1.Action Mechanism of Huamoyan Granules in Treatment of Knee Osteoarthritis Based on TRPV1/p38 MAPK Pathway
Jin ZHANG ; Lili YANG ; Canwen ZHENG ; Jing KANG ; Yanlei MA ; Yue SHI ; Lei LI ; Hongxu MENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):79-89
ObjectiveThis paper aims to observe the protective effect of Huamoyan granules on knee osteoarthritis (KOA) and explore whether its protective effect is oriented toward an anti-inflammatory direction by regulation of macrophage polarization, which can effectively inhibit the progression of pathological inflammatory response, reduce the release of inflammatory pain mediators, and downregulate the protein expression level of transient receptor potential vanilloid 1 (TRPV1), so as to provide experimental evidence for its clinical application and investigate its action mechanism. MethodsAfter adaptive feeding, Sprague-Dawley (SD) rats were randomly divided into six groups: sham group, model group, celecoxib group, and high, medium, and low-dose synovitis granule groups (9.6, 4.8, 2.4 g·kg-1). The administration dose of celecoxib capsules was 20 mg·kg-1. There were 10 rats in the sham group and 12 rats in the model group and each administration group. A KOA animal model was established by means of intra-articular injection of sodium iodoacetate into the knee joint. From the 10th day of the experiment, each administration group was given intragastric administration at a dose of 10 mL·kg-1 for 4 weeks. General conditions of rats in each group were assessed daily. The pressure pain threshold (PPT) to mechanical stimulation and joint diameter were recorded. X-ray examination was performed on the right knee joints of rats for imaging analysis. Enzyme linked immunosorbent assay (ELISA) was performed to detect the tumor necrosis factor-α (TNF-α), serum interleukin-1β (IL-1β), and other pro-inflammatory cytokines in rat serum samples, as well as the expression levels of neurogenic inflammatory mediators such as nerve growth factor (NGF) and calcitonin gene-related peptide (CGRP). Histopathological changes in the knee joint synovial tissues were examined by hematoxylineosin (HE) staining. Safranin O-fast green staining was performed to observe and evaluate the degree of knee cartilage lesions. Western blot was employed to quantitatively analyze TRPV1, p38 mitogen-activated protein kinase (p38 MAPK), and phosphorylated (p)-p38 MAPK in rat knee synovial tissues. Immunofluorescence (IF) was used to measure and assess M1/M2 macrophage polarization. ResultsCompared with those in the sham group, the circumference and joint diameter of the right knee were markedly enlarged in the model group (P<0.01), while PPTs of rats showed a significant reduction (P<0.01). The contents of IL-1β, TNF-α, CGRP, and NGF in rats' serum were significantly elevated (P<0.01), and the synovial Krenn score was increased (P<0.01). The Mankin score of cartilage tissue was increased (P<0.01), and the protein expressions of TRPV1 and p-p38 MAPK/p38 MAPK were significantly upregulated (P<0.01). The experimental intervention significantly reduced the proportion of pro-inflammatory M1 macrophages in the total macrophage population (P<0.01), and the percentage of M2 macrophages was decreased (P<0.01). The M1/M2 macrophage ratio was significantly elevated (P<0.01). Knee joint diameters of all dose groups of Huamoyan granules and the celecoxib group were reduced (P<0.01) compared with those of the model group, and the PPT recovery speeds in the high and medium-dose groups of Huamoyan granules were more obvious (P<0.05). The contents of IL-1β, CGRP, and NGF in the rats' serum in all administration groups were significantly reduced (P<0.05, P<0.01), and the content of TNF-α in rats' serum was significantly reduced (P<0.01). All dose groups of Huamoyan granules demonstrated significant reductions in both synovial Krenn score (P<0.05, P<0.01) and protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in rats' synovial tissues (P<0.01). The percentage of M1 macrophages in the synovial tissues of the celecoxib group and all dose groups of Huamoyan granules was decreased (P<0.01). The percentage of M2 macrophages was increased (P<0.05), and the M1/M2 ratio was decreased (P<0.01). ConclusionHuamoyan granules can alleviate the inflammatory response of KOA, reduce the release of inflammatory pain mediators, and downregulate TRPV1 protein expression by regulating macrophage polarization. Its mechanism may be related to the TRPV1/p38 MAPK signaling pathway, thereby achieving the effect of improving peripheral pain hypersensitivity in KOA.
