, the analysis focused on context-based interventions and dynamic closed-loop management strategies, exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore, this paper evaluated the applied value of the Guidelines and identified implementation challenges, such as insufficient capacity at the primary-care level and limited digital infrastructure. In response, the study proposed optimization strategies including establishing a dynamic updating mechanism, strengthening training at the grassroots level, and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders (including manufacturers), pharmaceutical distributors, healthcare institutions, and research organizations, ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.
关键词:oral Chinese patent medicine;clinical application;pharmacovigilance;interpretation of guidelines
摘要:ObjectiveTo investigate the therapeutic effect of Astragali Radix-mediated changes in gut microbiota on treating type 2 diabetes (T2DM).MethodsA 12-week randomized, placebo-controlled clinical trial enrolled eighty patients with newly diagnosed type 2 diabetes and poor glycemic control in the Qi deficiency type. All patients received insulin therapy. The observation group (40 cases) was administered with Astragali Radix Granules, while the control group (40 cases) received a placebo. Both treamtents were taken orally twice daily. Changes in gut microbiota were assessed by 16s rDNA sequencing. Serum glucagon-like peptide-1 (GLP-1) levels were measured using enzyme-linked immunosorbent assay (ELISA). Glucose metabolism indicators including fasting blood glucose (FPG), 2-hour postprandial blood glucose (2 h PG),glycated albumin(GA), and glycated hemoglobin (HbA1c) were evaluated. Pancreatic function was evaluated using fasting C-peptide (FCP), 2-hour postprandial C-peptide (2 h CP), and C-peptide area under the curve (AUCcp). Traditional Chinese medicine (TCM) syndrome scores, clinical efficacy, and safety indicators were also observed.ResultsIn terms of glucose metabolism indicators, compared with the baseline, both groups exhibited significantly lower FPG, 2 h PG, GA and HbA1C (P<0.01),while FCP, 2 h CP and AUCcp were significantly higher (P<0.01). Compared with the control group after the treatment, the observation group showed significantly lower FPG, 2 h PG, GA and HbA1C(P<0.05, P<0.01),and significantly higher FCP, 2 h CP and AUCcp (P<0.05, P<0.01), indicating that Astragali Radix can improve glucose metabolism. In terms of the diversity of gut microbiota, no significant differences were detected in the Chao1, Shannon and Simpson indexes of the two groups compared with their respective baselines. However, compared with the post-treatment control group, the observation group demonstrated significant increases in the Chao1, Shannon and Simpson indexes (P<0.05, P<0.01). The β-diversity analysis showed significant separation in gut microbiota composition before and after treatment in both groups, indicating that Astragali Radix can significantly alter the structure and improve the diversity of gut microbiota. At the phylum level, compared with the baseline, both groups showed a significant increase in the relative abundance of Bacteroidota(P<0.01). The relative abundance of the potentially harmful phylum Proteobacteria was significantly lower in the observation Group after treatment (P<0.01). Compared with the post-treatment control group, the observation group had a significantly higher relative abundance of Bacteroidota(P<0.01). No significant difference was found in Firmicutes/Bacteroidota (F/B) ratio between the two groups after treatment, and other phyla showed no significant differences. At the genus level, compared with the baseline, the observation group exhibited a significant increase in Bacteroides (P<0.01) and a significant decrease in Escherichia-Shigella (P<0.01), whereas no significant difference was seen in the control group . Compared with the control group after treatment, the observation group after treatment had a significantly higher relative abundance of Bacteroides (P<0.01). No significant differences were seen in other genera. Linear discriminant analysis (LDA) identified potential characteristics taxa: in the observation group, Bacteroidota at the phylum level and Bacteroides and Dubosiella at the genus level, in the control group, Proteobacteria at the phylum level as well as Barnesiella and Staphylococcus at the genus level. Correlation analysis based on a heatmap revealed that GLP-1 levels were positively correlated with Firmicutes, F/B ratio and Fusobacterium, and negatively correlated with Bacteroidota, Proteobacteria, Bacteroides and Escherichia-Shigella. In terms of clinical efficacy, compared with the control group, the total effective rate of the observation group was significantly higher (P<0.05). Compared with the baseline, the scores for shortness of breath, fatigue, weakness, spontaneous sweating and reluctance to speak significantly decreased in both groups (P<0.01). Compared with the control group after treatment, the score for weakness was significantly lower in the observation group (P<0.01),indicating that Astragali Radix could improve clinical symptoms and alleviate weakness symptoms. In terms of safety, compared with the baseline, alanine aminotransferase (ALT) levels significantly decreased in both groups (P<0.05,P<0.01),indicating that Astragali Radix did not induce any significant abnormalities in liver and kidney functions.ConclusionAstragali Radix demonstrates the potential to significantly improve the gut microbiota environment in patients of newly diagnosed type 2 diabetes with Qi deficiency. The therapeutic effect may contribute to glycemic control, possibly mediated by an elevation in GLP-1 level. These findings may support its further clinical investigations and potential applications.
