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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2019 · IF 4.784

Mussel polysaccharide α-D-glucan (MP-A) protects against non-alcoholic fatty liver disease via maintaining the homeostasis of gut microbiota and regulating related gut-liver axis signaling pathways

Jixu Wu,Huarong Shao,Jinhua Zhang,Yong Ying,Yanling Cheng,Dan Zhao,Xixi Dou,Huimin Lv,Shuaiguang Li,Fei Liu,Peixue Ling

We isolated and characterized a Mussel polysaccharide, α -D-glucan (MP-A), from Mytilus coruscus earlier. In this work, the pharmacological activity and mechanisms of MP-A as an oral supplement for non-alcoholic fatty liver disease (NAFLD) were explored. High fat diet (HFD) was utilized to induce NAFLD in Sprague Dawley male rats and MP-A (0.6 g/kg) was supplemented for 4 weeks. The results showed that MP-A supplementation reduced blood lipid levels, intrahepatic lipid accumulation and NAFLD activity score in HFD-fed rats. Additionally, the analysis of 16S rDNA sequencing on gut microbiota samples revealed that HFD could induce microbial dysbiosis. However, MP-A supplementation could remodel gut microbiota structure, inhibit LPS-TLR4-NF- κ B pathway activation, and restrain subsequent inflammation factors secretion. Furthermore, MP-A regulated the lipid metabolism by promoting the production of short chain fatty acids and suppressing PPAR γ and SREBP-1c expression. Our results support that MP-A can prevent against NAFLD and act as an oral supplementation for hepatoprotection via modulating gut microbiota and related gut-liver axis signaling pathways.

CAS / MDL: 64-19-7
研究领域: 药理学 · 胃肠病学 · 微生物学 · 代谢学
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BIOCHEMICAL PHARMACOLOGY · 2024 · IF 5.3

Piperlongumine, a natural alkaloid from Piper longum L. ameliorates metabolic-associated fatty liver disease by antagonizing the thromboxane A2 receptor

Yufeng Dai,Jinxiang Chen,Jialong Fang,Shuxiao Liang,Hao Zhang,Haitao Li,Wei Chen

Metabolic dysfunction-associated fatty liver disease (MAFLD) encompasses a broad spectrum of hepatic disorders, including hyperglycemia, hepatic steatosis, and insulin resistance. Piperlongumine (PL), a natural amide alkaloid extracted from the fruits of Piper longum L., exhibited hepatoprotective effects in zebrafish and liver injury mice. This study aimed to investigate the therapeutic potential of PL on MAFLD and its underlying mechanisms. The findings demonstrate that PL effectively combats MAFLD induced by a high-fat diet (HFD) and improves metabolic characteristics in mice. Additionally, our results suggest that the anti-MAFLD effect of PL is attributed to the suppression of excessive hepatic gluconeogenesis, inhibition of de novo lipogenesis, and alleviation of insulin resistance. Importantly, the results indicate that, on the one hand, the hypoglycemic effect of PL is closely associated with CREB-regulated transcriptional coactivators (CRTC2)-dependent cyclic AMP response element binding protein (CREB) phosphorylation; on the other hand, the lipid-lowering effect of PL is attributed to reducing the nuclear localization of sterol regulatory element-binding proteins 1c (Srebp-1c). Mechanistically, PL could alleviate insulin resistance induced by endoplasmic reticulum stress by antagonizing the thromboxane A 2 receptor (TP)/Ca 2+ signaling, and the TP receptor serves as the potential target for PL in the treatment of MAFLD. Therefore, our results suggested PL effectively improved the major hallmarks of MAFLD induced by HFD, highlighting a potential therapeutic strategy for MAFLD.

研究领域: 药理学 · 肝病学 · 代谢学 · 分子生物学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2022 · IF 5.895

Preventive Effect of Apple Polyphenol Extract on High-Fat Diet-Induced Hepatic Steatosis in Mice through Alleviating Endoplasmic Reticulum Stress

Bei Yan,Lei Chen,Yanhui Wang,Jiacheng Zhang,Hui Zhao,Qinglian Hua,Shengjie Pei,Zihang Yue,Hui Liang,Huaqi Zhang

In this work, the protective effect of apple polyphenol extract (APE) on hepatic steatosis was investigated. Thirty-two C57BL/6J mice were assigned randomly to control group, hepatic steatosis group, lovastatin group, and APE group. After 8 weeks of intervention, APE supplementation markedly decreased the body weight gain, liver weight, liver index, epididymal adipose weight, epididymal adipose index, serum, and hepatic lipid levels. Hematoxylin and eosin staining revealed that APE supplementation alleviated histopathological changes of hepatic steatosis. Western blot revealed that APE downregulated the protein levels of GRP78, IRE1α, p-IRE1α, XBP1, PERK, p-PERK, p-eIF2α, ATF6, PPAR-γ, SREBP-1c, FAS, and ACC1. In conclusion, this study found that APE inhibited IRE1α-XBP1, PERK-eIF2α, and ATF6 signaling pathways to alleviate endoplasmic reticulum stress, thereby improving HFD-induced hepatic steatosis.

CAS / MDL: 75330-75-5
研究领域: 药理学 · 营养学 · 分子生物学 · 病理学
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