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Curcumin Alleviates High-fat Diet-induced Nonalcoholic Steatohepatitis via Improving Hepatic Endothelial Function
Jiazhen Wu1,2, Mengyao Li1, Ning Huang1
1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Journal of Agricultural and Food Chemistry
|June 30, 2023
Summary
Curcumin improves nonalcoholic steatohepatitis (NASH) by enhancing liver endothelial function, with its metabolite tetrahydrocurcumin (THC) playing a key role. Intestinal microbes are crucial for this beneficial biotransformation.
Area of Science:
- Hepatology and Gastroenterology
- Endothelial Biology
- Microbiome Research
Background:
- Nonalcoholic steatohepatitis (NASH) pathogenesis involves hepatic endothelial dysfunction.
- Curcumin (Cur) shows potential hepatoprotective effects, but its role in NASH-related endothelial dysfunction and its bioavailability issues require investigation.
- The biotransformation of Curcumin may influence its therapeutic efficacy.
Purpose of the Study:
- To investigate the effects of Curcumin and its bioconversion products on hepatic endothelial function in a rat model of high-fat diet-induced NASH.
- To elucidate the underlying mechanisms, including the role of intestinal microbiota.
Main Methods:
- High-fat diet-induced NASH model in rats.
- Administration of Curcumin with and without antibiotics.
- Analysis of hepatic lipid accumulation, inflammation, and endothelial function markers.
- Assessment of Curcumin biotransformation to tetrahydrocurcumin (THC) in liver and intestinal contents.
- In vitro studies using L02 cells to evaluate the effects of Curcumin and THC on liver sinusoidal endothelial cells.
Main Results:
- Curcumin ameliorated hepatic lipid accumulation, inflammation, and endothelial dysfunction in NASH rats by inhibiting NF-κB and PI3K/Akt/HIF-1α pathways.
- Antibiotic treatment reduced these beneficial effects, correlating with decreased tetrahydrocurcumin (THC) levels, indicating the role of gut microbiota.
- Tetrahydrocurcumin (THC) demonstrated superior efficacy compared to Curcumin in restoring liver sinusoidal endothelial cell function and attenuating steatosis and injury in vitro.
Conclusions:
- Curcumin's therapeutic effects in NASH are significantly linked to the improvement of hepatic endothelial function.
- Intestinal microbial biotransformation of Curcumin into THC is a critical factor mediating its hepatoprotective effects against NASH.
- Targeting Curcumin biotransformation and the gut microbiome may offer novel therapeutic strategies for NASH management.
