Abstract
Purpose: To investigate the anti-rheumatic potential of Wu-Wei-Gui-Shao decoction (WGD) and its possible mechanism of action.
 Methods: Adjuvant arthritis (AA) rats were established using complete Freund's adjuvant. The rats were then given different doses of WGD (100, 200, and 400 mg/kg, for 28 days). The anti-arthritic effects of WGD were evaluated. Furthermore, the in vitro anti-arthritic effects of WGD and its related mechanisms were also determined in MH7A cells.
 Results: WGD (100 - 400 mg/kg) exhibited significant anti-rheumatic properties after 28 days of treatment, inhibiting paw edema in AA rats, reducing arthritis score and thymus and spleen index, and inhibiting the tumor necrosis factor (TNF)-α and the interleukin (IL)-6. In addition, the results of in vitro cell experiments also confirmed that WGD reduced the release of cytokines, as well as mRNA levels of matrix metalloproteinase (MMP) -2, -3, and -9.
 Conclusion: These findings suggest that WGD can be further developed as a traditional Chinese medicine to treat rheumatic arthritis.
 Keywords: Wu-Wei-Gui-Shao decoction, Complete Freund's adjuvant, Arthritis, Molecular mechanism, Traditional Chinese Medicine
Highlights
Rheumatic arthritis (RA) is a common acute or chronic connective tissue inflammation, mainly manifested by floating sores, and red, painful joints and muscles, with a wide incidence, long course of disease, high deformity and disability [1]
The high doses showed the same effect as that of the positive group. This finding confirmed that the paw volume of Adjuvant arthritis (AA) rats decreased after Wei-Gui-Shao decoction (WGD) treatment, and WGD could significantly improve the symptoms of the AA mace
We recorded the arthritis score of AA rats to assess the therapeutic efficacy of WGD
Summary
Rheumatic arthritis (RA) is a common acute or chronic connective tissue inflammation, mainly manifested by floating sores, and red, painful joints and muscles, with a wide incidence, long course of disease, high deformity and disability [1]. This study explored the therapeutic effect of WGD on AA model rats and an arthritis cell model, as well as to uncover its possible pharmacological mechanism, which will be of great reference value for the clinical use of WGD to cure RA. The animals were divided into six groups randomly: normal group, adjuvant arthritis (AA) model group, positive group, WGD treatment group (100, 200, and 400 mg/kg), and a group of eight animals. Arthritis index: the posterior foot volume of each rat was recorded with electronic water plethysmometer (TECHMAN Co., Chengdu, China) before modeling, and measured every 3 days after modeling. The paw volumes were detected and classified based on the erythema severity and swelling of the paw according to a 5-point rating scale: 0 points, no signs of change; 1-points, red and swelling in the ankle/wrist; Table 1: Composition of WGD. Where Ww and Aw are the wet weight of the (spleen or kidney) and animal weight, respectively
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