氧化应激
化学
芒果藤黄
丙二醛
药理学
髓过氧化物酶
肿瘤坏死因子α
超氧化物歧化酶
谷胱甘肽过氧化物酶
谷胱甘肽
刀豆蛋白A
NFKB1型
炎症
免疫学
生物化学
医学
转录因子
传统医学
基因
体外
酶
作者
Ahmed Shehata,Hossein M. Elbadawy,Sabrin R. M. Ibrahim,Gamal A. Mohamed,Wael M. Elsaed,Aisha Alhaddad,Naseer Ahmed,Hany M. Abo‐Haded,Dina S. El‐Agamy
出处
期刊:Plants
[MDPI AG]
日期:2022-09-19
卷期号:11 (18): 2441-2441
被引量:4
标识
DOI:10.3390/plants11182441
摘要
Alpha-mangostin (α-MN) is a xanthone obtained from Garcinia mangostana that has diverse anti-oxidative and anti-inflammatory potentials. However, its pharmacological activity against autoimmune hepatitis (AIH) has not been investigated before. Concanavalin A (Con A) was injected into mice to induce AIH and two doses of α-MN were tested for their protective effects against Con A-induced AIH. The results demonstrated the potent hepatoprotective activity of α-MN evidenced by a remarkable decrease of serum indices of the hepatic injury and amendment of the histological lesions. α-MN significantly attenuated the level and immuno-expression of myeloperoxidase (MPO) indicating a decrease in the neutrophil infiltration into the liver. Additionally, the recruitment of the CD4+ T cell was suppressed in the α-MN pre-treated animals. α-MN showed a potent ability to repress the Con A-induced oxidative stress evident by the reduced levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and protein carbonyl (PC), as well as the enhanced levels of antioxidants as the reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC). The ELISA, RT-PCR, and IHC analyses revealed that α-MN enhanced the sirtuin1/nuclear factor erythroid 2 related factor-2 (SIRT1/Nrf2) signaling and its downstream cascade genes concurrently with the inhibition of the nuclear factor kappa B (NF-κB) and the inflammatory cytokines (tumor necrosis factor-alpha and interleukine-6) signaling. Taken together, these results inferred that the hepatoprotective activity of α-MN could prevent Con A-induced AIH through the modulation of the SIRT1/Nrf2/NF-κB signaling. Hence, α-MN may be considered as a promising candidate for AIH therapy.
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