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- Chinese Journal of Integrative Medicine
- Protective Effect of <italic>Brassica napus</italic> L. Hydrosols against Inflammation Response in RAW 264.7 Cells
- Bloodletting Puncture at Hand Twelve Jing-Well Points Relieves Brain Edema after Severe Traumatic Brain Injury in Rats via Inhibiting MAPK Signaling Pathway
- Effect and Safety of Cinnamaldehyde on Immunosuppressed Mice with Invasive Pulmonary Candidiasis
- Edible Bird's Nest Attenuates Menopause-Related Bone Degeneration in Rats via Increasing Bone Estrogen-Receptor Expression
- Promising Antiviral Molecules from Ayurvedic Herbs and Spices against COVID-19
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Volume 32 Issue 10，2026
Original Article
Abstract：Objective: To evaluate the efficacy and safety of Linggui Yangyuan Paste (LG) in treating male infertility caused by asthenozoospermia (AZS) and oligoasthenozoospermia (OAZS) associated with the Chinese medicine (CM) pattern of Shen (Kidney) deficiency and blood stasis. Methods: This randomized, double-blind, double-dummy, parallel-group, multicenter clinical trial enrolled 162 male infertility patients at 5 hospitals in China from June 2023 to February 2024. Using block randomization within strata, participants were assigned (1:1) to LG + Wuzi Yanzong Oral Solution (WZ) placebo or WZ + LG placebo for 12 weeks (each LG 1 sachet and WZ 1 vial, twice daily), with a 12-week follow-up. The primary outcome was the change in total progressive motile sperm count (TPMSC) from baseline to week 12. Secondary outcomes included pregnancy rate, CM symptom score (CMSS), and semen parameters including semen volume (SV), sperm concentration (SC), total sperm count (TSC), progressive motility (PR), and PR+non-progressive motility (NP). Prespecified subgroup analyses on cumulative pregnancy rate and semen parameters were performed for participants with AZS and OAZS. Safety was monitored throughout the trial. Results: Of 162 randomized participants, 145 completed the trial (75 in the LG group and 70 in the WZ group) and were included in the per-protocol analysis. At week 12, the LG group showed significantly greater improvement in TPMSC compared to the WZ group, with an adjusted between-group difference of 8.81×106 sperm (P＜0.05, 95% confidence interval 2.75-14.87). The cumulative pregnancy rate at week 24 was significantly higher in the LG group than the WZ group [24.0% (18/75) vs. 10.0% (7/70), P＜0.05)]. CMSS decreased significantly in both groups, with greater reduction in the LG group (P＜0.05). Subgroup analysis showed that cumulative pregnancy rates were higher in the LG group than in the WZ group in the AZS subgroup at both weeks 12 and 24 (both P＜0.05). In the AZS subgroup analysis, PR and PR+NP showed significantly greater improvements in the LG group (P＜0.05). In the OAZS subgroup, SV, SC, TSC, PR, and PR+NP all showed greater improvements in the LG group (P＜0.05). No adverse events or adverse drug reactions were reported in either group. Conclusions: LG demonstrates significant efficacy and safety in treating male infertility associated with Shen deficiency and blood stasis syndrome, supporting its clinical application as an integrative therapy for male infertility. (Registration No. ITMCTR2023000009)Keywords：male infertility;asthenozoospermia;oligoasthenozoospermia;Linggui Yangyuan Paste;randomized controlled trial;Chinese medicine33|0|0Updated：2026-09-23Original Article
Abstract：Objective: To evaluate the efficacy and safety of Qushi Juanbi Granules (QSJB) combined with Shenling Baizhu Powder (SLBZ) for treating rheumatoid arthritis (RA) patients with low disease activity (LDA) and Pi (Spleen) deficiency and dampness dampness pattern. Methods: This is a single-centre, randomized, double-blind, placebo-controlled clinical trial executed from November 29, 2022 to August 15, 2024. Participants were randomly assigned to the QSJB (with placebo) group or the QSJB+SLBZ group at a ratio of 1:1 using block randomization method. QSJB, SLBZ and placebo were given twice per day for 12 weeks. The primary outcome was the Disease Activity Score-28 with C-reactive protein (DAS28-CRP), assessed both as the between-group