Objective To optimize the extraction process of the classic prescription Baizhu Powder (白术散), and verify its anti-inflammatory activity through cell anti-inflammatory activity experiments, providing a basis for the development of Baizhu Powder. Methods An HPLC detection method was established for the index components puerarin, daidzin, ginsenoside Rg₁, daidzein, ginsenoside Rb₁, and ammonium glycyrrhizinate. Taking the content of index components, paste yield and oil extraction volume as evaluation indicators, the comprehensive weights of each index were determined by analytic hierarchy process (AHP)-entropy weight method. Based on the single-factor experiment, the Box-Behnken design-response surface method (BBD-RSM) was adopted to optimize the Baizhu Powder extraction process. The anti-inflammatory activity of Baizhu Powder was investigated by inducing an inflammatory model of human normal colonic epithelial cells (NCM460) with lipopolysaccharide (LPS), and the feasibility of the process was verified. Results The optimized extraction process of Baizhu Powder was 10 times the volume of water, soaking for 30 min, extraction time for 90 min, and extraction twice. Under these conditions, the average comprehensive score of the three batches of process validation was 0.974, and the RSD value was 1.94%. The pharmacodynamic verification results of Baizhu Powder indicated that the Baizhu Powder prepared by the optimized process could significantly reduce the levels of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the LPS-induced NCM460 cell inflammatory model. The level of the anti-inflammatory factor IL-10 was increased, and there was no significant difference compared with the Baizhu Powder benchmark sample. Conclusion The Baizhu Powder extraction process optimized by AHP-entropy weight method combined with BBD-RSM is stable and reliable, which can provide a basis for the subsequent research and development of Baizhu Powder.

Objective To investigate the correlation between intrinsic components, visual color, and antioxidant activity during the “nine-steaming and nine-sun-drying” processing of Heshouwu (Polygoni Multiflori Radix, PMR), providing a reference for determining the processing degree and quality control. Methods A colorimeter was used to objectively quantify the color of samples at different steaming and sun-drying cycles. HPLC was used to establish fingerprints, HPLC-Q-TOF-MS was employed to analysis characteristic peaks. Alcohol-soluble extract content was determined according to the Chinese Pharmacopoeia (2025 edition). Polysaccharide content was measured using the phenol-sulfuric acid method. Antioxidant activity was evaluated through DPPH radical scavenging capacity, ABTS radical scavenging assays, and ferric reducing antioxidant power (FRAP) method to determine total antioxidant capacity. Pearson correlation and regression analyses were conducted between the components, color values, and antioxidant activity. Cluster analysis, principal component analysis (PCA), and partial least squares regression (PLSR) were applied to determine the processing stages of “nine-steaming and nine-sun-drying” PMR, while entropy-weighted TOPSIS was used to identify its the optimal processing endpoint. Results During processing, the sample color gradually darkened, and chromaticity values decreased. Polysaccharide content increased progressively, while alcohol-soluble extract content first increased and then declined. A total of 26 chromatographic peaks were identified in the fingerprints, and the components of 25 of them were identified. Correlation analysis revealed significant relationships between intrinsic components, color values, and antioxidant activity. The processing stages were divided into initial, middle, and final phases, with the seven steaming and sun-drying cycle achieving the highest comprehensive score. Conclusion Significant changes in component content, color, and antioxidant activity occur during the processing of PMR, with notable correlations among them. The integrated “color-component-antioxidant activity” analysis enables objective discrimination of processing techniques and quality control in “nine-steaming and nine-sun-drying” PMR.

