<i>In vivo</i> determination of analgesic and anti-inflammatory activities of isolated compounds from <i>Cleome amblyocarpa</i> and molecular modelling for the top active investigated compounds

Abstract

<i>Cleome amblyocarpa</i> Barr. and Murb. from the family Cleomaceae is used in folk medicine as it has analgesic, anti-inflammatory, antibacterial and antioxidant activities. In this study, ten compounds from the whole plant of <i>C. amblyocarpa</i>, a wild plant that grows in the Sinai Peninsula of Egypt, were isolated. Six compounds, β-sitosterol 3-<i>O</i>-β-d-glucoside 2, calycopterin 5, rhamnocitrin 6, 17α-hydroxycabraleahy-droxylactone 7, cleogynol 8, and β-sitosterol 10 were first isolated from this species. In addition, four previously reported compounds, kaempferol-3, 7-dirhamnoside 1, 15α-acetoxycleomblynol A 3, and 11-α-acetylbrachy-carpone-22(23)-ene 4, as well as cleocarpanol 9, were isolated and identified. Isolated compounds were evaluated to determine their analgesic properties utilizing a hot-plate test method, and their anti-inflammatory effects utilizing rat paw edema. In a hot-plate test, compounds 3, 4, 7, 8, and 9 showed significant pain inhibition in latency time as compared to the normal group. Compounds 3-9 exhibited a significant inhibition of carrageenan-induced inflammation. According to the results of this work, compounds 3 and 4 (Dammarane triterpenoid) have the strongest analgesic/anti-inflammatory activity as compared to the other tested compounds. These results give support to the medicinal benefits of the plant as an analgesic along with an anti-inflammatory agent in traditional therapy. Molecular modelling studies of the isolated compounds 3 and 4 assessed the molecular affinity and binding interaction patterns for these compounds towards COX-2 as compared to specific COX-2 inhibitors and in relation to COX-1 isozyme. Compound 3 revealed extended accommodation across COX-2's hydrophobic sub-pockets and preferential thermodynamic stability across molecular dynamics simulations.