Gynostemma pentaphyllum polysaccharides ameliorate non-alcoholic steatohepatitis in mice associated with gut microbiota and the TLR2/NLRP3 pathway DOI Creative Commons

Siran Yue,

Yi-Yun Tan,

Lei Zhang

et al.

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: July 22, 2022

Recent studies have revealed the pivotal role of gut microbiota in progress liver diseases including non-alcoholic steatohepatitis (NASH). Many natural herbs, such as Gynostemma pentaphyllum (GP), been extensively applied prevention NASH, while bioactive components and underlying mechanism remain unclear. The aim this study was to investigate whether polysaccharides GP (GPP) a protective effect on NASH explore potential these effects. C57BL/6 male mice were fed with methionine-choline-deficient (MCD) diet for 4 weeks induce administered daily oral gavage sodium carboxymethylcellulose (CMC-Na), low dose GPP (LGPP), high (HGPP), polyene phosphatidylcholine capsules (PPC), compared methionine-choline-sufficient (MCS) group. Our results showed that symptoms hepatic steatosis, hepatocyte ballooning, fibrosis, oxidative stress could be partially recovered through intervention dose-dependent effect. Furthermore, microbiome sequencing HGPP altered composition microbiota, mainly characterized by enrichment genera Akkermansia , Lactobacillus A2 . Moreover, transcriptome analysis indicated anti-inflammatory might associated toll-like receptor (TLR) nod-like (NLR) signaling pathways. inhibit expression TLR2 downregulate NLRP3 inflammasome, well pro-inflammatory cytokine tumor necrosis factor (TNF)-α interleukin (IL)-1β. In summary, ameliorate possibly mediated via modulation TLR2/NLRP3 pathway, indicating tested prebiotic agent NASH.

Language: Английский

Treatment for liver cancer: From sorafenib to natural products DOI
Shuli Man,

Chen Luo,

Mengyao Yan

et al.

European Journal of Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 224, P. 113690 - 113690

Published: July 5, 2021

Language: Английский

Citations

139
PPAR-γ signaling in nonalcoholic fatty liver disease: Pathogenesis and therapeutic targets DOI
Hao Chen, Huabing Tan, Juan Wan

et al.

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 245, P. 108391 - 108391

Published: March 22, 2023

Language: Английский

Citations

128
Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction DOI Creative Commons
Karli R. LeFort, Wiramon Rungratanawanich, Byoung‐Joon Song

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 12, 2024

Abstract This review provides an update on recent findings from basic, translational, and clinical studies the molecular mechanisms of mitochondrial dysfunction apoptosis hepatocytes in multiple liver diseases, including but not limited to alcohol-associated disease (ALD), metabolic dysfunction-associated steatotic (MASLD), drug-induced injury (DILI). While ethanol-inducible cytochrome P450-2E1 (CYP2E1) is mainly responsible for oxidizing binge alcohol via microsomal ethanol system, it also metabolizing many xenobiotics, pollutants, chemicals, drugs, specific diets abundant n-6 fatty acids, into toxic metabolites organs, liver, causing pathological insults through organelles such as mitochondria endoplasmic reticula. Oxidative imbalances (oxidative stress) promote covalent modifications lipids, proteins, nucleic acids enzymatic non-enzymatic mechanisms. Excessive changes stimulate various post-translational (PTMs) transcription factors, histones. Increased PTMs proteins inactivate enzymes involved reduction oxidative species, acid metabolism, mitophagy pathways, leading dysfunction, energy depletion, apoptosis. Unique other organelles, control signaling cascades bioenergetics (fat metabolism), inflammation, apoptosis/necrosis hepatocytes. When homeostasis shifted, these pathways become altered or shut down, likely contributing death with activation inflammation hepatic stellate cells, fibrosis cirrhosis. will encapsulate how contributes hepatocyte several types diseases order provide recommendations targeted therapeutics.