关键词:Astragali Radix;gut microbiota;glucagon-like peptide-1 (GLP-1);newly diagnosed type 2 diabetes;Qi deficiency type
摘要:ObjectiveTo observe the clinical efficacy of Tangshen Dihuang decoction in treating diabetic kidney disease (DKD) with liver-kidney Yin deficiency and blood stasis syndrome and its impact on gut microbiota.MethodsA randomized controlled clinical trial was conducted, in which 102 DKD patients with liver-kidney Yin deficiency and blood stasis syndrome were randomly assigned to the Tangshen Dihuang decoction group and the control group. Each group consisted of 51 cases, and the treatment period was 3 months. The primary efficacy indicators included urinary albumin-to-creatinine ratio (UACR), fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 hPBG), glycated hemoglobin (HbA1C), serum creatinine (SCr), blood urea nitrogen (BUN), angiotensinⅡ (AngⅡ), serum cystatin C (Cys-C), urinary N-acetyl-β-D-glucosaminidase (NAG), urinary β2-microglobulin (Uβ2-MB), traditional Chinese medicine (TCM) symptom scores, and gut microbiota.ResultsAfter treatment, the total response rate in the Tangshen Dihuang decoction was 87.23% (41/47), which was higher than that (69.57%, 32/46) in the control group (Z=4.30, P<0.05). After treatment, the TCM symptom scores decreased in both groups (P<0.01) and were lower in the Tangshen Dihuang decoction group than in the control group (P<0.01). After treatment, the control group showed decreases in UACR, Uβ2-MG, AngⅡ, and FBG (P<0.05) as well as 2 hPBG and HbA1C (P<0.01), and no significant differences in BUN, Cys-C, eGFR, SCr, and NAG. The Tangshen Dihuang decoction group showed increased eGFR (P<0.05), declined levels of UACR, BUN, Cys-C, Uβ2-MB, AngⅡ, FBG, 2 hPBG, NAG, and HbA1C (P<0.01), and no significant difference in SCr. The Tangshen Dihuang decoction group had lower BUN (P<0.05), Cys-C (P<0.05), AngⅡ (P<0.05), 2 hPBG (P<0.05), Uβ2-MG (P<0.01), and NAG (P<0.01) and higher eGFR level (P<0.05) than the control group. After treatment, the control group showed declines in Shannon, Observed_species, and Chao1 indices (P<0.05). The samples from both groups showed statistically significant differences in the principal coordinates analysis (PCoA) plot based on Anosim analysis (P<0.05). After treatment, the Tangshen Dihuang decoction group showed decreased relative abundance of Actinobacteria (P<0.05). Moreover, the relative abundance of Actinobacteria was significantly lower in the Tangshen Dihuang decoction group than in the control group (P<0.05). At the genus level, the control group showed decreased relative abundance of Bifidobacterium (P<0.05), and the Tangshen Dihuang decoction group presented increased relative abundance of Bifidobacterium and Blautia_A (P<0.05). After treatment, the Tangshen Dihuang decoction group had higher relative abundance of Bifidobacterium than the control group (P<0.01).ConclusionTangshen Dihuang decoction has a significant therapeutic effect on DKD patients with liver-kidney Yin deficiency and blood stasis syndrome. It can markedly relieve clinical symptoms and reduce proteinuria and postprandial blood glucose by antagonizing the local renin-angiotensin system (RAS) and alleviating gut microbiota dysbiosis.
摘要:ObjectiveThis paper aims to clarify the material basis of Gualou Niubangtang and establish a quantitative analysis method for its main constituents, providing a reference for the overall quality control of this preparation.MethodsThe constituents in the formula were systematically characterized based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Identification was performed by matching with the UNIFI 9.6 software and utilizing database platforms such as PubChem, ChemicalBook, and ChemSpider, combined with relevant literature reports. A quantitative analysis method for the seven main constituents in Gualou Niubangtang was established by using high performance liquid chromatography (HPLC).ResultsUPLC-Q-TOF-MS/MS analysis identified 155 constituents, including 69 flavonoids, 36 terpenoids, 23 phenylpropanoids, 8 phenylethanoid glycosides, and 19 other types of constituents. In the established quantitative analysis method, the seven main constituents showed good linearity within their respective linear ranges. The precision, repeatability, stability, and spike recovery all met the required standards. The results showed that the content ranges of geniposide, liquiritin, hesperidin, arctiin, baicalin, oroxylin A-7-O-β-D-glucuronide, and wogonoside in 15 batches of Gualou Niubangtang were 13.67-21.25, 1.20-7.64, 5.45-7.45, 22.97-33.51, 29.95-39.07, 2.58-4.80, and 6.56-9.31 mg·g-1, respectively.ConclusionThis study successfully characterizes and attributes multi-category constituents in Gualou Niubangtang, clarifying that its material basis is primarily composed of flavonoids, terpenoids, phenylethanoid glycosides, and phenylpropanoids. Furthermore, it enables the quantification of seven constituents within the formula. This work lays a foundation for research on the quality control, action mechanism, and clinical application of this formula.
