摘要:ObjectiveThis study investigated the effects of Anmeidan on learning and memory impairment, as well as on the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway protein and autophagy in sleep-deprived (SD) mice.MethodsSixty C57BL/6 mice were randomly divided into six groups: a normal group, a model group, a low-, medium-, and high-dose Anmeidan groups ( 6.57, 13.13, 26.26 g·kg-1·d-1), and a melatonin group (1.3 g·kg-1·d-1 ). A mouse model was created using a custom-designed sleep deprivation box. The learning and memory performance of mice in different groups were evaluated using the Morris water maze experiment. The changes in pyramidal neurons and Nissl bodies were observed by hematoxylin-eosin (HE) and Nissl staining. The protein expression levels of microtubule-associated protein 1A/1B light chain 3 (LC3) and sequestosome 1 (p62) were detected using immunofluorescence. Western blot and Real-time polymerase chain reaction (Real-time PCR) were used to detect changes in the expression of proteins and mRNAs related to the PI3K/Akt/mTOR signaling pathway, as well as the protein and mRNA expression of LC3, benzyl chloride 1 (Beclin1), and p62 associated with autophagy, respectively.ResultsCompared with mice in the normal group, SD mice showed significantly impaired spatial learning and memory, as indicated by prolonged latency to reach the platform, increased total swimming distance, and decreased platform crossings and time spent in the target quadrant. Histological examination revealed a decreased number of neurons, increased cell degeneration, and a decreased number of Nissl bodies in the CA3 region of the hippocampus in the model group. In addition, Western blot, Real-time PCR, and immunofluorescence results showed that sleep deprivation decreased the protein and mRNA expression of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, and p62, while significantly elevating the LC3 Ⅱ/LC3 Ⅰ ratio and Beclin 1 protein and mRNA expression (P<0.01), indicating enhanced autophagy. Compared with the model group, groups treated with Anmeidan showed improved learning and memory performance, as shown by shortened latency to reach the platform, reduced swimming distance(P<0.05, P<0.01), and increased time spent in the target quadrant and platform crossings(P<0.01). Hippocampal neuronal damage was alleviated, and the number of Nissl bodies was increased in all Anmeidan dose groups. In addition, Anmeidan upregulated the protein and mRNA expression p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, and p62, while downregulating the LC3 Ⅱ/LC3 Ⅰ ratio and Beclin 1 protein and mRNA expression (P<0.05, P<0.01), thereby inhibiting neuronal autophagy.ConclusionAnmidan can effectively improve sleep deprivation-induced learning and memory impairment, and its mechanism of action may be related to the activation of the PI3K/Akt/mTOR signaling pathway and inhibition of hippocampal neuronal autophagy.
关键词:Anmeidan;sleep deprivation;learning and memory;autophagy;phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)
摘要:ObjectiveTo investigate the effect of Yanghetang (YHT) on the treatment of osteoarthritis (OA) and its mechanism.MethodsIn vivo experiments: After 1 week of acclimatization feeding, 30 C57BL/6J mice were randomly divided into normal group, model group, low and high dose groups of YHT (8.3, 16.6 g·kg-1), and celecoxib group (18 mg·kg-1), with six mice in each group. Except for the normal group, the remaining groups were constructed with the OA model by right-sided joint meniscus destruction surgery. After successful modeling, the normal group and the model group were given an equal amount of saline gavage daily, and each treatment group was given the corresponding dose of the drug, respectively. The intervention lasted for 4 weeks. Micro-computed tomography (Micro-CT) was used to scan the right knee of the sampled mice. Alisin blue (ABH) and hematoxylin-eosin (HE) staining were used to observe the pathologic morphology of synovium and cartilage in mice. Enzyme-linked immunosorbent assay (ELISA) was used to detect the effect of YHT on the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) inflammatory factors in mice, and immunohistochemistry was employed to observe the relevant pathways' expression. In vitro experiments: RAW264.7 cells were induced with lipopolysaccharides (LPSs) to establish an M1-type inflammation model, and 1%, 3%, and 5% YHT were added for intervention, and the above macrophage supernatant (CM) was collected and added to the chondrocyte culture medium for intervention, respectively. High performance liquid chromatography (HPLC) was used to determine the content of YHT for compositional analysis. Cell counting kit-8 (CCK-8) was used to detect the effect of YHT on cell viability. Immunofluorescence and flow cytometry were adopted to detect the degree of macrophage M1/M2 type polarization, and Annexin V apoptosis detection kit was used to detect the degree of apoptosis of chondrocytes. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western bolt were utilized to determine the expression of relevant proteins and mRNAs in RAW264.7 cells and chondrocytes.ResultsCompared with those of the normal group, the bone-related parameters such as BV/TV, Tb.N, and Tb.Th were significantly down-regulated (P<0.01), and Tb.Sp was significantly elevated (P<0.01) in mice of the model group, with significant pathological changes in synovium and cartilage, and the levels of inflammatory factors in serum including IL-6 and TNF-α, were significantly elevated (P<0.01). The viability of chondrocytes was significantly reduced, while the apoptosis rate was significantly higher (P<0.01), and the average fluorescence intensity of CD86 in RAW264.7 cells was significantly improved (P<0.01). Real-time PCR results showed that the levels of iNOS, IL-6, and IL-1β mRNA in RAW264.7 cells and chondrocytes were significantly higher (P<0.05, P<0.01), and Arg-1, IL-10, and CD206 mRNA levels were significantly decreased (P<0.01). Western blot assay revealed that the protein phosphorylation levels of PI3K, Akt, and NF-κB were significantly up-regulated in the LPS group (P<0.01), and the MMP-13 expression was up-regulated, but the Col-2 protein expression was down-regulated (P<0.05, P<0.01). Compared with the model group, YHT groups significantly improved bone-related parameters in mice (P<0.01), significantly reduced synovial cell thickness and cartilage surface abrasion, attenuated serum levels of IL-6 and TNF-α in mice (P<0.01), increased chondrocyte survival, attenuated chondrocyte apoptosis (P<0.01), and significantly attenuated M1-type RAW264.7 cell polarization (P<0.01). Real-time PCR results showed that iNOS, IL-6, and IL-1β mRNA levels in RAW264.7 cells and chondrocytes were significantly decreased (P<0.05, P<0.01), and Arg-1, IL-10, and CD206 mRNA levels were significantly up-regulated (P<0.05, P<0.01). Western blot assay revealed that YHT groups significantly down-regulated the protein phosphorylation levels of PI3K, Akt, and NF-κB (P<0.05, P<0.01), simultaneously inhibited the expression of MMP-13, and up-regulated Col-2 protein expression (P<0.05, P<0.01).ConclusionYHT significantly improved osteoarthritis caused by synovial macrophage inflammation. The pathway may be related to the inhibition of the PI3K/Akt/NF-κB signaling pathway.
关键词:Yanghetang;osteoarthritis;macrophage;chondrocyte;mechanism study
摘要:ObjectiveTo observe the effect of peroxidative stress on the PANoptosis of the lung tissue in the rat model of bleomycin-induced idiopathic pulmonary fibrosis (IPF) and explore the possible mechanism of Shengxiantang in alleviating the pathological changes of IPF.MethodsForty SPF-grade male SD rats were randomly assigned to five groups: sham, model, inducer (trimethylamine oxide solution, 110 mg·kg-1), Shengxiantang (aqueous solution of Shengxiantang granules, 0.81 g·kg-1), and inducer (trimethylamine oxide solution, 110 mg·kg-1) + Shengxiantang (aqueous solution of Shengxiantang granules, 0.81 g·kg-1), with 8 rats per group. The IPF model was established via intratracheal administration of bleomycin. Rats received corresponding agents once daily for 28 days. Pathological changes in the lung tissue were assessed by hematoxylin-eosin staining and Masson staining. Serum and lung tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were quantified. The reactive oxygen species (ROS) level in the lung tissue was measured by fluorescence staining. The immunohistochemical assay was conducted to detect gasdermin D (GSDMD), cysteinyl aspartate-specific proteinase (Caspase)-3, and mixed lineage kinase domain-like protein (MLKL). Western blot was adopted to determine the protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase-1, cleaved Caspase-1, GSDMD, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, cleaved Caspase-3, receptor-interacting serine/threonine kinase (RIPK) 1, RIPK3, MLKL, and phosphorylated MLKL (p-MLKL).ResultsCompared with the sham group, the model group showed exacerbated lung inflammation and fibrosis, a risen MDA level (P<0.05), decreased activities of SOD, CAT, and GSH-Px (P<0.05), enhanced positive expression of ROS and mRNA levels of GSDMD, Caspase-3, and MLKL (P<0.05), up-regulated expression levels of pyroptosis pathway-associated proteins (NLRP3, Caspase-1, cleaved Caspase-1, and GSDMD), apoptosis pathway-associated proteins (Bax, cleaved Caspase-3, and Caspase-3), and necroptosis pathway-associated proteins (RIPK1, RIPK3, p-MLKL, and MLKL) (P<0.05), and a down-regulated protein level of Bcl-2 (P<0.05). Compared with the model group, the inducer group exhibited elevated levels of MDA in the serum and lung tissue (P<0.05), reduced activities of SOD, CAT, and GSH-Px (P<0.05), enhanced positive expression of ROS and pyroptosis/apoptosis/necroptosis pathway-associated proteins, up-regulated mRNA levels of GSDMD, Caspase-3, and MLKL (P<0.05), and exacerbated pulmonary fibrosis. Compared with the inducer group, both Shengxiantang group and Shengxiantang + inducer group presented reductions in inflammation/fibrosis indices, oxidative stress biomarkers in the serum and lung tissue, expression levels of pyroptosis/apoptosis/necroptosis pathway-associated proteins, and mRNA levels of GSDMD, Caspase-3, and MLKL (P<0.05), and the Shengxiantang group outperformed the Shengxiantang + inducer group (P<0.05).ConclusionShengxiantang effectively mitigates PANoptosis through modulation over oxidative stress, thereby delaying/reversing early-stage pathological changes induced by bleomycin exposure in IPF.