Language: Английский

Citations

40
Polyphenols synergistic drugs to ameliorate non-alcoholic fatty liver disease via signal pathway and gut microbiota: A review DOI Creative Commons
Hongcai Li, Jingjing Liang, Mengzhen Han

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Non-alcoholic fatty liver disease (NAFLD) is a common chronic with an increasing incidence worldwide. Single drug therapy may have toxic side effects and disrupt gut microbiota balance. Polyphenols are widely used in intervention due to their distinctive nutritional properties medicinal value, which potential modulator. However, there lack of comprehensive review explore the efficacy mechanism combined drugs polyphenols for NAFLD. Based on this, this firstly discusses link between NAFLD microbiota, outlines microbiota. Secondly, it examined recent advances treatment therapeutic effect combination two. Finally, we highlight underlying mechanisms polyphenol This mainly terms signaling pathways (NF-κB, AMPK, Nrf2, JAK/STAT, PPAR, SREBP-1c, PI3K/Akt TLR) Furthermore, some emerging such as microRNA biomarker therapies provide avenues Drawing inspiration from strategies, use active substances holds transformative prospective potential, both improve restore balance while reducing required dosage. systematically bidirectional interactions NAFLD, summarizes synergistic by modulating Future researches should develop multi-omics technology identify patients who benefit devising individualized plans enhance its effect.

Language: Английский

Citations

21
Notoginsenoside Ft1 acts as a TGR5 agonist but FXR antagonist to alleviate high fat diet-induced obesity and insulin resistance in mice DOI Creative Commons
Lili Ding, Qiaoling Yang, Eryun Zhang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 11(6), P. 1541 - 1554

Published: March 30, 2021

Obesity and its associated complications are highly related to a current public health crisis around the world. A growing body of evidence has indicated that G-protein coupled bile acid (BA) receptor TGR5 (also known as Gpbar-1) is potential drug target treat obesity metabolic disorders. We have identified notoginsenoside Ft1 (Ft1) from Panax notoginseng an agonist in vitro. However, pharmacological effects on diet-induced obese (DIO) mice underlying mechanisms still elusive. Here we show (100 mg/100 diet) increased adipose lipolysis, promoted fat browning inguinal tissue induced glucagon-like peptide-1 (GLP-1) secretion ileum wild type but not Tgr5-/- mice. In addition, elevated serum free taurine-conjugated acids (BAs) by antagonizing Fxr transcriptional activities activate Tgr5 tissues. The benefits were abolished Cyp27a1-/- which much lower BA levels. These results identify single compound with opposite two key receptors alleviate high insulin resistance

Language: Английский

Citations

76
Targeting a novel inducible GPX4 alternative isoform to alleviate ferroptosis and treat metabolic-associated fatty liver disease DOI Creative Commons
Jie Tong, Dongjie Li,

Hongbo Meng

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(9), P. 3650 - 3666

Published: Feb. 12, 2022

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in tissues from MAFLD patients. The canonical-GPX4 (cGPX4), the most important negative controller downregulated at protein but not mRNA level. Interestingly, non-canonical GPX4 transcript-variant induced (inducible-GPX4, iGPX4) condition. high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient (MCD)-induced pathologies, including hepatocellular ballooning, steatohepatitis fibrosis, were attenuated aggravated, respectively, cGPX4-and iGPX4-knockin mice. cGPX4 iGPX4 isoforms also displayed opposing effects on oxidative stress ferroptosis hepatocytes. Knockdown siRNA alleviated stress, injury. Mechanistically, triggered interacts to facilitate transformation enzymatic-active monomer enzymatic-inactive oligomers upon thus promotes ferroptosis. Co-immunoprecipitation nano LC-MS/MS analyses confirmed interaction between cGPX4. Our results reveal detrimental role isoform indicate selectively targeting may be promising therapeutic strategy for MAFLD.

Language: Английский

Citations

70
Breviscapine alleviates NASH by inhibiting TGF‐β‐activated kinase 1‐dependent signaling DOI Creative Commons
Tian Lan, Shuo Jiang, Jing Zhang

et al.

