Alpha-glucosidase and Alpha-amylase Inhibitory Activities, Molecular Docking and Antioxidant Capacities of Salvia Aurita Constituents

Abstract

Diabetes mellitus (DM) is one of the most dangerous metabolic diseases with high rate of mortality worldwide. It is well known that insulin resistance and deficiency in insulin production from pancreatic β-cells are the main characteristic of DM. Due to the detrimental side effects of the current treatment, there is a considerable need to develop new effective antidiabetic drugs, especially alpha-glucosidase and alpha-amylase inhibitors with lesser adverse effects. These inhibitors are known to be directly involved in the delay of carbohydrate digestion, resulting in a reduction of glucose absorption rate and consequently reduce the post-prandial raise of plasma glucose, which can reduce the risk of long-term diabetes complications. Hence, natural products are well-known sources for the discovery of new scaffold for drugs discovery, including new antidiabetic drugs. The phytochemical investigation of Salvia aurita collected from Hogobach pass, Eastern Cape, South Africa (SA), yielded four known abietane diterpenes namely carnosol (1), rosmanol (2), 7-methoxyrosmanol (3), 12-methoxycarnosic acid (4) and one flavonoid named 4,7-dimethylapigenin (5). Structural characterization of these isolated compounds was conducted using 1 and 2D NMR, in comparison with reported spectroscopic data. These compounds are reported for the first time from S. aurita. The biological evaluation of the isolated compound against alpha-glucosidase exhibited strong inhibitory activities for 3 and 2 with IC50 values of 4.2 ± 0.7 and 16.4 ± 1.1 µg/mL respectively, while 4 and 1 demonstrated strong alpha-amylase inhibitory activity amongst the isolated compounds with IC50 of 16.2 ± 0.3 and 19.8 ± 1.4 µg/mL. Molecular docking analysis confirms strong inhibitory activity of 3 against alpha-glucosidase. Additionally, excellent antioxidant capacities were displayed by 2, 1 and 3 respectively as ORAC (25789.9 ± 10.5; 23961.8 ± 14.1; 23939.3 ± 2.4) µM TE/g; 1 and 2 as FRAP (3917.8 ± 2.1; 1522.3 ± 0.9) µM AAE/g; 5 and 2 as TEAC (3190.4 ± 2.8; 2055.0 ± 2.6) µM TE/g. The methanolic extract of S. aurita is a rich source of abietane diterpenes with excellent antioxidant and anti-diabetic activities that can be useful to modulate oxidative stress, and might possibly be excellent candidates for the management of diabetes. This is the first scientific report on the phytochemical isolation and biological evaluation of alpha-glucosidase and alpha-amylase inhibitory activities of Salvia aurita.

Synthesis of an amantadine-based novel Schiff base and its transition metal complexes as potential ALP, α-amylase, and α-glucosidase inhibitors

“…These bright yellow crystals were vacuum ltered, washed thrice with ice-cold ethanol, recrystallized from ethanol, and dried in the desiccator. Color: yellow; yield: 80%; melting point: 85 °C; UV/Vis: 271, 326, 420; ESI-MS: 296.20[M + H] + ; FT-IR: (KBr disc) n/cm −1 : 1618 (HC]N), 1547 (C]C), 1228 (C-N), 2908, 2848 (C-H-aromatic, str), 3317 (OHaromatic), 3062 (vinyl CH 2 , str); 1 H-NMR (400 MHz, DMSO-d 6 ) d ppm; 1.70 (m, CH 2 , 1-adamantane), 1.87 (d, CH 2 , 1-adamantane), 2.08 (m, CH 2 , 1-adamantane), 4.99 (d, CH 2 , methylene), 5.02 (t, H, 1-ethylene), 5.07 (t, H, 1-ethylene), 5.93 (m, H, 1ethylene), 14.83 (s, OH-alcohol), 6.79 (t, CH-benzylidenimin), 7.12 (d, CH-benzylidenimin), 7.33 (d, CH-benzylidenimin), 8.55 (s, CH]N) 13…”

“…α-Amylase is involved in the digestion of carbohydrates, while α-glucosidase is involved in the digestion of starch and disaccharides into glucose. 13 These enzymes can be suppressed by effective inhibitors to treat diabetes. 14 A large number of coordinated compounds such as chromium, cobalt, zinc, vanadium, tungsten, and molybdenum have been used in the remediation of diabetes.…”

Inhibition mechanism of alpha-amylase, a diabetes target, by a steroidal pregnane and pregnane glycosides derived from Gongronema latifolium Benth

“…The interaction analysis of the SPPs and reference acarbose showed that they have a close binding pattern as the native myricetin and interacted with the catalytic residues through hydrogen bonds and hydrophobic interactions. The acarbose structure conducted both hydrogen bonds and hydrophobic interactions with the active site residues of the target enzyme as reported in previous studies (Singla et al, 2016;Etsassala et al, 2020;Ogunyemi et al, 2020). The hydroxyl groups on C-20 and C-14 of the pregnane structure of the P1 donated hydrogen to the side chains of Glu233 and Asp300 of HPA, respectively, with bond distances less than 2.9 Å to form conventional hydrogen bonds.…”

In Silico Evaluation of Antidiabetic Activity and ADMET Prediction of Compounds from Musa acuminata Colla Peel

“…This prevents the postprandial glucose level from increasing, which plays a significant role in the development of cardiovascular diseases (Joshi et al 2015;Jiang et al 2017). Thus, there is an urgent need to discover AGI from plants since they are known sources of bioactive compounds (Etsassala et al 2020) and they are more accessible to people, especially to those who are in remote areas who use plants as their primary treatment (Singab et al 2014).…”