Hydrolyzable tannins from the fruits of Terminalia chebula Retz and their α-glucosidase inhibitory activities

Highlights

• Forty-eight hydrolyzable tannins including nine hitherto unknown were isolated from the fruits of Terminalia chebula.

• α-Glucosidase inhibitory activities of the all isolates were evaluated.

• Two at the nine above compounds showed significant inhibitory activities against α-glucosidase (IC₅₀ 2.9 and 6.4 μM).

Abstract

Nine hydrolyzable tannins, including three previously unknown and six artifacts, were isolated, together with thirty-nine known ones, from the fruits of Terminalia chebula Retz. (Combretaceae). They were identified as 1,2,3-tri-O-galloyl-6-O-cinnamoyl-β-d-glucose, 1,2,3,6-tetra-O-galloyl-4-O-cinnamoyl-β-d-glucose, 4-O-(2″,4″-di-O-galloyl-α-l-rhamnosyl)ellagic acid, 1′-O-methyl neochebulanin, dimethyl neochebulinate, 6′-O-methyl neochebulagate, dimethyl neochebulagate, dimethyl 4′-epi-neochebulagate, and methyl chebulagate by the spectroscopic interpretation. After evaluation for α-glucosidase inhibition of all isolated compounds, 1,2,3,6-tetra-O-galloyl-4-O-cinnamoyl-β-d-glucose and 4-O-(2″,4″-di-O-galloyl-α-l-rhamnosyl)ellagic acid showed significant inhibitory activities with IC₅₀ values of 2.9 and 6.4 μM, respectively. In addition, inhibition kinetic studies showed that both compounds have mixed-type inhibitory activities with the inhibition constants (Ki) of 1.9 and 4.0 μM, respectively.

Introduction

Type 2 diabetes mellitus (T2DM), known as non-insulin-independent diabetes, is a chronic metabolic disorder due to insulin-resistance in the tissue (Matthews et al., 1985). This results in elevating blood glucose level, which can damage many organs (Guo, 2014). One therapeutic approach for treating T2DM is to alleviate postprandial hyperglycemia. This is done by suppressing glucose absorption from the gut through inhibition of intestinal carbohydrate digesting enzymes, such as α-glucosidase (EC number 3.2.1.20) (Kim et al., 2000). Acarbose is a clinical α-glucosidase inhibitor which has been used as a first-line treatment for diabetic patients with postprandial hyperglycemia (Sivasothy et al., 2016). Acarbose is efficient in attenuating the rapid increase in the blood glucose level in patients, but its continuous use may cause side-effects, such as flatulence and diarrhea (Chiasson et al., 2002). From this point of view, many efforts have been extended in searching for effective and safe α-glucosidase inhibitors from the natural materials to develop bioactive functional food to treat T2DM (Bhandari et al., 2008, Kim et al., 2014, Wang et al., 2010).

Terminalia chebula Retz., which belongs to the family of Combretaceae, is widely distributed in India and Southeast Asia and extensively cultivated in Taiwan (Cheng et al., 2003). It has been commonly used in ethnomedicine due to its astringent, purgative, laxative, and diuretic properties (Ajala et al., 2014). In previous phytochemical studies, more than 150 compounds including hydrolysable tannins, phenolic acids, flavonoids, lignans, triterpenoids, and their glycosides were reported from the Terminalia genus. Extracts of T. chebula have beneficial properties, including antitumor, anti-inflammatory, wound healing, antifungal, antibacterial, and antiviral activities (Cock, 2015). In the current investigation, the methanolic extract and its n-BuOH soluble fraction of the fruits of T. chebula showed α-glucosidase inhibitory activity. Hence, the active constituents in this plant were studied. As a result, three new compounds (1, 2, 5) and six artifacts (9, 10, 13, 14, 16, and 17) along with thirty-nine known ones (3, 4, 6–8, 11, 12, 15, and 18–48) were obtained. Herein we described the isolation and structural elucidation of the new compounds, and the assessment of α-glucosidase inhibitory activity of the isolated compounds.