Classically, the major therapeutic approaches against gouty arthritis is to control serum urate concentration in a controllable level and treat the inflammation. This process could cause monocytes and T lymphocytes in blood flowing into the site of inflammation and enhance inflammatory reactions by activating the expression of Vascular cell adhesion protein 1 (VCAM-1) ( Carlos et al., 1991). Inflammasome in response to MSU crystals trigger caspase-1 activation and the maturation and release of interleukin 1 beta (IL-1β) in phagocytes, it also can promote the inflammation response by the release of cytokines,chemokines and expression of inflammatory enzymes (cyclooxygenase-2) and inducible nitric oxide synthase (iNOS) ( Kinne et al., 2000 Pétrilli and Martinon, 2007). When macrophage engulfs MSU crystals, it promotes the assembly and the activation of cytosolic NACHT-LRR-PYD-containing protein (NLRP3) inflammasome protein complex ( Cronstein and Terkeltaub, 2006 So and Martinon, 2017). TLR 2, TLR 4 and the TLR adaptor protein MyD88 can promote the phagocytosis of MSU crystals surrounding in the joints by phagocytes ( Martinon et al., 2006 Sabina et al., 2011 Rock et al., 2013). The recognition of MSU crystals can trigger innate host defense responses through Toll-like receptor (TLR) 2 and (TLR) 4. It is mainly manifested in redness, swelling, heat, and pain in the joints due to various inflammatory mediators. Moreover, high concentration of uric acid in the blood may result in monosodium urate crystals (MSU) deposition in the joint tissues and synovial membrane causing acute gout arthritis. ![]() The incidence of hyperuricemia in the world is gradually increasing, which is a risk factor for development of gout, cardiovascular disease, and diabetes ( Falasca, 2006 Johnson et al., 2013). Hyperuricemia associated with the overproduction and insufficient excretion of uric acid. In conclusion, three oleanolic acid glycosides were implied as mainly efficient compounds in Yi nationality herbal formula Wosi for arthritis therapy via selectively influencing COX-2 and VCAM-1 signaling. Meanwhile, the down-regulated protein expression of COX-2 and VCAM-1 in synovial tissue sections from ankle joints of experiments rats were confirmed by immunohistochemistry analysis after the Wosi treatment. The preferential selectivity toward inhibiting COX-2 enzyme over COX-1 of three compounds from Wosi were evaluated using in-vitro cyclooxygenases 1 and 2 (COX-1/2) inhibition assays. ![]() The result showed 3-O- oleanolic acid, 3-O-(β-D-pyran glucuronic acid)-oleanolic acid-28-O-β-D-pyran glucoside, and 3-O-oleanolic acid-28-O-β-D-pyran glucoside with a higher binding affinity for COX-2 than COX-1 which indicated relatively higher interaction than COX-1. This study also focuses on the screening of the main compounds from Wosi against cyclooxygenase for anti-inflammatory properties using molecular docking. The inhibition of IL-2, IL-1β, IFN-γ, and IL-6 secretion and IL-10 increase in the serum were also observed. Wosi significantly suppressed the degree of joint swelling and improved the symptoms of inflammation induced by MSU crystals. In this study, anti-hyperuricemia effect was assessed by reducing the serum uric acid levels and increasing uric acid excretion in the urine for the hyperuricemia rat model. This is the first time to identify the active compounds from Wosi with the aim at providing the potential effect of Wosi and exploring its underlying anti-inflammatory mechanism in monosodium urate crystals (MSU)-induced arthritis rats. ![]() Despite its widespread use, the active ingredients, and pharmacological mechanisms are not performed. The Yi nationality herbal formula Wosi is used in China as a folk medicine to treat arthritis and related diseases. 5Chengdu University of TCM, Chengdu, China.4Sichuan Academy of Chinese Medicine Sciences, Chengdu, China.3State Key Laboratories for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China.2Sichuan Provincial Qiang-Yi Medicinal Resources Protection and Utilization Technology and Engineering Laboratory, Chengdu, China. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |