Curcumin ameliorates immune dysregulation and bone destruction in rat models with collagen-induced arthritis via inhibiting the mTOR signaling pathway

doi:10.16352/j.issn.1001-6325.2026.11.1491

Abstract

Abstract: Objective To investigate the therapeutic effects of curcumin on immune dys-regulation and bone destruction in collagen-induced arthritis (CIA) rats. Methods A rat model of CIA was established. After successful modeling, the rats were divided into the model group, curcumin group, rapamycin group, and normal group. The general condition and degree of paw swelling in the rats were evaluated before and after treatment. Serum level of cytokines and matrix metalloproteinases(MMPs) was measured by ELISA. Histopathological changes in synovitis were observed by HE staining microscopy. The ratio of Treg to Th17 in peripheral blood was determined by flow cytometry. The number of osteoclasts in the foot joints was shown by using TRAP staining. Bone metabolism markers,RANK/RANKL/ OPG proteins, as well as the expression of mTOR, AKT, and p70S6K in synovial tissue were detected by Western blot analysis. Results Compared with the normal group, the model group exhibited synovial hyperplasia and inflammatory infiltration along with significantly elevated serum level of IL-1β, TNF-α, MMP-1, and MMP-3(P＜0.01). The Treg/Th17 ratio was decreased(P＜0.05), while osteoclast counting was increased(P＜0.01). Serum 1 collagen C-terminal peptide(CTX-1) level was elevated while that of osteocalcin(OC) was reduced(P＜0.001). The RANKL/RANK pathway was up-regulated, whereas OPG expression was down-regulated. Additionally, the expression level of AKT1, mTOR, and p70S6K in synovial tissue was increased(P＜0.01). Compared to model group, curcumin treatment significantly alleviated arthritis in CIA rats, reduced the level of pro-inflammatory cytokines and MMPs(P＜0.01), and up-regulated Treg/Th17 ratio(P＜0.01). IL-10 level was increased, while IL-17 level was decreased(P＜0.01). Osteoclast numbers and activity were reduced, and the imbalance in the RANKL/RANK/OPG system was ameliorated. Furthermore, the expression level of AKT1, mTOR, and p70S6K was down-regulated(P＜0.05). Conclusions Curcumin restores the Treg/Th17 balance and suppresses osteoclast differentiation and activity, the potential mechanism is considered to be the inhibition of the mTOR signaling pathway.

Key words: curcumin, mTOR signaling pathway, collagen-induced arthritis (CIA), immune deregulation, bone destruction

CLC Number:

YU Jiawen, TANG Yuqi, CHEN Wu, XU Liping, ZHANG Yan, DAI Qiaoding. Curcumin ameliorates immune dysregulation and bone destruction in rat models with collagen-induced arthritis via inhibiting the mTOR signaling pathway[J]. Basic & Clinical Medicine, 2026, 46(11): 1491-1500.

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