摘要:ObjectiveTo systematically identify the chemical constituents of Xuefu Zhuyutang(XFZY) and quantitatively determine its main components, aiming to elucidate its pharmacodynamic material basis and provide a scientific foundation for improving its quality control standards.MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was employed for qualitative analysis of XFZY, and the identification of compounds was accomplished by comparing their retention times, secondary MS fragment ion information, 52 reference standards and relevant databases, followed by attribution of their herbal sources. A total of 22 representative compounds were screened out, and UPLC-quadrupole-linear ion trap mass spectrometry(UPLC-Q-TRAP-MS/MS) was applied for quantitative analysis of the compounds in the formula.ResultsA total of 77 compounds were identified in XFZY, including 31 flavonoids mainly derived from Aurantii Fructus, Glycyrrhizae Radix et Rhizoma, Persicae Semen, Carthami Flos, Bupleuri Radix, Paeoniae Radix Rubra and Achyranthis Bidentatae Radix, 24 terpenoids mainly derived from Platycodonis Radix, Glycyrrhizae Radix et Rhizoma, Paeoniae Radix Rubra and Rehmanniae Radix, 9 phenylpropanoids and their derivatives mainly derived from Chuanxiong Rhizoma, Angelicae Sinensis Radix and Rehmanniae Radix, 4 phenolic acids mainly derived from Chuanxiong Rhizoma, Angelicae Sinensis Radix and Paeoniae Radix Rubra, 3 saccharides mainly derived from Rehmanniae Radix and Achyranthis Bidentatae Radix, and 6 other compounds mainly derived from Persicae Semen, Rehmanniae Radix and Angelicae Sinensis Radix. The results of quantitative analysis showed that the contents of protocatechuic acid, hydroxypaeoniflorin, amygdalin, vanillic acid, paeoniflorin, liquiritin apioside, liquiritin, isoquercitrin, naringin, cosmosiin, hesperidin, neohesperidin, isoliquiritin, liquiritigenin, naringenin, benzoylpaeoniflorin, hesperetin, isoliquiritigenin, formononetin, glycyrrhizic acid, nobiletin and ligustilide in XFZY were determined to be 0.12, 1.57, 54.53, 0.29, 36.17, 4.29, 4.84, 0.09, 46.67, 0.04, 3.44, 31.95, 0.82, 0.10, 0.11, 0.43, 0.07, 0.03, 0.01, 8.24, 0.13, 1.81 mg·g-1.ConclusionThe qualitative method established in this study enables rapid and sensitive analysis of the chemical constituents in XFZY. Among the identified compounds, 52 are confirmed by reference standards, ensuring the accuracy of identification. The quantitative analysis of 22 key components provides a reliable experimental basis for the pharmacodynamic material basis research and quality control standard improvement of XFZY.
关键词:Xuefu Zhuyutang;ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS);UPLC-quadrupole-linear ion trap mass spectrometry(UPLC-Q-TRAP-MS/MS);famous classical formulas;traditional Chinese medicine;qualitative analysis;quantitative analysis
摘要:ObjectiveHistorically documented Zhejiang Atractylodis Macrocephalae Rhizoma(Baizhu) possesses premium characteristics such as phoenix-like head and crane-like neck, pronounced sweetness, and fragrant aroma. However, its current market circulation is low, and the processed products with Zhejiang-style characteristics are at the risk of being lost. This study aims to preserve the ancient Zhejiang-style processing techniques and evaluate them using modern scientific methods.MethodsMultidimensional intelligent sensory evaluation was used to digitally characterize the "quality-structure" of the external appearance of nine-steamed and nine-processed Baizhu medicinal materials(intermediate processed products) and the "odor-taste" of the internal quality of its decoction pieces(slices), and the appearance parameters were digitally characterized by colorimeter, texture analyzer, electronic nose and electronic tongue, the chemical composition was analyzed via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS). Then, cluster analysis on the differences in odor between the medicinal materials(intermediate processed products) and decoction pieces(slices) of nine-steamed and nine-processed Baizhu was conducted, as well as the differences in taste between water-soluble and alcohol-soluble extracts of the decoction pieces(slices), and the correlation analysis of chroma value-alcohol-soluble extract content-component response value.ResultsThe nine-steamed and nine-processed Baizhu had a dark brown to black epidermis, a brownish-yellow to brownish-gray cross-section, a slightly tough texture, a faint odor, and a slightly sweet, bitter and pungent taste. Texture analyzer measurements revealed minimal adhesion and maximum recovery in the middle section of the characteristic processed Baizhu, consistent with the processing endpoint of thorough steaming and cooking. The head section showed the highest internal hardness, elasticity and chewiness, indicating a denser texture in this area. The electronic nose sensor could clearly distinguish the difference between the medicinal materials and its decoction pieces, with a more significant clustering effect at 60 ℃ for 30 minutes compared to ambient temperature headspace for 2 hours, highlighting the significant impact of the baking degree before slicing on the quality. The electronic tongue taste signal map clearly distinguished the differences between water-soluble and alcohol-soluble extracts of nine-steamed and nine-processed Baizhu decoction pieces, and the addition of auxiliary materials during processing could enhance its alcohol-soluble extract content. A total of 82 chemical components were identified in the characteristic processed Baizhu. After processing, the contents of 58 components increased, while 24 components decreased. Correlation analysis revealed significant negative correlations(P<0.01) between ethanol-soluble extract content and colorimetric values of brightness(L*), yellow-bule value(b*), and total color difference(E*ab). E*ab showed marked negative correlations(P<0.05) with the response values of isochlorogenic acid A and C.ConclusionThis study establishes a modern intelligent sensory evaluation model for multidimensional holographic characterization of nine-steamed and nine-processed Baizhu, clarifying the correlation between increased isochlorogenic acid content and the visual color appearance after different steaming cycles, as well as its intrinsic alcohol-soluble extracts. This provides a reference for quality evaluation and processing standards of the Zhejiang-style characteristic processed products.
