Computational study and in vitro alpha-glucosidase inhibitory effects of medicinal plants from a Thai folk remedy

Abstract

The number of patients with type 2 diabetes mellitus (T2DM) has increased worldwide. Although an instant cure was achieved with the standard treatment acabose, unsatisfactory symptoms associated with cardiovascular disease after acabose administration have been reported. Therefore, it is important to explore new treatments. A Thai folk recipe has long been used for T2DM treatment, and it effectively decreases blood glucose. However, the mechanism of this recipe has never been proven. Therefore, the potential anti-T2DM effect of this recipe, which is used in Thai hospitals, was determined to involve alpha-glucosidase (AG) inhibition with a half maximal inhibitory concentration (IC 50 ). In vitro experiments showed that crude Cinnamomum verum extract (IC 50 ¼ 0.35 AE 0.12 mg/mL) offered excellent inhibitory activity, followed by extracts from Tinospora crispa (IC 50 ¼ 0.69 AE 0.39 mg/ mL), Stephania suberosa (IC 50 ¼ 1.50 AE 0.17 mg/mL), Andrographis paniculate (IC 50 ¼ 1.78 AE 0.35 mg/mL), and Thunbergia laurifolia (IC 50 ¼ 4.66 AE 0.27 mg/mL). However, the potencies of these extracts were lower than that of acabose (IC 50 ¼ 0.55 AE 0.11 mg/mL). Therefore, this study investigated and developed a formulation of this recipe using computational docking. Among 61 compounds, 7 effectively inhibited AG, including chlorogenic acid (IC 50 ¼ 819.07 pM) through 5 hydrogen bonds (HBs) and 2 hydrophobic interactions (HIs); β-sitosterol (IC 50 ¼ 4.46 nM, 6 HIs); ergosterol peroxide (IC 50 ¼ 4.18 nM, 6 HIs); borapetoside D (IC 50 ¼ 508.63 pM, 7 HBs and 2 HIs); borapetoside A (IC 50 ¼ 1.09 nM, 2 HBs and 2 His), stephasubimine (IC 50 ¼ 285.37 pM, 6 HIs); and stephasubine (IC 50 ¼ 1.09 nM, 3 HBs and 4 HIs). These compounds bind with high affinity to different binding pockets, leading to additive effects. Moreover, the pharmacokinetics of six of these seven compounds (except ergosterol peroxide) showed poor absorption in the gastrointestinal tract, which would allow for competitive binding to AG in the small intestine. These results indicate that the development of these 6 compounds into oral antidiabetic agents is promising.

Homology Modeling, Molecular Docking, Molecular Dynamic Simulation, and Drug-Likeness of the Modified Alpha-Mangostin against the β-Tubulin Protein of Acanthamoeba Keratitis

“…Both AutoDock and ArgusLab are used to compute molecular docking, and both programs are compared [ 32 ]. Homology-modeled beta-tubulin is derived from a Swiss model, and its energy consumption is lowered using the Swiss-Pdb Viewer and Chiron online web.…”

“…Homology-modeled beta-tubulin is derived from a Swiss model, and its energy consumption is lowered using the Swiss-Pdb Viewer and Chiron online web. The chemicals displayed in Table 2 are docked with BT; compared to AutoDock, the ArgusLab docking study has a higher binding score [ 32 ]. In autodock, the highest docking score was −10.56 kcal/mol for 1,6-dihydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1-yl)-9H-xanthen-9-one, and the lowest docking score was −10.18 kcal/mol for alpha mangostin.…”

Machine Learning and In Vitro Chemical Screening of Potential α-Amylase and α-Glucosidase Inhibitors from Thai Indigenous Plants

“…Complementary and alternative medicines have been widely used for the treatment of diabetes mellitus worldwide [39], as well as in Thailand. Traditional Thai medicines (TTM) have long been used for lowering blood sugar [13,40]. In this study, we screened the potential inhibitory activities of selected TTM against α-amylase and α-glucosidase enzymes.…”

The Cholesterol-Modulating Effect of the New Herbal Medicinal Recipe from Yellow Vine (Coscinium fenestratum (Goetgh.)), Ginger (Zingiber officinale Roscoe.), and Safflower (Carthamus tinctorius L.) on Suppressing PCSK9 Expression to Upregulate LDLR Expression in HepG2 Cells

“…All docking was confirmed with Autodock3 through the Lamarckian genetic technique to ensure reliable results. The following are the optimal autodocking run parameters: number of GA runs: 50; population size: 200; and all other run parameters: default [ 44 , 52 ].…”