The flower of Hagenia abyssinica (Rosaceae) has been used in traditional health systems to treat diabetes mellitus in Ethiopia and Tanzania. However, the antidiabetic activity of this medicinal plant is not scientifically validated and authenticated. The present study aimed to investigate the in vitro and in vivo anti-diabetic activity of flower crude extract and solvent fractions of Hagenia abyssinica. Methods: The in vitro α–amylase inhibition and antioxidant activity of the crude extract and solvent fractions of Hagenia abyssinica were evaluated by using 3,5-dinitrosalicylic acid (DNSA) and diphenyl-2-picrylhydrazyl (DPPH) assay model, respectively. Blood glucose lowering activity of 80% methanolic flower crude extract and solvent fraction was studied in four animal models: normoglycemic mice model, oral glucose loaded mice model, single dose-treated streptozotocin-induced diabetic mice model, and repeated dose-treated streptozotocin-induced diabetic mice model. The effect of the crude extract and solvent fraction of Hagenia abyssinica on diabetic lipid profile and body weight was also studied. Results: The acute toxicity study of Hagenia abyssinica flower extract did not show mortality in the animals at the limit dose of 2g/kg during the observation period. The result of α–amylase enzyme inhibition activity was found in a dose-dependent manner, the strongest activity was shown by ethyl acetate fraction (54.23% inhibition at 800 μg/mL) compared to the standard acarbose having 91.87% inhibition at 800 μg/mL. Among these extracts, the crude extract had the highest antioxidant activity (58.38% inhibition at 500 μg/mL). The crude extract of H. abyssinica showed significant blood glucose-lowering effect on normoglycemic mice and oral glucose loaded mice. In streptozotocin-induced diabetic mice model, the crude extract and ethyl acetate fraction significantly decreased the fasting blood glucose level after 14 days of treatment. There were significant reductions in serum total cholesterol, serum triglycerides, very low-density lipoprotein, and low-density lipoprotein. However, there were significant increments in body weight and high-density lipoprotein as compared to untreated diabetic mice. Conclusion: The result demonstrated the beneficial biochemical effects of Hagenia abyssinica extract by inhibiting α–amylase, scavenging diphenyl-2-picrylhydrazyl (DPPH) and improving serum lipid profile levels. The flower crude extract and solvent fractions of Hagenia abyssinica are effective in lowering blood glucose levels in diabetic and normoglycemic mice. The claimed traditional use as antidiabetic has scientific ground. Keywords: antidiabetic, anti-hyperlipidemic, antioxidant, α-amylase, Hagenia abyssinica, streptozotocin Correspondence: Zemene Demelash Kifle University of Gondar, College of Medicine and Health Sciences, School of Pharmacy, Department of Pharmacology, Gondar, Ethiopia

Abstract

The flower of Hagenia abyssinica (Rosaceae) has been used in traditional health systems to treat diabetes mellitus in Ethiopia and Tanzania. However, the antidiabetic activity of this medicinal plant is not scientifically validated and authenticated. The present study aimed to investigate the in vitro and in vivo anti-diabetic activity of flower crude extract and solvent fractions of Hagenia abyssinica. Methods: The in vitro α–amylase inhibition and antioxidant activity of the crude extract and solvent fractions of Hagenia abyssinica were evaluated by using 3,5-dinitrosalicylic acid (DNSA) and diphenyl-2-picrylhydrazyl (DPPH) assay model, respectively. Blood glucose lowering activity of 80% methanolic flower crude extract and solvent fraction was studied in four animal models: normoglycemic mice model, oral glucose loaded mice model, single dose-treated streptozotocin-induced diabetic mice model, and repeated dose-treated streptozotocin-induced diabetic mice model. The effect of the crude extract and solvent fraction of Hagenia abyssinica on diabetic lipid profile and body weight was also studied. Results: The acute toxicity study of Hagenia abyssinica flower extract did not show mortality in the animals at the limit dose of 2g/kg during the observation period. The result of α–amylase enzyme inhibition activity was found in a dose-dependent manner, the strongest activity was shown by ethyl acetate fraction (54.23% inhibition at 800 μg/mL) compared to the standard acarbose having 91.87% inhibition at 800 μg/mL. Among these extracts, the crude extract had the highest antioxidant activity (58.38% inhibition at 500 μg/mL). The crude extract of H. abyssinica showed significant blood glucose-lowering effect on normoglycemic mice and oral glucose loaded mice. In streptozotocin-induced diabetic mice model, the crude extract and ethyl acetate fraction significantly decreased the fasting blood glucose level after 14 days of treatment. There were significant reductions in serum total cholesterol, serum triglycerides, very low-density lipoprotein, and low-density lipoprotein. However, there were significant increments in body weight and high-density lipoprotein as compared to untreated diabetic mice. Conclusion: The result demonstrated the beneficial biochemical effects of Hagenia abyssinica extract by inhibiting α–amylase, scavenging diphenyl-2-picrylhydrazyl (DPPH) and improving serum lipid profile levels. The flower crude extract and solvent fractions of Hagenia abyssinica are effective in lowering blood glucose levels in diabetic and normoglycemic mice. The claimed traditional use as antidiabetic has scientific ground. Keywords: antidiabetic, anti-hyperlipidemic, antioxidant, α-amylase, Hagenia abyssinica, streptozotocin Correspondence: Zemene Demelash Kifle University of Gondar, College of Medicine and Health Sciences, School of Pharmacy, Department of Pharmacology, Gondar, Ethiopia Tel +251918026724