关键词:Atractylodis Macrocephalae Rhizoma;nine-steamed and nine-processed;colorimeter;texture analyzer;electronic nose;electronic tongue;Zhejiang-style distinctive processing
摘要:ObjectiveTo analyze the pharmacodynamic substance basis of Shangkeling Spray and its potential mechanisms in intervening knee osteoarthritis (KOA) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS), network pharmacology, and molecular docking technology.MethodsUPLC-MS was used to identify the chemical components of Shangkeling Spray. Pharmacokinetic properties were employed to screen potential active ingredients. Network pharmacology methods were utilized to collect potential targets of these ingredients and the pathological gene set of KOA. An "active ingredient-disease" target network was constructed using databases such as STRING. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed using clusterProfiler. Libraries including NumPy were employed to calculate shortest path lengths to identify dominant pharmacodynamic links. Core gene clusters were identified using MCODE, validated through the Gene Expression Omnibus (GEO) database, and molecular docking was performed between key active ingredients and core targets.ResultsA total of 322 and 314 chemical components were identified under positive and negative ion modes, respectively, with 410 components in total after de-duplication, mainly including flavonoids, coumarins, terpenoids, organic acids, and alkaloids. Analysis of the "active ingredient-disease" network identified "development and regeneration", "cell growth and death", "immune system", and "nervous system" as the dominant pharmacodynamic links of Shangkeling Spray in the treatment of KOA. Molecular docking showed that key active ingredients, such as bletillin A, formononetin, morin, oxymatrine, aconitine, gallic acid, curdione, apigenin, naringenin, and oleanolic acid, tightly bound to functional domains of 10 key targets including Jun proteins(JUN), interleukin-6 (IL-6), protein kinase B1 (Akt1), Caspase-3, nuclear transcription factor-κB subunit p65(RELA), nuclear factor-kappaB1(NF-κB1), Cyclin D1, mammalian target of rapamycin(mTOR), tumor necrosis factor (TNF), and Fos proto-oncogene protein (FOS). These interactions synergistically regulated the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR-related signaling axis and nervous system-related pathways, mediating cartilage repair, reducing inflammation and pain, and improving KOA.ConclusionThis study preliminarily clarifies the pharmacodynamic substance basis of Shangkeling Spray and suggests that its main active ingredients may improve KOA by synergistically regulating the PI3K/Akt/mTOR-related pathways, providing a reference for subsequent exploration of its substance benchmark and mechanism of action.
关键词:Shangkeling Spray;knee osteoarthritis;network pharmacology;pharmacodynamic substances;mechanism of action
摘要:ObjectiveTo establish a high-performance liquid chromatography(HPLC) for the quantitative analysis of multiple components in Gegen Qinlian tablets, and to comprehensively evaluate the quality of samples from different manufacturers by integrating chemical pattern recognition and technique for order preference by similarity to ideal solution(TOPSIS), in order to provide a reference basis for quality evaluation and control of Gegen Qinlian tablets.MethodsHPLC was employed to determine the contents of 10 components in 28 batches of Gegen Qinlian tablets collected from 6 manufacturers, and taking the detection results as variables, SIMCA 14.1 and SPSS 26.0 were employed for cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) to identify key components affecting the quality. Then, TOPSIS analysis was employed to rank the quality of Gegen Qinlian tablets from the 6 manufacturers and establish a comprehensive quality evaluation method.ResultsA quantitative method for Gegen Qinlian tablets was established. After methodological validation, the method was found to be stable and reliable, and could be used for the quantitative analysis of this preparation. The contents of 3′-hydroxy puerarin, puerarin, 3′-methoxy puerarin, daidzein, coptisine hydrochloride, epiberberine, jatrorrhizine hydrochloride, berberine hydrochloride, palmatine hydrochloride and baicalin in 28 batches of samples were 3.58-7.35, 24.88-42.32, 4.20-9.36, 4.33-7.60, 2.52-6.44, 0.93-4.10, 0.58-3.05, 10.68-22.92, 0.82-4.82, 11.73-60.16 mg·g-1, respectively. Among them, puerarin, berberine hydrochloride and baicalin all met the limit requirements for this preparation specified in the 2025 edition of the Pharmacopoeia of the People's Republic of China. CA and PCA clustered the 28 batches of samples into 5 categories, PCA extracted 2 principal components with a cumulative variance contribution rate of 90.588%, and OPLS-DA screened out 4 differential markers with variable importance in the projection(VIP) values>1.0, namely baicalin, 3′-hydroxy puerarin, coptisine hydrochloride and palmatine hydrochloride, which might be the main components affecting the quality of Gegen Qinlian tablets. TOPSIS analysis showed that the comprehensive score of each evaluation index(Ci) values of different manufacturers were different. Among them, the Ci of manufacturer B was ranked higher, indicating potentially superior quality, while the Ci of manufacturer A was ranked lower, suggesting potentially inferior quality.ConclusionThis study establishes a quantitative method for Gegen Qinlian tablets, and the content uniformity of the same manufacturer is good, while there are differences in the contents of active components among different manufacturers. Through the chemical pattern recognition analysis, it is found that the content differences of Gegen Qinlian tablets may be related to baicalin, 3′-hydroxy puerarin, coptisine hydrochloride and palmatine hydrochloride.
