Andaliman (Zanthoxylum acanthopodium DC.) fruit ethanolic extract exerts attenuative effect on hyperglycemia, sensory and motoric function's disorders in alloxan-induced diabetic mice

Abstract

Objective: Andaliman (Zanthoxylum acanthopodium) is a potent medicinal plant in Asia. This present study aimed to reveal the effectivity of Andaliman fruit extract in alleviating hyperglycemia, sensory and motoric balance disorders, histopathology of the cerebellum, and tissue oxidative stress in diabetic mice induced by alloxan.

Materials and methods: Diabetes induction was performed by intraperitoneally injecting alloxan monohydrate [200 mg/kg body weight (BW)]. Subsequently, the mice were treated daily with an ethanolic extract of Andaliman fruit (0, 150, 300, 450 mg/kg BW per oral) for 28 days, followed by measurements of blood glucose, paw sensitivity, motoric balance, histopathology of the cerebellum, and malondialdehyde (MDA) levels. Moreover, the phytochemical constituents of the extract were elucidated by liquid chromatography.

Results: Higher doses of Andaliman fruit extract could significantly attenuate the elevation of random and fasting blood glucose (p < 0.05) and improve paw sensitivity responses (p < 0.05) and motoric balances (p < 0.05) in diabetic mice. Moreover, Andaliman fruit extract could significantly attenuate the degeneration of cerebellar Purkinje cells (p < 0.05) and suppress MDA levels in the blood (p < 0.05) while blunting the MDA in the brain tissue (p < 0.05). Phytochemical screening revealed 39 compounds in the Andaliman extract belonging to the groups of alkaloids (26 compounds), flavonoids (12 compounds), and terpenoids (1 compound).

Conclusion: The ethanolic extract of Andaliman fruit is capable of ameliorating diabetic neuropathy, motor balance disorders, and Purkinje cell degeneration while also reducing oxidative stress in the peripheral system. Hence, Andaliman extract is a promising candidate for formulation as an herbal remedy against the detrimental outcomes of diabetes mellitus.

Keywords: Alkaloids; diabetes mellitus; diabetic neuropathy; herbal remedies; malondialdehyde.

Figure 1.. Effect of Andaliman fruit ethanolic extract on the levels of blood glucose and BW changes of mice. (A) The levels of nonfasting blood glucose, (B) fasting blood glucose, and (C) BW of mice. Non-DM (nondiabetic; healthy mice), DM (diabetic mice), Ext (extract), and lowercase letters depicted above each bar show statistical differences (p < 0.05).

Figure 2.. Effect of Andaliman fruit ethanolic extract on response latency of paw against hot plate in mice. Lowercase letters depicted above each bar show statistical differences (p < 0.05).

Figure 3.. Effect of Andaliman fruit extract on motoric balance in mice. (A) Time needed to cross the balance beam and (B) frequency of falling from the rotarod. Lowercase letters depicted above each bar show statistical differences (p < 0.05).

Figure 4.. Effect of Andaliman fruit extract on histology of cerebellum in mice. M (molecular layer), G (Granular layer), black arrows (normal Purkinje cells), and red arrows (degenerated Purkinje cells). Tissues were stained with HE.

Figure 5.. Effect of extract of Andaliman fruit on cerebellar Purkinje cells and MDA concentration in the brain tissue and blood plasma of mice. (A) Percentage of degenerated Purkinje cells in the cerebellum, (B) MDA concentration in the cerebellar tissue, and (C) MDA concentration in the blood plasma. Lowercase letters depicted above each bar show statistical differences (p < 0.05).