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Hypercalin B alleviates nonalcoholic steatohepatitis progression via suppressing mTORC1 signaling pathway
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Yan-qiu ZHANG, Meng-meng HE, Xue-yan LI, Wen-jun XU, Hao ZHANG*
Acta Pharmaceutica Sinica | 2023, 58(8) : 2391 - 2401
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Acta Pharmaceutica Sinica | 2023, 58(8): 2391-2401
Hypercalin B alleviates nonalcoholic steatohepatitis progression via suppressing mTORC1 signaling pathway
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Yan-qiu ZHANG, Meng-meng HE, Xue-yan LI, Wen-jun XU, Hao ZHANG*
Affiliations
  • Jiangsu Key Laboratory of Bioactive Natural Product Research, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
Published: 2023-08-12 doi: 10.16438/j.0513-4870.2023-0543
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The global incidence rate of nonalcoholic steatohepatitis (NASH) continues to rise. The pathogenesis of NASH is complex, and there is no effective clinical treatment. Previous study has shown that DEAD box protein 5 (DDX5) can significantly alleviate the NASH process in mice. This study screened the natural product library of the research group and found that the active compound hypercalin B (HB) in Hypericum beanii N. Robson, a traditional Chinese medicine, can upregulate the expression of DDX5 protein in a dose-dependent manner. In this study, an in vitro model of NASH stimulated by palmitic acid (PA) and an animal model of NASH induced by the methionine- and choline-deficient diet (MCD) were constructed. Different concentrations of HB were used to investigate the effect and mechanism of HB in alleviating NASH progression. All animal experiments in this paper were approved by the Ethics Committee of China Pharmaceutical University (NO: 2021-02-003). In vitro model results showed that HB significantly reduced the intracellular lipid deposition induced by free fatty acid (FFA). Animal experiments showed that HB improved liver injury by significantly reducing lipid accumulation in the liver of NASH mice, and reducing serum aspartate transaminase (AST) and alanine transaminase (ALT) levels. Moreover, HB could inhibit liver inflammation by reducing the mRNA levels of liver pro-inflammatory cytokines including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNFα). Further research showed that HB could reduce the phosphorylation level of the mechanical target of rapamycin (mTOR) and reduce the expression of sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN), thereby improving lipid metabolism and alleviating NASH progression, and the effects of HB against NASH were dependent on DDX5. In conclusion, HB can improve lipid metabolism and inhibit inflammatory activation by suppressing mTORC1 pathway via upregulating DDX5 protein, and showed promising anti-NASH activity in vitro and in vivo.

nonalcoholic steatohepatitis  /  hypercalin B  /  mechanistic target of rapamycin complex 1  /  lipid metabolism  /  inflammation
Yan-qiu ZHANG, Meng-meng HE, Xue-yan LI, Wen-jun XU, Hao ZHANG. Hypercalin B alleviates nonalcoholic steatohepatitis progression via suppressing mTORC1 signaling pathway[J]. Acta Pharmaceutica Sinica, 2023 , 58 (8) : 2391 -2401 . DOI: 10.16438/j.0513-4870.2023-0543
Year 2023 volume 58 Issue 8
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doi: 10.16438/j.0513-4870.2023-0543
  • Receive Date:2023-04-28
  • Online Date:2025-11-21
  • Published:2023-08-12
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  • Received:2023-04-28
  • Revised:2023-06-30
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    Jiangsu Key Laboratory of Bioactive Natural Product Research, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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