Emerging targets and potential therapeutic agents in non-alcoholic fatty liver disease treatment

Yu, Yang; Zhao, Yu; Li, Wenzhen; Wu, Yuyao; Wang, Xin; Wang, Yijie; Liu, Ting-Mei; Ye, Tinghong; Xie, Yongmei; Cheng, Zhiqiang; He, Jiang; Bai, Peng; Zhang, Yiwen; Ouyang, Liang

doi:10.1016/j.ejmech.2020.112311

Cited by 12 publications

(4 citation statements)

References 287 publications

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“…To better understand the efficacy of CHMs for the treatment of NAFLD via modulation of gut microbiota, researchers have attempted to depict the potential material basis of CHMs and their key roles as modulators to maintain the intestinal microbiota. In the future, more state-of-the-art techniques including microbial metagenome, microbial metabolomics, microbial proteomics and multiomics integration analysis should be applied to discover the key targets and the molecular mechanisms of herbal constituents in the management of NAFLD [114,115].…”

Section: Discussionmentioning

confidence: 99%

Herbal therapy for ameliorating nonalcoholic fatty liver disease via rebuilding the intestinal microecology

et al. 2021

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The worldwide prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, and this metabolic disorder has been recognized as a severe threat to human health. A variety of chemical drugs have been approved for treating NAFLD, however, they always has serious side effects. Chinese herbal medicines (CHMs) have been widely used for preventing and treating a range of metabolic diseases with satisfactory safety and effective performance in clinical treatment of NAFLD. Recent studies indicated that imbanlance of the intestinal microbiota was closely associated with the occurrence and development of NAFLD, thus, the intestinal microbiota has been recognized as a promising target for treatment of NAFLD. In recent decades, a variety of CHMs have been reported to effectively prevent or treat NAFLD by modulating intestinal microbiota to further interfer the gut-liver axis. In this review, recent advances in CHMs for the treatment of NAFLD via rebuilding the intestinal microecology were systematically reviewed. The key roles of CHMs in the regulation of gut microbiota and the gut-liver axis along with their mechanisms (such as modulating intestinal permeability, reducing the inflammatory response, protecting liver cells, improving lipid metabolism, and modulating nuclear receptors), were well summarized. All the knowledge and information presented here will be very helpful for researchers to better understand the applications and mechanisms of CHMs for treatment of NAFLD.

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Section: Discussionmentioning

confidence: 99%

Herbal therapy for ameliorating nonalcoholic fatty liver disease via rebuilding the intestinal microecology

et al. 2021

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“…Furthermore, it has been demonstrated that the activation of hepatic stellate cells (HSCs) by ROS and oxidized low-density lipoprotein (LDL) might result in liver fibrosis. To summarize, insulin resistance, oxidative stress, and inflammation all play critical roles in the development of MASLD, and a better knowledge of the etiology of MASLD is required to create new therapeutic options (Figure 2) [19].…”

Section: Pathogenesis Of Masldmentioning

confidence: 99%

“…The most widely used PPARγ agonists are the thiazolidinediones, which improve NASH, including rosiglitazone, and pioglitazone [19,48]. There are some other PPARγ agonists, such as saroglitazar, AMG-131, etc.…”

Section: Pparβ/δmentioning

confidence: 99%

Therapeutic targets for metabolic dysfunction-associated steatotic liver disease and their roles in hepatocellular carcinoma

Wei,

Wu,

Zhang

et al. 2023

Explor Dig Dis

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Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common chronic liver diseases. Over time, there has been a significant increase in the prevalence of MASLD. It has become one of the leading causes of hepatocellular carcinoma (HCC) in the United States, France, and the United Kingdom. Globally, the incidence of HCC related to MASLD may further increase with the growing prevalence of obesity. Non-alcoholic steatohepatitis (NASH) is an important stage of MASLD, which is more likely to cause cirrhosis and even HCC. And patients with NASH cirrhosis have a much higher incidence of hepatocellular cancer than patients with non-cirrhotic MASLD. As a result, it is critical to investigate the targets of MASLD therapy in HCC. This article reviews therapeutic targets of MASLD, such as farnesoid X receptor (FXR), peroxisome proliferator activated receptor (PPAR), fibroblast growth factor-21 (FGF-21), etc., and introduces the drugs related to these targets and their mechanisms of action in HCC. In addition, the developmental process and pathogenesis of MASLD, as well as risk factors for HCC development, are discussed. These are of great significance for the prevention and treatment of HCC.

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“…Until now, there is no approved drug by the US FDA to treat patients with NAFLD [ 4 ]. The therapeutic trial agents such as insulin sensitizers (metformin, glitazones, pioglitazone), nuclear receptor agonists (elafibranor, obeticholic acid, GFT505), and glucagon-like peptide-1 receptor agonists are still in the clinical trial process against NAFLD [ 5 ]. Thus, there is a need to develop novel therapeutic agents against NAFLD, and to elucidate possible molecular mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Methyl Brevifolincarboxylate Attenuates Free Fatty Acid-Induced Lipid Metabolism and Inflammation in Hepatocytes through AMPK/NF-κB Signaling Pathway

Geethangili

Lin

Mersmann

et al. 2021

IJMS

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The prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases worldwide. This study examined the potential protective effects of a naturally occurring polyphenolic compound, methyl brevifolincarboxylate (MBC) on fatty liver injury in vitro. The results showed that MBC at its non-cytotoxic concentrations, reduced lipid droplet accumulation and triglyceride (TG) levels in the oleic acid (OA)-treated human hepatocarcinoma cell line, SK-HEP-1 and murine primary hepatocytes. In OA-treated SK-HEP-1 cells and primary murine hepatocytes, MBC attenuated the mRNA expression levels of the de novo lipogenesis molecules, acetyl-coenzyme A carboxylase (Acc1), fatty acid synthase (Fasn) and sterol regulatory element binding protein 1c (Srebp1c). MBC promoted the lipid oxidation factor peroxisome proliferator activated receptor-α (Pparα), and its target genes, carnitine palmitoyl transferase 1 (Cpt1) and acyl-coenzyme A oxidase 1 (Acox1) in both the SK-HEP-1 cells and primary murine hepatocytes. The mRNA results were further supported by the attenuated protein expression of lipogenesis and lipid oxidation molecules in OA-treated SK-HEP-1 cells. The MBC increased the expression of AMP activated protein kinase (AMPK) phosphorylation. On the other hand, MBC treatment dampened the inflammatory mediator’s, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-8, and IL-1β secretion, and nuclear factor (NF)-κB expression (mRNA and protein) through reduced reactive oxygen species production in OA-treated SK-HEP-1 cells. Taken together, our results demonstrated that MBC possessed potential protective effects against NAFLD in vitro by amelioration of lipid metabolism and inflammatory markers through the AMPK/NF-κB signaling pathway.

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Emerging targets and potential therapeutic agents in non-alcoholic fatty liver disease treatment

Cited by 12 publications

References 287 publications

Herbal therapy for ameliorating nonalcoholic fatty liver disease via rebuilding the intestinal microecology

Herbal therapy for ameliorating nonalcoholic fatty liver disease via rebuilding the intestinal microecology

Therapeutic targets for metabolic dysfunction-associated steatotic liver disease and their roles in hepatocellular carcinoma

Methyl Brevifolincarboxylate Attenuates Free Fatty Acid-Induced Lipid Metabolism and Inflammation in Hepatocytes through AMPK/NF-κB Signaling Pathway

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