摘要:ObjectiveTo clarify the effect of Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma on myocardial ischemia-reperfusion injury in rats and explore its mechanism.MethodsSeventy-two male SD rats were randomized into sham, model, low-, medium-, and high-dose (3.09, 6.71, and 12.34 g·kg-1) Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma, and trimetazidine (20 mg·kg-1) groups. After 10 consecutive days of drug administration, except for the sham operation group which only had threading without ligation, the remaining groups underwent left anterior descending artery ligation for 45 min followed by 3 h of reperfusion. After reperfusion, Evans blue staining and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to detect the area of myocardial infarction and the area at risk. Biochemical methods were adopted to determine the levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), and malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Terminal deoxynucleotidyl transferase dUTP nick end labeling was employed to detect apoptosis in the myocardial tissue, and immunofluorescence assay was employed to assess the reactive oxygen species (ROS) level. Western blot was employed to determine the protein levels of microtubule-associated protein 1 light chain 3 (LC3) and FUN14-domain containing 1 (FUNDC1).ResultsCompared with the sham group, the model group showed increased myocardial infarction area and area at risk (P<0.01), elevated levels of CK-MB, LDH, and MDA (P<0.01), decreased activities of SOD and GSH-Px (P<0.01), increased apoptosis index in the myocardial tissue (P<0.01), and up-regulated FUNDC1 expression and LC3Ⅱ/LC3Ⅰ (P<0.01). Compared with the model group, the three Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma groups and the trimetazidine group showed reduced myocardial infarction area and area at risk (P<0.05, P<0.01), declined levels of CK-MB and MDA (P<0.01), and increased activities of SOD and GSH-Px (P<0.05). The medium-dose Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma group and the trimetazidine group showed reduced apoptosis index in the myocardial tissue (P<0.01) and down-regulated expression of FUNDC1 and LC3Ⅱ/LC3Ⅰ in the myocardial tissue (P<0.05).ConclusionAstragali Radix-Salviae Miltiorrhizae Radix et Rhizoma can ameliorate myocardial ischemia-reperfusion injury and reduce myocardial cell apoptosis and oxidative stress damage in rats by inhibiting the excessive activation of mitophagy mediated by FUNDC1.
关键词:oxidative stress;cell apoptosis;microtubule-associated protein 1 light chain 3 (LC3)Ⅱ/LC3Ⅰ;traditional Chinese medicine;mitochondria
摘要:ObjectiveTo explore the mechanism by which Aconiti Lateralis Radix Praeparata(ALRP) regulates lipid metabolism in the liver of Yang-deficient mice by modulating the protein kinase A (PKA)/peroxisome proliferator-activated receptor alpha (PPARα)/carnitine palmitoyltransferase 1α (CPT1α) signaling pathway.MethodsForty male Kunming mice were randomly divided into five groups: a control group, a model group, a low-dose ALRP group, a high-dose ALRP group, and a positive control group. A Yan-deficient and high-fat diet mouse model was established by intramuscular injections of hydrocortisone combined with a high-fat diet in all groups except the control. Hydrocortisone was injected into the hind limb muscle at a dose of 0.025 g·kg-1 daily, along with a high-fat diet. The control group received an equivalent volume of normal saline intramuscularly to maintain consistent handling. This modeling continued for nine consecutive days. Starting on day 10, the treatment groups received daily intragastric administrations of low-dose ALRP water extract (0.25 g·mL-1), high-dose ALRP water extract (0.5 g·mL-1), and fenofibrate suspension (0.005 g·mL-1), respectively. The model and control groups were administered an equivalent volume of distilled water intragastrically to maintain similar conditions. After continuous administration for 10 days, the body weight and plasma cyclic adenosine monophosphate/cyclic guanosinc monophosphate (cAMP/cGMP) ratio of the mice were observed. Plasma triglyceride (TG), total cholesterol (TC), and hepatic TC and TG levels were measured using enzyme-linked immunosorbent assay. Histopathological changes in the liver were examined using hematoxyl-eosin (HE) staining. Real-time polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of PPARα, CPT1α, adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and stearoyl-CoA desaturase-1 (SCD1) in liver tissue. Western blot analysis was performed to evaluate the protein expression of phosphorylated PKA (p-PKA), PPARα, and CPT1α.ResultsCompared to the control group, the model group exhibited significant increases in plasma and hepatic TC and TG levels (P<0.05, P<0.01). In liver tissue, the mRNA expression levels of PPARα, CPT1α, ATGL, and HSL were significantly decreased (P<0.01), whereas the mRNA expression level of SCD1 was significantly increased (P<0.01). Additionally, the protein expression levels of p-PKA, PPARα, and CPT1α were notably reduced (P<0.01). Compared to the model group, all treatment groups showed significant reductions in plasma and hepatic TC and TG levels (P<0.05, P<0.01). The mRNA expression levels of PPARα, CPT1α, ATGL, and HSL in liver tissue were significantly increased (P<0.05, P<0.01), whereas the mRNA expression level of SCD1 was significantly decreased (P<0.05, P<0.01). Moreover, the protein expression levels of p-PKA, PPARα, and CPT1α were significantly elevated (P<0.05, P<0.01).ConclusionALRP improves dysregulated lipid metabolism in Yang-deficient and high-fat diet mice via modulating the PKA/PPARα/CPT1α pathway.
摘要:ObjectiveTo investigate the effect of gallic acid (GA) on exercise-induced muscle damage (EIMD) in mice and explore its therapeutic mechanism in regulating ferroptosis in skeletal muscle cells.MethodsA total of 60 SPF-grade C57 mice were used, with 10 randomly selected as the control group. The remaining mice underwent treadmill exercise for the modeling of EIMD and were then randomly assigned into five groups: treadmill, ferrostatin-1 (Fer-1, 0.005 g·kg-1), low-dose (0.2 g·kg-1) GA, high-dose (0.4 g·kg-1) GA, and high-dose (0.4 g·kg-1) GA + Erastin (0.03 g·kg-1). After intervention, muscle damage was assessed by a balance beam test, hematoxylin-eosin (HE) staining, and Sirius red staining. Enzyme linked immunosorbent assay (ELISA) was used to measure the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), and iron ions in skeletal muscle. Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were employed to determine the protein and mRNA levels, respectively, of p53, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in skeletal muscle. Immunohistochemistry (IHC) was performed to evaluate the expression of p53 in the muscle tissue. In the cell experiment, Western blot was employed to determine the expression of ferroptosis-related proteins in C2C12 cells.ResultsCompared with the control group, the treadmill group exhibited increased balance beam crossing time and paw slips, obvious inflammatory infiltration and fiber rupture in the skeletal muscle tissue, along with elevated levels of IL-6, TNF-α, CK, LDH, MDA, and iron ions (P<0.05). Additionally, the treadmill group presented up-regulated protein and mRNA levels of p53, down-regulated protein and mRNA levels of SLC7A11 and GPX4 (P<0.05), and increased p53 (P<0.05). Compared with the treadmill group, the Fer-1, low-dose GA, and high-dose GA groups demonstrated reduced balance beam crossing time and paw slips, decreased inflammatory infiltration and fiber rupture in the skeletal muscle tissue, and lowered levels of IL-6, TNF-α, CK, LDH, MDA, and iron ions (P<0.05). In addition, these groups exhibited down-regulated protein and mRNA levels of p53, up-regulated protein and mRNA levels of SLC7A11 and GPX4 (P<0.05), and decreased p53 (P<0.05). However, compared with the high-dose GA group, the high-dose GA + Erastin group showed increased balance beam crossing time and paw slips, obvious inflammatory infiltration and fiber rupture, elevated levels of IL-6, TNF-α, CK, LDH, MDA, and iron ions (P<0.05), up-regulated protein and mRNA levels of p53, down-regulated protein and mRNA levels of SLC7A11 and GPX4 (P<0.05), and an increase in the MD of p53 (P<0.05). The cell experiment showed that compared with the blank group, the tension group showed an increase in the protein level of p53 and decreases in the protein levels of SLC7A11 and GPX4 in C2C12 cells (P<0.05). Compared with the tension group, the GA group showcased down-regulated expression of p53 and up-regulated expression of SLC7A11 and GPX4 (P<0.05). Compared with the GA group, the GA + Erastin group demonstrated an increase in the protein level of p53 and decreases in the protein levels of SLC7A11 and GPX4 (P<0.05).ConclusionGA may exert therapeutic effects on EIMD by inhibiting ferroptosis through regulation of the p53/SLC7A11/GPX4 pathway.
关键词:gallic acid;recombinant tumor protein p53(p53);solute carrier family 7 member 11 (SLC7A11);glutathione peroxidase 4 (GPX4);exercise-induced muscle damage (EIMD)
ZHANG Xiaomeng, LI Chunying, HAN Jiayin, YI Yan, PAN Chen, ZHAO Yong, LIU Suyan, TIAN Jingzhuo, WANG Lianmei, CHENG Xi, LIU Chenyue, WANG Xingwen, GAO Feng, WU Jingwen, CAI Rushuang, YUAN Haisheng, LIANG Aihua, ZHANG Yushi
摘要:ObjectiveTo elucidate the molecular mechanisms underlying the vascular irritation reaction induced by Huachanshu injection (HCSI) and screen the related substances.MethodsFirstly, the model of vascular irritation reaction induced by HCSI and its components was established in rabbits. Sixteen clean-grade male white rabbits were randomly allocated into six groups: blank (2 rabbits, normal saline), HCSI (2 rabbits, 0.16 L·L-1), polypeptide (3 rabbits,0.232 g·L-1), nucleic acid (3 rabbits,0.232 g·L-1), tryptamine (3 rabbits,0.022 4 g·L-1), and toxic ligand (3 rabbits,0.016 8 g·L-1). The rabbits were administrated with corresponding agents once a day for three consecutive days. Visual observation, pathological examination, and scoring were performed 24 h after the last administration. The model of increased vascular permeability was established in mice. According to the body weight, 78 ICR mice were assigned into 13 groups (n=6): blank (normal saline), positive drug (histamine, 20 mg·kg-1), high- and low-dose (12.8,3.2 mg·kg-1) HCSI, high-, medium-, and low-dose (3, 1.5, and 0.75 mg·kg-1) 5-hydroxytryptamine (5-HT), high-, medium-, and low-dose (3, 1.5, and 0.75 mg·kg-1) bufotenine (BUF), and high-, medium-, and low-dose (3, 1.5, and 0.75 mg·kg-1, respectively) bufotenidine (BTD). The ear blue staining was observed within 30 min after administration. Evans blue (EB) exudation from the mouse ear tissue was detected by spectrophotometry (a microplate reader). The serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of p38 mitogen-activated protein kinase (p38 MAPK), p-p38 MAPK, inhibitor of nuclear factor-κB (IκB), p-IκB, IκB kinase (IKK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the lung tissue of mice. Digital quantitative polymerase chain reaction(Digital PCR) was employed to detemine the mRNA levels of nuclear factor-κB (NF-κB) and p-NF-κB p65 in the ear tissue and the lung tissue.ResultsThe rabbit model induced by HCSI showed obvious vascular irritation reaction, which was mild in the tryptamine group and not observed in the nucleic acid group, peptide group, or toxic ligand group. This result suggested that tryptamine may be the main contributor of the vascular irritation reaction induced by HCSI. High-dose HCSI, 5-HT, BUF, and high-dose BTD increased the ear blue staining reaction rate, ear blue staining score, and EB exudation compared with the blank group (P<0.05, P<0.01), and the degree of reaction was positively correlated with the dose. High-dose HCSI and high-dose BUF increased the content of TNF-α and IL-6 (P<0.01) and up-regulated the protein levels of p-p38 MAPK/p38 MAPK, p-IκB/IκB, and IKK (P<0.05, P<0.01) and the mRNA levels of NF-κB and p-p65 (P<0.05, P<0.01).ConclusionThe p38 MAPK signaling pathway and NF-κB activation are involved in the vascular hyperpermeability and vascular irritation reaction induced by HCSI and BUF in mice. Indole derivatives such as BUF may be key contributors to the vascular irritation reaction induced by HCSI.
