CBD Alleviates Liver Injuries in Alcoholics With High-Fat High-Cholesterol Diet Through Regulating NLRP3 Inflammasome-Pyroptosis Pathway.

Yuanling Huang,Xuye Jiang,Jing Luo,Zhaoyang Tang,Zhenfeng Zhang,Lili Yang,Yingying Gu,Yujia Zhou,Nengzhi Pang

doi:10.3389/fphar.2021.724747

Abstract

Alcohol abuse and high-fat diet–induced liver diseases have been the most prevalent chronic liver diseases and the leading reasons for liver transplantation around the world. Cannabidiol (CBD) is a botanical component extracted from marijuana plants without psychoactive impact. In our previous reports, we found that CBD can prevent fatty liver induced by Lieber–DeCarli ethanol diet or non-alcoholic fatty liver disease (NAFLD) induced by high-fat high-cholesterol diet. The current work is a further study on whether CBD can alleviate liver injuries induced by ethanol plus high-fat high-cholesterol diet (EHFD), which is a model simulating heavy alcohol drinkers in a Western diet. A mice liver injury model induced by EHFD for 8 weeks was applied to explore the protective properties of CBD and the underlying mechanisms. We found that CBD prevented liver steatosis and oxidative stress induced by EHFD. CBD treatment inhibited macrophage recruitment and suppressed activation of NFκB–NLRP3–pyroptosis pathway in mice livers. The hepatoprotective property of CBD in the current model might be a result of inhibition of inflammation via alleviating activation of the hepatic NFκB–NLRP3 inflammasome–pyroptosis pathway by CBD.

Highlights

Prolonged heavy consumption of alcohol-induced liver injuries accounts for the increasing morbidity and mortality rates worldwide (Xu et al, 2017)
Our results demonstrated that CBD exerted a beneficial effect in preventing liver injury induced by ethanol plus high-fat high-cholesterol diet (EHFD) diet; 1) CBD reduced lipid accumulation, liver injury, and oxidative stress induced by EHFD diet; 2) CBD attenuated inflammation, by suppressing activation of NF-κB and activation of the NLRP3 inflammasome; and 3) CBD inhibited cleaved GSDMD formation induced by EHFD treatment
Our research is the first to have examined the function of CBD, which protected the liver from injury and inflammation induced by EHFD diet, by regulating the NFκB–NLRP3 inflammasome–pyroptosis pathway

Summary

Introduction

Prolonged heavy consumption of alcohol-induced liver injuries accounts for the increasing morbidity and mortality rates worldwide (Xu et al, 2017). Individuals abusing alcohol are usually accompanied with a superfluous calorie intake which will raise their predisposition of developing a metabolic disorder such as obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM) (Boyle et al, 2018). It has been recognized for many years that chronic heavy alcohol drinking can have synergistic or exacerbating effects on obesity and metabolic syndrome, CBD Alleviates Liver Pyroptosis which can further promote the formation of fatty Rinella (2015a) liver and aggravate the progression of ALD (Boyle et al, 2018) (Rinella, 2015b). We applied chronic administration of alcohol with a high-fat high-cholesterol diet (EHFD) to induce hepatic injury in mice

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