Objective This study investigated the effects of critical process parameters (CPPs, e.g., extraction temperature, time, and solid-liquid ratio) on the physical properties and the content of 12 effective components in both alcoholic and aqueous extracts of Guizhi Fuling Capsules (GFC, 桂枝茯苓胶囊). The correlations between physical properties and effective components were analyzed to provide a basis for process optimization and quality control. Methods A single-factor experimental design was adopted. Different process parameters such as extraction temperature (set control temperature of electric heating jacket), extraction time and solid-liquid ratio were set to prepare the corresponding alcohol extract and water extract, and the particle size, polydispersion index (PDI), ζ potential, conductivity, pH value, total solid content and refractive indexof each intermediate were determined. The contents of 12 effective components (gallic acid, 4-hydroxybenzoic acid, oxypaeoniflorin, ethyl gallate, benzoic acid, 1,2,3,4,6-O-pentagalloylglucose, cinnamaldehyde, amygdalin, albiflorin, paeoniflorin, cinnamic acid, paeonol) were quantified by UPLC. Correlations among CPPs, physical parameters, and effective components were analyzed via the chemometric analysis, including orthogonal partial least squares-discriminant analysis (OPLS-DA), Pearson correlation, grey relational analysis, and linear regression model analysis. Results The CPPs exert certain influences on the physical parameters and effective components of GFC alcoholic extracts and aqueous extracts. Specifically, for the alcoholic extraction process, when the temperature of the electric heating mantle is controlled at ≤ 200 ℃, with an extraction duration of 1.5 h and a solid-liquid ratio ranging from 1:6 to 1:8; and for the aqueous extraction process, when the electric heating mantle temperature is maintained at 200—250 ℃, extraction time is set to 1.5—2.0 h and the solid-liquid ratio is 1:6—1:8, the contents of most bioactive substances are relatively high. Furthermore, the chemometric analysis results indicated that ζ potential, conductivity, and total solids correlated well with the content of amygdalin in alcoholic extracts under different solid-liquid ratios (well-fitted, R² > 0.7). And in aqueous extracts under different temperatures, particle size and conductivity showed some correlation with cinnamic acid content, but with poor fitting. Conclusion Critical process parameters significantly influence the correlation between physical properties and effective components by modulating the solution microenvironment and dissolution behavior. Conductivity, ζ potential and total solid content can serve as important bases for the study of the “quantity-quality” transfer law in the process of traditional Chinese medicine manufacturing.

Objective To elucidate how Tongmai Yangxin Pill (通脉养心丸, TMYX) confers cardioprotective effects during myocardial ischemia/reperfusion injury (MI/RI) through the regulation of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)-mediated mitochondrial function. Methods A hypoxia-reoxygenation (H/R) model in cardiomyocytes was established. After intervention with TMYX, intracellular reactive oxygen species (ROS) levels were measured using DCFH-DA and MitoSOX^TM red fluorescent probes. Cellular adenosine triphosphate (ATP) content was quantified using an enhanced ATP assay kit. Changes in mitochondrial membrane potential were evaluated by JC-1 staining. Mitochondrial respiratory function was assessed using Seahorse XF cell mitochondrial stress test. Mitochondrial morphology and ultrastructural alterations were examined using MitoTracker staining and transmission electron microscopy. Western blotting and qRT-PCR were used to determine the expression levels of proteins and genes associated with mitochondrial fusion and fission [mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), fission 1 (Fis1), dynamin-related protein 1 (Drp1)], biogenesis [nuclear respiratory factor 1 (Nrf1), mitochondrial transcription factor A (TFAM), mitochondrial DNA (mtDNA) copy number] and autophagy [Beclin1, PTEN-induced putative kinase 1 (PINK1), Parkin, p62]. To further investigate the effects of TMYX on the above-mentioned functions of H9c2 cells after PGC-1α silencing expression through PGC-1α siRNA transfection experiment. Results Compared with model group, TMYX significantly enhanced mitochondrial ATP synthesis (P < 0.01), improved mitochondrial membrane potential (P < 0.01), reduced oxidative stress (P < 0.01), and promoted mitochondrial autophagy (P < 0.05, 0.01). After silencing PGC-1α, the protective effect of TMYX on mitochondrial function was significantly weakened (P < 0.05, 0.01). Conclusion TMYX could effectively improve mitochondrial dysfunction and morphological changes induced by MI/RI by regulating mitochondrial biosynthesis, dynamic balance and autophagy through PGC-1α. This study reveals PGC-1α as a core factor regulating mitochondrial function and its potential therapeutic value in MI/RI, providing new ideas for the treatment of MI/RI.

