Study on the mechanism of action of Saposhnikovia divaricata and its key phytochemical on rheumatoid arthritis based on network pharmacology and bioinformatics.

ETHNOPHARMACOLOGICAL RELEVANCE: Saposhnikovia divaricata (Turcz.) Schischk (SD; called "fangfeng" in China) has been widely used in the clinical treatment of rheumatoid arthritis (RA) and has shown well therapeutic effects, but the specific mechanisms of action of its bioactive phytochemicals remain unclear. AIM OF THE STUDY: This study aimed to investigate the molecular biological mechanism of SD in treating RA through a pharmacology-based strategy. The SD-specific core ingredient Prangenidin was screened for further in-depth study. MATERIALS AND METHODS: The bioactive phytochemicals of SD and potential targets for the treatment of RA were screened by network pharmacology, and phytochemicals-related parameters such as pharmacology, and toxicology were evaluated. The protein interaction network was established to screen the core targets, and the correlation between the core targets and RA was further validated by bioinformatics strategy. Finally, molecular docking of core components and corresponding targets was performed. The in vitro experiments were performed to elucidate the regulation of Prangenidin on MH7A cells and on the PI3K/AKT pathway, and the in vivo therapeutic effect of Prangenidin was validated in collagen-induced arthritis (CIA) mice. RESULTS: A total of 18 bioactive phytochemicals and 66 potential target genes intersecting with the screened RA disease target genes were identified from SD. Finally, core ingredients such as wogonin, beta-sitosterol, 5-O-Methylvisamminol, and prangenidin and core targets such as PTGS2, RELA, and AKT1 were obtained. The underlying mechanism of SD in treating RA might be achieved by regulating pathways such as PI3K/AKT, IL-17 pathway, apoptosis, and multiple biological processes to exert anti-inflammatory and immunomodulatory effects. Molecular docking confirmed that all core ingredients and key targets had great docking activity. Prangenidin inhibited viability, migration, and invasion, and induced apoptosis in MH7A cells. Prangenidin also reduced the production of IL-1ß, IL-6, IL-8, MMP-1, and MMP-3. Molecular analysis showed that Prangenidin exerts its regulatory effect on MH7A cells by inhibiting PI3K/AKT pathway. Treatment with Prangenidin ameliorated synovial inflammation in the joints of mice with CIA. CONCLUSION: Our findings provide insights into the therapeutic effects of SD on RA, successfully predicting the effective ingredients and potential targets, which could suggest a novel theoretical basis for further exploration of its molecular mechanisms. It also revealed that Prangenidin inhibited viability, migration, invasion, cytokine, and MMPs expression, and induced apoptosis in RA FLSs via the PI3K/AKT pathway.

Effect of mesenchymal stem cell therapy in animal models of allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: Allergic rhinitis (AR) is a worldwide problem that affects people of all ages, impairing patients' physical and mental health and causing great social expenditure. Animal studies have suggested the potential efficacy of mesenchymal stem cell (MSC) therapy in treating AR. Our meta-analysis was performed to evaluate the effect of MSC therapy in animal models of AR by pooling animal studies. METHODS: The search was executed in PubMed, Embase, Web of Science, OVID, and the Cochrane Library for relevant studies up to February 2023. The applicable data were extracted from the eligible studies, and the risk of bias was assessed for each study. The meta-analysis was conducted using Review Manager (version 5.4.1) and Stata (version 15.1). RESULTS: A total of 12 studies were included in the final analysis. Compared to the model control group, the MSC therapy group presented lower frequency of sneezing [(Standardized mean difference (SMD) -1.87, 95% CI -2.30 to -1.43)], nasal scratching (SMD -1.41, 95% CI -1.83 to -0.99), and overall nasal symptoms (SMD -1.88, 95% CI -3.22 to -0.54). There were also remarkable reductions after transplantation with MSCs in the levels of total immunoglobulin E (IgE) (SMD -1.25, 95% CI -1.72 to -0.79), allergen-specific IgE (SMD -1.79, 95% CI -2.25 to -1.32), and allergen-specific immunoglobulin G1 (SMD -1.29, 95% CI -2.03) in serum, as well as the count of eosinophils (EOS) in nasal mucosa (SMD -3.48, 95% CI -4.48 to -2.49). In terms of cytokines, MSC therapy significantly decreased both protein and mRNA levels of T helper cell 2 (Th2)-related cytokines, including interleukin (IL)-4, IL-5, IL-10, and IL-13. CONCLUSION: MSC therapy has the potential to be an effective clinical treatment for AR patients by attenuating Th2 immune responses, reducing secretion of IgE and nasal infiltration of EOS, and consequently alleviating nasal symptoms.

Efficacy of different oral H1 antihistamine treatments on allergic rhinitis: a systematic review and network meta-analysis of randomized controlled trials

Abstract Introduction Oral H1 antihistamines are the first-line treatment for patients with allergic rhinitis, while it is uncertain which kind and dosage of the antihistamines are more effective in improving symptoms of patients. Objective To evaluate the efficacy of different oral H1 antihistamine treatments on patients with allergic rhinitis by performing a network meta-analysis. Methods The search was executed in PubMed, Embase, OVID, the Cochrane Library and ClinicalTrials.gov for relevant studies. The network meta-analysis was performed by using Stata 16.0, and the outcome measures of the analysis were symptom score reductions of patients. Relative risks with 95% Confidence Intervals were used in the network meta-analysis to compare the clinical effect of treatments involved, and Surface Under the Cumulative Ranking Curves (SUCRAs) were also calculated to rank the treatments' efficacy. Results 18 eligible randomized controlled studies, involving a total of 9419 participants, were included in this meta-analysis. All the antihistamine treatments outperformed placebo in total symptom score reduction and each individual symptom score reduction. According to the results of SUCRA, rupatadine 20 mg and rupatadine 10 mg were ranked relatively high in reductions of total symptom score (SUCRA: 99.7%, 76.3%), nasal congestion score (SUCRA: 96.4%, 76.4%), rhinorrhea score (SUCRA: 96.6%, 74.6%) and ocular symptom score (SUCRA: 97.2%, 88.8%); rupatadine 20 mg and levocetirizine 5 mg were ranked relatively high in reductions of nasal itching score (SUCRA: 84.8%, 83.4%) and sneezing score (SUCRA: 87.3%, 95.4%); loratadine 10 mg was ranked the lowest in each symptom score reduction besides placebo. Conclusion This study suggests that rupatadine is the most effective in alleviating symptoms of patients with allergic rhinitis among different oral H1 antihistamine treatments involved, and rupatadine 20 mg performs better than rupatadine 10 mg. While loratadine 10 mg has inferior efficacy for patients to the other antihistamine treatments.