TABLE 1.

Pharmacological details of action of Danshen compounds in experimental colitis.

Compound/Product	Animal model	Colitis symptoms	Immunology and cytokines	Free radicals and oxidative stress	Cell death	Multiple signaling pathways		Intestinal barrier	Microenvironment	Cites
Danshen powder for injection	BALB/C mice (TNBS(100 mg/kg)); BALB/C mice (TNBS(1%) )	DAI↓ Colorectal damage↓	TNF-α↓ T-bet↓ T-bet (mRNA)↓ MPO activity↓ Foxp3 (mRNA)↑ Foxp3↑							Xu Dekui et al. (2012) Xu et al. (2014)
Total phenolic acids + Tanshinones	C57BL/6 mice (DSS (2%))	DAI↓ Colon length↑ Colorectal damage↓	TNF-α↓ IL-6↓ IL-1β↓ COX-2↓			NF-κB↓ TLR4↓ p-PI3K↓ p-AKT↓ mTOR↓				Peng et al. (2020)
Salvianolic acid A	Sprague Dawley rats (DSS (3%))	Body wight↑ Liver weight↓ DAI↓ Colorectal damage↓	TNF-α(mRNA)↓ IL-1β(mRNA)↓ IL-6 (mRNA)↓ TGF-β(mRNA)↓				ZO-1 (mRNA) ↑ Occuldin (mRNA)↑		Gut microbial diversity↑ Akkermansia spp.↑	Wang et al. (2018)
Salvianolic acid B	C57BL/6 mice (DSS(2.2%)) Sprague-Dawley rats (TNBS/IL-1β); C57BL/6 mice (DSS(4%)) (IL-1β; 200 mg/kg)	DAI↓ Colon length↑ Body weight↑ Colorectal damage↓ Food intake↑	Infiltration: CD3+↓ CD177+↓ F4/80+↓ TNF-α↓ IL-6↓ IL-1β↓ MPO↓	iNOS↓ MDA↓ GSH↑ SOD↑ ROS↓	Apoptosis↓ Bax↓ Bcl-2↑	Production of acetic acid, propionic acid and valeric acid ↑ MLCK↓ miRNA-1↑ NOX4↓	ZO-1↑ Claudin-2↓ Monolayer integrity↑ Occludin↑		S24-7↑ Bacteroides↓	Xiong et al. (2016), Wu et al. (2018), Feng et al. (2020)
Tanshinol	C57BL/6J mice (5% DSS)	Colon length↑ Colorectal damage↓ Percent survival↑	TNF-α↓ IL-6↓ IL-1β↓			VLDLR↑				Zhu et al. (2021)
Tanshinone IIA sodium sulfonate	C57BL/6J mice (LPS(30 mg/kg))	Colorectal damage↓ Length of jejunum and ileum villus↑	TNF-α↓ IL-6↓ IL-1β↓ TNF-α(mRNA)↓ IL-6 (mRNA)↓ IL-1β(mRNA)↓		LC3-II/LC3-I ↑ Beclin-1↑ Beclin-1 (mRNA)↑ LC3 (mRNA)↑ Autophagosome formation↑					Yang et al. (2018)
Tanshinone IIA	BALB/C mice (DSS( 4%) ); BALB/c mice (TNBS); BC57BL/6 mice (DSS( 3%) )	Diarrhea↓ Bleeding↓ Body weight↑ Colorectal damage↓ Colon length↑ DAI↓	TNF-α(mRNA)↓ IL-6 (mRNA)↓ MCP(mRNA)↓ TNF-α↓ IL-1β↓ MPO↓ Ly6G positive lymphocyte infiltrates↓ MMP-8↓ IL-6↓ IL-10↓	iNOS (mRNA)↓ GSH↑ ROS↓		PXR transactivation↑ DNA-binding by PXR↑ PXR↑ PXR (mRNA)↑ CYP3A4↑ CYP3A4 (mRNA)↑ CYP3A11 (mRNA)↑ CYP3A13 (mRNA)↑ MDR1α(mRNA)↑ GSTα1 (mRNA)↑ NF-κB p65↓	Intestinal permeability↓			Zhang et al. (2015), Bai et al. (2008), Liu et al. (2016)
15,16-Dihydrotanshinone Ӏ	C57BL/6 mice (DSS(5%))	DAI↓Colon length↑ Body weight↑ Colorectal damage↓	TNF-α↓ MPO↓ IL-6↓ COX-2↓ IL-1β↓	iNOS↓	RIP1↓ RIP3↓ caspase-8↑ MLKL↓	HMGB1↓				Guo et al. (2018)
Cryptotanshinone	C57BL/6 mice (DSS(4.5%))	DAI↓ Colon length↑ Body weight↑ Colorectal damage↓	TNF-α↓ MPO↓ IL-6↓ IL-1β↓ COX-2↓	iNOS↓						Min et al. (2020)
