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 a high rate of mortality worldwide. It is well known that insulin resistance and deficiency in insulin production from pancreatic β-cells are the main characteristics 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, reducing the postprandial rise of plasma glucose, which can reduce the risk of long-term diabetes complications. Furthermore, natural products are well-known sources for the discovery of new bioactive compounds that can serve as scaffolds for drug discovery, including that of new antidiabetic drugs. The phytochemical investigation of Salvia aurita collected from Hogobach Pass, Eastern Cape Province, 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 the half maximal inhibitory concentration (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 values of 16.2 ± 0.3 and 19.8 ± 1.4 µg/mL. Molecular docking analysis confirms the strong inhibitory activity of 3 against alpha-glucosidase. Additionally, excellent antioxidant capacities were displayed by 2, 1, and 3, respectively, with oxygen radical absorbance capacity (ORAC) (25.79 ± 0.01; 23.96 ± 0.01; 23.94 ± 0.02) mM Trolox equivalent (TE)/g; 1 and 2 as ferric-ion reducing antioxidant power (FRAP) (3.92 ± 0.002; 1.52 ± 0.002) mM ascorbic acid equivalent (AAE)/g; 5 and 2 as Trolox equivalent absorbance capacity (TEAC) (3.19 ± 0.003; 2.06 ± 0.003) mM TE/g. The methanolic extract of S. aurita is a rich source of abietane diterpenes with excellent antioxidant and antidiabetic 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 the alpha-glucosidase and alpha-amylase inhibitory activities of Salvia aurita.

Effect Of Fruit And Cork Extract Of Ficus Lacor Buch Ham On α/β -Glucosidase, α -Amylase, Lipase, Glucose Absorption And Uptake

“…The common approach used to maintain blood glucose level within normal range is targeting the enzymes responsible for metabolism of carbohydrates which may elevate blood glucose level. 28 αglucosidase, β-glucosidase and α-amylase are the enzymes responsible for metabolism of polysaccharides to glucose molecules which increases absorption of glucose responsible for hyperglycemia in diabetes mellitus. 29,30 Metabolism of lipids by lipase enzyme was also studied as dyslipidemia is common with diabetes mellitus.…”

Salvia Species as Nutraceuticals: Focus on Antioxidant, Antidiabetic and Anti-Obesity Properties

“…leiocalycina and S.verticillata subsp. amasiaca [27,51,53,58,63,64,[87][88][89], which in some cases were even more effective than the antidiabetic pharmaceutical drug acarbose (Table 3). In these studies, the authors have essentially correlated this ability with the phenolic constituents of the extracts; e.g., a strong correlation (r = 0.995) was found for the contents of caffeic acid and of caffeic acid derivatives (ranging from 20.8 to 74.1 mg/g extract), in aqueous extracts of S. officinalis, S. elegans and S. greggii, and α-glucosidase inhibition [27].…”

“…In addition to caffeic acid derivatives and flavonoids, some authors also underlined the efficacy of phenolic terpenoids from sage origin to inhibit α-glucosidase and/or αamylase [63,64]. In particular, 7-methoxyrosmanol and rosmanol purified from S. aurita, were reported to be potent α-glucosidase inhibitory agents (IC 50 of 4.2 and 16.4 µg/mL, respectively), while 12-methoxycarnosic acid and carnosol actively inhibited α-amylase (IC 50 of 16.2 and 19.8 µg/mL, respectively) [64].…”

“…In addition to caffeic acid derivatives and flavonoids, some authors also underlined the efficacy of phenolic terpenoids from sage origin to inhibit α-glucosidase and/or αamylase [63,64]. In particular, 7-methoxyrosmanol and rosmanol purified from S. aurita, were reported to be potent α-glucosidase inhibitory agents (IC 50 of 4.2 and 16.4 µg/mL, respectively), while 12-methoxycarnosic acid and carnosol actively inhibited α-amylase (IC 50 of 16.2 and 19.8 µg/mL, respectively) [64]. Note that phenolic diterpenic compounds have been also claimed to act as antidiabetic agents by several other mechanisms, such as by reversing insulin resistance, modulating mediators of the insulin signaling pathway, promoting glycogen synthesis, inhibiting glycogen degradation, decreasing free fatty acids, inhibition of gluconeogenesis and decreasing blood glucose levels [82,83].…”

“…In particular, the authors described a strong activity of 19-acetoxy-12-methoxycarnosic acid and clinopodiolides A on ORAC (1.5and 1.7-fold that of the reference antioxidant epigallocatechingallate, respectively), and a high antioxidant potential of 3b-acetoxy-7a-methoxyrosmanol and clinopodiolides A on FRAP (about 3.3-fold that of the control). The same group of researchers [64] demonstrated that rosmanol, carnosol and 7-methoxyrosmanol exerted excellent scavenging abilities for peroxyl radicals, as estimated by ORAC assay (six times higher than those of the reference commercial compound), while carnosol and rosmanol also exerted high antioxidant capacity in FRAP, and in 4,7-dimethylapigenin and rosmanol with TEAC.…”