difference in DAS28-CRP values and the proportion of patients achieving remission (DAS28-CRP＜2.6). The secondary outcomes included the 28-tender joint count (TJC28), 28-swollen joint count (SJC28), morning stiffness time, resting pain, Health Assessment Questionnaire (HAQ) score, Physician's Global Assessment of Disease Activity (PhGADA) score, Patient's Global Assessment of Disease Activity (PtGADA) score, rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), erythrocyte sedimentation rate (ESR) and CRP. Safety was monitored during the trial. Results: In total, 60 participants were enrolled, 7 dropped out. Fifty-three patients completed the study, with 30 cases in the QSJB+SLBZ group and 23 cases in the QSJB group. Between-group comparisons of DAS28-CRP value at weeks 4 and 12 were not significant (P=0.702, P=0.520). For remission, the week-12 remission rate was numerically higher in the QSJB+SLBZ group than in the QSJB group, without statistical significance (P=0.745). In the QSJB group, both DAS28-CRP and TJC28 were improved after 12 weeks of treatment (P=0.024, P=0.014, respectively), but RF level was elevated at weeks 4 and 12 (both P=0.021). In the QSJB+SLBZ group, DAS28-CRP, TJC28 and SJC28 were improved after 4 weeks (P=0.002, P=0.029 and P=0.001, respectively), TJC28 and SJC28 also improved after 12 weeks (P=0.018, P=0.004, respectively). However, there was no significant difference in DAS28-CRP, anti-CCP, RF, ESR, CRP, TJC28, PhGADA, PtGADA, HAQ, morning stiffness time or resting pain between the two groups (P＞0.05). No significant differences were noted between groups in overall adverse events (AEs) and AE-related discontinuation rates (all P＞0.05). Conclusions: QSJB alone achieved beneficial clinical responses with acceptable tolerability in treating RA patients with LDA and dampness pattern, while QSJB+SLBZ relieved joint pain faster and thus could be a better alternative option. (Trial registration No.ChiCTR2100053894)Keywords：rheumatoid arthritis;low disease activity;Chinese medicine;randomized controlled trial;Shenling Baizhu Powder;Qushi Juanbi Granules6|0|0Updated：2026-09-23Original Article
Abstract：Objective: To evaluate the effect of berberine (BBR) and elucidate its underlying mechanisms through both in vivo and in vitro models of reproductive dysfunction associated with type 2 diabetes mellitus (T2DM). Methods: In vivo, after acclimation, db/db mice (n=32) were randomized into model, low-dose BBR, high-dose BBR, and metformin groups of 8 in each, while BKS mice served as controls (n=8). Mice received daily gavage for 6 weeks (BBR: 150 or 300 mg/kg per day; metformin: 100 mg/kg per day; vehicle for controls). Ovarian and uterine morphology were assessed by HE staining, including follicle classification/counting and endometrial thickness measurement. Systemic metabolism was evaluated by oral glucose tolerance test and serum lipid profiling, including total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low density lipoprotein cholesterol. Serum metabolomics was performed using LC-MS to measure hormonal level. Ovarian and uterine transcriptomes were profiled by RNA sequencing; differentially expressed genes were identified and subjected to GO/KEGG enrichment and PPI network analysis. Key targets, including aquaporin (Aqp), 3, 5 and 7, were validated by qPCR and immunohistochemistry. In vitro, KGN cells were exposed to high glucose (30 mmol/L) and treated with BBR (10 or 25μmol/L) or metformin (12.5 or 25 mmol/L). CCK-8, immunofluorescence, TUNEL staining, and Western blotting (apoptosis markers and cAMP-PKA pathway proteins) were used to evaluate cellular phenotypes and signaling changes. Results: High-dose BBR improved follicle development, restored glycolipid metabolism, and balanced hormonal levels, particularly dehydroepiandrosterone sulfate (P＜0.05). It modulated the expressions of Crhr1 and Adrb2 in granulosa cells, alleviatied apoptosis through the cAMP-PKA signaling pathway (P＜0.05). BBR also enhanced Bcl2 expression while reducing Bax and Caspase-3 levels (P＜0.05). Furthermore, it restored endometrial thickness and the expressions of Aqp3, Aqp5, and Aqp7 (P＜0.05). Conclusions: BBR effectively improves ovarian function and endometrial receptivity in T2DM by regulating the cAMP-PKA pathway and apoptosis. These findings highlight its potential as a therapeutic agent for reproductive dysfunction in women with T2DM.Keywords：type 2 diabetes mellitus;reproduction disorder;berberine;Chinese medicine7|1|0Updated：2026-09-23Original Article
