The potentials of red betel (piper crocatum ruiz & pav) terpenoid compounds as microsomal prostaglandin E synthase-1 (mPGES-1) enzyme inhibitor of rheumatoid arthritis through virtual screening

Abstract

Rheumatoid Arthritis (RA) is an inflammatory disease of synovium and key enzyme serving as mPGES-1, catalyzing conversion PGH2 into PGE2. PGE2 is a primary prostaglandin. When PGE2 binds to receptors PGE2, it can activate the transcription factor. In 2010, WHO released data on the prevalence of RA sufferers, which is relatively high. The synthetic drugs for RA commonly used piroxicam & meloxicam due to hepatotoxic condition, so that a safe alternative using herbal medicine such as Red Betel was then employed. Red Betel leaves contain terpenoid compounds such as β-amyrin, Spathulenol, Caryophyllene, and Humulene. Several previous studies have revealed that terpenoid can inhibit prostaglandin biosyntheses such as terpenoid in Boswellia species & Salvia officinalis. Thereby, the purpose of this study is to predict the potential of β-amyrin, Spathulenol, Caryophyllene, and Humulene terpenoid compounds in Red Betel as mPGES-1 inhibitor through virtual screening using software and web servers. The docking results showed four terpenoid compounds and drugs on the same site, bound with enzyme through alkyl bond, while β-amyrin is also hydrogen bond. The binding affinity of four terpenoid compounds was not significantly different from drugs. Conversely, the potentials of antiinflammatory, antiarthritic, NSAID, transcription factor inhibitor, and pharmacokinetic are better than drugs. This work concluded that β-amyrin, Spathulenol, Caryophyllene, Humulene in Red Betel is potential for RA drug candidate.