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KSFY06 可预防 D-Gal/LPS 诱导的小鼠急性肝损伤中的炎症反应和氧化应激。

KSFY06 Prevents Inflammatory Response and Oxidative Stress in Acute Liver Injury Induced by D-Gal/LPS in Mice.

机构信息

Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing 400067, People's Republic of China.

Chongqing Engineering Research Center of Functional Food, Chongqing University of Education, Chongqing 400067, People's Republic of China.

出版信息

Drug Des Devel Ther. 2021 Jan 6;15:37-50. doi: 10.2147/DDDT.S286104. eCollection 2021.

DOI:10.2147/DDDT.S286104
PMID:33442235
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7797359/
Abstract

AIM

The purpose of this study is to investigate the preventive effect of KSFY06 (LP-KSFY06) on D-galactose/lipopolysaccharide (D-Gal/LPS)-induced acute liver injury (ALI) in mice.

METHODS

We evaluated the antioxidant capacity of LP-KSFY06 in vitro, detailed the effects of LP-KSFY06 on the organ index, liver function index, biochemical index, cytokines, and related genes, and noted the accompanying pathological changes.

RESULTS

The results clearly showed that LP-KSFY06 can remove 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzthiazoline -6-sulphonic acid) diammonium salt (ABTS) free radicals in vitro. The analysis of the organ index and pathology demonstrated that LP-KSFY06 significantly prevented ALI. Biochemical and molecular biological analysis showed that LP-KSFY06 prevented a decrease in the antioxidant-related levels of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC), and also prevented an increase in aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) levels. LP-KSFY06 upregulated the anti-inflammatory factor interleukin (IL)-10 and downregulated the pro-inflammatory factors IL-6, IL-1β, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). These oxidative and inflammatory indicators were consistent with the results of gene detections. Furthermore, we determined that LP-KSFY06 downregulated Keap1, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), IL-18, and mitogen-activated protein kinase 14 (MAPK14 or p38), upregulated Nrf2, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase [quinone] 1 (NQO1), B-cell inhibitor-α (IκB-α), and thioredoxin (Trx) mRNA expression. These may be related to the regulation of the Kelch-like ECH-associated protein-1 (Keap1)-nuclear factor-erythroid-2-related factor (Nrf2)/antioxidant response element (ARE) and NLRP3/NF-κB pathways.

CONCLUSION

LP-KSFY06 is an effective multifunctional with strong anti-oxidant and anti-inflammatory ability that can prevent D-gal/LPS-induced ALI in mice and assist in maintaining health.

摘要

目的

本研究旨在探讨 KSFY06（LP-KSFY06）对 D-半乳糖/脂多糖（D-Gal/LPS）诱导的急性肝损伤（ALI）小鼠的预防作用。

方法

我们评估了 LP-KSFY06 的体外抗氧化能力，详细阐述了 LP-KSFY06 对器官指数、肝功能指数、生化指标、细胞因子和相关基因的影响，并观察了伴随的病理变化。

结果

结果清楚地表明，LP-KSFY06 可以清除 1,1-二苯基-2-苦基肼基（DPPH）和 2,2'-联氮-双（3-乙基苯并噻唑啉-6-磺酸）二铵盐（ABTS）自由基。器官指数和病理学分析表明，LP-KSFY06 显著预防了 ALI。生化和分子生物学分析表明，LP-KSFY06 可预防抗氧化相关水平超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶（CAT）和总抗氧化能力（T-AOC）的降低，并可预防天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、丙二醛（MDA）、髓过氧化物酶（MPO）和一氧化氮（NO）水平的升高。LP-KSFY06 上调抗炎因子白细胞介素（IL）-10，并下调促炎因子白细胞介素（IL）-6、白细胞介素（IL）-1β、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）。这些氧化和炎症指标与基因检测结果一致。此外，我们确定 LP-KSFY06 下调 Kelch 样 ECH 相关蛋白 1（Keap1）、NLRP3、凋亡相关斑点样蛋白含有 CARD（ASC）、半胱氨酸天冬氨酸蛋白酶 1（caspase-1）、核因子κ轻链增强子的 B 细胞（NF-κB）、白细胞介素（IL）-18 和丝裂原激活蛋白激酶 14（MAPK14 或 p38），上调核因子红细胞 2 相关因子 2（Nrf2）、血红素加氧酶 1（HO-1）、NAD（P）H 醌氧化还原酶 1（NQO1）、B 细胞抑制剂-α（IκB-α）和硫氧还蛋白（Trx）mRNA 表达。这些可能与 Kelch 样 ECH 相关蛋白 1（Keap1）-核因子-红细胞 2 相关因子（Nrf2）/抗氧化反应元件（ARE）和 NLRP3/NF-κB 通路的调节有关。

结论

LP-KSFY06 是一种有效的多功能药物，具有强大的抗氧化和抗炎能力，可预防 D-半乳糖/脂多糖（D-Gal/LPS）诱导的急性肝损伤（ALI）小鼠，并有助于维持健康。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b277/7797359/d056b15d875b/DDDT-15-37-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b277/7797359/f8573750789d/DDDT-15-37-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b277/7797359/e7acaf46e892/DDDT-15-37-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b277/7797359/ff51e94bb3a0/DDDT-15-37-g0005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b277/7797359/d81de8f728ce/DDDT-15-37-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b277/7797359/d056b15d875b/DDDT-15-37-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b277/7797359/d056b15d875b/DDDT-15-37-g0008.jpg

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