2.Epidemiological characteristics and influencing factors of severe fever with thrombocytopenia syndrome in Zhejiang Province
LÜ ; Jing ; XU Xinying ; QIAO Yingyi ; SHI Xinglong ; YUE Fang ; LIU Ying ; CHENG Chuanlong ; ZHANG Yuqi ; SUN Jimin ; LI Xiujun
Journal of Preventive Medicine 2026;38(1):10-14
Objective:
To analyze the epidemiological characteristics and influencing factors of severe fever with thrombocytopenia syndrome (SFTS) in Zhejiang Province from 2019 to 2023, so as to provide the reference for strengthening SFTS prevention and control.
Methods:
Data on laboratory-confirmed SFTS cases in Zhejiang Province from 2019 to 2023 were collected through the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. Meteorological data, geographic environment and socioeconomic factors during the same period were collected from the fifth-generation European Centre for Medium-Range Weather Forecasts, Geospatial Data Cloud, and Zhejiang Statistical Yearbook, respectively. Descriptive epidemiological methods were used to analyze the epidemiological characteristics of SFTS from 2019 to 2023, and a Bayesian spatio-temporal model was constructed to analyze the influencing factors of SFTS incidence.
Results:
A total of 578 SFTS cases were reported in Zhejiang Province from 2019 to 2023, with an annual average incidence of 0.23/105. The peak period was from May to July, accounting for 52.60%. There were 309 males and 269 females, with a male-to-female ratio of 1.15∶1. The cases were mainly aged 50-<80 years, farmers, and in rural areas, accounting for 82.53%, 77.34%, and 75.43%, respectively. Taizhou City and Shaoxing City reported more SFTS cases, while Shaoxing City and Zhoushan City had higher annual average incidences of SFTS. The Bayesian spatio-temporal interaction model showed good goodness of fit. The results showed that mean temperature (RR=1.626, 95%CI: 1.111-2.378) and mean wind speed (RR=1.814, 95%CI: 1.321-2.492) were positively correlated with SFTS risk, while altitude (RR=0.432, 95%CI: 0.230-0.829) and population density (RR=0.443, 95%CI: 0.207-0.964) were negatively correlated with SFTS risk.
Conclusions
SFTS in Zhejiang Province peaks from May to July. Middle-aged and elderly people and farmers are high-risk populations. Taizhou City, Shaoxing City, and Zhoushan City are high-incidence areas. Mean temperature, mean wind speed, altitude, and population density can all affect the risk of SFTS incidence.
