INTERNATIONAL IMMUNOPHARMACOLOGY
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2018
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IF 3.118
Zheng Li,Haihua Feng,Yue Wang,Bingyu Shen,Ye Tian,Lin Wu,Qiaoling Zhang,Meiyu Jin,Guowen Liu
Rosmarinic acid (RA) has antioxidation, anticancer, antibacterial, anti-inflammatory and various biological functions. In our study, we aim to evaluate effects of RA on acute liver injury caused by LPS and d -galactosamine ( d -GalN) and its underlying molecular mechanism in mice. Our findings showed that RA could protect C57BL/6 mice from LPS/ d -GalN-induced acute liver injury, which not only reflected on declining aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of the serum, but also restrained the phosphorylation of nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinase (ERK1/2) and p38 protein expression and the content of tissue myeloperoxidase (MPO) elevation. Moreover, RA could enhance the level of glutathione-dependent peroxidase (GSH-PX). Furthermore, RA promoted that nuclear factor erythroid-2-related factor 2 (Nrf2) transported into nucleus, and then up-regulated heme oxygenase 1 (HO-1), glutamate-cysteine ligase catalytic (GCLC), glutamate cysteine ligase modifier (GCLM) and quinone oxidoreductase (NQO1). These results indicated that RA could protect the mice from acute liver injury induced by LPS/ d -GalN.
研究领域:
药理学
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肝病学
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免疫学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2024
·Vol. 25
·期 23
·12844
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IF 4.9
Zhining Gao,Haoyang Dai,Qinqin Zhang,Fan Yang,Chenxi Bu,Suiqing Chen
Acute liver injury (ALI) is an injury to liver tissue caused by viruses, drugs, alcohol, and oxygen deprivation, and is one of the most common and serious clinical disorders. Hydroxytyrosol (HT) is a naturally occurring polyphenolic compound isolated from forsythia and has excellent anti-inflammatory properties. However, the effect and mechanisms of HT in ALI remain unclear. We used the LPS/D-GalN induced experimental ALI mouse model and AML12 cells to reveal the efficacy and potential mechanisms of HT in ALI, and HE staining was used for the evaluation of pathologies. A biochemical assay was used to detect changes in liver function, RNA-seq was conducted to reveal the underlying mechanisms of HT for ALI, and WB, RT-qPCR, and IF were used to assess the effects of HT action. Furthermore, an in vitro ALI model against HT in AML12 cells induced by LPS/D-GalN was used to assess the HT protection mechanism. HT significant alleviated LPS/D-GalN-induced ALI in the mice by suppressing inflammatory. In terms of RNA-seq, HT improved the TNF, ECM-receptor interaction, and PI3K/AKT signaling pathway, and it downregulated the mRNA levels of VCAM-1, CXCL5, TNF-α and IL-6 in the liver. Mechanically, HT alleviated LPS/D-GalN in the mice by targeting TNF-α, thereby inhibiting the TNF-α/PI3K/AKT signaling pathway.
研究领域:
药理学
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肝病学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2021
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IF 4.932
Lu Wang,Xiaohui Wang,Lina Kong,Shuyuan Wang,Kai Huang,Jingjing Wu,Changyuan Wang,Huijun Sun,Kexin Liu,Qiang Meng
Acute liver failure (ALF) is a dramatic liver disease characterized by large areas of inflammation. However, there are no available effective targeted drugs for ALF treatment. In the study, serum biochemical index and H&E were used to explore the amelioration of the liver histopathological changes. The oxidative stress kits, quantitative real-time PCR, western blot, immunohistochemistry, immunofluorescence staining, reactive oxygen species (ROS), and siRNA were used to elucidate the mechanisms underlying isoliquiritigenin (ISL) protection. The results showed that ISL significantly improved the liver pathological changes. Furthermore, ISL reduced oxidative stress by altering the expression of PGC-1α, Nrf2, HO-1, NQO1, Keap1, GCLC, and GCLM in damaged hepatocytes. Moreover, the levels of inflammation-related genes including NLRP3 inflammasome, IL-1β, IL-6, TNF-α, iNOS, and Mip-2 were repressed by ISL. In addition, ISL alleviated LPS/D-GalN-induced hepatocytes apoptosis by increasing the Bcl-2/Bax ratio and suppressing the expression of cleaved caspase-3. Further in vivo and in vitro evidence proved the involvement of the PGC-1α/Nrf2 signaling pathway in ISL protection. In conclusion, ISL improves the ability of anti-oxidative stress, alleviates inflammatory reaction, apoptosis, and inhibits NLRP3 inflammasome to protect lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALF through activating the PGC-1α/Nrf2 pathway, which provides the possibility for the treatment of ALF.