关键词:Gegen Qinlian tablets;chemical pattern recognition;technique for order preference by similarity to ideal solution(TOPSIS);quality evaluation;puerarin;berberine;baicalin
摘要:This article systematically analyzed the historical evolution of the origin, scientific name, producing area, quality evaluation, harvesting and processing, and other aspects of Quisqualis Fructus by consulting the ancient materia medica, medical books, prescription books, local literature and combining with the modern literature and standards, summarized and explored the development rules of its medicinal properties and efficacy along with their underlying causes, in order to provide support for the development and utilization of famous classical formulas containing this herb. According to the textual research, Shijunzi was first recorded as Liuqiuzi in Nanfang Caomuzhuang of the Jin dynasty, and the name of Shijunzi was first used in Kaibao Bencao of the Song dynasty, which has been consistently used throughout subsequent dynasties, and there were also aliases such as Junziren, Sijunzi, and Dujilizi. The mainstream source of Quisqualis Fructus used in the past dynasties has been the dried mature fruits of Quisqualis indica, a plant belonging to the family Combretaceae. In modern times, its variety Q. indica var. villosa has also been recorded as the medicinal material of Quisqualis Fructus. In 2007, the Flora of China(English edition) designated Q. indica var. villosa as a synonym of Q. indica. Today, the accepted name of Shijunzi is updated to Combretum indicum. According to ancient herbal records, the producing areas of Quisqualis Fructus were Guangdong, Hong Kong, Macao, Guangxi, Hainan, Sichuan and Fujian, and then gradually expanded to Yunnan, Taiwan, Jiangxi and Guizhou. Since the Song dynasty, two major production regions have gradually emerged in Sichuan, Chongqing and Fujian. Currently, it is primarily cultivated in Chongqing, Guangxi and other areas, with Chongqing yielding the highest output. Since modern times, superior quality has been defined by large size, a purple-black surface, plump grains, and a yellowish-white kernel. According to ancient herbal records, the harvesting period of Quisqualis Fructus was the July and August of the lunar calendar, mostly used raw after shelling or with the shell intact, it underwent processing methods such as cleaning, slicing, mixing, steaming, roasting, stewing, and frying. Currently, the harvesting period is autumn, followed by sun-drying or low-heat drying, with processing methods including cleaning, stir-frying, and stewing. In ancient and modern literature, the records of the properties, functions and indications of Quisqualis Fructus are basically the same, that is, sweet in taste, warm in nature, predominantly non-toxic, belonging to the spleen and stomach meridians. It possesses effects of insecticide, decontamination and invigorating spleen for ascariasis, enterobiasis, abdominal pain due to worm accumulation and infantile malnutrition.The contraindications for use primarily include avoiding consumption by individuals without parasitic infestations, limiting use for those with spleen-stomach deficiency-cold, refraining from drinking hot tea during medication, and avoiding excessive intake. Based on the textual research, it is suggested that the dried mature fruits of Q. indica should be used as the medicinal material for the development of famous classical formulas containing Quisqualis Fructus. Processing methods may be chosen according to prescription requirements, and the raw products is recommended for medicinal use if not specified.
关键词:Quisqualis Fructus;herbal textual research;origin;quality evaluation;harvesting and processing;processing methods;contraindications
ZHANG Qi, LIU Yingke, ZHANG Xiaoxiao, NI Guichen, XIAO Heyin, WANG Junhong, WU Liqun, YAN Zhanfeng, WANG Kundi, CHEN Jiajia, ZHENG Hong, GAO Xinying, WEI Liya, HE Qiang, ZHAO Qian, SU Huimin, LIU Zhaolan, LONG Dafeng
摘要:Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance, while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine (TCM) has a long history in the prevention and management of this condition, demonstrating eight distinct advantages, including systematic theoretical foundation, diversified therapeutic approaches, definite therapeutic efficacy, high safety profile, good patient compliance, comprehensive intervention strategies, emphasis on prevention, and stepwise treatment protocols. Additionally, TCM is characterized by six distinctive features: the use of natural medicinal substances, non-invasive external therapies, integration of medicinal dietetics, simple exercise regimens, precise syndrome differentiation, and diverse dosage forms. By combining internal and external treatments, TCM facilitates individualized regimen adjustment and holistic regulation, demonstrating remarkable effects in improving obesity-related metabolic indicators, regulating constitutional imbalance, and promoting healthy behaviors. However, challenges remain, such as inconsistent operational standards, insufficient high-quality clinical evidence, and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment, conducting multicenter randomized controlled trials, and fostering interdisciplinary integration, so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.
关键词:childhood simple obesity;dominant diseases;characteristic;expert guidance and recommendations
摘要:Diabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes. Traditional Chinese medicine (TCM) plays a unique role in improving clinical symptoms, reducing proteinuria, and delaying the initiation of dialysis. Over time, scholars have held diverse views on the etiology, pathogenesis, and treatment strategies of DKD. This paper systematically reviews the etiology and pathogenesis, syndrome differentiation and treatment, and medication rules of DKD, aiming to provide a reference for clinical practice. Regarding etiology, DKD is closely related to insufficient innate endowment, improper diet, emotional disorders, overexertion, and prolonged diabetes. Its pathogenesis evolves dynamically. Specifically, early stage is characterized by Yin deficiency with dryness-heat and subtle discharge. Middle stage involves both Qi and Yin deficiency with dampness and blood stasis. Late stage presents Yin and Yang deficiency with intrinsic turbidity toxins. Blood stasis and sugar toxicity are the core pathological factors, persisting throughout the disease course and accelerating renal collateral damage and fibrosis. In terms of diagnosis and treatment, contemporary scholars advocate stage-specific treatment, emphasize the integration of prevention and therapy, recommend whole-course management, and support comprehensive TCM and Western medicine approaches. Analysis of medication rules shows that treatment consistently addresses the core principle of deficiency at the root and excess at the surface, strengthens the body while dispelling pathogenic factors, emphasizes promoting blood circulation and removing blood stasis, consolidates the kidney and astringes essence, clears Fu-organs and eliminates turbidity and toxins, invigorates the spleen, replenishes Qi, protects the stomach, and advocates treatment based on pathogenic wind. Further refinement of the academic thoughts of classical TCM masters and research into innovative pathogenesis theories and clinically effective prescriptions are needed to enhance TCM's ability to prevent and treat major clinical diseases, including DKD.