3.Proteomic Analysis of Danlou Tablet in Improving Platelet Function for Treating Coronary Heart Disease with Phlegm-stasis Intermingling Syndrome in Minipigs
Ziyan WANG ; Ying LI ; Aoao WANG ; Hongxu MENG ; Yue SHI ; Yanlei MA ; Guoyuan ZHANG ; Lei LI ; Jianxun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):41-53
ObjectiveThis paper aims to observe the role of Danlou tablet in treating coronary heart disease (CHD) with phlegm-stasis intermingling syndrome in minipigs by improving platelet function and explore the potential pharmacological mechanism of Danlou tablet in regulating platelet function by using proteomics technology. MethodsThirty Bama minipigs were randomly divided into a normal control group (6 pigs) and a high-fat diet group (24 pigs). After 2 weeks of high-fat diet feeding, the high-fat diet group was randomly subdivided into a model group, an atorvastatin group (1 mg·kg-1), and Danlou tablet groups (0.6 g·kg-1 and 0.3 g·kg-1). All groups continued to receive a high-fat diet for 8 weeks after the procedure. The normal control group was given a regular diet, underwent only coronary angiography, and did not receive an interventional injury procedure. The model group and each administration group were fed a high-fat diet. Two weeks later, they underwent a coronary angiography injury procedure. After the procedure, drugs were mixed into the feed every morning for 8 consecutive weeks, with the minipigs maintained on a continuous high-fat diet during this period. Quantitative proteomics technology was further used to study platelet proteins, and differential proteins were obtained by screening. Bioinformatics analysis was performed to analyze key regulatory proteins and biological pathways involved in the therapeutic effect of Danlou tablet on CHD with phlegm-stasis intermingling syndrome. ResultsCompared with the normal control group, the model group showed a significant increase in total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) of minipigs' serum (P<0.01), a significant shortening in prothrombin time of (PT) (P<0.01), a coagulation function index, and an increase in whole blood viscosity (P<0.01) and platelet aggregation rate (P<0.01). Moreover, the platelet morphology was altered, and the contents of endothelin-1 (ET-1) and nitric oxide (NO) were significantly increased (P<0.01). Hemodynamic parameters were obviously abnormal, including significantly decreased systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), and left ventricular maximal positive dp/dt (LV+dp/dtmax) (P<0.01). Left ventricular maximal negative dp/dt (LV-dp/dtmax) was significantly increased (P<0.01). Besides, there were myocardial cell hypertrophy, obvious edematous degeneration, massive interstitial inflammatory cell infiltration, high degree of fibrosis, and coronary endothelial atherosclerosis. TC and TG levels in minipigs' serum were significantly reduced in Danlou tablet groups with 0.6 g·kg-1 and 0.3 g·kg-1 (P<0.05, P<0.01), compared with those in the model group. LDL-C was decreased in the Danlou tablet group with 0.6 g·kg-1 (P<0.05). The whole blood viscosity under low and high shear conditions was significantly reduced in the Danlou tablet group with 0.6 g·kg-1 (P<0.05). In groups with all doses of Danlou tablet, maximum aggregation rate (MAR) and average aggregation rate (AAR) were significantly decreased (P<0.05, P<0.01), and platelets' morphological changes such as pseudopodia extension were reduced. ET-1 levels in the serum were significantly reduced. In the Danlou tablet group with 0.6 g·kg-1, NO level in the serum was reduced (P<0.05). In groups with all doses of Danlou tablet, DBP and MAP were significantly increased (P<0.05). In the Danlou tablet group with 0.6 g·kg-1, LVSP and LV+dp/dtmax were significantly increased (P<0.05, P<0.01), and LV-dp/dtmax was significantly decreased (P<0.05). In groups with all doses of Danlou tablet, edematous degeneration in myocardial tissue was milder, and coronary artery lesion degree was significantly alleviated. Compared with the normal control group, there were 94 differentially expressed proteins in the model group, including 81 up-regulated and 13 down-regulated proteins. Compared with the model group, the Danlou tablet group with 0.6 g·kg-1 showed 174 differentially expressed proteins, including 100 up-regulated and 74 down-regulated proteins. A total of 30 proteins were reversed after Danlou tablet intervention. Bioinformatics analysis revealed that its pharmacological mechanism may exert anti-platelet activation, aggregation, and adhesion effects through biological pathways such as regulation of actin cytoskeleton, platelet activation pathway, Fcγ receptor-mediated phagocytosis, as well as proteins such as growth factor receptor-bound protein 2 (GRB2), Ras-related C3 botulinum toxin substrate 2 (RAC2), RAC1, and heat shock protein 90 alpha family class A member 1 (HSP90AA1). ConclusionDanlou tablet can effectively reduce platelet activation and aggregation, exerting a good therapeutic effect on CHD with phlegm-stasis intermingling syndrome in minipigs. Its pharmacological mechanism may involve regulating biological pathways such as actin cytoskeleton and platelet activation pathway, as well as proteins like GRB2, RAC2, RAC1, and HSP90AA1, thereby exerting a pharmacological effect in anti-platelet activation, aggregation, and adhesion.
