Toddalia asiatica extract attenuates adjuvant-induced arthritis by modulating colon Th17/Treg balance and colony homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Given the adverse effects of the current principal treatments, there is still a great need for effective cures for rheumatoid arthritis (RA), an immune-mediated disease. Toddalia asiatica (L.) Lam is a traditional medicinal herb that can be used for RA treatment because of its anti-inflammatory and analgesic properties. AIM OF THE STUDY: To investigate the possible effects of Toddalia asiatica extract (TAE) on intestinal immunity and the intestinal bacterial flora in a rat model of RA. MATERIALS AND METHODS: The anti-arthritis effect of TAE was evaluated in arthritis rats induced by complete Freund's adjuvant-induced arthritis (AIA). Arthritis index (AI) scores, systemic inflammation scores, histopathologic changes in the colon and ankle were detected by hematoxylin and eosin staining. Western blot analysis was performed to assess the protein expression of IL-17A, RORC, IL-1ß, IL-6, FOXP3, IL-10 in the colon. RT-PCR was performed to assess the expression of the colon's mRNA. Finally, changes to the gut microbiome by sequencing 16S rDNA. Microbial function prediction was performed using PICRUSt with the KEGG databases and correlation analysis was carried out by computing Spearman's rank correlations. RESULTS: demonstrated that TAE administration at a dose of 3 g/kg dramatically decreased AI scores, systemic inflammation scores, and histopathologic lesions of the ankle and colon in AIA rats. TAE was found to significantly reduce the expression levels of Th17-related proteins and mRNAs (IL-17A, RORC, IL-1ß and IL-6) in the colon, while increasing the expression levels of Treg-related proteins and mRNA (IL-10 and FOXP3), which helped restore the balance of Th17/Treg immune cells in the colon. Meanwhile, TAE was also found to be capable of remodeling the gut microbiota in AIA rats. Depleting RA-associated genera and thereby increasing α-diversity enriched the gut microbiota's diversity and shifted the community composition dramatically, leading to the increase of Firmicutes_unclassified, Ruminococcaceae_unclassified, Muribaculum, Subdoligranulum, Lachnospira, Marvinbryantia, and the reduction of RA-related bacteria Ligilactobacillus, Streptococcus and Eubacterium-eligens-group. Furthermore, PICRUSt analysis revealed that metabolic pathways were associated with TAE treatment, with metabolic pathways dominating. Among them, metabolic pathways were predominant. Correlation studies showed that a total of 9 microorganisms, including Ligilactobacillus, Eubacterium-eligens-group and Subdoligranulum, were significantly associated with Th17/Treg expression. CONCLUSIONS: This study demonstrates that TAE is a low-toxicity poly alkaline drug that can rapidly and effectively improve joint symptoms in RA rats and increases beneficial intestinal bacteria and decreases harmful ones, which is associated with modulating Th17/Treg interactions in intestinal T cells and reversing microbial disorders.

Efficacy and safety of acupoint injection therapy for allergic rhinitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Allergic rhinitis (AR), characterized by nasal itching, sneezing, and congestion, is a common disorder of nose. In the United States, AR affects 10% to 20% of adults. The negative impact of the high prevalence of AR has caused a great economic burdens worldwide. Modern Western Medicine mainly treats AR with antihistamine drugs, glucocorticoids, allergic immunotherapy (AIT), but it seriously affects patients compliance because of its long course of treatment, high medical costs and side effect. And now, as an important mean of treating AR, acupoint injection has been widely used in clinics, and has achieved significant efficacy. METHODS AND ANALYSIS: The following databases will be searched for relevant information before July 2020: PubMed, Embase, Cochrane Library, Web of Science, and CNKI. MAJOR RESULTS: scores of Rhinitis Quality of Life (RQLQ), Rhinitis Total Symptom Scores (RTSS). Secondary results: levels of antigen-specific serum immunoglobulin E (IgE), total effective rate, adverse event. Data will be collected independently by 2 researchers, and the risk of bias in meta-analysis will be evaluated according to "Cochrane Handbook for Systematic Reviews of Interventions". All data analysis will be conducted using Review Manager V.5.3. and Stata V.12.0. RESULTS: The curative effect and safety of acupoint injection treatment for AR patients will be evaluated systematically. CONCLUSION: The systematic review of this study will summarize the currently published evidence of acupoint injection treatment for AR to further guide its promotion and application. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.Open Science Framework (OSF) registration number: https://osf.io/fa9dq.