Role of baicalin as a potential therapeutic agent in hepatobiliary and gastrointestinal disorders: A review

Table 1 In vitro hepatoprotective effects of baicalin on different cell lines

Disease/type of study	Cell line	Dose	Mechanism/target pathways	Ref.
Palmitic acid-induced fatty liver	AML-12 hepatocytes	6.25-25 μM	ER stress↓; TXNIP/NLRP-3 pathway↓	[50]
Hypoxic liver injury	L02 human hepatocytes	100 μmol/L	Caspase-3, caspase-9, and Bax↓	[58]
Acetaldehyde induced EMT	HepG2 cells	20-100 mmol/L	TGF-β/Smad pathway↓	[59]
ns-PEF induced liver injury	L02 hepatocytes	60 μM	MTP stabilization, ROS↓	[60]
Hemin-nitrite-H2O2 induced liver injury	HepG2 cells	5 μM and 25 μM	Lipid peroxidation↓; GSH depletion↓	[61]
PDGF-BB induced fibrosis	HSCT6 hepatocytes	150 μM	miR-3595↓; ACSL-4↑	[69]
BDL-induced fibrosis	HSCs	67.5-270 μM	Wnt pathway↓; PPAR-γ↓	[70]
LPS-induced hepatitis	L20, THLE cell lines	25-100 μM	TUG-1↑; p38-MAPK↓; JNK pathway↓	[82]
Viral hepatitis	HuH7, HepG2 cells	75 μg/mL	NF-κB pathway↓	[83]
	pHBV1.2HepG2 cells	10 μM	HNF-4α/HNF-1α↓	[84]
	HepG2.2.15 cells	10 μg/kg	HBsAg, HBeAg↓	[85]
	PBMCs	50-200 mg/mL	Mitochondrial pathway↑; Caspase 3↑	[87]
HCC	HepG2-HCC	100 μmol/L	ER-mediated TF-6↑; S-2P protein↑	[94]
	SMMC7721-HCC cells	160 μM	CD47↓	[95]
	SMMC7721, HepG2-HCC cells	40 μM	STAT3, IFN-γ↓; Block PDL-1/PD-1 pathway	[96,97]

ACSL-4: Long chain fatty acid CoA ligase 4; AML: Alpha mouse liver; BDL: Bile duct ligation; EMT: Epithelial-mesenchymal transition; ER: Endoplasmic reticulum; GSH: Reduced glutathione; HCC: Hepatocellular carcinoma; HSCs: Hepatic stellate cells; LPS: Lipopolysaccharide; MAPK: Mitogen-activated protein kinase; MTP: Mitochondrial transmembrane potential; NLRP-3: Nod-like receptor protein 3; nsPEF: Nanosecond-pulse electric field; PBMCs: Peripheral blood mononuclear cells; PDGF-BB: Platelet-derived growth factor BB; PPAR-γ: Peroxisome proliferator-activated receptor-γ; ROS: Reactive oxygen species; THLE: Transformed human liver epithelial; TUG-1: Taurine upregulated-1; TXNIP: Thioredoxin-interacting protein.

Table 2 In vivo protective effects of baicalin on various hepatobiliary and colorectal disorders

