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Deciphering the Potential Pharmaceutical Mechanism of Chinese Traditional Medicine (Gui-Zhi-Shao-Yao-Zhi-Mu) on Rheumatoid Arthritis.

ABSTRACT: Gui-Zhi-Shao-Yao-Zhi-Mu (GSZ) decoction is a Traditional Chinese Medicine (TCM) formula commonly used for the treatment of Rheumatoid Arthritis (RA). The therapeutic effect of GSZ for RA treatment is supported by our clinical retrospective study. To uncover the potential mechanism underlying GSZ formula, we identified 1,327 targets of 673 compounds from 9 herbs that involve in Fc epsilon RI signaling pathway and regulation of immunoglobulin production. Comparison between formula targets with 79 RA drug targets and 675 RA disease genes showed that formula targets covered 31.6% RA drug targets and 19.9% RA disease genes. Formula specific targets presented expression patterns highly similar to the disease genes and drug targets based on the expression profiles of RA samples. Investigation of 10 inferred gene clusters from expression profiles with a target association network revealed that formula specific targets directly or indirectly interacted with disease genes that were essential for immune related biological processes (e.g. inflammatory responses, treatment response of rheumatoid arthritis, etc.). Our result indicated that GSZ disrupted the RA disease dysfunction modules and restored homeostasis in the human body. The systemic approach to infer therapeutic mechanisms of GSZ for RA treatment provides a new insight in the understanding of this TCM formula.

SUBMITTER: Huang L

PROVIDER: S-EPMC4776278 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Project description:Introduction: Jinteng Qingbi granules (JTQBG), a traditional Chinese medicine formulation, are widely used for the treatment of rheumatoid arthritis (RA) due to their satisfactory therapeutic efficacy. However, the underlying mechanism of action remains unclear. This study aims to investigate the protective effects of JTQBG against RA and elucidates its potential molecular mechanisms. Methods: A collagen-induced arthritis (CIA) rat model was utilized, and JTQBG (1.25, 2.5, 5 g/kg/day) or methotrexate (MTX, 1 mg/kg/week) was orally administered. The rats' weight, arthritis index (AI), and paw volume were measured weekly. Synovial hyperplasia of the joints was detected using a small animal ultrasound imaging system. Joint destruction was assessed using an X-ray imaging system. Histopathological examinations were performed using hematoxylin-eosin (H&E), Saffron-O and fast green staining. Serum inflammatory cytokines were detected using ELISA. Furthermore, 4D label-free quantitative proteomics of synovial tissues and non-targeted metabolomics of blood serum were conducted to analyze the molecular mechanisms. Results: JTQBG exerted a significant therapeutic effect on CIA rats by reducing inflammatory cell infiltration, synovial hyperplasia, cartilage erosion, and bone destruction. It also decreased the spleen index, inhibited hyperplasia of the white pulp, and decreased the serum levels of IL-1β and IL-18. Proteomics analysis identified 367 differentially expressed proteins (DEPs) between the Model and Normal groups, and 71 DEPs between the JTQBG and Model groups. These DEPs were significantly enriched in the NF-κB pathway. 11 DEPs were significantly reversed after treatment with JTQBG. Western blot results further validated the expression levels of Nfkb1, Pdk1, and Pecam1, and analyzed the expression levels of p-IKK, p-IκBα, and IκBα. The therapeutic efficacy of JTQBG was partly attributed to the suppression of the NF-κB pathway in synovial tissues. Serum metabolomics identified 17 potential biomarkers for JTQBG treatment of CIA rats, which were closely related to Alanine, aspartate and glutamate metabolism, Tryptophan metabolism, Ascorbate and aldarate metabolism, Arginine metabolism, and Inositol phosphate metabolism. Conclusion: Our findings demonstrated that JTQBG was effective against RA by alleviating synovial inflammation, synovial hyperplasia, and joint destruction. The anti-RA properties of JTQBG were likely attributed to the inhibition of the NF-κB pathway and the regulation of serum metabolite disorders.

Project description:ObjectiveIntegrated therapy of traditional Chinese medicine (TCM) and Western medicine (WM) has gradually been applied to the treatment of rheumatoid arthritis (RA). Recently published studies have provided a wealth of data and information about the effectiveness of combination treatments, but high-quality evidence-based meta-analysis on this issue is not available yet. This study was conducted to compare and evaluate the efficacy and safety of the integrated therapy for RA.MethodsPubMed, EMBASE, and the Cochrane Library were searched up to January 2020. Randomized controlled trials (RCTs) that compared the efficacy and safety of integrative TCM-WM with WM alone for RA were included. The outcome measures contained therapeutic effects (TEs), tender joint count (TJC), swollen joint count (SJC), duration of morning stiffness (DMS), grip strength (GS), disease activity score in 28 joints (DAS28), rheumatoid factor (RF), anti-cyclic peptide containing citrulline (anti-CCP), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and adverse events (AEs) to assess the efficacy and safety of different treatments.ResultsA total of 20 RCTs with 2269 patients met the inclusion criteria. TCM used in these studies included Chinese herbal decoctions and tablets or capsules made from herbs and their extracts, while WM included disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids (GC). Compared with patients receiving WM treatment alone, patients with integrative TCM-WM treatment showed better TEs (OR = 3.03, 95% CI [2.36, 3.88]). The integrative treatment group showed reductions in TJC (MD = -1.17, 95% CI [-2.12, -0.21]), SJC (MD = -0.87, 95% CI [-1.85, 0.10]), DMS (SMD = -0.69, 95% CI [-0.98, -0.41]), DAS28 (MD = -0.43, 95% CI [-0.57, -0.29]), RF (SMD = -0.59, 95% CI [-0.91, -0.27]), anti-CCP (SMD = -0.21, 95% CI [-0.36, -0.06]), ESR (MD = -8.36, 95% CI [-12.60, -4.12]), and CRP (MD = -6.73, 95% CI [-9.38, -4.08]), and increment in GS (SMD = 0.12, 95% CI [-0.63, 0.87]). AEs, especially gastrointestinal disorders, abnormal liver function, leukopenia, skin allergies and rashes, headaches and dizziness, and alopecia, significantly decreased (OR = 0.37, 95% CI [0.29, 0.47]) in the integrative treatment group.ConclusionsThe findings of this meta-analysis indicate that integrative TCM-WM could obtain effective and safe results in the treatment of RA. Using TCM as an adjunctive therapy in RA has great prospects for further development.

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Deciphering the Potential Pharmaceutical Mechanism of Chinese Traditional Medicine (Gui-Zhi-Shao-Yao-Zhi-Mu) on Rheumatoid Arthritis.

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