Mangiferin exerts neuroprotective activity against lead-induced toxicity and oxidative stress via Nrf2 pathway
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摘要:
Abstract:
Objective: The study was designed to assess the beneficial role of mangiferin (MGN) in lead (Pb)-induced neurological damages in the activation of Nrf2-governed enzymes, genes and proteins. Methods: A total of 96 weaned Wistar rats (48 males and 48 females, 26- to 27-day-old), weighing 50?80 g were used. The experiment was performed in six groups: normal group (control, n = 16), model group (chronic Pb exposed, n = 16), Dimercaptosuccinic acid (DMSA)-treated group (positive control, Pb + DMSA, n = 16), three MGN-treated groups with different doses (Pb + MGN, n = 48). Normal group freely had access to purified water. DMSA-treated group was given DMSA, which was clinically used as the standard treatment for moderate Pb poisoning, at 50 mg/kg (2 mL suspension with purified water) by intragastric gavage (ig) 4 continual days a week for 4 weeks, MGN-treated groups were given MGN at 50, 100, or 200 mg/kg (2 mL suspension with purified water) by ig daily for 4 weeks. At the end of the treatment, all rats were sacrificed and the brain samples were collected. The haematoxylin and eosin (H&E) staining was used for observation of histopathology. Commercial kit, real-time quantitative poly- merase chain reaction (RT-qPCR), Western-blot and immunohistochemistry (IHC) detection were used to detect the mRNA and protein expression. Results: Eight weeks exposure to Pb-containing water resulted in pathological alterations, anti-oxidative system disorder in the brain, all of which were blocked by MGN in a Nrf2-dependent manner. Nrf2 down- stream enzymes such as HO-1, NQO1, γ -GCS were activated. Nrf2, GCLC, GCLM, HO-1 mRNA and total Nrf2, Nuclear Nrf2, γ -GCS, HO-1 protein expression were affected too. Conclusion: MGN ameliorated morphological damage in the hippocampus. Its neuroprotective effects were achieved by the activation of the Nrf2 downstream genes. The data from this in vitro study indi- cates that MGN targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with Pb exposure. Thus, MGN could be an effective candidate agent for the Pb-induced oxidative stress and neurotoxicity in the human body.
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This study was supported by grants from Guangxi Natural Science Foundation Program (No. 2014GXNSFBA118153); Science and Technology Basic Condition Platform of Guangxi Zhuang Au- tonomous Region, Republic of China (No. 10-046-04); Natural Sci- ence Foundation of Guangxi University of Chinese Medicine (No. 2015MS016); Guangxi Natural Science Foundation Program (Nos. 2016GXNSFBA380200, 2016JJA140513).
Hao-wen Li a, c,d, Tai-jin Lan b, d, Chen-xia Yun b, Ke-di Yang c, Zheng-cai Du d, Xue-fei Luo e, Er-wei Hao d, Jia-gang Deng d. Mangiferin exerts neuroprotective activity against lead-induced toxicity and oxidative stress via Nrf2 pathway[J]. Chinese Herbal Medicines (CHM),2020,12(1):36-46
