Therapeutic Effects of Turnera diffusa Extract Against Amitriptyline-Induced Toxic Hepatic Inflammation

Effective, targeted therapy for chronic liver disease nonalcoholic steatohepatitis (NASH) is imminent. MicroRNAs (miRNAs) are a potential therapeutic target, and natural products that regulate miRNA expression may be a safe and effective treatment strategy for liver disease. Here, we investigated the functional role of miR-451 and the therapeutic effects of genistein in the NASH mouse model. MiR-451 was downregulated in various types of liver inflammation, and subsequent experiments showed that miR-451 regulates liver inflammation via IL1β. Genistein is a phytoestrogen with anti-inflammatory and anti-oxidant effects. Interestingly, we found that the anti-inflammatory effects of genistein were related to miR-451 and was partially antagonized by the miR-451 inhibitor. MiR-451 overexpression or genistein treatment inhibited IL1β expression and inflammation. Taken together, this study shows that miR-451 has a protective effect on hepatic inflammation, and genistein can be used as a natural promoter of miR-451 to ameliorate NASH.

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Eritoran Attenuates Hepatic Inflammation and Fibrosis in Mice with Chronic Liver Injury

Cells ◽

10.3390/cells10061562 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1562

Author(s):

Yun-Cheng Hsieh ◽

Kuei-Chuan Lee ◽

Pei-Shan Wu ◽

Teh-Ia Huo ◽

Yi-Hsiang Huang ◽

...

Keyword(s):

Liver Injury ◽

Fast Food ◽

Transforming Growth Factor ◽

Nuclear Translocation ◽

Chronic Liver ◽

Therapeutic Effects ◽

Hepatic Inflammation ◽

Chronic Liver Injury ◽

Tlr4 Signaling ◽

Primary Mouse

Toll-like receptor 4 (TLR4) signaling plays a key role in liver inflammation and fibrosis. The therapeutic effects of eritoran, a TLR4 antagonist, in mice with chronic liver injury remained unclear. C57BL/6 mice were fed a fast-food diet (FFD) or treated with carbon tetrachloride (CCl4) to induce chronic liver injury. Eritoran (10 mg/kg) or a vehicle was randomly intraperitoneally administered to the FFD-fed mice and the CCl4-injured mice. Primary mouse liver cells were cultured with lipopolysaccharide (LPS) or eritoran. In both FFD and CCl4 mouse models, eritoran significantly reduced serum ALT levels and decreased hepatic inflammatory cell infiltration without altering hepatic steatosis. Additionally, eritoran attenuated liver fibrosis by decreasing hepatic stellate cells (HSCs) activation and the abundance of α-smooth muscle actin and transforming growth factor-β1. Hepatic TLR4 downstream signaling including MyD88 expression, NF-κB p65 nuclear translocation, p38 and JNK phosphorylation were successfully inhibited by eritoran. In the in vitro study, LPS-induced nuclear translocation of NF-κB in primary HSCs and Kupffer cells was significantly suppressed by eritoran. In conclusion, eritoran attenuated hepatic inflammation and fibrosis by inhibition of the TLR4 signaling pathway in mice with chronic liver injury. Eritoran may serve as a potential drug for chronic liver disease.

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Nor-Ursodeoxycholic Acid as a Novel Therapeutic Approach for Cholestatic and Metabolic Liver Diseases

Digestive Diseases ◽

10.1159/000454904 ◽

2017 ◽

Vol 35 (3) ◽

pp. 288-292 ◽

Cited By ~ 13

Author(s):

Emina Halilbasic ◽

Daniel Steinacher ◽

Michael Trauner

Keyword(s):

Ursodeoxycholic Acid ◽

Therapeutic Approach ◽

Liver Diseases ◽

Side Chain ◽

Therapeutic Effects ◽

Hepatic Inflammation ◽

Parenchymal Liver ◽

Health And Disease ◽

Metabolic Liver Diseases ◽

Novel Therapeutic

Norursodeoxycholic acid (norUDCA) is a side-chain-shortened derivative of ursodeoxycholic acid with relative resistance to amidation, which enables its cholehepatic shunting. Based on its specific pharmacologic properties, norUDCA is a promising drug for a range of cholestatic liver and bile duct disorders. Recently, norUDCA has been successfully tested clinically in patients with primary sclerosing cholangitis (PSC) as first application in patients. Moreover, hepatic enrichment of norUDCA facilitates direct therapeutic effects on both parenchymal and non-parenchymal liver cells, thereby counteracting cholestasis, steatosis, hepatic inflammation and fibrosis, inhibiting hepatocellular proliferation, and promoting autophagy. This may open its therapeutic use to other non-cholestatic and metabolic liver diseases. This review article is a summary of a lecture given at the XXIV International Bile Acid Meeting (Falk Symposium 203) on “Bile Acids in Health and Disease” held in Düsseldorf, on June 17-18, 2016 and summarizes the recent progress of norUDCA as novel therapeutic approach in cholestatic and metabolic liver disorders with a specific focus on PSC.

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The Effect of Dietary Glutathione and Coenzyme Q10 on the Prevention and Treatment of Inflammatory Bowel Disease in Mice

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.74.1.74 ◽

2004 ◽

Vol 74 (1) ◽

pp. 74-85 ◽

Cited By ~ 5

Author(s):

Liu ◽

Russell ◽

Smith ◽

Bronson ◽

Milbury ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Dextran Sulfate ◽

Coenzyme Q ◽

Histological Evaluation ◽

Therapeutic Effects ◽

Prevention Study ◽

Prevention And Treatment ◽

Inflammatory Bowel ◽

Pre Treatment

Because reactive oxygen species have been implicated as mediators of inflammatory bowel disease (IBD), we evaluated the potential preventive and therapeutic effects of two dietary antioxidants, glutathione (GSH) and coenzyme Q10 (CoQ10) on dextran sulfate sodium (DSS)-induced colitis in mice. Fifty female 8-wk old Swiss-Webster mice were randomly assigned to 4 groups for a pre-treatment 'prevention' study: (1) GSH (1% of diet); (2) CoQ10 (200 mg/kg/d); (3) DSS only (3% of drinking water); (4) control (no treatment). The mice in groups 1 and 2 were fed with GSH or CoQ10 for 21 wks, and the mice in groups 1, 2 and 3 were provided DSS from wk 7 for 4 cycles (1 cycle = 1 wk DSS followed by 2-wk water). Another 50 mice were randomly assigned to 4 groups for a 21-wk 'treatment' study where the mice in groups 1, 2, and 3 were administered DSS for 6 cycles (18 wks) to induce colitis. GSH and CoQ10 were added from wk 7 until the completion of the protocol. Loose stools and hemocult positivity were modestly but significantly reduced with GSH or CoQ10 at several periods during the intervention in both the prevention and treatment studies. In contrast, histological evaluation revealed increases in colonic dysplasia and ulceration with GSH or CoQ10. Thus, in this mouse model, GSH and CoQ10 appear to have a beneficial effect on acute signs of IBD, but may have an adverse impact on the chronic pathophysiology of the disease. Further studies using additional animal models are required to determine whether GSH or CoQ10 provide a favorable or unfavorable benefit:risk ratio in the prevention or treatment of IBD.

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