CHRONOTROPIC, INOTROPIC, AND RADICAL SCAVENGING ACTIVITY OF Curcuma heyneana EXTRACT BY MOLECULAR DOCKING SIMULATION AND In-vitro STUDY ON THE HEART OF Fejervarya cancrivora FROG

Abstract

The β-1 adrenergic receptor belongs to GPCRs which communicates via the Gs-α subunit, thus initiating the cAMPdependent pathway through the upregulation of adenylyl cyclase. The activation of the β-1 adrenergic receptor in the heart triggers the activation of the sinoatrial node and atrioventricular nodes, hence escalating heart rate (positive chronotropic) and contractility (positive inotropic). Flavonoids and terpenes have been reported for their inotropic effect in animal models. In this work, we examined the chronotropic and inotropic activity of Curcuma heyneana Valeton and Zijp rhizome by determining the molecular interaction between the bioactive compounds, namely, αsitosterol, stigmasterol, quercetin, and curcumenol, with human G-protein-coupled receptor kinase 2 (hGRK2), and in vitro study of C. heyneana extract on the heart of crab-eating Fejervarya cancrivora frog. Moreover, the total phenol content in the extract and the radical scavenging activity were also determined. The results indicated that C. heyneana positively contains phenolic compounds and weakly inhibits the radicals of the DPPH reagent (IC50 = 320.0 µg/mL). The molecular docking study revealed that α-sitosterol and quercetin have the best interaction with important residues in hGRK2, similar to that of the enzyme’s inhibitor. C. heyneana decreases the heart rate and increases the heart contractility of crab-eating F. cancrivora frogs. Based on these findings, C. heyneana is the potential in helping the heart pump more blood to fulfill the oxygen demands, but with lesser heartbeats, thus it is useful for patients with cardiovascular disorders.