摘要:ObjectiveTo study the molecular mechanism of Kelong capsules in improving benign prostatic hyperplasia(BPH) based on nuclear transcription factor E2-related factor 2(Nrf2).MethodsSixty SPF male SD rats were randomly divided into normal group, model group, sham operation group, positive drug group(finasteride group, 0.45 mg·kg-1), and high, medium and low dose groups of Kelong capsules(14.4, 7.2, 3.6 g·kg-1). The BPH model was established by subcutaneous injection of testosterone propionate after orchiectomy. Except for the normal group and sham operation group, rats in the other groups were given testosterone propionate by subcutaneous injection and the corresponding drugs by intragastric administration(pure water was given to the model group) on the 8th day after orchiectomy. After continuous administration for 28 d, the body weight of rats was measured, then rats were executed and prostate was removed, the prostate wet weight of rats was measured and the prostate index was calculated. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of prostate tissue, the levels of CD68, Nrf2, reduced nicotinamide adenine dinucleotide or phosphate[NAD(P)H]quinone oxidoreductase 1(NQO1), interleukin(IL)-6, tumor necrosis factor(TNF) -α and IL-1β in prostate tissues of rats were detected by immunohistochemistry(IHC), the mRNA expression levels of CD68, CD80 and CD86 in rat prostate tissues were detected by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the protein expression levels of CD68, Nrf2 and NQO1 in prostate tissues of rats were detected by Western blot.ResultsCompared with the sham operation group, the prostate index of rats in the model group was significantly increased(P<0.01), and typical pathological changes were presented, including thickening of glandular epithelium, reduction of acinar cavity area and increase of secretions in the glandular cavity, the infiltration of CD68+ macrophages in the prostate tissues significantly increased(P<0.01), and the expressions of pro-inflammatory indexes(CD68, IL-6, TNF-α, IL-1β proteins and mRNA) were significantly up-regulated(P<0.01), while the expressions of antioxidant indexes(Nrf2 and NQO1 proteins) were down-regulated(P<0.01). Compared with the model group, the prostate index in each administration group decreased significantly(P<0.01), and the pathological characteristics improved significantly, manifested as an increase in the area of acinar cavity and a decrease in the thickness of glandular epithelium and smooth muscle. High and medium doses of Kelong capsules could significantly reduce the infiltration of CD68+ macrophages(P<0.05, P<0.01), down-regulate the mRNA expression levels of macrophage-related markers(CD68, CD80 and CD86)(P<0.01), while simultaneously up-regulate the protein expression levels of Nrf2、NQO1(P<0.05, P<0.01), and reduce the levels of inflammatory factors such as IL-6, TNF-α and IL-1β(P<0.05, P<0.01).ConclusionKelong capsules may exert its therapeutic effect on BPH through multiple mechanisms such as inhibiting macrophage activation, reducing oxidative stress and inflammatory response.
摘要:ObjectiveTo explore the mechanism by which Shugan Bushen Yunlin decoction enhances the spermatogenic function in the rat model of oligoasthenospermia based on the insulin receptor substrate (IRS)/protein kinase B (Akt)/forkhead box protein O1 (FoxO1) signaling pathway.MethodsForty-eight male rats were randomly assigned to the blank, model, low-, medium-, and high-dose (5.175, 10.35, and 20.7 g·kg-1, respectively) Shugan Bushen Yunlin decoction, and levocarnitine (0.27 g·kg-1) groups, with 8 rats in each group. Apart from the blank group, the other groups were administrated with adenine (50 mg·kg-1) by gavage for 14 days for modeling. Once the model was established, rats in the blank and model groups were administrated with normal saline, and those in other groups were administrated with corresponding agents by gavage for 28 consecutive days. Twenty-four hours after the last administration, the rats were sacrificed, and their body weights, testis weights, and epididymis weights were measured. The pathological alterations in the testis and epididymis were inspected through hematoxylin-eosin staining, and the spermatogenic function of the testis was assessed. The levels of testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and malondialdehyde (MDA) in the serum, as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were measured by enzyme-linked immunosorbent assay. The rate of apoptosis in the testis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The protein and mRNA levels of insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), Akt, phosphorylated Akt (p-Akt), FoxO1, and phosphorylated FoxO1 (p-FoxO1) were determined by Western blot and Real-time quantitative polymerase chain reaction(Real-time PCR), respectively.ResultsCompared with the blank group, the model group exhibited declined testis and epididymis indexes, impaired spermatogenesis, conspicuously decreased sperm density and activity, significantly lowered serum levels of FSH, LH, and T, significantly reduced activities of SOD and GSH-Px, and a significantly elevated MDA level. Moreover, the model group exhibited increased apoptosis, down-regulated protein and mRNA levels of IRS1, IRS2, and Akt, and up-regulated protein and mRNA levels of FoxO1 in the testis tissue (P<0.01). Compared with the model group, the three groups of Shugan Bushen Yulin decoction exhibited increased testis and epididymis indexes, improved spermatogenesis, sperm density, and sperm activity, risen levels of FSH, LH, and T in the serum, enhanced activities of SOD and GSH-Px, suppressed apoptosis in the testis, up-regulated protein and mRNA levels of IRS1, IRS2, and Akt, and down-regulated protein and mRNA levels of FoxO1 (P<0.05, P<0.01).ConclusionShulian Bushen Yulin decoction is capable of regulating the IRS/Akt/FoxO1 signaling pathway to prevent the apoptosis of spermatogenic cells in the rat model of oligoasthenospermia, thereby enhancing spermatogenesis and improving sperm quality.
关键词:Shugan Bushen Yulin decoction;oligoasthenospermia;oxidative stress;sperm quality;insulin receptor substrate (IRS)/protein kinase B (Akt)/forkhead box protein O1 (FoxO1) signaling pathway
摘要:ObjectiveTo investigate the effects of herb-partitioned moxibustion on B-cell activating factor (BAFF) and the chemokine (C-X-C motif) ligand 13 (CXCL13)/C-X-C motif chemokine receptor 5 (CXCR5) signaling pathway in immunosuppressed rats and elucidate the potential molecular mechanisms underlying the regulatory effects of herb-partitioned moxibustion on B cells in the body.MethodsForty SD rats were randomly allocated into four groups (n=10): blank, model, herb-partitioned moxibustion, and moxa stick moxibustion. The model was established by intraperitoneal injection of cyclophosphamide at 30 mg·kg-1 for 3 consecutive days in other groups except the blank group. Shenque (CV8), Guanyuan (CV4), Zhongwan (CV12), and Zusanli (ST36, bilateral) were selected for intervention in the two moxibustion groups for 10 consecutive days. The body weight of each rat was recorded every day. On the day following the end of intervention, the rats were weighed and anesthetized. Then, venous blood and spleen samples were collected, and the spleen index was calculated. The enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of interferon-γ (IFN-γ), cluster of differentiation 19 (CD19), cluster of differentiation 79 (CD79), cluster of differentiation 27 (CD27), immunoglobulin G (IgG), immunoglobulin M (IgM), interleukin-4 (IL-4), and interleukin-21 (IL-21) in the serum, and the Th1/Th2 ratio was calculated. Hematoxylin-eosin staining was used to examine the morphological alterations in the spleen tissue. Real-time quantitative polymerase chain reaction(Real-time PCR) was utilized to determine the mRNA levels of immunoglobulin-like transcript 4 (ILT4) and B cell activating factor (BAFF) in the spleen tissue. Western blot was employed to measure the protein levels of CXCL13 and CXCR5 in the spleen tissue.ResultsCompared with the blank group, the model group exhibited a decrease in body weight (P<0.05), an increase in spleen index (P<0.01), cell disarrangement in the spleen tissue, an obscure boundary between the white pulp and the red pulp, and fuzzy spleen nodules. In addition, the modeling led to declined serum levels of CD19 (P<0.01), CD27 (P<0.01), CD79 (P<0.01), IL-21 (P<0.01), IL-4 (P<0.05), and IgG and IgM (P<0.05), elevated IFN-γ and Th1/Th2 levels (P<0.05), up-regulated mRNA level of ILT4 (P<0.01), and down-regulated mRNA level of BAFF (P<0.01) and protein levels of CXCL13 and CXCR5 (P<0.01). Compared with the model group, the herb-partitioned moxibustion and moxa stick moxibustion groups showed an increase in body weight (P<0.05), a decrease in spleen index (P<0.01), alleviated diffuse proliferation and infiltration of lymphocytes in the spleen, and a clear boundary between the white pulp and the red pulp. Furthermore, both moxibustion groups showcased elevated serum levels of CD19 (P<0.01), CD27 (P<0.01), CD79 (P<0.01), IL-21 (P<0.01), IL-4 (P<0.01), and IgG and IgM (P<0.05), declined IFN-γ and Th1/Th2 levels (P<0.05), down-regulated mRNA level of ILT4 (P<0.01), and up-regulated mRNA level of BAFF (P<0.01) and protein levels of CXCL13 and CXCR5 (P<0.01). The herb-partitioned moxibustion group and the moxa stick moxibustion group showed differences in other indicators (P<0.05, P<0.01) except the body weight, IL-4, and IgG.ConclusionHerb-partitioned moxibustion can improve the immune status and immune function by regulating B cells, CXCL13, CXCL5, and BAFF.
