Molecular interaction between xanthorrhizol with ghrelin-o-acyl transferase (goat) and growth hormone SECRETAGOG3UE receptor (GHS-R): a docking analysis

After curcuminoids, xanthorrhizol is the second primary bioactive compound from Curcuma xanthorrhiza. Traditionally, the rhizome of Curcuma xanthorriza is well-known for its appetite stimulation. However, the mechanism of appetite stimulation is still unclear, particularly its interaction with the appetite-related ghrelin system. Therefore, understanding interactive molecular modulations of xanthorrhizol with ghrelin, GOAT (ghrelin-O-acyl transferase), and ghrelin receptor (GHS-R: growth hormone secretagogue receptor is essential. Xanthorrhizol, an appetite stimulant, may interact with ghrelin, GOAT, and GHS-R. Herein, this study aimed to do in silico analysis to hypothetically predict the molecular interaction of xanthorrhizol with ghrelin, ghrelin-O-acyl transferase (GOAT), and growth hormone secretagogue receptor (GHS-R). Docking analysis was conducted to understand the interactive molecular patterns of xanthorrhizol, ghrelin, GOAT, and GHS-R. The docking studies showed that the molecular interaction of xanthorrhizol is with Arg10 of ghrelin and not with Ser2, which is essential for the linkage of octanoic acid. The molecular interaction of xanthorrhizol with GOAT is in the active sites of either deacylated ghrelin or octanoic acid. Therefore, xanthorrhizol is a competitive inhibitor of GOAT. It inhibits GOAT activity. Xanthorrhizol interacts with GHS-R in its small cavity II. Itnis still unclear whether this interaction is agonist or antagonist. This in silico analysis showed that xanthorrhizol is probably not a stimulating appetite natural drug via stimulating GHS-R signaling.