Objective To investigate the therapeutic effect and mechanism of tanshinone II_A on motor function recovery after brachial plexus root avulsion (BPA) using a rat brachial plexus root avulsion (BPA)-replantation model and an hydrogen peroxide (H₂O₂)-induced oxidative damage model in NSC-34 cells. Methods A total of 60 SD rats were randomly divided into sham group, model group, tanshinone II_A low- and high-dose (10, 30 mg/kg) groups, with 15 rats in each group. After modeling, continuous administration was performed for eight weeks. Motor function recovery was evaluated using Terzis grooming test (TGT). The biceps brachii muscle was weighed and processed for hematoxylin-eosin (HE) staining to assess morphological changes. Motor neuron survival in the spinal cord was determined by neutral red staining. Axonal regeneration was assessed by Fluoro-Gold retrograde labeling and immunofluorescence staining for choline acetyltransferase (ChAT) and neurofilament 200 (NF200) in the musculocutaneous nerve. Immunofluorescence was performed to detect ionized calcium-binding adapter molecule 1 (Iba1), glial fibrillary acidic protein (GFAP) and neuronal nitric oxide synthase (nNOS) expressions. Level of malondialdehyde (MDA) and activity of superoxide dismutase in the injured spinal cord were measured. The protein expressions of Ras-related C3 botulinum toxin substrate l (Rac1), cell division control protein 42 (Cdc42), c-Jun N-terminal kinase (JNK) and c-Jun in the injured spinal cord were detected by Western blotting. In vitro, control group, model group, tanshinone II_A group and Rac1 inhibitor group were established. NSC-34 cells were induced with 400 μmol/L H₂O₂ to cause oxidative damage. After intervention with tanshinone II_A or NSC 23766, cell viability was assessed using CCK-8 assay. Levels of MDA, reactive oxygen species (ROS) and activity of SOD were measured, and the expressions of Rac1/JNK pathway-related proteins was analyzed by Western blotting. Results The BPA model was successfully established as evidenced by consistently 0 TGT scores in model group at 1 week post-surgery. Compared with model group, tanshinone II_A significantly improved the TGT scores (P < 0.05, 0.01), enhanced axonal regeneration (P < 0.01), increased motor neuron count (P < 0.01), mitigated muscle atrophy (P < 0.05, 0.01), and reduced the expressions of Iba1 and GFAP (P < 0.05, 0.01). Meanwhile, tanshinone II_A improved oxidative stress damage, including decreased nNOS positive motor neurons (P < 0.05, 0.01), reduced MDA level (P < 0.001), elevated SOD activity (P < 0.01), while up-regulating Rac1, Cdc42, JNK and c-Jun expressions in spinal cord tissue (P < 0.01, 0.001). In vitro, tanshinone II_A significantly increased viability of H₂O₂-injured NSC-34 cells (P < 0.01), elevated SOD activity (P < 0.01), decreased MDA and ROS levels (P < 0.01), up-regulated Rac1, Cdc42, JNK and c-Jun protein expressions (P < 0.05, 0.01, 0.001). Notably, these protective effects of tanshinone II_A were partially attenuated by co-administration of Rac1 inhibitor NSC 23766 (P < 0.05, 0.01). Conclusion Tanshinone II_A promotes motor function recovery following brachial plexus root avulsion by activating Rac1/JNK signaling pathway, which attenuates oxidative stress and neuroinflammation, thereby enhancing motor neuron survival and axonal regeneration.