Disease/type of study	Dose	Mechanism/target pathway	Ref.
MCD induced NASH	200 mg/kg	TNF-α, MCP-1, IL-1β↓; Caspase-3↓; SREBP-1c, FASN, PPAR-α, CPT-1α↓	[46]
	50 mg/kg	TNF-α, IL-6, IL-1β↓; TLR-4 pathway↓	[47]
High fat diet induced non- alcoholic FLS	25-100 mg/kg	PPAR-γ receptors↑	[48]
	5 g/kg	AST, ALT↓; TNF-α, MCP-1↓; JNK-P↓; COX-2, CYP-2E1↓	[49]
Orotic acid induced FLS	12.5-50 mg/kg	SREBP-1c↓; AMPK↑	[45]
Alcohol-induced liver injury	120 mg/kg	TNF-α, IL-6, IL-1β↓; SOD, GSH-Px↑; Block sonic-hedgehog pathway	[19]
	200 mg/kg	HO-1, NRF-2 pathway↑	[54]
Acetaminophen-induced liver injury	30 mg/kg	IL-17↓	[53]
	80 mg/kg	NRF-2, Keap-1↓	[55]
	60 mg/kg	ERK↓	[56]
NG-nitro-L-arginine methyl ester induced liver injury	100 mg/kg	Caspases-3 and 9↓; Bcl-2↑	[57]
LPS-induced sepsis	74 mg/kg	Amino acid metabolism↑; TCA cycle↑	[62]
BDL-induced liver fibrosis	200 mg/kg	SMA, CTGF↓; TNF-α, MIP-1α, IL-1β, MIP-2↓	[68]
CCl4-induced fibrosis	100 mg/kg	TGF-β1, hydroxyproline, type III collagen, hyaluronic acid laminin↑; SOD, GSH-Px↓	[71]
	25-100 mg/kg	PPAR-γ↓; TGF-β1↓	[72]
17α- ethinyl estradiol-induced cholestasis	50-200 mg/kg	TBA, AST, ALT, ALP↓; TNF-α, IL-6 and IL-1β↓	[75,76]
		Sirt1/HNF-1α/FXR pathway↓	[77]
Hepatitis B in young duck model	10 μg/kg	HBsAg, HBeAg↓; HNF-4α/HNF-1α↓	[85]
Hepatitis in male BALB/c mouse model	100-200 mg/kg	TNF-α, IL-6 and IFN-γ↓	[86]
Hepatitis in male Sprague-Dawley rat model	0.5-5.0 mg/kg	ALT, AST↓	[86]
HCC	50 mg/kg	RelB/p52 pathway↑	[93]
CRC in mice	100, 200 mg/kg	TGF-β/Smad pathway↓	[100]
TNBS-induced UC	30-90 mg/kg	IL-1β, TNF-α↓; Caspase 9, Bcl-2↓; IKK/IKB/NF-κB pathway↓	[107]
	5-20 mg	IL-1β, TNF-α, IL-6↓; TLR4/NF-κB pathway↓	[108]
	30-120 mg/kg	Catalase, GSH-PX, SOD↑; Bcl-2↑; MDA↓; TGF-β, Bax↓	[109]
HTHE-induced UC	100 mg/kg	NF-κB, MAPK pathways↓	[110]
DSS-induced UC	50-150 mg/kg	MPO, NO↓; IL-1β, TNF-α and IL-6↑	[111]
	100 mg/kg	TLR-4/NF-κB-p65/IL-6 pathway↓; TNF-α, IL-6, IL-13↓	[112]
TNBS-induced UC	10 mg/kg	MIF, MCP-1, MIP-3a↓	[113]
	20-100mg/kg	Maintain Th17/Treg balance	[114]

ALP: Alkaline phosphatase; ALT: Alanine transaminase; AST: Aspartate transaminase; AMPK; AMP-activated protein kinase; Bcl-2: B-cell lymphoma 2; CCL₄: Carbon tetrachloride; COX-2: Cyclooxygenase-2; CPT-1α: Carnitine palmitoyl-transferase-1α; CRC: Colorectal cancer; CTGF: Connective tissue growth factor; CYP-2E1: Cytochrome P450 2E1; DSS: Dextran sulfate sodium; ERK: Extracellular signal-regulated kinase; FASN: Fatty acid synthase; FLS: Fatty liver syndrome; FXR: Farnesoid X receptor; GSH-Px: Glutathione peroxidase; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; HNF: hepatic nuclear factor; HO-1: Heme oxygenase 1; HTHE: High temperature and humid environment; IL-1: Interleukin-1; JNK: c-Jun N-terminal kinase; Keap-1: Kelch-like ECH-associated protein 1; MCD: Methionine- and choline-deficient; MCP-1: Monocyte chemoattractant protein-1; MIP-1α: Macrophage inflammatory protein-1 alpha; NASH: Non-alcoholic steatohepatitis; NF-κB: Nuclear factor-kappa B; NRF2: Nuclear factor-erythroid factor 2-related factor 2; PPAR-γ: Peroxisome proliferator-activated receptor-γ; Sirt: Sirtuin; SMA: Smooth muscle actin; SOD: Superoxide dismutase; SREBP: Sterol regulatory element-binding protein; TBA: Total bile acid; TCA: Tricarboxylic acid cycle; Th17: T helper 17 cells; TLR-4: Toll-like receptor 4; TNBS: 2,4,6-trinitrobenzenesulfonic acid; TNF-α: Tumor necrosis factor-alpha; Treg: Regulatory T cells; UC: Ulcerative colitis.