摘要:ObjectiveTo study the tumor inhibition effect of Wenyang Sanjie prescription on lung cancer tumor-bearing mice and elucidate the mechanism of Wenyang Sanjie prescription on lung cancer tumor-bearing mice based on signal transducer and activator of transcription 3 (STAT3)/hypoxia inducible factor-1α (HIF-1α) pathway.MethodsA Lewis cell axillary inoculation method was used to establish a lung cancer tumor-bearing mouse model. After modeling, mice were randomly divided into a lung cancer tumor-bearing group, a low-dose group of Wenyang Sanjie prescription (2.5 g·kg-1), a medium-dose group of Wenyang Sanjie prescription (5 g·kg-1), a high-dose group of Wenyang Sanjie prescription (10 g·kg-1), and a cisplatin group, with 10 mice for each group. Interleukin (IL)-2, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-10 in serum were detected by enzyme-linked immunosorbent assay (ELISA). Percentages of CD4+ T cells, CD8+ T cells, and B lymphocytes were measured by flow cytometry. Tumor weight, tumor volume, and tumor inhibition rate were calculated. Levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and Acyl-CoA synthetase long-chain family member 4 (ACSL4) mRNAs in tumor tissue were measured by real-time quantitative polymerase chain reaction (Real-time PCR). Tumor histopathology was detected by hematoxylin-eosin (HE) staining. Tumor cell apoptosis was assessed by TdT-mediated dUTP nick-end labeling (TUNEL), and levels of phospho-signal transducer and activator of transcription 3 (p-STAT3), STAT3, and HIF-1α proteins in tumor tissue were measured by Western blot.ResultsCompared with those in the lung cancer tumor-bearing group, the levels of IL-2 and IFN-γ, the percentages of CD4+ T cells, CD8+ T cells, and B lymphocytes, the level of ACSL4 mRNA, and the tumor apoptosis rate were increased in the low-dose, medium-dose, and high-dose groups of Wenyang Sanjie Prescription and the cisplatin group, which was significant (P<0.05). The levels of TNF-α and IL-10, the tumor weight and volume, the levels of GPX4 and SLC7A11 mRNAs, and the levels of p-STAT3/STAT3 and HIF-1α proteins were decreased, which was significant (P<0.05). Compared with those in the low-dose group of Wenyang Sanjie prescription, the levels of IL-2 and IFN-γ, the percentages of CD4+ T cells, CD8+ T cells, and B lymphocytes, the level of ACSL4 mRNA, the tumor cell apoptosis rate, and the tumor inhibition rate were increased in the medium-dose and high-dose groups of Wenyang Sanjie prescription, which was significant (P<0.05). The levels of TNF-α and IL-10, the tumor weight and volume, the levels of GPX4 and SLC7A11 mRNAs, and the levels of p-STAT3/STAT3 and HIF-1α proteins were decreased, which was significant (P<0.05). Compared with those in the medium-dose group of Wenyang Sanjie prescription, the levels of IL-2 and IFN-γ, the percentages of CD4+ T cells, CD8+ T cells, and B lymphocytes, the level of ACSL4 mRNA, the tumor cell apoptosis rate, and the tumor inhibition rate were increased in the high-dose group of Wenyang Sanjie prescription, which was significant (P<0.05). The levels of TNF-α and IL-10, the tumor weight and volume, the levels of GPX4 and SLC7A11 mRNAs, and the levels of p-STAT3/STAT3 and HIF-1α proteins were decreased, which was significant (P<0.05).ConclusionWenyang Sanjie prescription can significantly inhibit tumor growth, regulate the immune function and iron death of lung cancer tumor-bearing mice, and promote the apoptosis of lung cancer cells, which may be related to the regulation of STAT3/HIF-1α pathway.
关键词:Wenyang Sanjie prescription;lung cancer;tumor-bearing mice;signal transducer and activator of transcription 3/hypoxia inducible factor-1α (STAT3/HIF-1α) signaling pathway
摘要:ObjectiveTo screen and evaluate the new prescription and dosage of traditional Chinese medicine for the treatment of chronic atrophic gastritis (CAG), to screen out the active components and targets of the new prescription of traditional Chinese medicine for the treatment of CAG through network pharmacology, to construct the relationship between the new prescription of traditional Chinese medicine and the disease, and to explore the mechanism of the new prescription of traditional Chinese medicine for the treatment of CAG.MethodsChina National Knowledge Infrastructure(CNKI), VIP and Wanfang databases were searched to search for relevant literature on CAG treated by traditional Chinese medicine compound prescriptions. The database was established by using the traditional Chinese medicine inheritance support platform V3.0 to obtain the combination of core drugs and new prescriptions of traditional Chinese medicine. The Delphi questionnaire was used to evaluate the new prescriptions of traditional Chinese medicine.Through network pharmacology research, the effective components of new prescriptions of traditional Chinese medicine were searched based on Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and HERB databases, and the effective targets of CAG were searched using nline Mendelian Inheritance in Man(OMIM), GeneCard and DisGeNET databases. Venny database was used to screen out the common targets of new Chinese medicine and CAG.Protein-protein interaction (PPI) network was carried out based on STRING database. DAVID database was used to screen out the core targets for GO and KEGG enrichment analysis, and the effective components, potential targets and signaling pathways of new Chinese medicine in the treatment of CAG were predicted. In the experimental study, 55 male SD rats were divided into blank group and model group. The model group was modeled by multi-factor method. After successful modeling, the model group was randomly divided into model group, new Chinese medicine group and Yangweishu group, with 12 rats in each group. Continuous gavage for 56 days. After anatomical sampling, hematoxylin-eosin (HE) staining was used to detect the pathological conditions of gastric mucosa in rats. The levels of interleukin-1β ( IL-1β ), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and gastrin-17 (G-17) in serum of rats were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of mitogen-activated protein kinase(MAPK), extracellular regulated protein kinases(ERK) and nuclear factor E2-related factor 2 (Nrf2) protein in gastric tissue of rats were detected by Western blot.ResultsThrough data mining and Delphi questionnaire evaluation, the composition of the new prescription of traditional Chinese medicine was composed of Curcumae Rhizoma 15 g, Paeoniae Radix Alba 15 g, Angelicae Sinensis Radix 15 g, Lycii Fructus 10 g, Toosendan Fructus 15 g and japonica rice 15 g. Through network pharmacology analysis, the main components of the new prescription of traditional Chinese medicine are β-sitosterol, ethyl linoleate, quercetin, phytosterol (stigmasterol ) and cholesterol. Five common components, 94 common targets between the new prescription of traditional Chinese medicine and CAG were analyzed, of which transforming growth factor-β1(TGF-β1), Fructooligosaccharides(FOS), TNF, IL-1α, IL-1β, Caspase-3, protein kinase B1(Akt1), TP53 were the core targets , a total of 401 items were screened out by GO analysis, and 133 items such as MAPK signaling pathway were analyzed by KEGG enrichment.The results of animal experiments showed that HE staining showed that the new Chinese medicine group and Yangweishu group had certain improvement in gland atrophy and intestinal metaplasia. ELISA results showed that compared with the model group, the expression levels of IL-1β, IL-6 and TNF-α in the serum of the new Chinese medicine group and Yangweishu group decreased ( P<0.05, P<0.01 ), and the expression level of G-17 increased ( P<0.01 ). Western blot results showed that compared with the model group, the expression levels of MAPK and ERK proteins in gastric tissue decreased (P<0.01). The expression level of Nrf2 protein was increased (P<0.01).ConclusionThrough data mining, it is screened that the new Chinese medicine group can effectively improve the atrophy of gastric mucosa in rats, which is mainly closely related to the regulation of inflammatory response and oxidative stress response, and may be related to the MAPK/ERK/Nrf2 signaling pathway predicted by network pharmacology.
关键词:new prescription of traditional Chinese medicine;chronic atrophic gastritis;traditional Chinese medicine inheritance auxiliary platform;network pharmacology;mitogen-activated protein kinase(MAPK)/extracellular regulated protein kinases(ERK)/nuclear factor E2-related factor 2(Nrf2) signaling pathway;gastric mucosa
摘要:ObjectiveTo evaluate the clinical efficacy of Shexiang Tongxin dropping pills in the treatment of coronary slow flow (CSF) and observe its impact on inflammatory factors.MethodsA randomized, double-blind, placebo-controlled trial design was adopted. Patients with CSF were randomly divided into a test group and a control group at a 1∶1 ratio. The test group was given Shexiang Tongxin dropping pills in addition to conventional basic treatment, while the control group was given a placebo in addition to conventional basic treatment, with the treatment lasting for a total of 12 weeks. The summed rest score (SRS) of myocardial perfusion imaging was used as the primary efficacy indicator, and the Seattle Angina Questionnaire (SAQ) and angina symptom scores were used as secondary efficacy indicators to evaluate the clinical efficacy. The levels of serum interleukin-1α (IL-1α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were measured before and after treatment to observe the impact of Shexiang Tongxin dropping pills on inflammatory factors, and its safety was also evaluated.ResultsUltimately, 64 patients diagnosed with CSF by coronary angiography were included in this study, with 32 patients in each group. In terms of clinical efficacy, the SRS score of the patients in the test group was significantly improved after treatment compared with before treatment (χ2=12.70, P<0.05). After treatment, compared with the control group, the test group showed significantly improved SRS score (χ2=7.63, P<0.05). The scores of angina stability (AS), angina frequency (AF), treatment satisfaction (TS), and disease perception (DS) and the angina symptom score were all significantly improved in the test group after treatment compared with before treatment (P<0.05). In the control group, the DS score was significantly improved (P<0.05). After treatment, compared with the control group, the test group exhibited significantly improved scores of AS, AF, and TS and the angina symptom score (P<0.05). In terms of inflammatory factors, the levels of IL-1α, IL-1β, and IL-6 in the test group decreased after treatment compared with before treatment (P<0.05). After treatment, compared with the control group, the test group had decreased levels of IL-1α, IL-1β, and IL-6 (P<0.05).ConclusionShexiang Tongxin dropping pills can effectively improve the clinical symptoms of patients with CSF and significantly reduce the levels of inflammatory factors in serum.
摘要:ObjectiveTo investigate the effects of Gandouling decoction combined with sodium dimercaptopropanesulfonate (DMPS) on sleep disorders in patients with Wilson's disease (WD) due to combined phlegm and stasis.MethodsA total of 92 hospitalized patients with WD and sleep disorders due to combined phlegm and stasis at the Encephalopathy Center of Anhui Province Hospital of Chinese Medicine from June 2019 to December 2024 were randomly allocated into a control group and an observation group, with 46 patients each. The control group received conventional DMPS chelation therapy, while the observation group received Gandouling decoction combined with DMPS. Each treatment course lasted for 8 days, and the patients were treated for 2 courses. Polysomnography (PSG) and the Pittsburgh Sleep Quality Index (PSQI) were adopted to assess objective sleep parameters [total sleep time (TST), sleep efficiency (SE), sleep latency (SL), and number of microarousals] and subjective sleep quality, respectively, before and after treatment. The Hamilton Depression Rating Scale-17 (HAMD-17) and Hamilton Anxiety Rating Scale (HAMA) were used to evaluate depression and anxiety symptoms, respectively. Total response rates were compared between the two groups. The sleep quality, psychological status, 24 h-urinary copper levels, traditional Chinese medicine (TCM) symptom scores, and incidence of adverse reactions were compared between and within groups before and after treatment.ResultsThe total response rate in the observation group was 91.31% (42/46), which was higher than that (71.74%, 33/46) in the control group (χ2=5.85,P<0.05). After treatment, both groups showed increased TST and SE, and reduced SL and microarousals (P<0.05). In addition, after treatment, both groups presented decreased PSQI, HAMD-17, HAMA, and TCM symptom scores and increased 24-h urinary copper level (P<0.05). Moreover, the observation group outperformed the control group regarding the above indicators (P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups.ConclusionGandouling Decoction combined with DMPS significantly improves sleep quality and enhances copper excretion in WD patients with the syndrome of combined phlegm and stasis, demonstrating both safety and efficacy.
