Involvement of activation of PLIN5-Sirt1 axis in protective effect of glycycoumarin on hepatic lipotoxicity

Zhang, Enxiang; Yin, Shutao; Zhao, Chong; Fan, Lihong; Hu, Hongbo

doi:10.1016/j.bbrc.2020.05.072

Cited by 7 publications

(6 citation statements)

References 27 publications

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“…It has been shown that steatosis alone does not cause complications, but some patients develop severe liver damage such as steatohepatitis, liver fibrosis, and cirrhosis (Ratziu and Poynard 2010 ), which can lead to liver cancer in more severe cases. Zhang et al ( 2016 , 2017a , b ) used a cell culture model of palmitate-induced hepatocyte apoptosis and a methionine/choline-deficient diet–induced non-alcoholic steatohepatitis mouse model to demonstrate that 1 protects against non-alcoholic fatty liver disease both in vitro and in vivo . In vitro , 1 significantly attenuated palmitic acid (PA)–mediated activation of JNK and C/EBP-homologous protein (CHOP); expression of the pro-apoptotic proteins Bax, Bak, PUMA, and Bim; and PA-reduced expression of the anti-apoptotic protein BCL2, thereby inhibiting adipocyte apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Activities and Pharmacokinetics of Glycycoumarin

Tang

et al. 2022

Rev. Bras. Farmacogn.

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Glycycoumarin is a representative coumarin compound with significant pharmacological activities isolated from Glycyrrhiza uralensis Fisch., Fabaceae. Studies have shown that glycycoumarin has many biological activities, such as anti-tumor, liver protection, antispasmodic, antibacterial, and antivirus. However, the poor solubility of glycycoumarin in water and the accompanying reactions of the phase I (hydroxylation) and II (glucuronidation) metabolism limit its druggability, which manifests as low absorption in the body after oral administration and low free drug concentration, ultimately leading to low bioavailability. Therefore, a comprehensive review of the pharmacological effects and pharmacokinetics of glycycoumarin is presented to provide a reference for further research and application as a therapeutic agent. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s43450-022-00342-x.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Activities and Pharmacokinetics of Glycycoumarin

Tang

et al. 2022

Rev. Bras. Farmacogn.

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“…A previous study showed that activation of PLIN5 enhanced the expression of its downstream target gene, SIRT1 and protected against palmitate-induced hepatocyte lipoapoptosis and inflammatory responses. 58 …”

Section: Other Regulation Of Sirt1 Targets In Nafld Development and T...mentioning

confidence: 99%

Biological Role and Related Natural Products of SIRT1 in Nonalcoholic Fatty Liver

Meng,

Zhang,

et al. 2023

DMSO

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Non-alcoholic fatty liver disease(NAFLD) is an umbrella term for a range of diseases ranging from hepatic fat accumulation and steatosis to non-alcoholic steatohepatitis (NASH) in the absence of excessive alcohol consumption and other definite liver damage factors. The incidence of NAFLD has increased significantly in recent years and will continue to grow in the coming decades. NAFLD has become a huge health problem and economic burden. SIRT1 is a member of Sirtuins, a group of highly conserved histone deacetylases regulated by NAD+, and plays a vital role in regulating cholesterol and lipid metabolism, improving oxidative stress, inflammation, and insulin resistance through deacetylating some downstream transcription factors and thus improving NAFLD. Although there are no currently approved drugs for treating NAFLD and some unresolved limitations in developing SIRT1 activators, SIRT1 holds promise as a proper therapeutic target for NAFLD and other metabolic diseases. In recent years, natural products have played an increasingly important role in drug development due to their safety and efficacy. It has been discovered that some natural products may be able to prevent and treat NAFLD by targeting SIRT1 and its related pathways. This paper reviews the mechanism of SIRT1 in the improvement of NALFD and the natural products that regulate NAFLD through SIRT1 and its associated pathways, and discusses the potential of SIRT1 as a therapeutic target for treating NAFLD and the effectiveness of these related natural products as clinical drugs or dietary supplements. These works may provide some new ideas and directions for finding new therapeutic targets for NAFLD and the development of anti-NAFLD drugs with good pharmacodynamic properties.

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“…Similarly, PLIN5 plays a role in autophagy by diminishing inflammation through deacetylase activity of SIRT1 in hepatocytes under fasting conditions. SIRT1 deacetylates nuclear factor-kappa B (NF-κB), thus inflammation is attenuated by the decreased levels of target genes of NF-κB such as Il-6 , Il-1β , and Tnf-α [ 71 ]. Furthermore, PLIN5 acts as a scaffold in chaperone-mediated autophagy in HepG2 cells demonstrating that co-localization of heat shock protein 70 (Hsp70) and PLIN5 serves as a substrate allowing degradation of LD in cells under FA stimuli, which mimics NAFLD [ 12 ].…”

Section: The Role Of Plin5 In Lipid Metabolism and Nafldmentioning

confidence: 99%

“…The respective report showed that, GCM treatment increased SIRT1 expression in palmitic acid-derived lipotoxicity in AML-12 cells, which in consequence led to decreased expression of inflammatory genes such as Tnf-α and Il -6. Thus depletion of Plin5 or Sirt1 decreases GCM effectivity, revealing the coupled effect of these proteins to balance inflammatory response and lipoapoptosis [ 71 ].…”

Section: The Role Of Plin5 In Lipid Metabolism and Nafldmentioning

confidence: 99%

Understanding the Role of Perilipin 5 in Non-Alcoholic Fatty Liver Disease and Its Role in Hepatocellular Carcinoma: A Review of Novel Insights

Sanchez

Krizanac

Weiskirchen

et al. 2021

IJMS

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Consumption of high-calorie foods, such as diets rich in fats, is an important factor leading to the development of steatohepatitis. Several studies have suggested how lipid accumulation creates a lipotoxic microenvironment for cells, leading cells to deregulate their transcriptional and translational activity. This deregulation induces the development of liver diseases such as non-alcoholic fatty liver disease (NAFLD) and subsequently also the appearance of hepatocellular carcinoma (HCC) which is one of the deadliest types of cancers worldwide. Understanding its pathology and studying new biomarkers with better specificity in predicting disease prognosis can help in the personalized treatment of the disease. In this setting, understanding the link between NAFLD and HCC progression, the differentiation of each stage in between as well as the mechanisms underlying this process, are vital for development of new treatments and in exploring new therapeutic targets. Perilipins are a family of five closely related proteins expressed on the surface of lipid droplets (LD) in several tissues acting in several pathways involved in lipid metabolism. Recent studies have shown that Plin5 depletion acts protectively in the pathogenesis of liver injury underpinning the importance of pathways associated with PLIN5. PLIN5 expression is involved in pro-inflammatory cytokine regulation and mitochondrial damage, as well as endoplasmic reticulum (ER) stress, making it critical target of the NAFLD-HCC studies. The aim of this review is to dissect the recent findings and functions of PLIN5 in lipid metabolism, metabolic disorders, and NAFLD as well as the progression of NAFLD to HCC.

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Involvement of activation of PLIN5-Sirt1 axis in protective effect of glycycoumarin on hepatic lipotoxicity

Cited by 7 publications

References 27 publications

Pharmacological Activities and Pharmacokinetics of Glycycoumarin

Pharmacological Activities and Pharmacokinetics of Glycycoumarin

Biological Role and Related Natural Products of SIRT1 in Nonalcoholic Fatty Liver

Understanding the Role of Perilipin 5 in Non-Alcoholic Fatty Liver Disease and Its Role in Hepatocellular Carcinoma: A Review of Novel Insights

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