Identification of α-Glucosidase Inhibitors from Scutellaria edelbergii: ESI-LC-MS and Computational Approach

Abstract

The recent study investigated the in vitro anti-diabetic impact of the crude extract (MeOH) and subfractions ethyl acetate (EtOAc); chloroform; n-butanol; n-hexane; and aqueous fraction of S. edelbergii and processed the active EtOAc fraction for the identification of chemical constituents for the first time via ESI-LC-MS analysis through positive ionization mode (PIM) and negative ionization mode (NIM); the identified compounds were further validated through computational analysis via standard approaches. The crude extract and subfractions presented appreciable activity against the α-glucosidase inhibitory assay. However, the EtOAc fraction with IC50 = 0.14 ± 0.06 µg/mL revealed the maximum potential among the fractions used, followed by the MeOH and n-hexane extract with IC50 = 1.47 ± 0.14 and 2.18 ± 0.30 µg/mL, respectively. Moreover, the acarbose showed an IC50 = 377.26 ± 1.20 µg/ mL whereas the least inhibition was observed for the chloroform fraction, with an IC50 = 23.97 ± 0.14 µg/mL. Due to the significance of the EtOAc fraction, when profiled for its chemical constituents, it presented 16 compounds among which the flavonoid class was dominant, and offered eight compounds, of which six were identified in NIM, and two compounds in PIM. Moreover, five terpenoids were identified—three and two in NIM and PIM, respectively—as well as two alkaloids, both of which were detected in PIM. The EtOAc fraction also contained one phenol that was noticed in PIM. The detected flavonoids, terpenoids, alkaloids, and phenols are well-known for their diverse biomedical applications. The potent EtOAc fraction was submitted to computational analysis for further validation of α-glucosidase significance to profile the responsible compounds. The pharmacokinetic estimations and protein-ligand molecular docking results with the support of molecular dynamic simulation trajectories at 100 ns suggested that two bioactive compounds—dihydrocatalpol and leucosceptoside A—from the EtOAc fraction presented excellent drug-like properties and stable conformations; hence, these bioactive compounds could be potential inhibitors of alpha-glucosidase enzyme based on intermolecular interactions with significant residues, docking score, and binding free energy estimation. The stated findings reflect that S. edelbergii is a rich source of bioactive compounds offering potential cures for diabetes mellitus; in particular, dihydrocatalpol and leucosceptoside A could be excellent therapeutic options for the progress of novel drugs to overcome diabetes mellitus.

Phytochemical Profiling and Bio-Potentiality of Genus Scutellaria: Biomedical Approach

“…The most prominent compounds isolated from Scutellaria species are baicalin, baicalein, and wogonin. Figure 2 reflects the dominant chemical ingredients contributed by the genus Scutellaria , which have wide pharmacological properties, including antioxidant, analgesic, laxative, diuretic, anti-diabetic, anti-allergy, anti-inflammatory, and regulator of lipid and arachidonate metabolism [ 1 , 76 ].…”

“…Inhibiting AChE and Butyrylcholinesterase (BChE) has developed into a standard method for treating the symptoms of neurodegenerative diseases like Alzheimer’s disease [ 99 ]. A-amylase and a-glucosidase are two other key glycaemic control enzymes (Shah et al [ 1 ]). The finding of new and reverse tyrosinase enzyme inhibitors, on the other hand, has enabled scientists to develop more accurate Parkinson’s disease prevention measures.…”

“…The genus Scutellaria is comprised of over three hundred and fifty (350) plant species, cosmopolitan by habitat, and its species have served as a natural remedy since ancient times throughout the globe [ 1 ]. Therapeutic herbs have been proven to be a significant origin of medication for the mitigation of human diseases [ 2 ].…”

“…Dominant compounds isolated from Scutellaria species.The chemical constituents of medicinal plants are mainly influenced by various environmental gradients.The study described by Malikov and Yuledashev[77] revealed that approximately 208 bioactive ingredients were isolated and identified as representing phenols from Scutellaria species and mainly contributed by S. baicalensis. In addition, Shah et al[1] described the tentative identification of 16 compounds from S. edelbergii. Baicalin and baicalein are the major compounds reported from Scutellaria.…”

Scutellaria petiolata Hemsl. ex Lace & Prain (Lamiaceae).: A New Insight in Biomedical Therapies

“…Besides this, they also function as steroidal drugs, which are known as steroidal alkaloids [ 9 ]. The genus Scutellaria is mainly represented by flavonoids and phenolic constituents [ 10 ], such as glucuronides comprises baicalin and wogonin-7-Oglucuronide or aglycones that are wogonin-7-Oglucuronide baicalein and wogonin. Phenolic constituents can scavenge the free radicals, resist the pathogenic microbes and inhibit the platelet aggregation [ 11 , 12 ].…”