关键词:Wilson's disease;sleep disorders;syndrome of combined phlegm and stasis;Gandouling decoction;polysomnography
摘要:ObjectiveTo observe the clinical efficacy of compound Langdu tincture in the treatment of multiple palmoplantar warts of dampness-toxin accumulation type and explore the potential treatment mechanism based on network pharmacology and experimental verification.MethodsA prospective randomized controlled single-blind trial design was adopted. Seventy-six patients with multiple palmoplantar warts were assigned into two groups according to the random number table method, with 38 patients in each group. The observation group was treated with compound Langdu tincture, and the control group was treated with 15% salicylic acid ointment. The skin lesion clearance rate, cured and marked response rate, total response rate, skin lesion number, skin lesion size, skin lesion area, skin lesion thickness, pain degree, and Dermatology Life Quality Index (DLQI) were compared before and after treatment, and the safety and recurrence were analyzed. The drug components were screened out from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease-related genes were retrieved from Online Mendelian Inheritance in Man (OMIM) and Genecards. The protein-protein interaction (PPI) network was constructed and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The key targets were verified by Real-time PCR.ResultsBefore treatment, there was no significant difference in the skin lesion number, skin lesion size, skin lesion area, skin lesion thickness, pain degree or DLQI between the two groups. After treatment, both groups were improved in terms of the skin lesion clearance rate, cured and marked response rate, total response rate, skin lesion number, skin lesion size, skin lesion area, skin lesion thickness, pain degree, and DLQI (P<0.05), and no serious adverse reaction was observed in the observation group. Furthermore, the observation was superior to the control group regarding the skin lesion clearance rate, skin lesion number, and pain degree (P<0.05). The results of network pharmacology showed that compound Langdu tincture may act on targets such as protein kinase B1 (Akt1), epidermal growth factor receptor (EGFR), tumor protein p53 (TP53) to play a therapeutic role via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT), phosphatidylinositol 3-kinase (PI3K)/Akt and other signaling pathways. The mRNA levels of Akt1 and EGFR were down-regulated and that of TP53 was up-regulated in the skin lesions of patients after 12 weeks of treatment.ConclusionCompound Langdu tincture has a definite clinical effect on multiple palmoplantar warts of the dampness-toxin accumulation type. The network pharmacology preliminarily revealed the treatment mechanism, and the key targets were verified by Real-time PCR, which provided a basis for subsequent experimental research.
摘要:ObjectiveTo observe the effect of early application of Da Xianxiongtang on the progression toward severe acute pancreatitis (SAP) in acute pancreatitis patients with the syndrome of thoracic accumulation and interior excess.MethodsA total of 124 acute pancreatitis patients with the syndrome of thoracic accumulation and interior excess treated in the Chongqing Traditional Chinese Medicine Hospital from January 2022 to June 2024 were included. The patients were assigned with the random number table method into a control group and an observation group, with 62 patients in each group. The control group received standard Western medicine treatment, while the observation group received oral or nasogastric administration of Da Xianxiongtang within 24 h of onset in addition to the therapy in the control group, for a course of 5 days. The Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Modified Balthazar CT Severity Index (MCTSI) score, levels of inflammation markers [interleukin-6 (IL-6) and C-reactive protein (CRP)], plasma level of free mitochondrial DNA (mtDNA), traditional Chinese medicine (TCM) symptom scores, and bladder pressure on days 0, 5, and 10 of treatment were measured. In addition, the 28-d mortality rate and the occurrence of adverse reactions were recorded.ResultsA total of 122 patients completed the trial, with 61 patients in the observation group and 61 patients in the control group. There were no statistically significant differences in baseline characteristics between the two groups. The incidence of SAP and organ dysfunction was lower in the observation group than in the control group (P<0.05). The total response rate in the observation group was 81.97% (50/61), which was higher than that (57.38%, 35/61) in the control group (Z=8.728, P=0.003). After treatment, both groups showed declined APACHEⅡ score, MCTSI score, inflammation marker levels, mtDNA level, TCM symptom score, and bladder pressure (P<0.05). On day 5 of treatment, the observation group had lower APACHE Ⅱ score, inflammatory marker levels, mtDNA level, TCM symptom scores, and bladder pressure than the control group (P<0.05), while there was no statistically significant difference in MCTSI score between the two groups. On day 10 of treatment, the observation group demonstrated lower inflammation marker levels, mtDNA level, TCM symptom scores, and bladder pressure than the control group (P<0.05), and there was no statistically significant difference in APACHE Ⅱ score or MCTSI score. Neither the 28-d mortality rate nor the incidence of adverse reactions differed between the two groups.ConclusionOn the basis of comprehensive Western medical treatment, the early application of Da Xianxiongtang can reduce the incidence of severe cases, alleviate pancreatitis symptoms, lower intra-abdominal pressure, promote intestinal function recovery, and decrease the release of inflammatory factors in acute pancreatitis patients with the syndrome of thoracic accumulation and interior excess, thereby mitigating the progression toward SAP.
关键词:Da Xianxiongtang;acute pancreatitis;thoracic accumulation and interior excess;inflammatory factors;mitochondrial DNA
摘要:ObjectiveLeveraging large-scale real-world data and machine learning algorithms, this study conducted a precision analysis to identify the characteristics of the optimal population benefiting from Quanduzhong capsules in treatment of osteoporosis(OP), thereby providing evidence-based guidance for clinical practice.MethodsThe data were derived from 1 144 screened patients across 162 hospitals in China between 2020 and 2021, who received Quanduzhong capsules for two months under medical prescription or package insert guidance, and multidimensional clinical data of the patients were analyzed. Efficacy outcomes, including visual analogue scale (VAS) scores and OP symptom scores, served as classification labels. The XGBoost model coupled with SHAP(SHapley Additive exPlanations) quantified feature contributions through Shapley values, determining their magnitude and directional effects, thereby enabling the identification of potential optimal population characteristics.ResultsWhen applying Quanduzhong capsules for OP treatment, the machine learning algorithms identified that age, low back pain symptoms and blood pressure significantly influenced the classification of superior and non-superior therapeutic efficacy. Three characteristics showed positive impacts on efficacy, including age in the range of 45-60 years, baseline low back pain score≥6(median), and baseline knee weakness score≥4(median). Conversely, three factors demonstrated negative impacts, including baseline systolic blood pressure≥132 mmHg(1 mmHg≈0.133 kPa), diastolic blood pressure≥85 mmHg, and body mass index(BMI) reaching the overweight/obesity classification.ConclusionThrough the real-world research-machine learning dual-driven research method, it is clear that there are six main characteristics of the dominant population in the treatment of OP with Quanduzhong capsules, and patients with three or more at the same time are more likely to be classified as superior population, showing more significant clinical advantages.
关键词:real-world research;machine learning;interpretable analysis;osteoporosis;Quanduzhong capsules;advantageous population characteristics
摘要:ObjectiveTo explore the changes in soil fertility indicators of Fritillaria taipaiensis after inoculation with different potassium-solubilizing bacteria, providing a basis for selecting elite potassium-solubilizing microbial fertilizer during artificial cultivation of this plant.MethodsSeven bacterial inoculation groups were designed, including S1 (Bacillus cereus), S2 (Burkholderia hospita), S3 (Ba. subtilis), S4 (Ba. cereus and Bu. hospita), S5 (Ba. cereus and Ba. subtilis), S6 (Bu. hospita and Ba. subtilis) and S7 (Ba. cereus, Bu. hospita and Ba. subtilis). Additionally, a blank control group (CK group) was included. Twenty soil physical and chemical indicators of each group were measured. The cluster analysis, correlation analysis, and principal component analysis (PCA) were performed to construct the minimum data set of indicators influencing soil fertility. The soil fertility was compared between groups to select the optimal strain.ResultsThe constructed minimum data set included available potassium content, available phosphorus content, available nitrogen content, soil moisture content, bacterial count, potassium-solubilizing bacterial content, fungal count, and pH. The full data set and the minimum data set showed a significant positive correlation regarding the soil fertility index, with R2 of 0.914, Nash efficiency coefficient of 0.825, and deviation coefficient of 0.108. The membership radar chart showed that the area of each potassium-solubilizing bacterial inoculation group was larger than that of the CK group, with the S7 group having the largest area. The soil fertility index of the total data set ranged from 0.258 (S3) to 0.891 (S7), and that of the minimum data set ranged from 0.264 (S2) to 0.760 (S7), with average values of 0.44 and 0.39, respectively.ConclusionThe minimum data set constructed by cluster analysis, principal component analysis, and correlation analysis has a high degree of simplification. The application of potassium-solubilizing bacteria significantly improves the soil fertility of F. taipaiensis, with the S7 group showing the best overall performance.
关键词:potassium-solubilizing bacteria;Fritillaria taipaiensis;soil physical and chemical properties;soil fertility;minimum data set
摘要:ObjectiveTo investigate the effects of various phosphorus-solubilizing bacteria and their combinations on the soil fertility of Fritillaria taipaiensis and to furnish a reference for the cultivation of this plant and the development of bacterial fertilizer.MethodsA total of 17 indicators,such as organic matter,available phosphorus and available potassium,were determined for the cultivated soil samples from 6 bacterial groups and a blank(CK) group. A minimum data set(MDS) was established to screen the most sensitive indicators for evaluating soil fertility.ResultsCompared with the CK group,phosphorus-solubilizing bacteria treatment groups presented increases in soil organic matter,available potassium,available phosphorus,bacterial count,actinomycetes count,and sucrase activity. The MDS was established with four indicators: Bacterial count,available phosphorus,fungal count,and alkaline phosphatase activity. The membership radar map indicated that the soil fertility of each fertilization group was superior to that of the CK group,following the trend of Y12(Bacillus cereus YP5-1 and YP3-1) > W12(B. cereus WP7-2 and Serratia plymuthica WP2-2) > Y2(B. cereus YP5-1) > W2(Serratia plymuthica WP2-2) > Y1(B. cereus YP3-1) > W1(B. cereus WP7-2) > CK(distilled water). The soil fertility was the highest in the Y12 group and the lowest in the CK group. The soil quality index of the total data set was positively correlated with that of MDS,suggesting that the MDS could be utilized in place of the total data set to evaluate the soil fertility of F. taipaiensis. The clustering outcomes demonstrated that the cultivated soil fertility of F. taipaiensis was classified into 4 grades,with most(15) samples in grades Ⅱ(good) and Ⅲ(medium). In addition,3 samples in the Y12 group showed the soil fertility of grade Ⅰ(excellent) and 3 samples in the CK group showed the soil fertility of grade Ⅳ(poor).ConclusionThe application of different phosphorus-solubilizing bacteria can enhance soil fertility,facilitate nutrient circulation,increase beneficial enzyme activity,and improve the microbial community structure. The soil fertility of the bacterial combination groups Y12 and W12 is higher than that of the corresponding single bacterial strain groups. However,the content of availabe nitrogen in the combination groups is insufficient,and appropriate nitrogen fertilizer should be applied during the cultivation process.
