Cannabidiol regulates the activation of hepatic stellate cells by modulating the NOX4 and NF-xB pathways

Cannabidiol (CBD) is an extract of natural cannabinoids that has therapeutic implications for a variety of ailments, such as neurological diseases, cardiomyopathy, and diabetes, due to its strong anti-inflammatory and oxidative stress properties. Our purpose was to reveal the possible underlying mechanisms and effect of CBD on the glucose oxidase (GO)-induced activation of HSC-T6 and LX-2 cells. The results showed that CBD effectively inhibited the proliferation and activation of HSC-T6 and LX-2 cells, and reduced the production of profibrotic factors to different degrees. CBD disrupted the NOX4 signalling pathway in activated HSC-T6 and LX-2 cells, reduced ROS and MDA levels, and increased SOD and GSH levels, thereby stabilizing the oxidative imbalance. CBD significantly inhibited the phosphorylation and degradation of NF-xB and IxB alpha, and decreased the release of TNF-alpha, IL-1 beta and IL-6. Moreover, CBD and an NF-xB-specific inhibitor (CAPE) effectively inhibited the expression of alpha-SMA, COL I, TNF-alpha and IL-1 beta to promote collagen metabolism and inhibit the inflammatory response. Overall, CBD inhibited HSCs activation through a and the mechanism involving the inhibition of NOX4 and NFxB-dependent ROS regulation, thereby reducing inflammation and ameliorating oxidative imbalances.