TABLE 4.

Anti-fibrotic effect of cannabinoids.

Compound	The mechanism of action	References
Endocannabinoids
	Suppressing the proliferation of HSCs and induces their necrosis	Parfieniuk and Flisiak (2008)
	Generally considered as a fibrogenic agent, however, it is able to suppress fibrosis via the membrane cholesterol-dependent mechanism.	Tam et al. (2011)
	The inhibition of collagen deposition and suppression of collagen type I and III gene expression, α-SMA, MMP2, MMP9, and TIMP1. These effects were mediated through the PPARα mechanisms.	McVicker and Bennett (2017)
Phytocannabinoids
	The apoptosis induction of HSCs as result of the induction of endoplasmic reticulum stress and the enhancement of the pro-apoptotic pathway IRE1/ASK1/c-Jun N-terminal kinase.	Lim et al. (2011)
	The inhibition of miofibroblast proliferation and stellate cells, the induction of their apoptosis via CB2 receptors.	Tam et al. (2011)
Synthetic cannabinoids
	The suppression of collagen type I and α-SMA, inhibition of fibroblast proliferation and migration. The down-regulation of the TGF-β1/Smad2 pathway.	Fu et al. (2017) Muñoz-Luque et al. (2008)
	The suppression of expression of fibrogenic mediators (TIMP-1, TGF-β, MMP13, MMP2, MMP9, MMP1, MMP8, TNF-α, MCP-1)	Giannone et al. (2012)
	The downregulation of expression of collagen I, collagen III, TIMP-1, and plasminogen activator inhibitor. The inhibition of the TGF-β1/SMAd3 pathway.	Li et al. (2016)
	The suppression of glucose transporter 2; reduction in glucose reabsorption.	Hinden et al. (2018)
	The suppression of glucose transporter 2; reduction in glucose reabsorption.	Hinden et al. (2018)
	Stimulating PPAR-γ signaling	Gonzalez et al. (2012)