关键词:phosphorus-solubilizing bacteria;Fritillaria taipaiensis;cultivated soil;minimum data set;soil fertility
摘要:ObjectiveTo investigate the effects of three different phosphorus-solubilizing fungal fertilizers on soil quality in the planting area of Fritillaria taipaiensis and quantitatively evaluate soil quality, providing a basis for the development and utilization of fungi fertilizers for F. taipaiensis.MethodsThe rhizosphere soil of F. taipaiensis was collected and allocated into eight groups: Z1 (Aspergillus tubingensis), Z2 (Aspergillus niger), Z3 (Aspergillus fumigatus), Z12 (A. tubingensis and A. niger), Z13 (A. tubingensis and A. fumigatus), Z23 (A. niger and A. fumigatus), Z123 (A. tubingensis, A. niger, and A. fumigatus), and CK (no bacterial fertilizer). Seventeen indicators including soil pH, physical and chemical properties, microbial counts, and enzyme activities were measured after different fungal fertilizers were applied. The correlation analysis, principal component analysis, and other methods were adopted to establish a minimum data set for evaluating soil quality.ResultsThe effects of different treatment groups on the basic physical and chemical indicators of soil varied. The bacterial count in the Z3 group was significantly higher than that of other treatment groups. The highest available potassium and available nitrogen content in soil appeared in the Z13 group, and the highest available phosphorus, total phosphorus, and organic matter content appeared in the Z123 group. Among the 7 indicators selected by the minimum data set for evaluating soil quality, neutral phosphatase activity had the greatest impact on soil quality. The fertility of each fertilization group was superior to that of the CK group, following the trend of Z123 group (0.746)>Z3 group (0.617)>Z23 group (0.535)>Z13 group (0.533)>Z12 group (0.408)>Z1 group (0.397)>Z2 group (0.338)>CK group (0.269). The soil fertility was the highest in Z123 group and the lowest in CK group. The SFQI values of the total data set and the minimum data set were correlated (P<0.01), indicating that the established minimum data set could replace the total data set.ConclusionApplying fungal fertilizer is an effective way to improve the soil quality of F. taipaiensis. Applying combined fungal strains outperforms applying single strains, and the Z123 group has the best improvement effect on soil.
关键词:cultivated soil;phosphorus-solubilizing fungi;Fritillaria taipaiensis;minimum data set;soil fertility
摘要:ObjectiveTo explore the effects of different nitrogen-fixing bacteria and their combinations on soil fertility of Fritillaria taipaiensis and provide reference for the cultivation of this plant and the development of bacterial fertilizer.MethodsSeven inoculation groups:N1 (Rahnella aquatilis WX-5),N2 (Pseudomonas chlororaphis TB-1),N3 (Paenibacillus stellifer DY-5),N4 (R. aquatilis WX-5 and P. chlororaphis TB-1),N5 (R. aquatilis WX-5 and P. stellifer DY-5),N6 (P. chlororaphis TB-1 and P. stellifer DY-5),and N7 (R. aquatilis WX-5,P. chlororaphis TB-1,and P. stellifer DY-5),and one control group were set up. Sixteen indicators such as organic matter,available phosphorus,and available potassium were measured for the cultivated soil. The soil fertility was evaluated by establishing the minimum data set (MDS) to screen out the most sensitive indicators.ResultsEight indicators including neutral phosphatase activity,urease activity,actinomycetes count,protease activity,bacterial count,nitrogen-fixing bacterial count,organic matter content,and acid phosphatase activity were selected to construct the MDS. The membership radar chart showed that other bacterial application groups except N1 and N2 groups had higher soil fertility than the CK group. The area followed the trend of N5>N7>N4>N6>N3>CK>N2>N1,which meant that the soil fertility was the highest in the N5 group and the lowest in the CK group. The soil quality index of the total data set had a significantly positive correlation with that of the MDS,indicating that the MDS could be used instead of the total data set to evaluate the soil fertility of F. taibaiensis cultivation. The cluster analysis results showed that the soil fertility was classified into 4 grades,with most (21) soil samples showing the soil fertility of grade Ⅱ (good),grade Ⅲ (medium),and grade Ⅳ (poor). Additionally,2 samples in N1 group had the soil fertility of grade I (excellent),and 8 samples (3 samples in the N7 group,3 samples in the CK group,and 2 samples in the N6 group) showed the soil fertility of grade Ⅳ (poor).ConclusionThe application of different nitrogen-fixing bacteria can improve the soil fertility of F. taibaiensis. The established MDS of soil quality evaluation is representative,accurate,and reliable. The results can provide a solid theoretical basis and parameter support for soil health quality assessment,rational planning of regions,scientific fertilization,and selection of appropriate farmland management measures in F. taibaiensis planting bases.
关键词:nitrogen-fixing bacteria;Fritillaria taipaiensis;cultivated soil;minimum data set;soil fertility
摘要:ObjectiveTo explore the material connotation of the change of volatile components during the processing of Gardeniae Fructus Carbonisata(GFC) in order to provide data support for the characterization of volatile components and the material basis of odor components.MethodsGFC decoction pieces were stir-fried at 300 ℃ and samples were taken for analysis at different time points, the volatile components during the processing of GFC were analyzed by headspace-gas chromatography-ion mobility spectrometry(HS-GC-IMS), and the volatile components were identified according to the National Institute of Standards and Technology(NIST) 2020 database and the IMS database, the fingerprint of GFC samples with different processing degrees were compared by VoCal 04.07 software and Gallery Plot plug-in accompanying the instrument, and the differential components were analyzed. Then, SIMCA 14.1 software was used for chemometric analysis, and the top 20 volatile components were screened as the odor difference markers of GFC by the variable importance in the projection(VIP) value>1, and the changes of the key odors during the frying process of GFC were discussed in combination with the relative odor activity value(ROAV).ResultsA total of 172 volatile components were detected by HS-GC-IMS, and 124 compounds were identified according to the database, including 11 kinds of compounds such as alcohols, ketones, aldehydes, organic acids, esters, ethers, benzenes, terpenes, alkenes, alkanes, and heterocyclic compounds, etc. And esters, aldehydes and ketones were the main volatile components in GFC. Difference comparison diagram and fingerprint showed that there were large differences between GFC samples with different processing degrees, and the samples could be clearly distinguished from each other in terms of clustering, with aldehydes, ketones and heterocyclic compounds being produced in stages or newly generated during the processing. Combined with VIP value and ROAV value, it was found that the contents of compounds such as butyl butanoate[dimer(D)], propyl heptanolactone(D), 1,4-cineole, 2-hexanol, 4-hydroxy-2,3-dimethyl-2H-furan-5-one(D) were higher in the raw products, and the contents of carbonyl compounds such as furfural, 5-methyl furfural, 2,3-butanedione were gradually increased during the stir-frying process, and reached the maximum in stir-frying for 12 min, indicating that 12 min was the turning point of GFC processing, that was the moderate point. In the frying process, the flavor-contributing substances such as 3-(methylthio)propionaldehyde with onion, meaty and fruity odors increased. In the stage of GFC stir-frying, the Maillard reaction, caramelization and lipid degradation reaction mainly occurred, and the total content of esters, aldehydes, ketones and heterocyclic compounds increased significantly, which was the important material basis for the formation of GFC aroma flavor.ConclusionEsters, aldehydes and ketones are the main volatile components of GFC, and their contents show an increasing trend during the process of charcoal stir-frying, and they are the important source of GFC aroma flavor, which provides a reference for the comprehensive characterization of the volatile components in GFC and the research of pharmacological material basis of the odor components.
摘要:ObjectiveTo investigate the pharmacokinetics and tissue distribution of free anthraquinones and gallic acid from Rhei Radix et Rhizoma Carbonisata(RRRC) and its raw products in mice with ulcerative colitis(UC), and to explore the mechanism of the pharmacodynamic difference in the treatment of UC before and after processing of RRRC from the perspective of in vivo process.MethodsA total of 126 male C57BL/6JNifdc mice were randomly divided into 21 groups, of which 1 group was the blank group, 10 groups were RRR group, and 10 groups were RRRC group, with 6 mice per group. Except for the blank group, other groups were given 3.5% dextran sulfate sodium(DSS) in drinking water to induce a mouse model of UC. After intragastric administration of RRR or RRRC water extracts at a crude drug dose of 6.5 g·kg-1, plasma and liver, small intestine, and colon samples were collected at different time points, and the concentrations of rhein, emodin, aloe-emodin, physcion, chrysophanol and gallic acid in plasma and tissues of mice were determined by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS). Pharmacokinetic parameters of the components were calculated using the non-compartmental model with DAS 2.0 software, and the data were statistically analyzed by IBM SPSS Statistics 20.ResultsPharmacokinetic results indicated that compared with RRR, the time to peak concentration(tmax) of the six components in RRRC was significantly shortened, with statistically significant differences specifically observed for chrysophanol and gallic acid (P<0.05, P<0.01), and the area under the concentration-time curve(AUC), the peak concentration(Cmax) and elimination half-life(t1/2z) of five free anthraquinones exhibited increases. Tissue distribution results showed that there were significant differences in the distribution patterns of gallic acid and free anthraquinones between RRR and RRRC, the RRR group reached the maximum drug concentration in tissues at 4-6 h, while the RRRC group had relatively higher tissue drug content at 0.25-1 h.ConclusionThe carbonization significantly alters the pharmacokinetic and tissue distribution behaviors of five free anthraquinones and gallic acid in RRR, increases the in vivo exposure of the active components, and accelerates the absorption rate, which may be one of the reasons why RRRC is superior to the raw products in the treatment of UC.
