Wu-Teng-Gao External Treatment Improves Th17/Treg Balance in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) represents the consequence of an immune response of the body’s immune system attacking healthy cells. This chronic inflammatory disorder has complicated pathogenesis. Traditional Chinese medicine (TCM) is well recognized as an effective therapy in treating RA and has been widely applied for centuries. Wu-Teng-Gao (WTG) is used as a representative natural herb formula in RA treatment in China, while its mechanisms are to be fully clarified. The present study attempted to explore mechanisms of WTG on RA treatment in a network pharmacological approach and verified using experiments in vitro. Following the establishment of a rat model of collagen-induced arthritis (CIA), WTG was applied externally on the metapedes of rats. HE staining was subsequently performed to visualize the pathological changes of synovium and bone. Simultaneously, flow cytometry was conducted to detect the cell ratio of T helper 17 (Th17) and Regulatory T cells (Treg) in splenic lymphocytes. Additionally, ELISA, qRT-PCR, and Western blot assays were adopted to determine expressions of RA-related factors in joints and serum. Results of network pharmacological analysis suggested that Th17 cell differentiation might serve as a potential signaling pathway of WTG therapy for RA. Animal experiments demonstrated that WTG ameliorated the articular inflammation and effectively inhibited the destruction of articular cartilage, and decreased Th17 and Treg cell ratios in CIA rats. Furthermore, WTG also greatly suppressed relevant levels of inflammatory cytokines (IL-17, TNF-α, IL-1, and IL-6) and RNAKL, whereas it elevated expressions of anti-inflammatory cytokines IL-10 and TGF-β. Our results confirmed that WTG might improve the imbalance of Th17/Treg cells in CIA animals through differentiation regulation, thus alleviating joint inflammation and bone destruction.

The effect of Boric Acid and Calcium Fructoborate on T Helper Cell Differentiation by Influencing Foxp3 and Ror-γt in Rheumatoid Arthritis and Systemic Lupus Erythematosus

“…An increase in Foxp3 expression and a decrease in Ror-γt expression were observed. In addition, a decrease in pro-in ammatory cytokines (IL-1, IL-6, TNF-α, IL-17) and an increase in anti-in ammatory cytokines (IL-10 and TGF-β) were observed, and it was found that bone damage was inhibited in histological staining [22]. In a study conducted in a lupus mouse model, the effect of Cucurbitacin IIb on Th17 and Treg cell percentages, Foxp3 and Ror-γt expression levels in cells isolated from the spleen of mice was investigated.…”

“…Th17/Treg ratio in our study were found to be lower in RA group compared to the HC group. This maybe because CD4 + Ror-γt + cells were investigated as Th17 in our study and in many other studies investigating Treg and Th17, CD4 + IL-17A + Th17 cells were studied [42,22]. We aimed to investigate the effects of BA and CaF on CD4 + Foxp3 + cells and CD4 + Ror-γt + cells.…”

“…Yao M.X. et al found Th17(CD4 + IL-17A + )/Treg(CD4 + Foxp3 + ) ratio were higher in collagen induced arthritis Rat model [22]. Oxidative stress and metabolic abnormalities have been found to related to the imbalance of Treg and Th17 in SLE [23,24].…”

Research progress of targeted therapy regulating Th17/Treg balance in bone immune diseases

“…For example, Yao et al. ( 238 ) performed animal experiments and showed that the external application of Wuteng ointment greatly inhibited the expression levels of inflammatory cytokines IL-17, TNF-α, IL-1, IL-6, and RNAKL, and improved the expression of anti-inflammatory cytokines IL-10 and TGF. Through further experiments, it was found that different doses of Wuteng ointment significantly reduced the ROR-γt level in spleen tissue, increased the Foxp3 level, altered the Th17/Treg cell ratio, improved the Th17/Treg cell imbalance in CIA rats, inhibited bone destruction, and played an effective therapeutic role in RA.…”

“…In reports (237), Chinese medicine application technology has been recognised by patients because of its advantages in reducing toxic damage to the gastrointestinal tract, liver, kidney, and other organs, its convenient use, and its therapeutic effects in RA. For example, Yao et al (238) performed animal experiments and showed that the external application of Wuteng ointment greatly inhibited the expression levels of inflammatory cytokines IL-17, TNF-a, IL-1, IL-6, and RNAKL, and improved the expression of antiinflammatory cytokines IL-10 and TGF. Through further experiments, it was found that different doses of Wuteng ointment significantly reduced the ROR-gt level in spleen tissue, increased the Foxp3 level, altered the Th17/Treg cell ratio, Based on the above research, we can conclude that both Western medicine and traditional Chinese medicine.…”