AUTHOR=Liu Yuan , Luo Pei , Zhang Ji-Zhong , Chen Xiao-Yi , Li Li-Min , Wu You-Jiao , Yin Qiao-Zhi , Huang Li 

TITLE=Identification of Active Compounds From Yi Nationality Herbal Formula Wosi Influencing COX-2 and VCAM-1 Signaling

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.568585

DOI=10.3389/fphar.2020.568585

ISSN=1663-9812

ABSTRACT=<p>The Yi nationality herbal formula <italic>Wosi</italic> is used in China as a folk medicine to treat arthritis and related diseases. Despite its widespread use, the active ingredients, and pharmacological mechanisms are not performed. This is the first time to identify the active compounds from <italic>Wosi</italic> with the aim at providing the potential effect of <italic>Wosi</italic> and exploring its underlying anti-inflammatory mechanism in monosodium urate crystals (MSU)-induced arthritis rats. 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. <italic>Wosi</italic> significantly suppressed the degree of joint swelling and improved the symptoms of inflammation induced by MSU crystals. The inhibition of IL-2, IL-1β, IFN-γ, and IL-6 secretion and IL-10 increase in the serum were also observed. This study also focuses on the screening of the main compounds from <italic>Wosi</italic> against cyclooxygenase for anti-inflammatory properties using molecular docking. The result showed 3-O-[α-L-pyran rhamnose(1-3)-β-D-pyran glucuronic acid]- oleanolic acid, 3-O-(β-D-pyran glucuronic acid)-oleanolic acid-28-O-β-D-pyran glucoside, and 3-O-[α-L-pyran rhamnose(1-3)-β-D-pyran glucuronic acid]-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. The preferential selectivity toward inhibiting COX-2 enzyme over COX-1 of three compounds from <italic>Wosi</italic> were evaluated using <italic>in-vitro</italic> cyclooxygenases 1 and 2 (COX-1/2) inhibition assays. 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 <italic>Wosi</italic> treatment. In conclusion, three oleanolic acid glycosides were implied as mainly efficient compounds in Yi nationality herbal formula <italic>Wosi</italic> for arthritis therapy via selectively influencing COX-2 and VCAM-1 signaling.</p>