4.Research progress on the mechanisms of traditional Chinese medicine in treating functional constipation based on the gut microbiota-bile acid axis
Xiangrui KONG ; Qimeng ZHANG ; Yue ZOU ; Yong LIANG ; Yu SHI ; Yang ZHANG ; Hongxi ZHANG
China Pharmacy 2026;37(2):244-249
Functional constipation (FC) is a common functional disorder of the intestines, mainly characterized by reduced bowel movement frequency, difficulty in defecation, a sensation of incomplete evacuation, and hard stools, which severely affect patients’ quality of life. Research indicates that the pathogenesis of FC is closely related to gut microbiota dysbiosis and abnormal bile acid secretion. Bile acids, as endogenous natural laxatives, promote bowel movements by enhancing colonic secretion and regulating intestinal motility; meanwhile, gut microbiota influence colonic transit function by regulating the enteric nervous system, immune system, and their metabolic products. Based on an overview of the relationship between gut microbiota and bile acid metabolism, this article systematically reviews the current research status on the mechanisms of traditional Chinese medicine (TCM) in treating FC by regulating the balance of the gut microbiota-bile acid axis. It is found that single Chinese medicinal herbs (such as Atractylodes macrocephala), isolated compounds (such as Platycodon grandiflorum polysaccharides), herbal formulas (such as Shanger huang pill), acupuncture, and moxibustion can up-regulate the abundance of beneficial bacteria, reshape the microbial structure, correct bile acid metabolism, and activate the Takeda G-protein receptor 5/farnesoid X receptor pathway to treat FC.
5.Research progress on traditional Chinese medicine regulation of MAPK signaling pathway in intervening slow transit constipation
Xiangrui KONG ; Qimeng ZHANG ; Yue ZOU ; Yong LIANG ; Yu SHI ; Yang ZHANG ; Ke MENG ; Hongxi ZHANG
China Pharmacy 2026;37(11):1508-1514
low transit constipation (STC) is a common functional intestinal disorder caused by impaired colonic transit function, characterized by reduced bowel movement frequency, hard stools, and difficulty in defecation. The mitogen-activated protein kinase (MAPK) signaling pathway, which mainly includes extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 subtypes, plays a critical regulatory role in the occurrence and development of STC. This paper systematically reviews the multiple pathogenic mechanisms of the MAPK signaling pathway in STC and the research progress of traditional Chinese medicine (TCM) intervention.At the mechanistic level, the MAPK signaling pathway promotes the progression of STC through the following links:(1) Activation of p38 upregulates the expression of aquaporin 3 (AQP3)/AQP4 in the colon, leading to excessive reabsorption of water in the intestinal lumen; (2) It forms a positive feedback loop with nuclear factor-κB (NF-κB) to maintain low-grade intestinal inflammation, releases inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and inhibits smooth muscle contraction; (3) Overactivation of p38 downregulates the expression of occludin and mucin 2 while upregulates the expression of claudin-2, thereby disrupting the mucosal barrier; (4) The JNK/p38 signaling pathway activates the caspase cascade to induce apoptosis of intestinal epithelial cells, neurons, and interstitial cells of Cajal; (5) Abnormal ERK signaling and excessive activation of p38/JNK inhibit intestinal smooth muscle contraction and reduce 5-hydroxytryptamine secretion, ultimately resulting in impaired colonic transit function.At the intervention level, TCM compound formulas and single herbs have been proven to improve STC by regulating the MAPK signaling pathway. Their effects are syndrome type-dependent:yin-nourishing formulas (Zengye Chengqi Tang, Tongbian Tang) mainly regulate the ERK/AQP axis; yang-warming formulas (Jichuan Jian) target both ERK/JNK and anti-apoptosis; heat-clearing formulas (Sanren Tang) focus on p38/NF-κB anti-inflammation. A single drug can simultaneously cover multiple aspects including water metabolism, inflammation, barrier function, apoptosis, and intestinal motility.Current relevant studies still have limitations such as mechanisms mostly remaining at the correlational level and a lack of disease-syndrome integrated research models. Future studies should combine specific inhibitors or gene knockout to identify core targets, establish disease-syndrome integrated STC models, and use network pharmacology and molecular docking techniques to deeply analyze the fine mechanism of “component-target-phenotype”, so as to provide high-quality evidence for the precise regulation of the MAPK signaling pathway by TCM in the intervention of STC.
