Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Ursolic acid mitigates cognitive dysfunction through amelioration of oxidative stress, inflammation and apoptosis in diabetic rats

Liu Xianchu^1,2, Liu Kang¹, Peng Huan³, Liu Ming¹

¹College of Life Science, Hunan University of Arts and Science, 415000, Changde; ²Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, Hunan Normal University, Changsha 410081; ³Department of Hematology, Xiangya Changde Hospital, Changde 415000, PR China.

For correspondence:-

Accepted: 18 March 2021 Published: 30 April 2021

Citation: Xianchu L, Kang L, Huan P, Ming L. Ursolic acid mitigates cognitive dysfunction through amelioration of oxidative stress, inflammation and apoptosis in diabetic rats. Trop J Pharm Res 2021; 20(4):803-807 doi: 10.4314/tjpr.v20i4.21

© 2021 The authors.
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Abstract

Purpose: To determine the effect of ursolic acid (UA) on diabetes-induced cognitive defect, as well as its mechanism of action in streptozotocin (STZ) -induced diabetic rats.

Methods: A rat model of diabetes was established by administration of STZ. The rats received UA via gastric perfusion for 56 successive days. Learning and memory functions were assessed using Morris water maze. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in hippocampus tissues were determined spectrophotometrically. Tumor necrosis factor-a (TNF-a), interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were assayed by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The protein expression levels of nuclear factor erythroid-2-related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), Bcl-2 and Bax were evaluated by western blotting.

Results: Learning and memory impairment in STZ-induced diabetic rats was mitigated by UA (p < 0.05). In hippocampus tissue, UA reduced oxidative stress by enhancing SOD activity and reducing MDA levels. Furthermore, UA reduced inflammatory response by downregulating TNF-α, IL-1β and IL-6 levels (p < 0.05). Concomitantly, the lower protein concentrations of Nrf-2 and HO-1 were elevated by administration of UA. Furthermore, UA suppressed Bax/Bcl-2 ratio to ameliorate apoptosis (p < 0.05).

Conclusion: UA reduces diabetes-induced hippocampal oxidative stress, inflammation and apoptosis. Thus, it might be a potential drug candidate for delaying diabetes-associated cognitive decline (DACD).

Keywords: Apoptosis, Cognitive dysfunction, Inflammation, Oxidative stress, Ursolic acid