Objective To investigate the therapeutic effect and mechanism of total triterpenoid from Cyclocarya paliurus (CPT) on high-fat diet (HFD)-induced metabolic-associated fatty liver disease (MAFLD) mice. Methods C57BL/6J mice were randomly divided into control group, model group, CPT (100 mg/kg) group, metformin (MET, 100 mg/kg) group and CPT + MET group. Except for the control group receiving regular feeding, all other groups were fed HFD for 12 weeks to establish MAFLD models. After successful establishment of MAFLD model, drugs were given eight weeks. During the experiment, the activity levels of mice were observed, their body weight and food intake were measured regularly. One week before the end of medication, the oxygen consumption (VO₂), carbon dioxide production (VCO₂) and energy consumption of mice were measured using indirect calorimetry. After the end of administration, glucose tolerance test and insulin resistance test were conducted to detect glucose tolerance. Liver weight was measured, and liver index was calculated. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), fasting insulin (FINS) in serum were detected, and insulin resistance index (HOMA-IR) was calculated. The levels of TC and TG in hepatic tissues and feces, as well as the levels of total bile acids (TBA) in serum, hepatic tissues and feces were measured. Hematoxylin-eosin and oil red O staining were used to observe the pathological changes in hepatic tissues of mice. Five hepatic tissue and five colon content samples from each group were randomly selected for bile acid (BAs) metabolomics analysis. The mRNA expressions of cholesterol 7α-hydoxylase 1 (Cyp7a1), Cyp7b1, Cyp27a1, Cyp8b1, bile acid coenzyme A synthetase (Bacs), bile acid coenzyme a: amino acid N-acyltransferase (Baat), bile salt export pump (Bsep), recombinant Na⁺ taurocholate cotransporting polypeptide (Ntcp), farnesoid X receptor (FXR), small heterodimeric partner (SHP), fibroblast growth factor receptor 4 (FGFR4), sterol regulatory element-binding protein-1c (SREBP-1c), stearyl coenzyme A desaturation enzyme 1 (SCD1), fatty acid synthetase (FASN), peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transferase 1 (CPT1), lipoprotein lipase (LPL), microsomal triglyceride transfer protein (MTTP) in hepatic tissues and FXR, fibroblast growth factor 15 (FGF15), apical sodium-dependent bile acid transporter (Abst), intestinal bile acid-binding protein (Ibabp), organic solute transporter-α (Ost-α), Ost-β in ileum tissues were determined by qRT-PCR. Western blotting was used to detect the protein expressions of CYP7a1, Cyp7b1, Cyp27a1, Cyp8b1, FXR, SHP, FGFR4, SREBP-1c, SCD1, FASN, PPARα, CPT1, LPL, MTTP in hepatic tissues and FXR, FGF15, Abst in ileum tissues. Results Compared with model group, CPT and its association with MET significantly reduced the body weight, improved glucose tolerance, elevated insulin sensitivity, lowered liver weight and liver index, raised VO₂, VCO₂, VO₂/VCO₂, and daytime and nighttime energy consumptions and total energy consumption in mice (P < 0.01). CPT and its association with MET reduced ALT, AST, ALP, γ-GT, TC, TG, LDL-C, FINS, FBG, TBA levels in serum and TC and TG levels in hepatic tissue as well as HOMA-IR, elevated levels of HDL-C in serum and TC, TG, TBA in feces, reduced liver histopathological scores and lipid deposition (P < 0.01). CPT and its association with MET elevated hepatic tissue TBA level, lowered the contents of unconjugated BAs, primary BAs, secondary BAs and the ratio of primary BAs/secondary BAs in hepatic tissues, as well as the levels of unconjugated BAs and secondary BAs in colon contents, elevated the content of conjugated BAs and the ratio of conjugated BAs/unconjugated BAs in hepatic tissue, as well as the levels of conjugated BAs, primary BAs and the ratios of conjugated BAs/unconjugated BAs, primary BAs/secondary BAs in colon contents (P < 0.01). In addition, CPT and its association with MET elevated Cyp7a1, Cyp7b1, Cyp27a1, Bacs, Baat, FXR, SHP, Bsep, Ntcp, PPARα, CPT1, LPL, MTTP mRNA expressions and Cyp7a1, Cyp7b1, Cyp27a1, FXR, SHP, PPARα, CPT1, LPL, MTTP protein expressions in hepatic tissues, reduced the mRNA and protein expressions of Cyp8b1, FGFR4, SREBP-1c, SCD1, FASN in hepatic tissues, depressed FXR, FGF15, Asbt, Ibabp, Ost-α, Ost-β mRNA expressions and FXR, FGF15, Asbt protein expressions in ileum tissues (P < 0.01). The combination of CPT and MET showed better efficacy than CPT alone (P < 0.05, 0.01). Conclusion CPT may activate the hepatic FXR/SHP pathway by inhibiting intestinal FXR/FGF15 signaling, facilitating the synthesis of BAs in the hepatic intestinal circulation, repressing their ileal reabsorption, and boosting the excretion of BAs with feces. The activated hepatic FXR/SHP pathway restrains lipid synthesis by suppressing SREBP-1c/SCD1/FASN signaling axis, while activated hepatic FXR promotes lipid oxidation and lipid decomposition through activating the PPARα/CPT1 and LPL/MTTP signaling axes to treat MAFLD.