关键词:diabetic kidney disease;etiology;pathogenesis;stage-specific differentiation and treatment;medication rule
摘要:Idiopathic pulmonary fibrosis (IPF) is a chronic and fibrotic lethal interstitial lung disease with poor prognosis. It is mainly treated by organ transplantation and administration of chemical drugs, which have poor efficacy and induce side effects, failing to meet the clinical needs. Therefore, it is urgent to develop more safe and effective drugs to treat IPF. Traditional Chinese medicine (TCM) has garnered increasing attention in recent years in the treatment of IPF due to its unique advantages. Increasing studies have shown that TCM has remarkable therapeutic effects on IPF and thus demonstrate broad application prospects. Modern medical research shows that the pathogenesis of IPF can be discussed from inflammation (macrophage polarization), oxidative stress, epithelial-mesenchymal transition (EMT), autophagy inhibition and other related signaling pathways, while few studies systematically explain the relationship between the signaling pathways and TCM theory. According to the theory of TCM, lung collateral obstruction is the basic pathogenesis of IPF. Therefore, according to the principle of dredging and replenishing lung collaterals, IPF can be treated with the methods of reinforcing healthy qi and eliminating pathogen, replenishing qi and activating blood, and detoxifying and dredging collaterals, which demonstrate definite curative effect and can effectively relieve clinical symptoms, restore the lung function and blood oxygen partial pressure, improve the quality of life of patients, and reduce adverse reactions. Experimental studies have found that dredging and replenishing lung collaterals have significant effects on IPF inflammation (macrophage polarization), oxidative stress, EMT, autophagy inhibition and other signaling pathways. Therefore, from the perspective of impediment, this article reviews pathogenesis of IPF, the research progress in TCM treatment of IPF, and the treatment of IPF from active components, single herbs, and compound prescriptions of TCM, with the aim of revealing the scientific connotation of the treatment of IPF from impediment and providing a new theoretical basis for enriching the TCM methods of treating IPF.
摘要:Digital and intelligent technologies serve as the core engine driving the inheritance of the essence and the innovation while upholding the fundamentals of traditional Chinese medicine(TCM). Currently, the digital and intelligent transformation of TCM has undergone four developmental stages, exhibiting inherent characteristics such as long-term inevitability, objective standardization, and ecological evolution. By introducing quantitative metrics, digital and intelligent technologies have achieved breakthroughs in TCM knowledge inheritance and innovation, clinical diagnosis and treatment, and herbal medicine supply. The practical applicability of methodological innovations has been empirically validated, though significant disparities exist in technological adaptability and application depth across different fields. Overall, the digital and intelligent transformation of TCM remains in its nascent stage, grappling with multiple structural challenges:weak data foundations, inadequate technological adaptability, incomplete institutional frameworks, shortages of multidisciplinary talent, lagging policies and regulations, and urban-rural digital divide. In order to foster sustainable development and modernization of TCM, this paper establishes a six-dimensional collaborative governance framework of encompassing data, technology, organization, institutions, environment and ethics, which is rooted in data governance and digital governance theories. Future efforts should center on standardization, integration, and ecosystem development to build a data and technology foundation. Focus should be placed on deepening innovation and application of key TCM-specific technologies, while simultaneously strengthening interdisciplinary talent cultivation, improving institutional mechanisms and policy frameworks, and increasing support for rural areas. By adopting a people-centered and technology-empowered approach, we can overcome developmental constraints and unleash the powerful driving force of digital and intelligent technologies for the inheritance of TCM.
关键词:traditional Chinese medicine;digital and intelligent transformation;development achievements;current challenges;breakthrough pathways;data governance;digital governance
摘要:Gouty arthritis (GA) is caused by monosodium urate(MSU) deposition due to purine metabolism disorders. In traditional Chinese medicine (TCM), it falls under the category of "dampness-heat Bi syndrome", with core pathogenesis involving dampness-heat accumulation and dysfunction of the spleen and kidney. The dampness-heat syndrome is the most common and the primary syndrome type during acute attacks. In Western medicine, GA is associated with purine metabolism imbalance and inflammation triggered by MSU crystals, involving pathways such as NOD-like receptor protein 3 (NLRP3) inflammasome activation and Toll-like receptor 2/4 (TLR2/4) signaling. Clinically, colchicine and similar drugs are commonly used to treat GA, although long-term use carries potential side effects. Ermiao Formula analogs originate from ancient prescriptions, including Ermiao, Sanmiao, and Simiao compound formulas. All contain Atractylodis Rhizoma and Phellodendri Chinensis Cortex. Ermiaowan follow a 1∶1 formulation ratio. Sanmiaowan add Cyathulae Radix. Simiaowan further incorporate Coicis Semen. These formulas are rich in active ingredients, including alkaloids, terpenoids, flavonoids, and sterols, and treat GA through multi-component, multi-pathway, and multi-target mechanisms. Ermiaosan primarily exerts anti-inflammatory effects by inhibiting pathways such as TLR4/nuclear factor kappa-B (NF-κB) or regulating immune responses to reduce the release of inflammatory mediators, while also suppressing xanthine dehydrogenase (XDH) and xanthine oxidase (XO) activity to decrease uric acid production. Sanmiaowan enhance uric acid-lowering and anti-inflammatory effects through the guiding herb Cyathulae Radix, while also protecting cartilage from damage. Simiaowan utilizes Coicis Semen to regulate intestinal flora, alleviate dampness-heat symptoms, and exert multi-pathway anti-inflammatory and uric acid-lowering effects. The active ingredients contribute differently to uric acid metabolism regulation, anti-inflammation, antioxidant activity, and bone repair, resulting in varying therapeutic effects due to differences in formula composition. In summary, formulas derived from Ermiaosan demonstrate significant efficacy in treating dampness-heat type GA. This review summarizes their research progress and mechanisms, providing a reference for clinical application, new drug development, and further studies.
