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米糠活性肽 KF-8 减轻 d-半乳糖诱导衰老小鼠的氧化应激

Active Peptide KF-8 from Rice Bran Attenuates Oxidative Stress in a Mouse Model of Aging Induced by d-Galactose.

机构信息

Molecular Nutrition Branch, National Engineering Laboratory for Rice and By-product Deep Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China.

出版信息

J Agric Food Chem. 2020 Nov 4;68(44):12271-12283. doi: 10.1021/acs.jafc.0c04358. Epub 2020 Sep 30.

Abstract

This study investigated the effects of a physiologically active peptide derived from rice bran (KF-8) on oxidative stress in d-galactose (d-gal)-induced aging mice and the underlying molecular mechanisms. The aging model was developed by subcutaneously injecting Institute of Cancer Research mice with 250 mg/kg d-gal daily for 12 weeks and simultaneously treating them with 30 mg/kg KF-8. The relative expression levels of Nrf2 and NF-κB in the liver were determined by the western blot. The regulation of Nrf2 and NF-κBp65 by KF-8 was further validated in NIH/3T3 cells. Compared with the control mice, the aging mice had significantly decreased body weights as well as superoxide dismutase and GSH-Px levels ( < 0.05); however, they had increased serum reactive oxygen species and malondialdehyde and 8-hydroxydeoxyguanosine levels accompanied by aortic and brain injuries. They also had elevated RAGE, TLR4, IκB, Bax, and caspase-8 expressions and NF-κB/p65 phosphorylation but reduced BcL-2 expression in the liver. Moreover, experiments demonstrated that the pretreatment of HO-treated NIH/3T3 cells with KF-8 significantly mitigated the NF-κB signaling and attenuated the Nrf2 nuclear transport (both < 0.05). In conclusion, KF-8 treatment inhibited aging-induced oxidative stress-related organ injury in mice by attenuating NF-κB/p38 signaling and preserving Nrf2 activity.

摘要

本研究探讨了来源于米糠的具有生理活性的肽(KF-8)对 D-半乳糖(D-gal)诱导的衰老小鼠氧化应激的影响及其潜在的分子机制。通过每周两次向 ICR 小鼠皮下注射 250mg/kg D-gal 建立衰老模型,同时用 30mg/kg KF-8 处理。通过 Western blot 测定肝脏中 Nrf2 和 NF-κB 的相对表达水平。在 NIH/3T3 细胞中进一步验证 KF-8 对 Nrf2 和 NF-κBp65 的调控作用。与对照组小鼠相比,衰老组小鼠体重明显减轻,超氧化物歧化酶和 GSH-Px 水平降低( < 0.05);然而,血清活性氧、丙二醛和 8-羟基脱氧鸟苷水平升高,伴有主动脉和脑组织损伤。肝脏中 RAGE、TLR4、IκB、Bax 和 caspase-8 表达升高,NF-κB/p65 磷酸化增强,BcL-2 表达降低。此外,实验表明,用 KF-8 预处理 HO 处理的 NIH/3T3 细胞可显著减轻 NF-κB 信号转导,减弱 Nrf2 核转运(均 < 0.05)。综上所述,KF-8 通过抑制 NF-κB/p38 信号通路和维持 Nrf2 活性,抑制衰老诱导的氧化应激相关的器官损伤。

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