Apigenin alleviates diabetic endothelial dysfunction through activating AMPK/PI3K/Akt/eNOS and Nrf2/HO-1 signaling pathways

 Food Frontiers, 4(1) 420-431 (2023)

Apigenin (4′,5,7-trihydroxyflavone) is a natural flavone reported to present anti-diabetic and anti-oxidative bioactivities. The effect of apigenin to mitigate endothelial dysfunction in diabetes remains to be investigated. In the present study, the vaso-protective effect of apigenin as well as its underlying action mechanisms was investigated using in vitro- and in vivo-based assays. Aortas were detached from C57BL/6J mice for ex vivo treatment, and primary rat aortic endothelial cells (RAECs) were cultured and further stimulated using high glucose (HG) with or without apigenin. In-vivo diabetic model was established by feeding male C57BL/6J mice with a high-fat diet (60% kcal% fat) for a total of 14 weeks, whereas the treatment group was orally administered apigenin (25 mg/kg/day) during the last 4 weeks. Exposure to HG (30 mM, 48 h) impaired acetylcholine-induced endothelium-dependent relaxation (EDR) in mouse aortas and induced oxidative stress with the downregulation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/phosphatidyl inositol 3-kinase (PI3K)/protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling pathways in aortas and RAECs. These impairments were reversed by apigenin treatments. However, the vaso-protective effects of apigenin were abolished by Compound C (AMPK inhibitor) and wortmannin (PI3K inhibitor). Chronic oral administration with apigenin ameliorated EDR and reduced oxidative stress in the aortas of high-fat diet (HFD)-induced obese and diabetic mice. In conclusion, this study revealed that apigenin improved endothelial function and suppressed oxidative stress in the vasculature in diabetes through the activation of AMPK/PI3K/Akt/eNOS and Nrf2/HO-1 pathways, suggesting its therapeutic potential as a natural dietary flavonoid against vascular diseases associated with diabetes.

Hypoglycaemic effect of total alkaloids extracted from Sambucus wightiana Wall. ex Wight & Arn. in streptozotocin-nicotinamide induced diabetic rats

 South African J Bot. 154, 330-355, 2023

Diabetes mellitus is the most prevalent metabolic disease, and almost 1200 plants are reported with hypoglycaemic potential. Some of these plants are scientifically proven for the hypoglycaemic and antidiabetic effects. This study was designed to assess the hypoglycaemic effect of Sambucus wightiana Wall. ex Wight & Arn. extract in streptozotocin-nicotinamide induced diabetic Wistar Albino rats. An acute toxicity study was performed to establish the safe dose of total alkaloids extracted from S. wightiana (TASW). TASW was administered orally (50 mg, 100 mg, and 200 mg/kg body weight per day) to diabetic rats for 21 days. Fasting blood glucose level was determined, along with other associated parameters that may fluctuate in diabetes, consisting of the lipid profile, body weight, serum liver marker enzymes and Hb level. The test groups that were administered TASW at three different doses showed a marked reduction in hyperglycaemia when compared to the control group. Moreover, body weight and food intake improved among test group animals. Administration of TASW also reduced the levels of triglycerides, cholesterol and LDL while increasing HDL and Hb levels. Serum liver enzyme activity is generally increased in diabetes, and this was reduced after dosing with TASW. The findings of this study elucidate that the total alkaloids extracted from S. wightiana are not toxic at the tested doses, and present potential hypoglycaemic activity.

Starch-digesting product analysis based on the hydrophilic interaction liquid chromatography coupled mass spectrometry method to evaluate the inhibition of flavonoids on pancreatic α-amylase

 Food Chem. 372, 131175, 2022

An accurate hydrophilic interaction liquid chromatography coupled mass spectrometry (HILIC-MS) method is presented to characterize starch digestion by α-amylase and measure the inhibition properties of flavonoids against α-amylase in vitro. Eleven products were found as 1 → 4 linkage glucose oligosaccharides with different degrees of polymerization (DPs) from 2 to 12. The products with DPs of 2, 3, 6, 7, and 9 had higher yields. The product with DP of 9 had the highest yields, which first increased and then decreased with the reaction time. Pelargonidin has the best inhibition activity on all enzyme products. The 3′-hydroxyl of B-ring enhanced the inhibition activity of flavonol and flavone but weakened that of anthocyanin. The C-ring 3-hydroxyl increased the inhibition effect of flavonol on maltose but decreased that on the products with higher DPs than flavone. The HILIC-MS method can provide more detailed information on enzyme products for the study of flavonoids inhibiting α-amylase.