Chuanxiong Rhizoma extracts alleviate hyperuricaemia-induced renal injury by reducing serum UA levels and renoprotection

Abstract

Chuanxiong Rhizoma is the dried rhizome of the Apiaceae plant Ligusticum chuanxiong Hort (Chuanxiong). Previously, we demonstrated the antihyperuricaemic and anti-acute gouty arthritis effects of Chuanxiong Rhizoma ethyl acetate extracts (ECX B) in mice. However, it is unclear whether ECX B is optimal for lowering urate levels. This study aims to find the optimal extraction of the Chuanxiong Rhizoma in hyperuricemia rats. Further to explore the anti-hyperuricemia effects, underlying mechanism, and the main active compounds in vitro and in vivo. This study demonstrated that ECX B was the most effective extract in lowering uric acid levels and protecting the kidneys in vivo among the different tested extracts. ECX B significantly reduced the serum uric acid (UA), blood urea nitrogen (BUN), creatinine (CRE) and xanthine oxidase (XOD) levels and alleviated kidney pathology in hyperuricaemic rats, modulated the mRNA and protein expression of the UA transporters urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporter 1 (OAT1) and ATP binding cassette subfamily G member 2 (ABCG2). Subsequently, 23 compounds were prepared and characterized by a series of natural medicinal chemistry techniques. Then, we found that (Z)-3-butylidene-4,5-dihydroxyphthalide (CX-F14) was the main active compound produced by ECX B. Overall, this work revealed that ECX B was the optimal Chuanxiong Rhizoma extract for the treatment of hyperuricaemia. ECX B exerted an antihyperuricaemic effect mainly by modulating UA transporters and protecting the kidney. CX-F14 is a possible active compound of ECX B. These findings could lead to new applications for Chuanxiong Rhizoma.