INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Shaoyang Zhi,Junli Wang,Yiran Wang,Yijie Li,Mengjuan Zhao,Liping Yang,Chaobin Qin,Xiao Yan,Guoxing Nie
AMPKα1 and AMPKα2, key kinases in regulating energy homeostasis, have not been previously cloned or characterized in common carp ( Cyprinus carpio ). This study identified the open reading frame (ORF) sequences of ampkα1 (1722 bp, encoding 573 amino acids) and ampkα2 (1659 bp, encoding 552 amino acids) through homologous cloning. Sequence alignment and phylogenetic analysis showed a high similarity of both genes with fish homologs. Expression analysis revealed that ampkα1 and ampkα2 are widely expressed across tissues in carp, with ampkα1 highly expressed in the gonads and ampkα2 in the heart. Fasting significantly reduced ampkα1 expression in the heart, adipose tissue, and foregut but increased it in the hindgut and white muscle. Similarly, ampkα2 expression decreased in the hypothalamus and muscle during fasting, with an increase in the midgut. Glucose tolerance tests showed dynamic regulation of ampkα1 and ampkα2 , with initial downregulation followed by upregulation in the hepatopancreas, red muscle, and brain. High-glucose and high-fat diets significantly increased ampkα1 and ampkα2 expression in multiple tissues. Insulin and glucagon treatment induced time-dependent changes in both genes in hepatocytes, while Aeromonas hydrophila infection, LPS, and Poly (I:C) stimulation upregulated ampkα1 and ampkα2 in immune-related tissues. Knockdown of ampkα2 , but not ampkα1 , reduced glut1b mRNA levels, while both knockdowns of ampkα1 and ampkα2 promoted the expression of gsk3β , pygm , acc , fas , srebp , cs , and pro-inflammatory cytokines, suggesting their involvement in metabolic and immune regulation in carp.
研究领域:
分子生物学
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营养学
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免疫学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2026
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IF 11.3
Rui Yin,Lu He,Liangli Dai,Ling Chen,Tao Liang,Jinli Han,Juan Chen
Background Hypoxic–ischemic encephalopathy (HIE) is a serious neonatal neurological disorder in which microglia-mediated acute neuroinflammation serves as a critical driver of disease progression. Our previous work revealed that H3K9 lactylation-driven microglial M1 polarization promotes neuroinflammation as a key mechanism in HIE. Baicalin, a natural compound isolated from the traditional Chinese herb Scutellaria baicalensis , is well known for its anti-inflammatory effect, but whether it can treat HIE through this anti-inflammatory effect remains unclear. Purpose This study aimed to determine whether baicalin can inhibit H3K9 lactylation-mediated microglial M1 polarization and neuroinflammation in HIE. Methods In vivo, an HIE rat model was established in which rats were treated with intraperitoneal injections of baicalin. In vitro, an oxygen‒glucose deprivation model was constructed using BV2 microglia. Network pharmacology and molecular docking were employed to predict and validate the potential targets of baicalin, after which functional assays were performed. Co-immunoprecipitation combined with mass spectrometry was further used to explore the underlying molecular mechanisms. Results Through network pharmacology analysis, molecular docking and validation experiments, we revealed that baicalin exerts its anti-inflammatory effects via the activation of adenosine 5′-monophosphate-activated protein kinase α subunit 1 (AMPKα1). Further co-immunoprecipitation and mass spectrometry analyses revealed that AMPKα1 activation promotes the phosphorylation of histone deacetylase 1 (HDAC1), a key delactylase, thus inhibiting the degradation of HDAC1 mediated by the E3 ligase ubiquitin protein ligase E3A (UBE3A). Finally, baicalin increases HDAC1 protein levels to inhibit H3K9 lactylation-mediated microglial M1 polarization via targeting AMPKα1. Conclusion These findings suggest that, when administered at an early stage after HIE, baicalin may contribute to the attenuation of HIE pathology, at least in part by increasing HDAC1 stability through AMPKα1- and UBE3A-mediated “phosphorylation–ubiquitination hierarchical regulation”, thereby reducing H3K9 lactylation and suppressing microglial M1 polarization. Download: Download high-res image (186KB) Download: Download full-size image
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Dong-xuan Zheng,Qiang Hou,Tao-tao Xue,Xiang Gao,Ruo-yu Geng,Li-mei Wen,Zhi Wang,Qiang Yin,Hai-long Yin,Jun-ping Hu,Jian-hua Yang
