An Integrated In Silico and In Vitro Assays of Dipeptidyl Peptidase-4 and α-Glucosidase Inhibition by Stellasterol from Ganoderma australe

Abstract

Background: Ganoderma fungus is rich in terpenoids. These compounds are known for their anti-hyperglycemic activities. However, the study of terpenoids as the secondary metabolite from Ganoderma as a dipeptidyl peptidase-4 (DPP-4) inhibitor remains unexplored. In addition, we examined the α-glucosidase inhibition activity. Objective: This study aimed to isolate the major terpenoid from non-laccate Ganoderma and examined its inhibitor activity on DPP-4 and α-glucosidase enzymes, and its interaction. Methods: The compound was isolated using column chromatography from Ganoderma australe. The structure of the isolated compound was confirmed by 1H and 13C nuclear magnetic resonance spectroscopy, while the inhibitory activity was evaluated using an enzymatic assay. The interaction of the isolated compound with DPP-4 and α-glucosidase enzymes was investigated using an in silico study. Results: The isolated compound was identified as stellasterol; IC50 values for DPP-4 and α-glucosidase inhibitor were 427.39 µM and 314.54 µM, respectively. This study revealed that the inhibitory effect of stellasterol on DPP-4 enzyme is through hydrophobic interaction, while the α-glucosidase enzyme is due to the interaction with six amino acids of the enzyme. Conclusion: Stellasterol is the major component of the steroid from G. australe. Enzyme inhibitory assay and in silico study suggest that stellasterol may contribute antidiabetic activity with a mechanism closer to acarbose rather than to sitagliptin.

Dipeptidyl peptidase-IV inhibitory action of Calebin A: An in silico and in vitro analysis

“…, further supports the current research work [ 48 ]. In silico studies on stellasterol isolated from Ganoderma australe highlighted the importance of hydrophobic interactions with Tyr631, Tyr662, Trp659, Tyr666, and Val711 for DPP-IV inhibition which further strengthen the current investigations [ 49 ]. Other natural compounds like malonylgenistein, Caffeic acid – 3-glucoside and Calenduloside E were proved to have interactions similar to that of CA [ 50 ].…”

α-Amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory effects of Melicope latifolia bark extracts and identification of bioactive constituents using in vitro and in silico approaches

“…Doty ex Silva (Solieriaceae) and Corallopsis opuntia J. Agardh (Hypneaceae) extracts have been observed to be more effective than M. latifolia extracts (Makkar and Chakraborty 2017). All the IC 50 of the positive controls used in the study were compared with literature and the validity of the assays were supported (Mzid et al 2017;Iheagwam et al 2019aIheagwam et al , 2020Budipramana et al 2019;Sarac et al 2019). The present study showed that the isolated compounds 1-4 inhibited a-amylase and thus contributed to the a-amylase inhibition activity of the M. latifolia chloroform extract.…”

The inhibition of Mpro, the primary protease of COVID-19, byPoria cocosand its active compounds: a network pharmacology and molecular docking study

“…53,54 kB pathway, 68 and other studies have shown that stellasterol has potential as a hypoglycemic agent. 73 In the present study, network pharmacology showed that Poria cocos may maintain internal water balance via G protein coupled receptor signaling pathways, regulating ion channel activity, and by regulating hormone levels. Furthermore, molecular docking studies involving AQP4 provided a preliminary verication of the molecular mechanisms underlying the efficacy of Poria cocos.…”