关键词:Rhei Radix et Rhizoma;charring;ulcerative colitis;pharmacokinetics;tissue distribution;free anthraquinones;gallic acid
摘要:Xiangsusan is composed of four herbs: Cyperi Rhizoma, Perillae Folium, Citri Reticulatae Pericarpium, and Glycyrrhizae Radix et Rhizoma. It is a classic formula for treating external sensations and Qi stagnation. This study was based on ancient and modern literature to conduct research on the composition, modification, dose conversion, original processing, indications, efficacy, and modern clinical applications of Xiangsusan, so as to provide a scientific basis for the development and clinical application of classic compound formulations of Xiangsusan. The research results found that the name "Xiangsusan" was first seen in the Bojifang, but the Xiangsusan recorded in the Taiping Huimin Hejiju Fang had a significant impact on later medical practitioners and was widely used by medical practitioners throughout history. In later generations, the formulation of boiled Xiangsusan powder was mostly used. The compatibility ratios recorded throughout history show that Cyperi Rhizoma and Perillae Folium occupy an absolute proportion in the formula. The dosage of Xiangsusan taken during the Song, Jin, and Yuan dynasties was greater than that during the Ming and Qing dynasties. The composition doses of Xiangsusan are 165.2 g Cyperi Rhizoma, 165.2 g Perillae Folium, 82.6 g Citri Reticulatae Pericarpium, and 41.3 g Glycyrrhizae Radix et Rhizoma. The above herbs were crushed into 10-mesh coarse powder, with a dosage of 12.39 g per dose, or crushed into 80-mesh fine powder, with a dosage of 8.26 g per dose. The amount of water added is 300 mL, and the solution is decocted to 210 mL. Cyperi Rhizoma is the dry rhizome of Cyperus rotundis, a plant of the Cyperus family, and it is fried. Perillae Folium is a dried leaf (or with tender branches) of Perilla frutescens var. frutescens (purple leaf type), and it is purified. Citri Reticulatae Pericarpium is the dry and mature peel of the Citrus reticulata and its cultivated varieties in the Rutaceae family, and the raw product is used as medicine. Glycyrrhizae Radix et Rhizoma is the dried roots and rhizomes of the leguminous plant Glycyrrhiza uralensis and fried. Xiangsusan can treat both external and internal diseases, including external wind-cold or plague, as well as gynecological diseases caused by Qi depression, with symptoms manifested as malignant cold and body heat, headache without sweating, coughing and wheezing, body pain, chest and diaphragm full of stuffiness, belching and anorexia. Perillae Fructus in the formula can relieve external colds and regulate Qi, making it the main medicine in the formula. Cyperi Rhizoma can assist in promoting Qi and relieving depression, while Citri Reticulatae Pericarpium can assist Perillae Fructus and Cyperi Rhizoma in regulating Qi and resolving stagnation. Glycyrrhizae Radix et Rhizoma can regulate the stomach and formula. The whole formula can disperse wind and cold, regulate Qi, and balance the body. It is often used in combination with drugs that can dissipate phlegm and regulate Qi, dispel wind and relieve pain, promote diuresis and alleviate swelling, strengthen the spleen and improve dry dampness, smooth Qi and reduce dampness, reduce phlegm and stimulate appetite, and promote Qi and eliminate bloating. The modern clinical application of Xiangsusan mainly focuses on the respiratory system, digestive system, and gynecological system. The specific diseases and syndromes mainly focus on cold, chronic gastritis, and idiopathic edema.
摘要:By referring to ancient and modern literature, the systematic textual research was carried out on the origin, scientific name evolution, harvesting, functional indications and other aspects of Chebulae Fructus(CF), in order to provide a basis for the development and utilization of famous classical formulas containing this herb. Through textual research, it could be known that CF was first recorded in Synopsis of Golden Chamber(《金匮要略》), named Helile, and then there were other aliases such as Hezi, Zangqingguo and Suifengzi. Since the Yuan dynasty, Bencao Yanyi Buyi(《本草衍义补遗》) first took Hezi as its name, which has been used for many generations and has been the mainstream name together with Helile, and the 1963 edition of Chinese Pharmacopoeia has taken CF as the official name, which is continued to this day. According to the origin and original plant research, ancient CF was introduced into China from Persia, and was first cultivated in Guangzhou. Therefore, Guangzhou was the Dao-di producing area, the imported variety was also used, and the main source of CF was Terminalia chebula. After that, the wild resources of CF were found in Yunnan, and there was T. chebula var. tomentella wild resource of CF, which was classified as the origin of CF together with T. chebula, and Yunnan became the modern Dao-di producing area. The best quality of CF in ancient times was six arrises, black color and thick meat, and modern times is solid, thick flesh, yellowish-brown skin, slightly wrinkled and glossy. In ancient times, CF were mostly harvested in July and August of the lunar calendar without mentioning the drying method, and nowadays, CF is mostly harvested in the late autumn and early winter and then dried in the sun. The processing methods of CF in the past dynasties were varied, and the processing forms depended on the medicinal efficacy, including simmering and stir-frying, of which the raw products for clearing the lung and promoting Qi, and processed products for warming the stomach and strengthening the intestine, the used auxiliary materials were wine, vinegar, ginger juice, bran and others. In modern times, the mainstream processing method is slightly soaked, moistened, pitted and dried. In terms of properties, flavor and efficacy, CF was warm and bitter in nature in ancient times, and belonged to the large intestine meridian, with its efficacy focusing on strengthening the spleen and stopping diarrhea. While in modern times, CF is flat in nature, sour and astringent in taste, and belongs to the lung and large intestine meridians, with its efficacy focusing on astringing the lungs, stopping diarrhea and relieving sore throat. Based on the textual research results, it is suggested that T. chebula should be used in the development of famous classical formulas, the processing method can be selected according to the original prescription requirements, and the formulas without processing records are used in accordance with the 2020 edition of Chinese Pharmacopoeia.
关键词:famous classical formulas;Chebulae Fructus;scientific name;origin;producing area;quality;harvesting and processing;herbal textual research
摘要:Based on the theory of "state-targeted medicine", this paper discussed the application and clinical value of the "combined Bi of body constituents and Zang organs" theory in Sjögren's syndrome (SS). As a complex autoimmune disorder, SS is fundamentally characterized by Yin deficiency and body fluid depletion, which progress into three pathological states of "heat, toxicity, and stasis", leading to multi-system involvement. Building upon traditional Chinese medicine (TCM) theory and integrating modern medical research, Professor Jiang Quan proposed the "combined Bi of body constituents and Zang organs" theory, emphasizing systemic treatment via "regulating Zang to stabilize the body." The representative formula Shaoteng Decoction was developed with functions of clearing heat and detoxifying while nourishing Yin and activating blood circulation, achieving both macro-level state regulation and micro-level targeted therapy. Clinical studies have demonstrated Shaoteng Decoction's significant efficacy in immune modulation, glandular function improvement, and inflammatory marker reduction. Furthermore, this paper systematically summarized TCM treatment strategies for SS, including herbal formulations, acupuncture, and external therapies, highlighting the precision of "state–target integrated" therapy. The findings provide both theoretical foundation and practical guidance for integrated TCM and Western medicine in SS diagnosis and treatment, showcasing the unique advantages of TCM in treating complex immune disorders.
关键词:combined Bi of body constituent and Zang organ;harmonizing Zheng and regulating balance;state-targeted medicine;dry Bi syndrome;Sjögren's syndrome
摘要:ObjectiveCombined allergic rhinitis and asthma syndrome (CARAS) is a common respiratory disease in children, characterized by a combination of allergic rhinitis and bronchial asthma. Its primary clinical manifestations include recurrent nasal congestion, nasal itching, sneezing, rhinorrhea, wheezing, and irritant cough. Traditional Chinese medicine (TCM) offers unique advantages in the treatment of CARAS through individualized approaches and the integrated treatment of the lungs and nasal passages. However, further research on the specific mechanisms of TCM in treating CARAS requires an appropriate CARAS disease-syndrome model as a foundation. This study aims to evaluate existing CARAS animal models based on the clinical characteristics of CARAS in Western medicine and TCM syndromes, providing a reference for establishing a CARAS TCM disease-syndrome model.MethodsRelevant experimental literature on CARAS was retrieved from major Chinese and international databases. Based on CARAS diagnostic criteria in both Western medicine and TCM, modeling methods, advantages and disadvantages, and clinical alignment were summarized.ResultsCurrent CARAS animal models were primarily based on Western pathological models, with mice, rats, and guinea pigs commonly used. The models were mainly prepared by sensitizing animals with ovalbumin (OVA) combined with adjuvants, followed by OVA aerosol inhalation and nasal instillation. The models aligned well with Western evaluation indicators but failed to induce TCM syndromes, resulting in low alignment with TCM evaluation indicators.ConclusionThe current CARAS pathological models exhibit high alignment with Western medicine criteria. However, there is a lack of methods for inducing TCM disease syndromes, making it difficult to reflect TCM syndrome characteristics. The evaluation criteria for existing animal models are inconsistent, highlighting the need for more comprehensive and uniform evaluation methods. CARAS disease-syndrome models should be established based on combined rhinitis and asthma models. For model evaluation, behavioral characteristics, inflammatory markers, pathological changes in the airways, airway resistance, and exhaled nitric oxide should be considered to ensure models better reflect the pathological features of CARAS and the clinical syndrome characteristics in TCM, thereby providing a foundation for TCM-based CARAS research.
关键词:combined allergic rhinitis and asthma syndrome;disease-syndrome combination;animal model;clinical alignment;traditional Chinese and Western medicine
摘要:Sanrentang was first recorded in Detailed Analysis of Warm Diseases (Wen Bing Tiao Bian), a work by Wu Jutong in the Qing Dynasty. It is a classic formula for treating the early stages of dampness-warmth or summer heat-warmth with dampness, characterized by pathogenic factors in the Qi aspect and more dampness than heat. This formula has the effects of dispersing Qi and clearing dampness and heat, and it can thus address symptoms such as headache, aversion to cold, pale yellow complexion, heavy body, pain, fatigue, chest fullness with loss of appetite, afternoon fever, white tongue coating without thirst, and a wiry, thready, and soggy pulse. Traditional Chinese medicine (TCM) emphasizes the holistic approach and treatment based on syndrome differentiation, using precise diagnostic methods to understand the characteristics of disease mechanisms and provide targeted treatment with herbal formulas. In modern clinical practice, Sanrentang has been widely employed to treat multi-system diseases caused by dampness-heat accumulation and obstructed Qi movement, including disorders of the heart, lung, spleen, stomach, liver, gallbladder, kidney, and intestine, diabetes and its complications, and dermatological conditions, achieving remarkable therapeutic outcomes. Particularly, for refractory diseases characterized predominantly by dampness-heat syndromes with poor treatment outcomes, the combined use of Sanrentang can delay disease progression, extend the survival time, and highlight the advantages of TCM, fully embodying the diagnostic and therapeutic principle of treating different diseases with same therapy based on the concept that identical patterns warrant identical therapy. Modern pharmacological studies have demonstrated that Sanrentang exerts anti-inflammatory and antioxidant effects, enhances the immune function, repairs the mucosal barrier, regulates the gastrointestinal motility, and maintains the metabolic balance. These findings confirm that TCM compound formulas possess multi-target, multi-dimensional, multi-component, and multi-pathway characteristics, effectively treating multi-system diseases with common pathological foundations such as inflammation and immune imbalance. This paper reviews the relevant literature on the clinical application of Sanrentang in the treatment of multi-system diseases and its mechanism and explores treating different diseases with same therapy (Sanrentang). This review aims to provide insights and references for using TCM compound formulas in treating multi-system diseases, exploring the deeper implications of these formulas, establishing a TCM-based precise diagnosis and treatment system, and promoting the inheritance and innovative development of TCM.