Ethnopharmacological relevance Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a crucial component of this disease spectrum. The Yanxiao Di'naer formula (YXDNE) is an Uyghur medical extract that has been used in folk medicine to treat hepatitis for a long time. However, the role and mechanism of action of YXDNE in NASH treatment remains unclear. Objective The objective of this study was to assess the effectiveness of YXDNE in treating NASH induced by injections of carbon tetrachloride combined with a high-fat high-cholesterol diet (HFHCD), and to clarify the underlying mechanisms. Methods The compounds in the YXDNE extract were analysed for classification and proportions using ultra-performance liquid chromatography-mass spectrometry. The efficacy of YXDNE in treating abnormal lipid metabolism was evaluated in L02 cells in vitro . In addition, a C57BL/6 mouse model of NASH was established to evaluate the therapeutic efficacy of YXDNE in vivo . Metabolomics and RNA sequencing were used to analyse the therapeutic effects of YXDNE on the liver. The corresponding signalling pathways were found to target AMPKα1, PPARα, and NF-κB. The efficacy of YXDNE was validated using inhibitors or silencing RNA (siRNA) against AMPKα1 and PPARα. Results This study confirmed that YXDNE treatment ameliorated NASH in a murine model of this disease. Metabolomics analysis suggested that YXDNE efficacy was associated with fatty acid catabolism and AMPK signalling pathways. RNA sequencing results showed that YXDNE efficacy in treating NASH was highly correlated with the AMPK, PPARα and NF-κB pathways. Both in vitro and in vivo experimental data demonstrated that YXDNE affected the expression of p-AMPKα1, PPARα, p–NF–κB, IκB, and p-IκB. The efficacy of YXDNE in treating NASH in vitro was cancelled when AMPK was inhibited with Compound C or PPARα was modulated via siRNA. Conclusions YXDNE may have a therapeutic effect on abnormal lipid metabolism in L02 cells and in a murine model of NASH by affecting the AMPKα1/PPARα/NF-κB signalling pathway. Therefore, YXDNE has the potential for clinical application in the prevention and treatment of NASH.
研究领域:
药理学
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代谢组学
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分子生物学
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民族药理学
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肝病
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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
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2026
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IF 3.1
Yang Li,Xinchang Feng,Lingpeng Zheng
Type 2 diabetes mellitus (T2DM) has become a leading cause of chronic liver disease worldwide. Farrerol has been demonstrated to ameliorate multiple metabolic disorders. However, the role of farrerol in hepatic insulin resistance (IR) in T2DM, as well as the underlying mechanism, remain unclear. The present study aims to elucidate these issues. A rat model of T2DM was used to evaluate the effect of farrerol on IR in vivo. BRL 3 A cells were stimulated with palmitic acid to obtain an in vitro model of IR to further determine the role and mechanism of farrerol in hepatic IR. The involvement of the AMPK pathway was investigated using a selective and ATP-competitive AMPK inhibitor Compound C and specific siRNA targeting AMPKα1. The present study demonstrated that farrerol administration reduced HOMA-IR index, ameliorated dyslipidemia, and regulated glucose tolerance in diabetic rats. Additionally, farrerol administration alleviated hepatic damage, inflammation and oxidative stress accompanied by restored the AMPKα1/mTOR/SREBP-1 pathway in the liver of diabetic rats. Furthermore, in an in vitro model, farrerol enhanced glucose uptake, inhibited lipid accumulation, restored the membrane translocation of GLUT-2, suppressed inflammation and oxidative stress, and regulated the AMPKα1/mTOR/SREBP-1 pathway in palmitic acid-induced BRL 3 A cells. However, incubation with AMPK inhibitor or AMPKα1 knockdown reversed the protective effects of farrerol in vitro . Our findings demonstrate that farrerol ameliorates hepatic IR and associated metabolic dysfunctions by regulating the AMPKα1/mTOR/SREBP-1 pathway. Farrerol may be a promising therapeutic target for the treatment of IR in T2DM.
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产品关联
DOI
PubMed
高影响因子
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