6.Association of physical exercise with cognitive function and psychological health among primary school students
JIA Shuqi, LI Fei, LI Pan, ZHANG Wenqian, JIANG Hua, KONG Fansong, SHI Yue
Chinese Journal of School Health 2026;47(7):982-987
Objective:
To examine the association of physical activity with cognitive function and mental health among primary school students based on latent subgroup identification and dose response modeling, and to clarify cognitive-psychological profiles and the protective role of physical exercise, so as to provide evidence based support for physical exercise promoting mental health among primary school students.
Methods:
A study was conducted among 546 primary school students aged 8-12 years old from a primary school in Shanghai from March to June 2025. Physical fitness indicators, including vital capacity, 50 m sprint, sit and reach, and 1 min rope skipping were measured. Physical exercise was assessed by using the Physical Activity Rating Scale-3 (PARS-3), and mental health was assessed by using the Revised Child Anxiety and Depression Scale, 47-item version (RCADS-47). Cognitive function was assessed by using Stroop, N-back, and task-switching tasks. Latent profile analysis (LPA) was performed for cognitive-psychological health of primary school students based on seven cognitive indicators and six psychological indicators. Multivariable Logistic regression, trend test, and restricted cubic spline (RCS) analysis were used to examine associations between physical exercise and psychological highrisk status.
Results:
Five cognitive psychological health subgroups were identified:high symptom and impaired cognition group ( n =40, 7.3%), low cognition and low symptom group ( n =108, 19.8% ), and high cognition and high symptom group ( n =110, 20.2%), cognitive advantage and psychologically healthy group ( n = 272, 49.8%), and extremely high symptom and cognitively vulnerable group ( n =16, 2.9%). Among them, the high symptom and impaired-cognition group and extremely high symptom and cognitively vulnerable group were classified as psychologically high risk types. Significant differences were observed across subgroups in psychological symptoms, cognitive function, some physical fitness indicators and physical exercise level, except for body weight, body mass index, and sit and reach ( F =2.64-297.53, all P < 0.05). The results of the multivariate Logistic regression analysis indicated that high level sports, including high total volume of physical exercise, single session duration >30 min, high intensity, and frequency ≥3 times/week, was associated with lower psychological high risk status ( OR =0.20, 0.36, 0.33, 0.40, all P <0.05). Trend analysis showed that total volume of physical exercise and single session exercise duration were negatively associated with psychological high risk status among primary school students ( OR =0.98, 0.79, both P trend <0.05). RCS analysis showed no statistically significant overall or nonlinear association between total volume of physical exercise and psychological high risk status ( χ 2=2.92, 0.01, both P >0.05).
Conclusions
Cognitive-psychological health among primary school students is heterogeneous. Physical exercise is associated with psychological health improvement and may show a threshold effect, with total volume of physical exercise and single session exercise duration being the key dimensions.
7.Chinese expert consensus on the clinical application of recombinant human thyroid-stimulating hormone (2025 edition)
Chentian SHEN ; Yushen GU ; Hui TAN ; Anren KUANG ; Sijin LI ; Yaming LI ; Jing WANG ; Ningyi JIANG ; Jian TAN ; Zhuoying WANG ; Shaoyan LIU ; Xiaoyi LI ; Jugao FANG ; Dingcun LUO ; Youben FAN ; Hui WANG ; Yuetao WANG ; Xuemei WANG ; Feng WANG ; Wei FU ; Feng SHI ; Xuegong LIU ; Zhongwei LÜ ; Yan XING ; Lin LI ; Hui YANG ; Jun XIN ; Yifan ZHANG ; Yue CHEN ; Yansong LIN ; Wei OUYANG ; Shuzhan YAO ; Changjiu ZHAO ; Xinming ZHAO ; Zairong GAO ; Dingde HUANG ; Qiang WEN ; Xingmin HAN ; Cen LOU ; Weibing MIAO ; Wei FAN ; Quanyong LUO ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2026;33(5):932-944
The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before 131I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.
