Antidiabetic Flavonoids from Fruits of Morus alba Promoting Insulin-Stimulated Glucose Uptake via Akt and AMP-Activated Protein Kinase Activation in 3T3-L1 Adipocytes

Abstract

Morus alba (Moraceae), known as white mulberry, has been used to treat fever, protect against liver damage, improve eyesight, and lower blood sugar levels in traditional oriental medicine. Few studies have been conducted on the antidiabetic compounds identified from M. alba and their underlying mechanisms of action. Consequently, in this study, the fruits of M. alba were investigated for potential antidiabetic natural products using 3T3-L1 adipocytes. Phytochemical analysis of the ethanolic extract of M. alba fruits, followed by high-performance liquid chromatography (HPLC), purification led to the isolation of two main compounds: rutin and quercetin-3-O-β-d-glucoside (Q3G). Long-term use of available drugs for treating type 2 diabetes ((T2D) is often accompanied by undesirable side effects, which have generated increased interest in the development of more effective and safer antidiabetic agents. Examination of the isolated compounds, rutin and Q3G, for antidiabetic or anti-obesity properties or both in 3T3-L1 adipocytes demonstrated that they both improved glucose uptake via Akt-mediated insulin signaling pathway or AMP-activated protein kinase (AMPK) activation in 3T3-L1 adipocytes. The compounds also showed a positive effect on lipid accumulation in adipocytes, suggesting that glucose uptake occurred through activation of the Akt and AMPK signaling pathway without inducing adipogenesis. Taken together, our findings suggest that rutin and Q3G in M. alba fruits have the potential to induce fewer side effects such as weight gain, and these active compounds could be potential therapeutic candidates for the management of T2D.

Hypoglycemic and Antioxidant Properties of Extracts and Fractions from Polygoni Avicularis Herba

“…At present, antidiabetic drugs such as biguanides, sulfonylureas, meglitinides, thiazolidinediones, dipeptidyl peptidase IV inhibitors, and α -glucosidase inhibitors have many side effects, such as weight gain, hypoglycemia, gastrointestinal disorders, liver and kidney damage, and hypersensitivity reactions [ 15 ]. On the other hand, plants rich in certain types of flavonoids and other phenolics can exert a significant impact on diabetes via protecting pancreatic islet B cells, reducing the absorption of glucose in the digestive tract, and promoting glucose uptake in adipocytes [ 16 , 17 , 18 ]. Therefore, natural products from medicinal plants might have a good development prospect in the field of diabetes treatment.…”

Medicinal properties of Morus alba for the control of type 2 diabetes mellitus: a systematic review

“… 23 Both compounds, rutin, and quercetin-3-O-β-D-glucoside (Q3G), have been shown to enhance glucose uptake through the AKT-mediated insulin signaling pathway or AMP-activated protein kinase activation (AMPK) in 3T3L1 adipocytes and could potentially be used in therapy for T2DM management. 11 In addition to rutin, the leaves of Morus alba contain apigenin, quercetin-3-triglyceride, lupeol, β-sitosterol, moracetin, isoquercitrin, coumarin, volatile oil, alkaloids, amino acids, and organic acids, proving the hypoglycemic properties and their effect enhancer on diabetic nephropathy. 24 Four main chemical components were identified in the ethanol extract of Morus alba : chlorogenic acid, rutin, isoquercitrin, and quercitrin.…”

“…However, the studies carried out to date on the antidiabetic compounds in this product are insufficient. 11 …”

Rosinidin Flavonoid Ameliorates Hyperglycemia, Lipid Pathways and Proinflammatory Cytokines in Streptozotocin-Induced Diabetic Rats

“…These natural chemicals have a lot of pharmacological power. This subclass was chosen since numerous studies have revealed that such compounds possess a variety of beneficial properties, such as anti-diabetic, anti-oxidant, antitumor, cardioprotective and anti-inflammatory activities, in addition to anti-cancer, anti-allergy, anti-mutagenesis, antimicrobial and antiviral activities [ 5 ]. Flavonoids’ potential to alter the insulin signaling pathway in typical target tissues such as muscle, liver and adipose tissue has been shown in abundant scientific studies to help prevent or alleviate insulin resistance in diabetics [ 6 ].…”