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

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) = 0.35 ± 0.12 mg/mL) offered excellent inhibitory activity, followed by extracts from Tinospora crispa (IC(50) = 0.69 ± 0.39 mg/mL), Stephania suberosa (IC(50) = 1.50 ± 0.17 mg/mL), Andrographis paniculate (IC(50) = 1.78 ± 0.35 mg/mL), and Thunbergia laurifolia (IC(50) = 4.66 ± 0.27 mg/mL). However, the potencies of these extracts were lower than that of acabose (IC(50) = 0.55 ± 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) = 819.07 pM) through 5 hydrogen bonds (HBs) and 2 hydrophobic interactions (HIs); β-sitosterol (IC(50) = 4.46 nM, 6 HIs); ergosterol peroxide (IC(50) = 4.18 nM, 6 HIs); borapetoside D (IC(50) = 508.63 pM, 7 HBs and 2 HIs); borapetoside A (IC(50) = 1.09 nM, 2 HBs and 2 His), stephasubimine (IC(50) = 285.37 pM, 6 HIs); and stephasubine (IC(50) = 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.