8.Mechanisms of Shuangshen Ningxin Capsules in Modulating NF-κB and MAPK Signaling Pathways to Reduce Cardiac Inflammation and Alleviate Myocardial Ischemia-reperfusion Injury in Rats
Shujuan XU ; Gaojie XIN ; Ce CAO ; Zixin LIU ; Yuanyuan CHEN ; Ran ZHAO ; Lu XING ; Yehao ZHANG ; Yue SHI ; Yanlei MA ; Jianhua FU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(23):83-91
ObjectiveTo investigate the effect and mechanism of Shuangshen Ningxin capsules (SSNX) in regulating the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways to inhibit inflammation and alleviate myocardial ischemia-reperfusion injury (MIRI) in rats. MethodsThe 45 healthy male Sprague-Dawley (SD) rats were divided into sham operation group, model group, and SSNX capsules group (90 mg·kg-1). The left anterior descending coronary artery was ligated to establish the MIRI model. Cardiac function was evaluated by echocardiography, and microvascular reperfusion was analyzed using contrast echocardiography. Myocardial inflammation and injury were assessed by hematoxylin and eosin (HE) staining, immunohistochemistry, and TdT-mediated dUTP nick end labeling (TUNEL). The expression levels of cardiac inflammatory cytokines, including interleukin-1α (IL-1α), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Core differentially expressed genes (DEGs) and enriched pathways were screened by transcriptome sequencing. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to verify the mRNA expression of Toll-like receptor 2 (TLR2), chemokine (C-X-C motif) ligand 1 (CXCL1) and prostaglandin-endoperoxide synthase 2 (PTGS2), as well as the protein expression of Caspase-3, cleaved Caspase-3, p-NF-κB/NF-κB, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2/ERK1/2) and p-p38 MAPK/p38 MAPK. ResultsCompared with the sham operation group, the ejection fraction (EF), fractional shortening (FS), stroke volume (SV) and cardiac output (CO) of the model group were significantly decreased (P<0.01), the peak time of myocardial perfusion was prolonged (P<0.01), hypoxia-inducible factor (HIF)-1α and α-smooth muscle actin (SMA) expression increased (P<0.01), the concentrations of inflammatory factors IL-1α, IL-6, TNF-α, TLR2, CXCL1 and PTGS2 increased (P<0.01), and the expression of cleaved Caspase-3, p-NF-κB/NF-κB, p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins was significantly increased (P<0.01). SSNX could improve cardiac function (P<0.05, P<0.01), and significantly shorten the peak time of myocardial perfusion (P<0.01). Moreover, it could also down-regulate HIF-1α and a-SMA expression (P<0.05, P<0.01), and reduce the concentrations of IL-1α, IL-6, TNF-α (P<0.01), and the mRNA expression of TLR2, CXCL1 and PTGS2 (P<0.01). Additionally, SSNX inhibited the apoptosis rate (P<0.01) and significantly reduced the expression of Cleaved Caspase-3, p-NF-κB/NF-κB, p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins (P<0.01). ConclusionSSNX can alleviate cardiac inflammation by regulating the NF-κB and MAPK signaling pathways, thereby effectively preventing and alleviating myocardial reperfusion injury.