Objective To investigate the ameliorative effect of combination of schisandrin B (Sch B) and platycodin D (PD) on pulmonary fibrosis, and explore whether it acts by inhibiting Janus kinase 2 (JAK2)/signal transducer and activator of transcription 6 (STAT6) pathway and regulating the balance of macrophage M1/M2 polarization. Methods A rat model of pulmonary fibrosis was established by intratracheal instillation of bleomycin. The rats were randomly divided into control group, model group, prednisone (5 mg/kg) group, Sch B (10 mg/kg) group, PD (20 mg/kg) group and Sch B + PD group, with eight rats in each group. After 28 d of administration, lung index was measured. Pathological changes in lung tissue were observed using hematoxylin-eosin (HE), Masson and Sirius red staining. Levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF), as well as hydroxyproline (Hyp) level in lung tissue were detected. Expressions of α-smooth muscle actin (α-SMA) and E-cadherin in lung tissue were assessed by immunofluorescence. The mRNA expressions of M1/M2 macrophage markers [inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, cluster of differentiation 206 (CD206), arginase 1 (Arg1) and IL-10] in lung tissue were measured by qRT-PCR. The expressions of JAK2/STAT6 pathway related proteins in lung tissue was determined by Western blotting. In vitro experiments, the effect of Sch B combined with PD on JAK2/STAT6 pathway were validated using an IL-4/IL-13-induced macrophage M2 polarization model. Results Compared with control group, lung index of rats in model group was significantly increased (P < 0.01), with a large amount of inflammatory cell infiltration in alveoli, increased alveolar diaphragmatic rupture and severe alveolar damage, levels of IL-1β, TNF-α, IL-6 in BALF and Hyp in lung tissue were significantly increased (P < 0.01); The expression of α-SMA in lung tissue was significantly increased (P < 0.01), while the expression of E-cadherin was significantly decreased (P < 0.01); The expression levels of iNOS, TNF-α, IL-1β, CD206 and Arg1 mRNA in lung tissue were significantly increased (P < 0.01), while the expression level of IL-10 mRNA was significantly decreased (P < 0.01); The expression levels of JAK2 and p-STAT6/STAT6 proteins in lung tissue were significantly increased (P < 0.01). Compared with model group, the combination of Sch B and PD could significantly reduce the lung index of rats (P < 0.01), improve pulmonary fibrosis pathological damage, inhibit the release of inflammatory factors and Hyp level in lung tissue (P < 0.01), reduce α-SMA expression (P < 0.01), partially restore E-cadherin expression (P < 0.01), significantly down-regulate iNOS, TNF-α, IL-1β, CD206, Arg1 mRNA expressions in lung tissue (P < 0.01), up-regulate IL-10 mRNA expression (P < 0.01), inhibit JAK2 and p-STAT6/STAT6 protein expressions (P < 0.01). The in vitro experimental results showed that compared with control group, the expression levels of CD206 and Arg1 mRNA in model group were significantly increased (P < 0.01), and the expressions of JAK2 and p-STAT6/STAT6 proteins were significantly up-regulated (P < 0.01); Compared with model group, the combination of Sch B and PD significantly inhibited the expressions of M2 polarization markers CD206 and Arg1 (P < 0.01), and down-regulated the expressions of JAK2 and p-STAT6/STAT6 proteins (P < 0.01). Compared with the group treated alone, the combination of Sch B and PD showed better efficacy (P < 0.05, 0.01). Conclusion The combination of Sch B and PD could synergistically alleviate pulmonary fibrosis, and its mechanism may be related to inhibiting the activation of JAK2/STAT6 pathway, thereby correcting the imbalance of M1/M2 macrophage polarization.

