Network pharmacology identification and in vivo validation of key pharmacological pathways of Qin Jiao for gout and arthritis.

Context: Gout is a chronic disease that imposes a huge financial and health burden on patients, which might diminish quality of life. Qin Jiao, a perennial herb found in northwestern China and Japan, is commonly used for treating various ailments.Objective: This study investigates the effects of Qin Jiao on gout and joint inflammation and elucidates its potential mechanism for gouty arthritis.Materials and methods: Study 1, a literature review was conducted using PubMed, Web of Science, and CNKI to assess the applications of Qin Jiao in arthritis treatment. Study 2 was performed to discover the component targets and gouty disease targets via TCMSP, OMIM, GeneCards and DRUGBANK, and network pharmacology analysis. Study 3, male Sprague-Dawley (SD) rats were divided into normal, model, colchicine, Qin Jiao low-dose (QJL), and Qin Jiao high-dose group (QJH), oral gavage for 40 d. Serum, synovial fluid, and synovial membrane tissue were collected to measure the expression levels of IL-1ß, IL-6, and STAT3.Results: The research also identified potential targets and pharmacological pathways of Qin Jiao for gout treatment. In vivo study demonstrated Qin Jiao can reduce IL-1ß levels in serum and ankle flushing fluid. ELISA analysis confirmed that Qin Jiao significantly reduces the protein expression of IL-6 and STAT3.Discussion and conclusion: Qin Jiao exerts anti-inflammatory effects on gouty arthritis by modulating the IL-6/STAT3 pathway. This study provides a biological basis for the use of Qin Jiao in treating arthritis-related diseases and offers experimental evidence for potential future drug development.

Wuling San Based on Network Pharmacology and in vivo Evidence Against Hyperuricemia via Improving Oxidative Stress and Inhibiting Inflammation.

Background: Hyperuricemia (HUA) is a major public health issue with a high prevalence worldwide. Wuling San (WLS) is an effective treatment for HUA. However, the active compounds and the related mechanism are unclear. In this study, we aimed to explore the active compounds and the underlying pharmacological mechanisms of WLS against HUA. Methods: First, a network pharmacology approach was used to detect active compounds of WLS, and potential targets and signaling pathways involved in the treatment of HUA were predicted. Then, a molecular docking strategy was used to predict the affinity between active compounds and key targets. Finally, to verify the prediction, the HUA rat model was established. Results: 49 active compounds with 108 common targets were obtained. Besides, cerevisterol, luteolin, ergosterol peroxide, beta-sitosterol, and sitosterol were identified as key active compounds. In PPI analysis, TNF, IL6, CASP3, PPARG, STAT3, and other 12 core targets were obtained. GO enrichment analysis indicated that WLS was likely to interfere with oxidative stress in the treatment of HUA, and KEGG enrichment analysis indicated multiple inflammation-related signaling pathways possibly involved in the treatment of HUA by WLS, including TNF, and NOD-like receptor, HIF-1, PI3K-Akt, and IL-17 signaling pathways. The results of molecular docking indicated that the active compounds had good binding properties to their key targets. In the validation experiments, WLS significantly reduced the levels of serum uric acid (SUA) and serum malondialdehyde (MDA). Moreover, WLS not only significantly increased the levels of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD), but also inhibited the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Conclusion: In the present study, we demonstrate that WLS has multicomponent, multitarget, and multi-pathway properties in the treatment of HUA. Its potential capability to reduce SUA could be ascribed to oxidative stress improvement and inflammation inhibition.

Ramulus Mori (Sangzhi) alkaloids tablets for diabetes mellitus: A regulatory perspective.

The reform of the review and approval system for Traditional Chinese Medicine (TCM) continues to advance with the introduction of a new registration classification and the establishment of a review and approval evidence system. This new registration process established a novel review and approval evidence system, which combines the TCM theory, human use experience and clinical trials. Ramulus Mori (Sangzhi) alkaloids Tablets are a brand new drug. It is the first botanical natural hypoglycemic drug, and a new model of TCM review and approval evidence system has gradually been developed through contemporary research. In this paper, we discuss the registration process of new Chinese medicine drugs under the "three integrated review and approval system", retrace the development process of Mulberry alkaloid tablets, and discuss the opportunities and challenges encountered under the "three integrated" evidence system to provide feasible strategies and reference models for the development of Chinese medicine and the development of botanical drugs in the world.