Abstract：Objective: To investigate the effect and underlying mechanism of securinine (Sec) in ovarian cancer (OC) based on network pharmacology, in vivo experiments and proteomics. Methods: ES2 cells were treated with different concentrations of Sec (6.25, 12.5, 25, 50, and 100μmol/L) for 24 h. The cell viability was determined using the MTT assay. ES2 xenograft nude mice were randomly divided into 4 groups (5 mice per group): tumor control, positive control carboplatin (12.5mg/kg), low-dose of Sec (10mg/kg), and high-dose of Sec (20mg/kg). During the treatment period, body weight and tumor volume were monitored. Major organs and tumor tissues were collected for organ index calculation and HE staining. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine were measured using commercial kits. Network pharmacology was used to predict the targets of Sec in OC. The proteomics analysis of tumor tissues was employed to identify key pathways regulated by Sec. The mRNA and protein levels of epidermal growth factor receptor (EGFR), hypoxia-inducible factor alpha (HIF-α), matrix metalloproteinase-9 (MMP9), mechanistic target of rapamycin (mTOR), nuclear factor kappa-B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and the key targets in peroxisome proliferator-activated receptor (PPAR) signaling pathway were determined by qRT-PCR and Western blot, respectively. Molecular docking was used to analyze the interactions between Sec and the core targets. Results: Sec (6.25-100μmol/L) inhibited ES2 cell proliferation (P＜0.05 or P＜0.01). Sec inhibited tumor growth in ES2 xenograft nude mice without toxicity in heart, liver, spleen, lung, and kidneys (P＜0.05 or P＜0.01). Network pharmacology identified 6 core targets associated with Sec's activity: EGFR, HIF-α, MMP9, mTOR, NF-κB, and STAT3. Proteomics analysis revealed PPAR signaling pathway as a key role. qRT-PCR confirmed that Sec significantly inhibited the mRNA levels of mTOR, NF-κB, STAT3, fatty acid-binding protein 3 (FABP3), FABP4, peroxisome proliferator-activated receptor alpha (PPAR-α), and PPAR-δ (P＜0.05 or P＜0.01). Western blot analysis demonstrated that Sec markedly suppressed the expression of FABP3, STAT3, and NF-κB (P＜0.05 or P＜0.01). Molecular docking revealed high binding affinity between Sec and FABP3, FABP4, mTOR, and NF-κB. Conclusion: Sec inhibits OC cell proliferation and tumor growth through the NF-κB and PPAR signaling pathways.Keywords：ovarian cancer;securinine;network pharmacology;proteomics;PPAR signaling pathway8|0|0Updated：2026-09-23Original Article
Abstract：Objective: To study the anti-proliferative and anti-angiogenic mechanism of oridonin in psoriatic keratinocytes by blocking phosphatidylinositol 3-kinase (PI3K/Akt) signaling pathway based on system pharmacology. Methods: Protein targets of oridonin and psoriasis-related genes were predicted and their overlap was determined using the Venny package in R. The DAVID database was used for enrichment analysis. The oridonin-psoriasis-target and oridonin-target-pathway (OTP) networks associated with psoriasis, as well as a protein-protein interaction, were constructed using Cytoscape. Molecular docking with AutoDock was used to verify the relationships between oridonin and core targets, and ZDOCK was used to assess interactions between core proteins. All bioinformatics results were verified empirically. The mRNA levels of core targets in oridonin-treated cells were measured using real-time q-PCR. The HaCaT keratinocytes were divided to 4 groups: control, low-, medium-and high-concentration groups and treated with different concentrations of oridonin (1, 5 and 10μmol/L) for 18 h, and then stimulated with tumor necrosis factor (TNF)-α (20 ng/mL) for 6 h. Western blot was used to detect PI3K/Akt pathway protein levels. Results: Seventy-three targets were found to be strongly associated with the effects of oridonin on psoriasis. The Cluster ONE algorithm was