Study on the toxicity and in vitro and in vivo antidiabetic activities of Miliusa velutina stem bark ethanolic extract

• First report on antidiabetic effects of Miliusa velutina stem bark extract • LC-HRMS identified 19 bioactive compounds including flavonoids and phenolics • The extract showed strong antioxidant and enzyme inhibitory activities in vitro • In vivo , the extract reduced glucose and lipid levels in diabetic mice • Sub-chronic dosing (400 mg/kg, 150 days) showed no major toxicity in mice. The extracts from Miliusa velutina have been recently demonstrated to possess a range of biological activities. This study aimed to (i) identify the major bioactive compounds in M. velutina stem bark, (ii) evaluate their in vitro antioxidant, anti-inflammatory, and antidiabetic activities, and (iii) investigate the in vivo antidiabetic and toxicity profile in animal models. The M. velutina stem bark extract (MVSBE) exhibited the highest content of total polyphenols and flavonoids, significantly exceeding those found in the flower extract. Consequently, MVSBE demonstrated notable antioxidant, anti-inflammatory, and enzyme inhibitory properties, indicating its biological effectiveness. MVSBE was subsequently selected for testing its antidiabetic activity on alloxan monohydrate-induced diabetic mice. Remarkably, MVSBE effectively controlled diabetes and its complications in vivo . MVSBE strongly inhibited glucose-6-phosphatase activity, thereby reducing blood glucose levels. It significantly reduced triglycerides, cholesterol, LDL cholesterol, VLDL cholesterol, while increased HDL cholesterol. It helped to protect organs by reducing alanine transaminase (ALT) and aspartate transaminase (AST) in liver, reducing oxidative stress in liver, kidney, pancreas, heart and muscle organs based on its ability to reduce malondialdehyde (MDA) and increase glutathione (GSH). Sub-chronic administration of MVSBE at the tested dose was generally well tolerated in mice, without evidence of severe toxicity. The results from this study showed that stem bark extract of M. velutina can be a potential source for the development of antidiabetic drugs.