Hepatoprotective effects of silybin in liver fibrosis

Table 1 Different phases of inflammatory conditions in liver that progress towards the fibrosis of the liver tissues

Extent of damage	Possible cellular mechanisms
Stage 1: Cell recruitment	Neutrophills and macrophages activation, hence, activation of reticuloendothelial cells
Stage 2: Inflammatory cytokines	Increase in the levels of TNF-α, TGF-β, PGE2, IL-1 along with decrease in the levels of SOD, GSH
Stage 3: Tissue damage	Increase in extracellular matrix production, deposition and degradation along with decrease in Tissue inhibitors of matrix metalloproteinases
Stage 4: Fibrinogenesis	Persistant activation of inflammatory cascade is associated with the destruction or liver parenchyma which eventually leads to fibrosis

PGE₂: Prostaglandin E₂; TNF-α: Tumor necrosis factor α; IL: Interleukin; SOD: Superoxidedismutase; TGF-β: Transforming growth factor-β.

Table 2 Protection mechanisms to liver cells against various toxicities by silybin

Disease/liver toxicity	Silybin proposed mechanisms	Ref.
Acetaminophen, methotrexate, ethanol, carbon tetrachloride toxicity	Decreased cytotoxicity, increased antioxidant enzymes; i.e., SOD, GSH, decreased cytokines production; i.e., IL-1, IL-6, TNF production	[68-71]
Free radicals toxicity	Increased antioxidant enzymes, i.e., SOD, glutathione; decreased lipoxygenase and leukotrienes	[70,72]
Iron toxicity	Decreased inflammatory cytokines; i.e., TGF-β and interleukins, decreased lipid peroxidation and oxidative damage	[12]
Viruses & natural toxins	Decreased alanine transaminase, aspartate transaminase and γ-glutamyl transpeptidase	[72]

PGE₂: Prostaglandin E₂; TNF-α: Tumor necrosis factor α; IL: Interleukin; SOD: Superoxide dismutase; TGF-β: Transforming growth factor-β.