关键词:dampness-heat type gouty arthritis;Ermiaosan;Sanmiaowan;Simiaowan;active ingredients
摘要:Central nervous system diseases refer to complex disorders that affect the structure and function of the central nervous system (brain and spinal cord). Due to their complex pathogenesis and the lack of effective therapies, the diseases have become one of the leading causes of human death and have imposed a heavy economic burden on families and society. Rehmanniae Radix Preparata, a representative traditional Chinese medicine for "nourishing essence and enriching marrow", has multi-target and multi-pathway advantages in the treatment of central nervous system diseases. It contains various active components such as catapol, verbascoside, and echinacoside and has multiple pharmacological effects including anti-depression, neuroprotection, antioxidation, anti-inflammation, and immunomodulation. In Alzheimer's disease, Rehmanniae Radix Preparata can regulate the processing of beta-amyloid precursor protein to reduce its production, and its antioxidative and neuroprotective effects can alleviate related pathological damage. In Parkinson's disease, it can protect dopaminergic neurons by regulating intracellular signal transduction pathways. In ischemic stroke, its antioxidative, anti-inflammatory, and neuroprotective effects can alleviate pathological reactions. Multiple sclerosis is an autoimmune demyelinating disease, and its pathogenesis is related to the autoimmune response attacking the myelin sheath of the central nervous system. The anti-inflammatory effect of Rehmanniae Radix Preparata can help inhibit this autoimmune response, reduce the damage of inflammation to the myelin sheath, and protect damaged neurons while promoting myelin sheath repair. In depression, Rehmanniae Radix Preparata can improve neural plasticity, and its anti-inflammatory effect can regulate neuroendocrine function and influence the metabolism of neurotransmitters. This paper explored the action mechanism of Rehmanniae Radix Preparata in central nervous system diseases and summarized the relevant basic research and research progress on its active components and traditional Chinese medicine formulas for treating central nervous system diseases, providing a theoretical basis for the development of traditional Chinese medicine products for the prevention and treatment of central nervous system diseases with Radix Rehmanniae Preparata.
关键词:Rehmanniae Radix Preparata;central nervous system disease;research progress;active component;action mechanism
摘要:Atherosclerosis (AS) is a vascular disease primarily affecting large and medium-sized arteries. It serves as the pathological basis for many cardiovascular and cerebrovascular diseases and is associated with a relatively high incidence of complications and mortality worldwide. Traditional Chinese medicine (TCM) plays an important role in the prevention and treatment of AS, demonstrating unique therapeutic advantages through multiple targets and pathways. Ligusticum chuanxiong, a commonly used Chinese medicine in clinical practice, contains key active components against AS, including ligustrazine, senkyunolide, ligustilide, quercetin, ferulic acid, vanillic acid, chlorogenic acid, gallic acid, protocatechuic acid, caffeic acid, chrysophanol, and β-sitosterol. Recent literature indicates that these active components can regulate AS through multiple mechanisms, including improving endothelial cell dysfunction, alleviating lipid metabolism disorders, inhibiting macrophage foam cell formation, suppressing the invasion, proliferation, and migration of smooth muscle cells, inhibiting apoptosis, exerting anticoagulant effects and inhibiting platelet activation, protecting mitochondrial function, and modulating intestinal flora and its metabolites, demonstrating significant pharmacological activity and clinical potential. Clinically, L. chuanxiong is often combined with Salvia miltiorrhiza, Paeonia lactiflora, Angelica sinensis, and borneol to form compound formulations, enhancing therapeutic effects and achieving synergistic anti-AS activity. Compound treatment with L. chuanxiong primarily focuses on promoting blood circulation and shows significant efficacy for different AS syndrome types. This article provides an in-depth review of the active components, drug pairs, and compound preparations of L. chuanxiong in the prevention and treatment of AS, aiming to lay a foundation for subsequent theoretical research and clinical applications in managing AS and its related complications.
关键词:atherosclerosis;anti-atherosclerotic mechanism;Ligusticum chuanxiong and its active ingredients;Ligusticum chuanxiong herb pair;Chinese medicine compound formulas containing Ligusticum chuanxiong
摘要:Chronic atrophic gastritis (CAG) is a digestive system disease characterized by the reduction and atrophy of the intrinsic glands of the gastric mucosa. This disease is closely related to risk factors such as Helicobacter pylori (Hp) infection,long-term unhealthy eating habits and lifestyle. As CAG is a key link in the development of gastric cancer,effectively preventing its deterioration is of great significance for the prevention of gastric cancer. At present,Western medicine mainly uses symptomatic treatments such as eradicating Hp,protecting gastric mucosa, and promoting gastrointestinal motility. However, long-term use is prone to drug resistance and cannot reverse limitations such as gland atrophy, making it urgent to explore new intervention strategies. In recent years,with the deepening of CAG mechanism research,the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway,as one of the classic signaling pathways,plays a significant role in the occurrence and development of CAG,while its systematic summary is still blank. Based on the regulatory advantages of "multi-target,multi-pathway,and low toxicity",traditional Chinese medicine can improve the pathological process of CAG by intervening in key nodes of the PI3K/Akt pathway. In this paper,the research progress of traditional Chinese medicine regulating PI3K/Akt pathway to improve CAG was systematically reviewed for the first time. The expression of PI3K/Akt signaling pathway in CAG was discussed,including the regulation of inflammation and oxidative stress,cell proliferation and apoptosis,and autophagy. The traditional Chinese medicine flavonoids,alkaloids,terpenoids and other compounds that regulate this pathway were summarized. The traditional Chinese medicine compounds mainly include classic famous prescriptions such as Xiaochaihu Tang,Banxia Xiexin Tang,Morodan concentrated pills,Elian granules and other traditional Chinese patent medicines,as well as empirical prescriptions such as modified Leweiyin formula,and Qiling prescription. This study aims to give full play to the advantages of traditional Chinese medicine and lay a solid foundation for the wide application and further development of CAG treatment,and provide new ideas for clinical research and drug research on CAG.