Hepatology, Journal Year: 2021, Volume and Issue: 76(1), P. 155 - 171

Published: Oct. 30, 2021

NAFLD is a key component of metabolic syndrome, ranging from nonalcoholic fatty liver to NASH, and now becoming the leading cause cirrhosis HCC worldwide. However, due complex unclear pathophysiological mechanism, there are no specific approved agents for treating NASH. Breviscapine, natural flavonoid prescription drug isolated traditional Chinese herb Erigeron breviscapus, exhibits wide range pharmacological properties, including effects on metabolism. anti-NASH efficacy mechanisms breviscapine have not yet been characterized.We evaluated development hepatic steatosis, inflammation, fibrosis in vivo vitro under stress. Breviscapine treatment significantly reduced lipid accumulation, inflammatory cell infiltration, injury, mice fed high-fat diet, high-fat/high-cholesterol or methionine- choline-deficient diet. In addition, attenuated lipotoxicity hepatocytes undergoing RNA-sequencing multiomics analyses further indicated that mechanism linking was inhibition TGF-β-activated kinase 1 (TAK1) phosphorylation subsequent mitogen-activated protein signaling cascade. Treatment with TAK1 inhibitor 5Z-7-oxozeaenol abrogated breviscapine-mediated hepatoprotection Molecular docking illustrated directly bound TAK1.Breviscapine prevents stress-induced NASH progression through direct signaling. might be therapeutic candidate

Language: Английский

Citations

63
Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases DOI Creative Commons

Haowen Xu,

Jiahao Chen, Pan Chen

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 13(2), P. 678 - 693

Published: Sept. 25, 2022

The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient traditional Chinese medicinal herb Saussurea lappa anti-inflammatory activity, but principal mechanism molecular target COS remain unclear. Here, we show that covalently binds to cysteine 598 NACHT domain altering ATPase activity assembly inflammasome. We declare COS's great anti-inflammasome efficacy macrophages disease models gouty arthritis ulcerative colitis via inhibiting inflammasome activation. also reveal α-methylene-γ-butyrolactone motif sesquiterpene lactone certain group Taken together, identified as direct for its activity. COS, especially structure, might be used design produce novel inhibitors lead compound.

Language: Английский

Citations

58
Functional metabolomics innovates therapeutic discovery of traditional Chinese medicine derived functional compounds DOI
Tianyu Wang, Jingjing Liu,

Xialin Luo

et al.

Pharmacology & Therapeutics, Journal Year: 2021, Volume and Issue: 224, P. 107824 - 107824

Published: March 2, 2021

Language: Английский

Citations

57
Natural Compounds for Counteracting Nonalcoholic Fatty Liver Disease (NAFLD): Advantages and Limitations of the Suggested Candidates DOI Open Access
Noel Salvoza, Pablo J. Giraudi, Claudio Tiribelli

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2764 - 2764

Published: March 2, 2022

The booming prevalence of nonalcoholic fatty liver disease (NAFLD) in adults and children will threaten the health system upcoming years. "multiple hit" hypothesis is currently accepted explanation complex etiology pathophysiology disease. Some critical pathological events associated with development NAFLD are insulin resistance, steatosis, oxidative stress, inflammation, fibrosis. Hence, attenuating these may help prevent or delay progression NAFLD. Despite an increasing understanding mechanisms involved NAFLD, no approved standard pharmacological treatment available. only recommended alternative relies on lifestyle modifications, including diet physical activity. However, lack compliance still hampering this approach. Thus, there evident need to characterize new therapeutic alternatives. Studies food bioactive compounds became attractive approach overcome reticence toward changes. present study aimed review some reported beneficial properties NAFLD; namely, coffee (and its components), tormentic acid, verbascoside, silymarin. We provide details about their protective effects, mechanism action ameliorating clinical applications.

Language: Английский

Citations

41