Acanthoic acid modulates lipogenesis in nonalcoholic fatty liver disease via FXR/LXRs-dependent manner

Han, Xin; Cui, Zhenyu; Jiang, Song; Piao, Hu‐Ri; Lian, Li-Hua; Hou, Li‐Shuang; Wang, Ge; Zheng, Shuang; Dong, Xiu-Xiu; Nan, Ji‐Xing; Wu, Yan-Ling

doi:10.1016/j.cbi.2019.108794

Cited by 42 publications

(21 citation statements)

References 39 publications

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“…9 FXR is expressed in HSCs and negatively controls HSC activation. 10,11 Adenosine triphosphate (ATP)-activated purinergic ligand-gated ion channel 7 receptors (P2X7rs) play an important role in the generation of inflammatory responses. 12 P2X7r has been identified most frequently in immune cells such as mast cells, macrophages, microglia, and dendritic cells.…”

Section: Introductionmentioning

confidence: 99%

“…FXR could regulate the metabolism of bile acids and the inflammatory response in the liver and intestine. , The expression of FXR was lower in the human liver tissue of patients diagnosed with liver fibrosis or cirrhosis . FXR is expressed in HSCs and negatively controls HSC activation. , Adenosine triphosphate (ATP)-activated purinergic ligand-gated ion channel 7 receptors (P2X7rs) play an important role in the generation of inflammatory responses . P2X7r has been identified most frequently in immune cells such as mast cells, macrophages, microglia, and dendritic cells .…”

Section: Introductionmentioning

confidence: 99%

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20S-Protopanaxatriol Ameliorates Hepatic Fibrosis, Potentially Involving FXR-Mediated Inflammatory Signaling Cascades

Jiang

Cui

Lian

et al. 2020

J. Agric. Food Chem.

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Ginseng has been used as a functional food and tonic for enhancing immune power. Here, the potential protective effect of 20S-protopanaxatriol (M4), the metabolite of protopanaxatriol, against hepatic fibrosis is investigated, which could provide nutritional interventions for disease treatment. M4 could inhibit extracellular matrix (ECM) deposition and reduce the levels of proinflammatory cytokines such as caspase 1, interleukin 1 β (IL-1β), interleukin 1 receptor type 1 (IL1R1), and interleukin 6 (IL-6). M4 also significantly increased the expression of farnesoid X receptor (FXR), suppressed the purinergic ligand-gated ion channel 7 receptor (P2X7r) signaling pathway, and works as an FXR agonist, GW4064. In thioacetamide (TAA)-induced mice, M4 could attenuate the histopathological changes and significantly regulate the expression levels of FXR and P2X7r. M4 ameliorated TAA-induced hepatic fibrosis due to the reduction of P2X7r secretion, inhibition of hepatic stellate cell (HSCs) activation, and inflammation, which were all associated with FXR activation. Hence, M4 might be useful a nutritional preventive approach in antihepatic fibrosis and antihepatic inflammation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

20S-Protopanaxatriol Ameliorates Hepatic Fibrosis, Potentially Involving FXR-Mediated Inflammatory Signaling Cascades

Jiang

Cui

Lian

et al. 2020

J. Agric. Food Chem.

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“…Other research revealed that imperatorin exerts the protective effect against hepatotoxicity induced by excessive acetaminophen similarly by stimulating the SIRT1/FXR pathway (Gao et al, 2020). Moreover, studies have showed that NAFLD may be mitigated through the regulation of SIRT1/FXR signaling pathway (Han et al, 2019). Through the activation of FXR, a major adipogenic regulator called SREBP1 will be regulated and further reduced the protein levels of FASN, ACC1 and SCD in its downstream which are related to lipogenesis (Dong et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effect and Molecular Mechanisms of Hengshun Aromatic Vinegar on Non-Alcoholic Fatty Liver Disease

Zhu¹,

Guan

Tan

et al. 2020

Front. Pharmacol.

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Aromatic vinegar with abundant bioactive components can be used as a food additive to assist the treatment of various diseases. However, its effect on non-alcoholic fatty liver disease (NAFLD) is still unknown. The purpose of this study was to investigate the mechanism of Hengshun aromatic vinegar in preventing NAFLD in vivo and in vitro. Aromatic vinegar treatment was applied to rats fed with a high-fat diet (HFD) and HepG2 cells challenged with palmitic acid (PA). Our results showed that aromatic vinegar markedly improved cell viabilities and attenuated cell damage in vitro. The levels of TC, TG, FFA, AST, ALT, and malondialdehyde (MDA) in HFD-induced rats were significantly decreased by aromatic vinegar. Mechanism investigation revealed that aromatic vinegar markedly up-regulated the level of silent information regulator of transcription 1 (Sirt1), and thereby inhibited inflammation of the pathway through down-regulating the expressions of high mobility group box 1, toll-likereceptor-4, nuclear transcription factor-κB, tumor necrosis factor receptor-associated factor-6, and inflammatory factors. Aromatic vinegar simultaneously increased the expression of farnesoid X receptor and suppressed expressions of lipogenesis related proteins, including fatty acid synthase, acetyl-CoA carboxylase-1, sterol regulatory element binding transcription factor 1, and stearoyl-CoA desaturase-1. These results were further validated by knockdown of Sirt1 using siRNAs silencing in vitro. In conclusion, Hengshun aromatic vinegar showed protective effects against NAFLD by enhancing the activity of SIRT1 and thereby inhibiting lipogenesis and inflammation pathways, which is expected to become a new assistant strategy for NAFLD therapy in the future.

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“…During the development of AFLD, sterol regulatory-element-binding protein 1 (SREBP1) and peroxisome proliferator activated receptor α/γ (PPARα/γ) are important transcriptional regulatory factors that are involved in lipid production and fatty acid oxidation, respectively ( Menon et al ., 2001 ; Han et al ., 2019 ). Our previous study indicated that alcohol could downregulate SREBP1 and PPARα expression while upregulating PPARγ expression ( Yao et al ., 2017a ).…”

Section: Introductionmentioning

confidence: 99%

Betulin Targets Lipin1/2-Meidated P2X7 Receptor as a Therapeutic Approach to Attenuate Lipid Accumulation and Metaflammation

Dou

Jiang

et al. 2022

Biomol Ther (Seoul)

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The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch ( Betula pubescens ), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/kg) by oral gavage once per day. In vitro , MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo , BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7r-NLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

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Acanthoic acid modulates lipogenesis in nonalcoholic fatty liver disease via FXR/LXRs-dependent manner

Cited by 42 publications

References 39 publications

20S-Protopanaxatriol Ameliorates Hepatic Fibrosis, Potentially Involving FXR-Mediated Inflammatory Signaling Cascades

20S-Protopanaxatriol Ameliorates Hepatic Fibrosis, Potentially Involving FXR-Mediated Inflammatory Signaling Cascades

Hepatoprotective Effect and Molecular Mechanisms of Hengshun Aromatic Vinegar on Non-Alcoholic Fatty Liver Disease

Betulin Targets Lipin1/2-Meidated P2X7 Receptor as a Therapeutic Approach to Attenuate Lipid Accumulation and Metaflammation

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