9.Bioinformatics and Animal Experiments Reveal Mechanism of Shouhui Tongbian Capsules in Treating Constipation
Yong LIANG ; Qimeng ZHANG ; Bin GE ; Yang ZHANG ; Yu SHI ; Yue LU ; Hongxi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):150-157
ObjectiveTo explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments. MethodsThe drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules, and constipation-related targets were collected from disease databases. A protein-protein interaction (PPI) network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets, which was followed by gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. A "bioactive component-target-pathway" network was constructed, and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network. Molecular docking was employed to predict the binding affinity of core components to key targets. A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation. ResultsThe PPI network revealed six key constipation-related targets: protein kinase B (Akt1), B-cell lymphoma-2 (Bcl-2), glycogen synthase kinase-3β (GSK-3β), cyclooxygenase-2 (PTGS2), estrogen receptor 1 (ESR1), and epidermal growth factor receptor (EGFR). The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway was the most enriched. The topological parameter analysis of the "bioactive component-target-pathway" network screened out the top 10 core components: auranetin, isosinensetin, naringin, diosmetin, quercetin, apigenin, luteolin, hesperidin, isorhapontigenin, and chrysophanol. Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets. Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules, the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propulsion rate of mice were improved. After treatment with Shouhui Tongbian capsules, the colonic mucosal injury and glandular arrangement were alleviated, and the muscle layer thickness was increased. Western blot results showed that Shouhui Tongbian capsules recovered the expression of apoptosis-related molecules mediated by the PI3K/Akt pathway in the colonic tissue of constipated mice. Terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) results showed that the cell apoptosis rate of the colon significantly reduced after intervention with Shouhui Tongbian capsules. ConclusionThe results of network pharmacology and animal experiments confirmed that Shouhui Tongbian capsules can treat constipation through multiple targets and pathways. The capsules can effectively intervene in loperamide-induced constipation in mice by regulating the constipation indicators and reducing cell apoptosis in the colon tissue via activating the PI3K/Akt signaling pathway.
10.Clinical Efficacy of Modified Huangqi Chifengtang in Treatment of IgA Nephropathy Patients and Exploration of Dose-effect Relationship of Astragali Radix
Xiujie SHI ; Meiying CHANG ; Yue SHI ; Ziyan ZHANG ; Yifan ZHANG ; Qi ZHANG ; Hangyu DUAN ; Jing LIU ; Mingming ZHAO ; Yuan SI ; Yu ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):9-16
ObjectiveTo explore the dose-effect relationship and safety of high, medium, and low doses of raw Astragali Radix in the modified Huangqi Chifengtang (MHCD) for treating proteinuria in immunoglobulin A (IgA) nephropathy, and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy, diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity, were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo, while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix (60, 30, 15 g). Each group contained 30 patients, and the treatment period was 12 weeks. Changes in 24-hour urinary protein (24 hUTP), traditional Chinese medicine (TCM) syndrome scores, effective rate, and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment, 24 hUTP significantly decreased in the high, medium, and low-dose groups, as well as the control group (P<0.05, P<0.01). The TCM syndrome scores in the high, medium, and low-dose groups also significantly decreased (P<0.01). Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium, low-dose, and control groups (P<0.05, P<0.01), and the 24 hUTP in the medium-dose group was significantly lower than in the control group (P<0.05). The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups (P<0.05, P<0.01). The total effective rates for proteinuria in the high, medium, low-dose, and control groups were 92.59% (25/27), 85.19% (23/27), 60.71% (17/28), and 57.14% (16/28), respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups (χ2=13.185, P<0.05, P<0.01). The effective rates for TCM syndrome scores in the high, medium, low-dose, and control groups were 88.89% (24/27), 81.48% (22/27), 71.43% (20/28), and 46.43% (13/28), respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group (χ2=14.053, P<0.01). Compared with pre-treatment values, there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However, eGFR significantly decreased in the low-dose and control groups after treatment (P<0.05), and serum creatinine levels increased significantly in the control group (P<0.05). No statistically significant differences were observed in urea nitrogen, uric acid, albumin, total cholesterol, triglycerides, liver function, and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high, medium, and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.


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