Table 4.

The role of silybin in digestive system diseases.

Diseases	Key associated effect	Regulated factors	Reference
Liver fibrosis	↑Nrf2 signaling pathway; ↑ expression of antioxidant enzymes; ↓ and oxidative stress	↑ Nrf2 signaling pathway, ↑SOD, ↑GSH,↓ ROS	(61)
	Repair mitochondrial membrane phospholipids; ↓ succinate accumulation; ↓ and hepatic stellate cell activation	↑ CRLS1, ↓ MCT1, ↑ SDHA/SDHB	(63)
	↑SIRT2, deacetylation of NF-κB p65; ↓nuclear translocation, restore the activity of CYP3A	↓ NF-κB signaling pathway, ↓ PARP-1,↑ NAD+	(14)
	↑Activation of FXR regulates bile acid metabolism; ↓ HSC activation, and proliferation	↑ Cyp7a1,↑ Sult2a8,↓ Slc51b/OSTβ	(64)
	↑ AMPK signaling pathway; ↓ TGF-β1/Smad2/3 pathway; ↓liver inflammation and fibrosis	↑ AMPK signaling pathway,↓ TGF-β1/Smad2/3 pathway	(66)
	Blocks the oxidative stress activation loop from hepatocytes to HSCs, and exerts synergistic anti-fibrotic effects when combined with GS-9973	↓ ROS	(67)
	Synergistic anti-fibrotic effect in combination with the SYK inhibitor GS-9973	↓SYK kinase	(68)
Gastritis	↓ Phosphorylation and nuclear translocation of NF-κB p65 and STAT3 block their synergistic pro-inflammatory effect	↓ COX-2,↓ iNOS	(69)
Ulcerative colitis	Remodel the gut microbiome, ↑ (R)-2,3-dihydroxyisovaleric acid; the metabolite targets GAT-3; ↑ GAT-3/RARβ/RORγt signaling axis; ↓ pro-inflammatory Th17 cell differentiation	↑ GAT-3/RARβ/RORγt signaling axis	(70)
Intestinal tumor	For normal intestinal epithelial cells:↑mitochondrial membrane, metabolism, and proliferation	↑ TGF-β,↓ TNF-α	(17)
	For intestinal tumor cells: ↓proliferation, induce apoptosis	↓ IL-1, ↓ IL-6, ↓ TGF-β	(17)
Gut-liver axis-related injury	↑ Solubility of the HP-β-CD complex restores intestinal flora and barrier function, ↓ intestinal-derived liver inflammation, and lipid accumulation		(71)

“↑” represents silybin’s promoting effect. “↓” represents silybin’s inhibiting effect.