[Visual analysis of exosomes in traditional Chinese medicine research and application status based on CiteSpace knowledge map].

In this study, CiteSpace was used to conduct bibliometric statistics and visualization of the research papers on the exosomes in traditional Chinese medicine(TCM) and application status in CNKI, Wanfang, VIP, and Web of Science. The authors, research institutions, and keywords of the relevant papers were analyzed to summarize the research status, hotspots, and development trends of TCM application of exosomes, thereby providing references for future research. A total of 340 Chinese papers and 9 English papers were included. In Chinese papers, GUO Hai-dong is the author with the largest amount of research papers, and his research interest is the mechanism of electroacupuncture in promoting functional recovery after sciatic nerve injury by regulating the release of exosomes. Shanghai University of Traditional Chinese Medicine is the research institution with the largest amount of papers, followed by Nanjing University of Chinese Medicine and Hunan University of Chinese Medicine. There was less cooperation among these research institutions, and cooperation between teams and agencies should be strengthened. The overall volume of publications in English was comparatively small, and the connections between the authors were weak. The publishing organizations were mostly distributed in medical schools, hospitals, comprehensive universities, and the cooperation between institutions was scattered. The main keywords in Chinese papers include microRNA, mesenchymal stem cells, bone marrow mesenchymal stem cells, mechanism of action, and extracellular vesicles. The research of exosomes in TCM is increasing in recent years. The research hotspot is that exosomes can both serve as biomarkers for the diagnosis and prognosis of certain diseases in TCM and drug carriers of Chinese medicine for targeted treatment of diseases. Keyword prominence suggested that exosomes derived from osteoblasts and macrophages in the treatment of diseases might still be a future research trend.

An integrated study of Shenling Baizhu San against hyperuricemia: Efficacy evaluation, core target identification and active component discovery.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenling Baizhu San (SLBZ) is a famous Traditional Chinese Medicine (TCM) formula that strengthens the spleen for replenishing qi, removing dampness, and inducing diuresis to relieve diarrhea. Combining the TCM interpretation that dampness is a vital pathogenesis factor in hyperuricemia occurrence and development, SLBZ has excellent potential against hyperuricemia from the perspective of TCM theories. AIM OF THE STUDY: This study aimed to investigate the efficacy of SLBZ against hyperuricemia and its possible mechanism with emphasis on the active components and the core targets. MATERIALS AND METHODS: In the present study, we employed meta-analysis and a hyperuricemia quail model to evaluate the uric acid-lowering effect of SLBZ. Bodyweight, serum uric acid, and excreta uric acid levels in quails were assessed. Subsequently, we analyzed the potential active components and core targets of SLBZ against hyperuricemia by network pharmacology and calculated their interaction using molecular docking. Furthermore, the hyperuricemia rats treated with interfering agents of core targets were established to determine the central role of selected targets in hyperuricemia progression. Besides, we isolated and characterized the primary renal tubular epithelial cells of quails to verify the active components and core targets of SLBZ against hyperuricemia. Western blotting was used to observe the expression of core targets treated with active components under the stimulation of interfering agents. RESULTS: Data from meta-analysis and animal experiments showed that SLBZ could work effectively against hyperuricemia. Hyperuricemia quails treated with SLBZ displayed significantly reduced serum uric acid levels accompanied by increased excretion of uric acid. According to network pharmacology and molecular docking results, 34 potential active components and the core target peroxisome proliferator-activated receptor gamma (PPARγ) for SLBZ against hyperuricemia were identified. The decreased serum uric acid levels in hyperuricemia rats treated with rosiglitazone, an agonist of PPARγ, confirms the essential role of PPARγ in the pathological process of hyperuricemia. Moreover, we first successfully isolated and characterized the primary renal tubular epithelial cells of quails and observed enhanced phosphorylation of PPARγ at Ser273 in cells handled with high-level uric acid. Whereas, the enhanced expression of p-PPARγ Ser273 could be down-regulated by luteolin and naringenin, two active components of SLBZ against hyperuricemia. CONCLUSION: In summary, SLBZ is a promising anti-hyperuricemia agent, and luteolin and naringenin are the active components for SLBZ against hyperuricemia by down-regulating phosphorylation of PPARγ at Ser273.

Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice.

PURPOSE: Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. METHODS: KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. RESULTS: Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. CONCLUSIONS: Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.