Miltirone	C57BL/6 mice (TNBS (100 mg/kg))	DAI↓ Colon length↑ Body weight↑ Colorectal damage↓	TNF-α↓ IL-6↓ IL-1β↓ IL-8↓			TLR4↓ MyD88↓ NF-κB p65↓ TLR4 (mRNA)↓ MyD88 (mRNA)↓ IQGAP2↑ IQGAP2 (mRNA)↑				Wang et al. (2017a)
Rosmarinic acid	ICR mice (DSS(5%)); C57BL/6 mice (DSS(3%))	Body weight↑ DAI↓ Spleen weight↓ Colorectal damage↓	MPO↓ IL-6↓ IL-1β↓ IL-22↓ COX-2↓ TNF-α↓ COX-2 (mRNA)↓ TNF-α(mRNA)↓ IL-6 (mRNA)↓ L-1β(mRNA)↓	iNOS↓ NO↓ iNOS(mRNA)↓	Survivin↓ Bcl-2 ↓ Bcl-xL↓ XIAP↓ Cdk4↓ Cyclin D1↓	NF-κB p65↓ p65 translocation↓ p-IκBα↓ IκBα↑ p-STAT3↓ p-STAT3 translocation↓				Jin et al. (2017), Zhao et al. (2018)
Rosmarinic acid methyl ester	Rats (TNBS)	Colorectal damage↓	MPO↓ CINC-3↓ iNOS↓ COX-2↓	HIF-1α↑ Stabilization of HIF-1α↑ Inhibition of HPH↑ VEGF↑						Jeong et al. (2015)
Asiatic acid	C57BL/6 mice (DSS(2.5%))	DAI↓ Colon length↑ Body weight↑ Colorectal damage↓	TNF-α↓ IL-6↓ IL-1β↓ MPO↓ IFN-γ↓ TNF-α(mRNA)↓ IL-6 (mRNA)↓ IL-1β(mRNA)↓ IFN-γ(mRNA)↓		Caspase-1 activation↓ Caspase-1 p10↓					Guo et al. (2015)
β-Caryophyllene	CD1 mice (DSS(3%))	DAI↓ Colon length↑ Body weight↑ Colorectal damage↓	TNF-α(mRNA)↓ IL-1β(mRNA)↓ CXCL1/KC(mRNA)↓ IFN-γ(mRNA)↓ IL-4↑ MPO activity↓ Foxp3 (mRNA)↑ TNF-α↓ IL-1β↓ CXCL1/KC↓ IFN-γ↓ MIP-2↓			CB2(mRNA)↓ CINC-1 (mRNA)↓ PPARγ(mRNA)↑ NF-κB p65↓ p-CREB↓ p-ERK↓ p-IKKα/β↓ Cleaved caspase-3↓				Bento et al. (2011)
Protocatechuic acid	BALB/C mice (TNBS); Wistar rat (DSS(5%)); ICR mice (TNBS(2.5%))	Body weight↑ Colorectal damage↓DAI↓ Colon length↑	MPO↓ TNF-α↓ IL-6↓ IL-1β↓ COX-2↓ TNF-α(mRNA)↓ IL-6 (mRNA)↓ IL-1β(mRNA)↓ COX-2 (mRNA)↓	Nrf2↑ MDA ↓ GSH↑ SOD↑ CAT↑ GST↑ GPx↑ H2O2↓ iNOS↓ NO↓		SphK1↓ S1PR1↓ SphK1 (mRNA)↓ S1PR1(mRNA)↓ S1PL (mRNA)↑ SGPP2(mRNA)↓ S1P↓ p-STAT3↓ p-AKT↓ p-ERK1/2↓ NF-κB p65↓ AST↓ ALT↓ ALP↓				Crespo et al. (2017); Farombi et al. (2016); Jang et al. (2016)
Magnesium lithospermate B	BALB/C mice (DSS(5%))	Body weight↑ Colorectal damage↓ Microvilli integrity ↑	CD40/CD40L↓ IL-6↓ CD40 (mRNA)↓ CD40L (mRNA)↓		ASC↓ NLRP3↓ Caspase-1↓	PAI-1↓				Jiang et al. (2013), Jiang et al. (2016)
			TNF-α↓
Caffeic acid	C3H/HeOuJ mice (DSS(1.25%)); C57BL/6 mice (DSS(2.5%))	Food intake↓ Colon length↑ Body weight↑ Colorectal damage↓ DAI↓	MPO↓ IL-17 (mRNA)↓ IL-4 (mRNA)↑ IL-6↓ TNF-α↓ IFN-γ↓ IL-12↑ Infiltration of CD3+ T cells↓ CD177 + neutrophils↓ F4/80 + macrophage↓	iNOS(mRNA)↓		Cyp4b1 (mRNA)↑ Cytoplasmic IκBα↑ p65 translocation↓			Akkermansia↑	Ye et al. (2009), Zhang et al. (2016b)

PAI-1, Plasminogen activator inhibitor type-1; AST, aspertate aminotransferase; ALT, alanine transaminase; ALP, alkaline phosphatase; Cebpb, CCAAT/enhancer-binding protein and beta; Hp, haptoglobin; S100a8, S100 calcium binding protein a8; Saa3 = serum amyloid A3; DAI, disease activity index.