关键词:Sanrentang;treating different diseases with same therapy;clinical application;mechanism;research progress
摘要:Ulcerative colitis(UC) is a non-specific inflammatory disease of the intestinal tract, and its annually increasing incidence has become a global public health challenge. Oral drug delivery has become the preferred route of treatment for UC due to its convenience and improved patient compliance. However, achieving efficient delivery of oral drugs in the colon still faces many challenges. With the development of nanotechnology and material science, the study of colon targeted drug delivery systems has received increasing attention and demonstrated unique advantages in improving drug efficacy and minimizing adverse effects. Based on this, the paper systematically reviews the physiological factors and pathological microenvironment of the gastrointestinal tract to provide a design basis for the delivery systems to overcome gastrointestinal physiological barriers. And a comprehensive review of nano colon targeted drug delivery systems designed on the basis of endogenous stimulus responsive and active targeting mechanisms is presented. Additionally, four types of typical materials, categorized by their distinct properties and advantages, are introduced for application in these systems, illustrating how their material characteristics enable controlled drug release and targeted delivery. The goal is to provide theoretical basis and innovative insights for the research and development of the next generation colon targeted drug delivery system.
关键词:colon targeted drug delivery system;ulcerative colitis;nanoparticles;oral drug delivery;design strategy;physiopathological factors
摘要:The Shaoyao Gancaotang (SGT) originates from Zhang Zhongjing's Treatise on Cold Diseases during the Eastern Han Dynasty. It consists of two medicinal herbs, Paeoniae Radix Alba (Shaoyao) and Glycyrrhizae Radix et Rhizoma (Gancao) and is widely adopted by previous physicians due to its efficacy in alleviating spasms and pain. SGT has been included in the first batch of the classic formula directory by the National Administration of Traditional Chinese Medicine. In recent years, numerous studies in China and abroad have demonstrated the significant therapeutic effects of SGT in treating spasms and pain-related diseases from basic and clinical perspectives. The mechanism of action may be related to the inhibition of ion channels, anti-inflammatory and analgesic effects, and neuroprotection, among other factors, while also being influenced by variety processing, compatibility ratios, different dosage forms, and adverse reactions. This article reviewed the research on the classic formula SGT (known as Shakuyaku-kanzo-to/TJ-68 in Japan and Jakyak-Gamcho-Tang/JGT in Korea) in alleviating spasms and pain by scholars worldwide. In terms of basic research, the article explored the pharmacodynamic components based on the chemical constituents and physical interactions of SGT, the differences in spasmolytic and analgesic effects due to various processing methods and the compatibility ratios of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma, and the pharmacological mechanisms by which SGT exerted its spasmolytic and analgesic effects at different disease locations. In terms of clinical research, the article summarized the reported clinical efficacy of SGT for skeletal muscle spasm pain, smooth muscle spasm pain, and neuropathic spasm pain based on disease location classification and introduced related clinical trials. Additionally, this article briefly analyzed the modern dosage form research progress of SGT. By comparing the advantages and disadvantages of various dosage forms, prospects for the development of dosage forms beneficial for treating spastic pain were proposed. Finally, the article reported adverse reactions and precautions related to the clinical application of SGT for spastic pain, with a view to further promoting the modernization of the classic famous formula SGT and serving the health cause of the people in the new era.
关键词:Shaoyao Gancaotang;famous classic formula;basic and clinical research;adverse reaction
摘要:Puerariae Lobatae Radix (Pueraria root), derived from the dried root of Pueraria lobata, a leguminous plant, was first recorded in the Classic of the Materia Medica (Shennong Bencao Jing). It is characterized by a cool nature and a sweet-pungent taste, and it enters the spleen and stomach meridians. Traditionally, it is used to clear heat, promote fluid production, raise Yang, alleviate diarrhea, relieve muscle tension, and clear fever. In clinical practice, Puerariae Lobatae Radix is often combined with Trichosanthis Radix and Ophiopogonis Radix to enhance its effects in nourishing Yin, moistening dryness, and promoting fluid production, making it useful for treating diabetes caused by Yin deficiency and internal heat. Modern pharmacological studies have demonstrated that Puerariae Lobatae Radix is rich in bioactive compounds, including isoflavones (such as puerarin and daidzein), triterpenoid saponins, and polysaccharides. Its therapeutic effects on type 2 diabetes mellitus (T2DM) involve multi-target regulatory mechanisms. Specifically, it activates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway to improve insulin resistance, thereby facilitating glucose transporter 4 (GLUT4) translocation and increasing glucose uptake in peripheral tissues. Additionally, Puerariae Lobatae Radix regulates transcription factors to protect pancreatic β-cell function and promote insulin secretion. Moreover, it downregulates the nuclear factor-kappa B (NF-κB) signaling pathway and suppresses the expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), thereby improving the pancreatic microenvironment. These multi-faceted and synergistic effects provide a scientific basis for the use of Puerariae Lobatae Radix in diabetes treatment. This study systematically reviewed the traditional Chinese medicine theoretical foundation of Puerariae Lobatae Radix in treating T2DM, analyzed its core bioactive components, integrated findings from modern pharmacological research, and thoroughly explained its mechanisms of action. The aim is to provide a basis for the development of Puerariae Lobatae Radix resources and their application in the research and clinical treatment of T2DM.
摘要:Ferroptosis, as a distinctive form of cell death, is notably characterized by the accumulation of iron-dependent lipid peroxides in cell membranes. This mechanism differs from conventional cell death modalities such as apoptosis, autophagy, and necrosis, thereby exhibiting unique potential in disease treatment. Given the high incidence, chemotherapy resistance, and poor prognosis associated with gastric cancer, the exploration of novel therapeutic approaches becomes particularly crucial. In recent years, significant advancements have been made in research on ferroptosis in malignant tumors (including gastric cancer), neurological disorders, acute kidney injury, intestinal ischemia/reperfusion injury, and other areas, attracting widespread attention from the global scientific community. This article comprehensively reviews the research progress in ferroptosis regarding the molecular mechanisms and application in gastric cancer treatment, with the objective of gaining deeper insights into the role of ferroptosis in the pathogenesis of digestive tract tumors and providing new strategies and targets for cancer treatment.
摘要:As one of the most common malignant tumors in China, lung cancer has the highest morbidity and mortality among cancers in the world. Its high recurrence rate and high metastasis rate pose a serious threat to human life and health. It is worth noting that invasion and metastasis are important causes of poor prognosis and death of patients, and effective methods of inhibiting the invasion and metastasis of lung cancer are still a research hotspot. In clinical treatment, traditional Chinese medicine (TCM) plays an obvious role in relieving patients' clinical symptoms, improving patients' immune function and quality of life, inhibiting recurrence and metastasis, and enhancing efficacy and reducing toxicity in combination with Western medicine. More studies have recognized the advantages of TCM extracts and compounds in inhibiting tumor cell invasion and metastasis, such as multi-component, multi-pathway, and multi-target. This study summarized the theoretical and experimental contents of TCM in inhibiting the invasion and metastasis of lung cancer in recent years. In the theoretical research of TCM, despite different opinions among doctors and no unified standard, the perspective of deficient vital Qi and excessive pathogen remains accepted. On this basis, there are differences such as phlegm stasis, wind evil, and Yin and Yang imbalance. In terms of TCM experimental studies, the invasion and metastasis of lung cancer is a complex multi-step process, and the suppression of the invasion and metastasis of lung cancer by TCM involves multiple aspects. Early research focused on the regulation of epithelial-mesenchymal transition, the regulation of matrix metalloproteinase, and the signaling pathways related to invasion and metastasis. However, in recent years, the regulation of macrophage repolarization, microRNAs, and pre-metastatic niche has been the focus of research. From the theoretical and experimental perspectives, the study aims to provide more TCM insights into the comprehensive treatment of lung cancer and more research directions in the prevention and treatment of lung cancer by TCM in the future.
关键词:lung cancer;invasion;metastasis;traditional Chinese medicine;Chinese herbal monomer;Chinese herbal compound;signaling pathway
摘要:The Wnt/β-catenin signaling pathway is associated with the development and regeneration of tissue, including intestines, bones, and nerves. However, its aberrant activation leads to the onset and progression of multiple tumors, among which colorectal cancer (CRC) is most closely linked to it. At least one mutation in genes associated with the Wnt/β-catenin pathway can be observed in over 93% of CRC patients, and thus targeting the pathway holds substantial potential for CRC prevention and treatment. Clinically, traditional Chinese medicine (TCM) has been widely applied to the full-course treatment of CRC, yielding promising outcomes. Recent studies have demonstrated that TCM can inhibit CRC through multi-target modulation of the Wnt/β-catenin signaling pathway. However, there is a lack of a systematic review of these findings. This review summarized the research progress on the use of TCM monomers (such as berberine, ginsenosides, curcumin, and evodiamine) and compound formulas (such as Si Junzitang, Huangqintang, and Wumeiwan) in the prevention and treatment of CRC by regulating the Wnt signaling pathway, based on literature from PubMed and China National Knowledge Infrastructure (CNKI) databases between 2015 and 2024. These studies indicated that TCM could inhibit the activation of Wnt pathway target genes, such as c-Myc and matrix metalloproteinases (MMPs) by targeting Wnt ligands and their receptors (such as Wnt3a), the destruction complex, such as Axis suppressor protein(AXIN) and glycogen synthase kinase-3β (GSK-3β), and the transcriptional complex,such as β-catenin and T-cell factor/lymphoid enhancer-binding factor (TCF/LEF). Through these mechanisms, TCM exerted inhibitory effects on CRC proliferation, drug resistance, and invasion and metastasis. Additionally, the review discussed current research gaps, such as the low oral availability of some TCMs and the lack of clinical validation for efficacy and safety. The prospects of integrating multi-omics and gene editing technologies into the study of TCM's modulation of the Wnt signaling pathway were also explored. Ultimately, the review aims to provide a reference for research on the mechanisms of TCM in CRC prevention and treatment, as well as the development and clinical application of novel anti-CRC drugs targeting the Wnt pathway.
关键词:Wnt/β-catenin signaling pathway;colorectal cancer;traditional Chinese medicine;berberine;Si Junzitang;Huangqintang