used to extract 6 kernel clusters from the PPI network, and 9 PPI interaction pairs comprising 13 targets showed combined scores 0.999. The OTP network, molecular docking, and protein interaction simulations indicated that oridonin targeted Sirtuin 1 (SIRT1), cyclin dependent kinase 2 (CDK2), Src tyrosine protein kinase (SRC), protein-tyrosine phosphatase, nonreceptor-type (PTPN), and SIRT1-tumor protein p53 (TP53), with the CDK2-TP53, SRC-heat shock protein 90 alpha family class a member 1 (HSP90AA1), and PTPN1-epidermal growth factor receptor (EGFR) interaction pairs regulating the PI3K-Akt signaling pathway. Oridonin was observed to block hyperplasia in HaCaT keratinocytes, accompanied by reduced levels of TNF-α, interleukin (IL-)-6, and IL-1β (P＜0.05 or P＜0.01). qPCR measurements showed that oridonin significantly inhibited the expression of angiogenesis-related genes, including C-X-C chemokine receptor type 7, C-X-C motif chemokine ligand 12, and vascular endothelial growth factor (P＜0.05 or P＜0.01). In addition, the qPCR results showed significant changes in the mRNA levels of SIRT1, CDK2, SRC, PTPN1, TP53, HSP90AA1, and EGFR, and Western blot indicated marked changes in the protein levels of cleaved caspase-3, BAD, Bcl-2, p-ERK1/2, and p-p38 after oridonin treatment (P＜0.05 or P＜0.01). Conclusions: The study identified the primary oridonin targets during psoriasis treatment using network pharmacology. Bioinformatics analysis with empirical verification demonstrated strong associations between SIRT1, CDK2, SRC, PTPN1, TP53, HSP90AA1, and EGFR and oridonin. These interactions were positively correlated with an inhibition of proliferation and angiogenesis mediated by blocking PI3K-Akt signaling pathway.Keywords：oridonin;psoriasis;system pharmacology;keratinocyte proliferation;angiogenesis;PI3K/AKT signaling pathway6|0|0Updated：2026-09-23Original Article
Abstract：Objective: To elucidate the anti-rheumatoid arthritis (RA) mechanisms of Notopterygium incisum essential oil (NIEO) using an integrated strategy combining chemical profiling, network pharmacology, multi-omics data mining, and advanced machine learning, while developing an optimized nanoemulsion (NE) delivery system to enhance its therapeutic applicability. Methods: Gas chromatography-mass spectrometry was employed for chemical profiling of NIEO. Multi-omics integration and machine learning models were used to identify core therapeutic targets, with diagnostic potential assessed via receiver operating characteristic analysis. Computational modeling, including molecular docking and dynamics simulations, provided structural insights into NIEO components interacting with targets. An optimized NIEO-NE was developed and characterized for physicochemical properties [mean diameter, polydispersity index (PDI), encapsulation efficiency]. In vitro assays evaluated NIEO-NE effects on lipopolysaccharide-induced Caspase-1 (CASP1) expression, reactive oxygen species (ROS) production, and pro-inflammatory mediators including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, nitric oxide (NO) in RAW264.7 macrophages. Results:GC-MS identified a-terpineol as the predominant constituent among 17 primary volatile compounds in NIEO. CASP1 was identified as the core target, with an area under curve of 0.985 for RA diagnosis. Molecular docking and dynamics revealed strong interactions between key NIEO components and CASP1's active site. The optimized NIEO-NE exhibited a mean diameter of 82.3nm, PDI of 0.12, and encapsulation efficiency of 94.8%. In vitro, NIEO-NE significantly suppressed LPS-induced CASP1 expression, ROS production, and release of IL-6, TNF-α, IL-1β, and NO (P＜0.01). Conclusions: NIEO exerts anti-RA effects by downregulating CASP1 and modulating the inflammasome pathway, validated through multi-omics and functional assays. The NE formulation overcomes bioavailability limitations, providing a framework for natural product-based drug discovery and positioning NIEO as a promising therapeutic candidate for RA.Keywords：rheumatoid arthritis;Notopterygium incisum essential oil;machine learning;nanoemulsion;caspase-1;network pharmacology7|0|0Updated：2026-09-23
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