Objective To explore the effect and potential mechanism of harpagide on lipid metabolism and bone metabolism in atherosclerosis (AS) mice fed a high-fat diet. Methods AS model was constructed by feeding apolipoprotein E knock-out (ApoE^-/-) mice with high-fat diet for eight weeks, mice were randomly divided into model group, atorvastatin (2.6 mg/kg) group, and harpagide (20 mg/kg) group, with eight mice in each group. Additionally, eight C57BL/6N wild-type mice were included as control group and fed a standard diet. After nine weeks of drug intervention, micro-CT was used to analyze changes in bone microarchitecture. Infrared spectroscopy was employed to examine bone material composition. Hematoxylin-eosin (HE) staining was applied to observe the morphology of femoral trabeculae, and tartrate resistant acid phosphatase (TRAP) staining was used to quantify osteoclast numbers in the femur. Levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), TRAP and C-terminal telopeptide of type I collagen (CTX-1) in serum were measured using biochemical assays. Western blotting was performed to detect protein expression levels of nuclear factor of activated T cells 1 (NFATc1), Fos proto-oncogene (c-Fos), cathepsin K, peroxisome proliferator-activated receptor gamma coactivator-1β (PGC-1β), estrogen-related receptor α (ERRα) and peroxisome proliferator-activated receptor γ (PPARγ) in bone tissue. Results Harpagide significantly improved bone microarchitecture and bone material composition in AS mice (P < 0.05, 0.01), reduced levels of TC, LDL-C, HDL-C in serum and AS index (P < 0.05, 0.01), decreased levels of bone resorption markers CTX-1 and TRAP in serum (P < 0.01), down-regulated the expressions of bone resorption-related proteins c-Fos, NFATc1 and cathepsin K in bone tissue (P < 0.01). Additionally, harpagide suppressed the protein expression levels of PGC-1β, ERRα and PPARγ in bone tissue of AS mice (P < 0.05, 0.01). Conclusion Harpagide ameliorates dyslipidemia and suppresses bone resorption in AS mice, thereby exerting anti-osteoporotic effects. The mechanism may involve the inhibition of PPARγ/ERRα/PGC-1β signaling pathway.

Objective To explore the mechanism of Wutou Decoction (乌头汤) in treating knee osteoarthritis (KOA) by regulating Indian hedgehog factor (Ihh)-glioma associated oncogene homolog (Gli) signaling pathway. Methods Male SD rats were randomly divided into sham group, model group, celecoxib (24 mg/kg) group, Wutou Decoction low-, medium-, and high-dose (1.05, 2.10, 4.20 g/kg) groups, with 10 rats in each group. The improved anterior cruciate ligament resection technique was used to establish a KOA model, after eight weeks of drug intervention, mechanical pain threshold, thermal pain threshold and climbing ability were measured. ELISA was used to detect the levels of matrix metalloproteinase-3 (MMP-3), MMP-13 and type II collagen (Col II) in serum. The morphological changes of knee joint were observed by hematoxylin-eosin (HE) staining. Micro computed tomography (Micro-CT) technology was used to analyze the changes in bone microstructure of knee joint. Western blotting was used to detect the expressions of Ihh, patched 1 (Ptch1), Gli and MMP-13 proteins in knee joint. Results Compared with sham group, rats in model group showed defects and thinning of cartilage surface layer, decreased and disordered cell arrangement, decreased cross-sectional and coronal bone trabeculae, sparse distribution, decreased bone density, thermal pain threshold and mechanical pain threshold were significantly reduced (P < 0.001), slope angle was decreased (P < 0.001), levels of MMP-3 and MMP-13 in serum were significantly increased (P < 0.05, 0.01), Col II level was significantly decreased (P < 0.05), and expression levels of Ihh-Gli signaling pathway related proteins in knee joint were significantly increased (P < 0.001). Compared with model group, the cartilage surface of rats in Wutou Decoction group was smooth, the number of cells was increased, and the morphology was intact. The knee joint cross-section and coronal bone trabeculae were increased, and the distribution was dense. The thermal pain threshold and mechanical pain threshold were significantly increased (P < 0.05, 0.001), slope angle was increased (P < 0.01, 0.001), levels of MMP-3 and MMP-13 in serum were significantly reduced (P < 0.05), level of Col II was significantly increased (P < 0.05), and expression levels of Ihh-Gli signaling pathway related proteins in knee joint were significantly reduced (P < 0.05, 0.001). Conclusion Wutou Decoction protects articular cartilage by inhibiting excessive activation of Ihh-Gli signaling pathway, reducing abnormal proliferation and differentiation of chondrocytes.