摘要:Sarcopenia is a systemic skeletal muscle disease characterized by the gradual decline of muscle mass,strength,and function,and its occurrence and development are related to multiple factors,involving several signaling pathways. Among them,the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway,as a key pathway regulating cellular growth,survival,and metabolism,plays an important role in the formation and development of sarcopenia. Its abnormal activation or deactivation may lead to an imbalance in muscle protein metabolism,resulting in muscle atrophy and reduction. Modern medicine is still in the exploratory stage of treatment for sarcopenia. Traditional Chinese medicine (TCM),with its multi-pathway and multi-target characteristics,has shown increasing advantages in the prevention and treatment of sarcopenia. In recent years,various monomers, extracts,and compound formulas of TCM have been proven to effectively prevent and treat sarcopenia by promoting muscle cell protein synthesis,reducing protein degradation,inhibiting cell apoptosis and inflammatory response,and improving mitochondrial function. This paper reviewed the improvement effects of TCM on sarcopenia based on the PI3K/Akt pathway and explored its specific action mechanisms, aiming to provide new insights for the treatment of sarcopenia with TCM.
关键词:sarcopenia;phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway;monomer of traditional Chinese medicine;extract of traditional Chinese medicine;compound formula of traditional Chinese medicine
摘要:Hepatocellular carcinoma (HCC), the predominant subtype of primary liver cancer, ranks among the top in both incidence and mortality rates of malignant tumors in China. In its early stages, the disease may present with subtle or nonspecific symptoms, often leading to poor clinical prognosis and low patient survival rates, which makes it a significant public health concern. The pathogenesis is associated with multiple factors, including hepatitis virus infection, alcohol consumption, obesity, drug-induced liver injury, and immune disorders, which may interact synergistically to promote disease development. Currently, mainstream therapeutic approaches for HCC in modern medicine encompass surgical resection, liver transplantation, radiofrequency ablation, radiotherapy, and chemotherapy, but they all have certain limitations, such as large side effects and poor prognosis, imposing substantial psychological distress and financial strain on affected individuals. With a rich historical background in hepatic malignancy management, traditional Chinese medicine offers therapeutic benefits characterized by multi-targeted mechanisms, multi-level regulation, minimal adverse effects, and reduced likelihood of disease recurrence. It can not only enhance the curative effect, but also reduce the side effects of radiotherapy, chemotherapy, and surgery. Thus, it has attracted widespread attention. Extensive research has demonstrated that traditional Chinese medicine exhibits significant antitumor properties, along with notable anti-inflammatory and oxidative stress-reducing capabilities, and its mechanism may be related to the regulation of nuclear factor-kappa B (NF-κB) signaling pathway, which can affect multiple stages of hepatocarcinogenesis, such as cell proliferation, invasion, metastasis, and apoptosis. The mechanism of NF-κB signaling pathway in traditional Chinese medicine for HCC treatment has emerged as one of the pivotal research directions in current oncology studies. Based on the existing research foundation, a systematic literature review method was adopted to retrieve and analyze relevant Chinese and English literature in recent years. Integrating the molecular regulatory mechanisms of the NF-κB signaling pathway and its pivotal role in HCC pathogenesis and progression helped further explore the latest research advances in traditional Chinese medicine interventions targeting this pathway for HCC treatment. This approach may provide novel theoretical foundations and translational strategies for the prevention and management of HCC using traditional Chinese medicine.
关键词:nuclear factor-kappa B;signaling pathway;hepatocellular carcinoma;traditional Chinese medicine;research progress
摘要:Lung cancer is the leading cause of cancer-related deaths worldwide, and tumor metastasis is a key factor contributing to the mortality of most lung cancer patients. Aberrant activation of epithelial-mesenchymal transition (EMT) is a major driver of lung cancer progression and metastasis. EMT is characterized by the loss of apical-basal polarity and intercellular adhesion in highly differentiated, polarized, and organized epithelial cells, which acquire motility, migratory potential, and invasive properties. During this process, cells undergo cytoskeletal remodeling and transform into a mesenchymal phenotype, accompanied by associated changes in cellular markers. The EMT process is highly complex and is tightly regulated by intricate networks involving multiple transcription factors, post-translational controls, epigenetic modifications, and non-coding RNAs. Therefore, therapies targeting the mechanisms of malignant transformation and their associated pathways in lung cancer are of significant clinical importance. In recent years, EMT has attracted increasing attention as a potential target for cancer therapy. Chinese medicine, with its characteristics of multi-target action, low side effects, and good therapeutic efficacy, has demonstrated an important role in anticancer treatment. A series of studies have investigated the role of Chinese medicine in inhibiting EMT in lung cancer. Active ingredients of Chinese medicine, including flavonoids, glycosides, phenols, terpenoids, saccharides, and alkaloids, as well as Chinese medicine compound formulas, have shown significant regulatory effects on EMT. Their mechanisms mainly involve multiple pathways, targets, and links, including signaling pathways, exosomes, microRNAs (miRNAs), and the tumor-associated immune microenvironment. This article summarizes the mechanisms by which EMT promotes malignant tumor progression and reviews the current research on how Chinese medicine active ingredients, monomers, and compound formulas inhibit EMT and suppress lung cancer cell migration and invasion. This study is expected to provide comprehensive theoretical information for basic and translational research on lung cancer.