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Berberine ameliorates methotrexate-induced liver injury by activating Nrf2/HO-1 pathway and PPARγ, and suppressing oxidative stress and apoptosis in rats.
Biomed Pharmacother. 2017 Oct; 94:280-291.BP

Abstract

Berberine (BBR) is a natural isoquinoline alkaloid with very impressive health benefits. It is one of the most effective natural supplements available; however, its ameliorative mechanism against methotrexate (MTX)-induced liver injury is not well defined. This study investigated the protective effect of BBR against MTX hepatotoxicity, focusing on its ability to attenuate oxidative stress and apoptosis and to activate nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling and peroxisome proliferator activated receptor gamma (PPARγ). Rats received BBR (25 and 50mg/kg) orally for 7days before MTX injection. Other groups received MTX followed by BBR (25 and 50mg/kg) orally for 7 days. MTX-induced rats showed significant body weight loss, increased serum liver function marker enzymes, bilirubin and tumor necrosis factor alpha (TNF-α). Liver lipid peroxidation, nitric oxide (NO) and caspase-3 were significantly increased following MTX administration. BBR supplemented either before or after MTX significantly ameliorated body weight, liver function markers, TNF-α, lipid peroxidation, NO and caspase-3. BBR increased serum albumin and liver antioxidant defenses in MTX-induced rats. Histological and immunohistochemical examination showed improved histological structure and decreased expression of Bax in liver of MTX-induced rats treated with BBR. In addition, BBR up-regulated Nrf2, HO-1 and PPARγ expression in the liver of MTX-induced rats. In conclusion, BBR attenuated MTX-induced oxidative stress and apoptosis, possibly through up-regulating Nrf2/HO-1 pathway and PPARγ. Therefore, BBR can protect against MTX-induced liver injury.

Authors+Show Affiliations

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Egypt. Electronic address: ayman.mahmoud@science.bsu.edu.eg.Biochemistry Division, Chemistry Department, Faculty of Science, Beni-Suef University, Egypt; Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Egypt.Biochemistry Division, Chemistry Department, Faculty of Science, Beni-Suef University, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28763751

Citation

Mahmoud, Ayman M., et al. "Berberine Ameliorates Methotrexate-induced Liver Injury By Activating Nrf2/HO-1 Pathway and PPARγ, and Suppressing Oxidative Stress and Apoptosis in Rats." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 94, 2017, pp. 280-291.
Mahmoud AM, Hozayen WG, Ramadan SM. Berberine ameliorates methotrexate-induced liver injury by activating Nrf2/HO-1 pathway and PPARγ, and suppressing oxidative stress and apoptosis in rats. Biomed Pharmacother. 2017;94:280-291.
Mahmoud, A. M., Hozayen, W. G., & Ramadan, S. M. (2017). Berberine ameliorates methotrexate-induced liver injury by activating Nrf2/HO-1 pathway and PPARγ, and suppressing oxidative stress and apoptosis in rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 94, 280-291. https://doi.org/10.1016/j.biopha.2017.07.101
Mahmoud AM, Hozayen WG, Ramadan SM. Berberine Ameliorates Methotrexate-induced Liver Injury By Activating Nrf2/HO-1 Pathway and PPARγ, and Suppressing Oxidative Stress and Apoptosis in Rats. Biomed Pharmacother. 2017;94:280-291. PubMed PMID: 28763751.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Berberine ameliorates methotrexate-induced liver injury by activating Nrf2/HO-1 pathway and PPARγ, and suppressing oxidative stress and apoptosis in rats. AU - Mahmoud,Ayman M, AU - Hozayen,Walaa G, AU - Ramadan,Shimaa M, Y1 - 2017/07/29/ PY - 2017/07/05/received PY - 2017/07/20/revised PY - 2017/07/20/accepted PY - 2017/8/2/pubmed PY - 2018/5/19/medline PY - 2017/8/2/entrez KW - Apoptosis KW - Berberine KW - Methotrexate KW - Nrf2 KW - Oxidative stress KW - PPAR SP - 280 EP - 291 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 94 N2 - Berberine (BBR) is a natural isoquinoline alkaloid with very impressive health benefits. It is one of the most effective natural supplements available; however, its ameliorative mechanism against methotrexate (MTX)-induced liver injury is not well defined. This study investigated the protective effect of BBR against MTX hepatotoxicity, focusing on its ability to attenuate oxidative stress and apoptosis and to activate nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling and peroxisome proliferator activated receptor gamma (PPARγ). Rats received BBR (25 and 50mg/kg) orally for 7days before MTX injection. Other groups received MTX followed by BBR (25 and 50mg/kg) orally for 7 days. MTX-induced rats showed significant body weight loss, increased serum liver function marker enzymes, bilirubin and tumor necrosis factor alpha (TNF-α). Liver lipid peroxidation, nitric oxide (NO) and caspase-3 were significantly increased following MTX administration. BBR supplemented either before or after MTX significantly ameliorated body weight, liver function markers, TNF-α, lipid peroxidation, NO and caspase-3. BBR increased serum albumin and liver antioxidant defenses in MTX-induced rats. Histological and immunohistochemical examination showed improved histological structure and decreased expression of Bax in liver of MTX-induced rats treated with BBR. In addition, BBR up-regulated Nrf2, HO-1 and PPARγ expression in the liver of MTX-induced rats. In conclusion, BBR attenuated MTX-induced oxidative stress and apoptosis, possibly through up-regulating Nrf2/HO-1 pathway and PPARγ. Therefore, BBR can protect against MTX-induced liver injury. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/28763751/Berberine_ameliorates_methotrexate_induced_liver_injury_by_activating_Nrf2/HO_1_pathway_and_PPARγ_and_suppressing_oxidative_stress_and_apoptosis_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)33295-X DB - PRIME DP - Unbound Medicine ER -