Kadsura heteroclita stem suppresses the onset and progression of adjuvant-induced arthritis in rats.
BACKGROUND
Rheumatoid arthritis (RA) is a chronic autoimmune diseased state, characterized by hyperplasia of the synovial membrane, degradation of cartilage, and bone erosion of diarthrodial joints. Kadsura heteroclita (Roxb) Craib (Schizandraceae), a traditional Tujia ethnomedicine called Xue Tong in China, has been long used for the prevention and treatment of rheumatic and arthritic diseases, especially in the southern China. This study aimed to evaluate anti-arthritic effects of the ethanol extract of Kadsura heteroclita stems (KHS) on complete Freund's adjuvant (CFA)-induced arthritis (AIA) in rats, as well as to explore the underlying mechanisms of anti-arthritis.


METHODS
AIA was established in male Sprague-Dawley (SD) rats as described previously, and animals were daily treated by gavage with KHS ethanol extract (200, 400, or 800 mg/kg) or vehicle (0.3% CMCNa) throughout the 30-day experiment. The incidence and severity of arthritis were evaluated using clinical parameters. At the end of experiments, tissue swelling and bone destruction of the hind paws were assessed by computed tomography (CT) and histopathological analyses. Serum levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-17A and IL-17F were measured by ELISA, and protein expression of matrix metalloproteinases-1 (MMP-1), MMP-3 and tissue inhibitor of MMP-1 (TIMP-1) were detected by Western blot.


RESULTS
Treatment with KHS dose-dependently inhibited paw swelling and reduced arthritis scores of AIA rats. CT images displayed that KHS remarkably protected AIA rats from tissue swelling and bone erosion of joints. Histopathological analyses revealed that KHS markedly reduced inflammatory cell infiltration, synovial proliferation, and the formation of pannus in the ankle joints of AIA rats. KHS was found to significantly suppress the production of TNF-α, IL-1 β, IL-6, IL-17A and IL-17F, inhibited the protein expression of MMP-1 and MMP-3, and elevated the protein expressions of TIMP-1.


CONCLUSION
KHS demonstrates potential anti-arthritic effects via inhibiting pivotal mediators of inflammation and cartilage destruction. This study strongly supports identification and isolation of active fractions of KHS which would be a potential candidate for further investigation as a new anti-arthritic botanical drug.
['Yu|Huanghe|H|', 'Zeng|Rong|R|', 'Lin|Ye|Y|', 'Li|Xin|X|', 'Tasneem|Shumaila|S|', 'Yang|Zhen|Z|', 'Qiu|Yi-Xing|YX|', 'Li|Bin|B|', 'Wang|Yu-Hong|YH|', 'Cai|Xiong|X|', 'Wang|Wei|W|']
D000818:Animals D018501:Antirheumatic Agents D001169:Arthritis, Experimental D001172:Arthritis, Rheumatoid D004365:Drugs, Chinese Herbal D004487:Edema D005620:Freund's Adjuvant D007378:Interleukins D032135:Kadsura D008297:Male D018547:Plant Stems D017207:Rats, Sprague-Dawley D019715:Tissue Inhibitor of Metalloproteinase-1 D014409:Tumor Necrosis Factor-alpha
Kadsura heteroclita stem Adjuvant-induced arthritis Rheumatoid arthritis Tujia ethnomedicine Cytokines MMPS