研究领域:
药理学
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肝病学
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免疫学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2018
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IF 3.47
Cuicui Duan,Yujuan Zhao,Cheng Huang,Zijian Zhao,Lei Gao,Chunhua Niu,Chao Wang,Xiaoxiao Liu,Chuan Zhang,Shengyu Li
Acute liver failure (ALF) is a life-threatening clinical condition resulting from massive apoptosis of hepatocytes. This study aims to examine the protective effects of Lactobacillus plantarum C88 on LPS/D-GalN-induced ALF and elucidate its underlying molecular mechanisms in mice. The results showed that L. plantarum C88 pretreatment significantly reduced the levels of plasma ALT and AST in mice with LPS/D-GalN–induced liver injury. L. plantarum C88 pretreatment decreased the secretion of inflammatory cytokines. In addition, L. plantarum C88 remarkably increased the expression levels and nuclear translocations of Nrf2 mRNA in liver tissues, but inhibited NF-κB nuclear translocations and P65, P38 phosphorylation levels. Moreover, L. plantarum C88 enhanced the intestinal mucosal barrier by upregulating the expressions of tight junction proteins as well as HIF-1α. These results suggest that L. plantarum C88 protects against ALF associated with Nrf2 and the MAPK/NF-κB signaling pathways.
研究领域:
药理学
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免疫学
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分子生物学
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胃肠病学
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产品关联
DOI
高影响因子
Journal of Functional Foods
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2024
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IF 3.8
Zhi-guo Wu,Nan Jin,Yu-feng Deng,Xin-fang Shen,Cui-yun Liu,Bao-yue Ding,Long-hua Guo,Yun-xiao Liu,Zhen-rong Huang,Lei Li,Shui-lin Sun,Bao-gang Xie
The contents of selenomethionine (SeMet) and selenomethylcysteine (SeMC) in Selenium-Enriched black garlic extract (Se-BGE), a popular functional food in Asian countries, were 2.9 ± 0.6 μg/g and 12.2 ± 2.3 μg/g by PITC pre-column derivatization UPLC-MS method. Improved histological injury, significant extension of the median survival time, and attenuated serum levels of alanine aminotransferase, total bilirubin and SOD activity were observed in the acute liver failure (ALF) rats treated with Se-BGE (1.0 g/mL). 1 HNMR-based metabonomics revealed that serum levels of lactate, pyruvate, betaine, choline, taurine, and glycine were restored, and 16S rDNA sequencing analysis showed that the composition and number of the intestinal flora were regressed to healthy levels in ALF rats treated by Se-BGE. Serum choline and betaine showed significant correlations with g_Lactobacillus and g_Escherichia. Our findings demonstrated that Se-BGE protects against LPS/D-GalN-induced ALF in rats, possibly due to antioxidation, metabolism, and intestinal flora regulations of Se-BGE.
研究领域:
药理学
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肝病学
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营养保健品
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代谢组学
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微生物组
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产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2017
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IF 2.956
Xiaobao Gong,You Yang,Ligua Huang,Qingyan Zhang,Rong-Zhen Wan,Peng Zhang,Baoshun Zhang
To evaluate the hepatoprotective effects and potential mechanisms of paeonol (Pae) against acute liver failure (ALF) induced by lipopolysaccharide (LPS)/ d -galactosamine ( d -GalN) in mice, we examined anti-oxidative, anti-inflammatory and anti-apoptotic activities of Pae. We found that Pae pretreatment markedly reduced the activities of alanine transaminase and aspartate transaminase as well as the histopathological changes induced by LPS/ d -GalN. Catalase , glutathione and superoxide dismutase activities increased and reactive oxygen species activity decreased after Pae treatment compared with LPS/ d -GalN treatment. Pretreatment with Pae also significantly inhibited the expression levels of iNOS, nitric oxide (NO), COX-2 and prostaglandin E 2 (PGE 2 ). In addition, Pae administration prevented the phosphorylated expression of IκB kinase, inhibitor kappa B in the nuclear factor-kappa B (NF-κB) signaling pathway , and suppressed the phosphorylated expression of extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase and p38 in the MAPK signaling pathway. Pretreatment with Pae also inhibited hepatocyte apoptosis by reducing the expression of caspases 3, 8, 9, and Bax, and increasing Bcl-2. In total, protective effects of Pae against LPS/ d -GalN-induced ALF in mice are attributed to its antioxidative effect, inflammatory suppression in NF-κB and MARK signaling pathways, and inhibition of hepatocyte apoptosis inhibition. Therefore, Pae can be a potential therapeutic agent in attenuating LPS/ d -GalN-induced ALF in the future.
研究领域:
药理学
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肝病学
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免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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