Objective To overcome the clinical limitations of selective serotonin reuptake inhibitors (SSRIs), address the inadequate understanding of individual differences and pathological mechanisms in the antidepressant combination of Xiaoyao Powders with SSRIs, achieve precise combination medication, and promote the transformation of depression treatment toward a “data intelligence-driven” model. Methods A systematic search was conducted in CNKI, VIP, and Wanfang databases using combined subject terms: “Xiaoyaosan + Paroxetine” “Xiaoyaosan + Escitalopram/Citalopram” “Xiaoyaosan + Fluoxetine” “Xiaoyaosan + Sertraline” and “Xiaoyaosan + Fluvoxamine”. The search period spanned from the establishment of each database to May 10, 2025. Literatures were screened based on inclusion and exclusion criteria, and key data were extracted. A database titled “Xiaoyao Powders combined with SSRIs for treating depression” was constructed after verification and cleaning. The Apriori algorithm was applied to mine the association rules between “administration regimens and adverse reactions”, with lift used to quantify the association strength. A hypernetwork of “administration regimens-depression types” was built on the basis of hypergraphs, and the PageRank algorithm was integrated to calculate node weights. A comprehensive efficacy factor was introduced to optimize hyperedge weights, enabling precise matching between depression types and optimal traditional Chinese medicine combination regimens. Results A total of 78 literature was valid and included, with the most study on Xiaoyao Powders with Fluoxetine (33) whereas the least study on Xiaoyao Powders with Fluvoxamine (1). When depression subtypes are not differentiated, the combination of Xiaoyao Powders with Fluoxetine exhibits the highest utilization frequency. Jiawei Xiaoyao Powders was the most used among the applicaitons of Xiaoyao Powders with SSRIs (21). Apriori algorithm analysis showed that the combination of Xiaoyao Powders with Paroxetine was associated with a wide range of adverse reactions but weak single-type associations. Strong associations were observed between the combination with Escitalopram/Citalopram and dry mouth or gastrointestinal reactions, as well as between the combination with Sertraline and diarrhea or nausea. Hypergraph analysis revealed that the “Xiaoyao Powders with Fluoxetine” node had the highest hyperdegree, treating seven depression subtypes; the “depression” node also had the highest hyperdegree, matching five combination regimens; the ranking of hyperedge weights clarified the optimal regimens for different depression types. For example, the “Xiaoyao Powders with Escitalopram/Citalopram” combination was prioritized for senile depression patients, while the “Xiaoyao Powders with Fluoxetine” regimen was preferred for postpartum depression patients. Conclusion The Apriori algorithm can accurately analyze the association characteristics between “combination regimens and adverse reactions”, while hypergraphs can effectively achieve high-order matching between “administration regimens and depression types”. The combination of the two methodologies provides a quantitative basis for the precision medication strategy of depression integrating “disease-symptom-medicine”, and lays a foundation for establishing a new evidence-based, quantitative, and predictable paradigm for the combinations of traditional Chinese and Western medicines.