TABLE 4.

Mechanism of Chinese herbal extracts or natural compounds interfering with cardiac fibrosis by regulating TGF-signaling pathway.

Classify	Natural products	Targets of research	Efficacy	References
Alkaloids	Neferine	collagen I and III 、 TGF-β1	Restrain the migration of CFs	Zhao et al. (2010)
		TGF-β1-Smad、ERK、p38MAPK	Improving myocardial function in diabetic mice	Liu et al. (2016)
	Picrasidine	TGF-β1、Smad2/3	Improving the cardiac compliance and cardiac function	Zhang et al. (2018b)
Terpenoids	Zerumbone	TGF-β1、p-Smad2/3、MMP-2/9、Smad7	Inhibits the conversion of cardiac fibroblasts to myofibroblasts	Li et al. (2022c)
	Ginkgolide B	ERK1/2、JNK、38MAPK	Restraining the development of diabetic MF	Wu et al. (2013)
				Jang et al. (2020)
	Centella asiatica	Smad2/3、Smad7	Alleviating the overburden pressure-induced cardiac fibrosis	Lu et al. (2018)
	Betulinic acid	Smad2/3、TGF-β1	Relieving the hyperglycaemia-induced cardiac fibrosis	Jiang et al. (2017)
Flavonoids	Daidzein	Smad2/3、TGF-β1	Suppressing the development of cardiac disease	Yu et al. (2020)
	Apigenin	miR-122-5p、TGF-β1、Smad2/3、HIF-1α、Smad7	Anti-fibrosis effect	Zhou et al. (2016)
				Feng et al. (2021)
	Glycyrrhizin	TGF-β1、Smad2	Relieved fibrosis in mice and cardiomyocytes by suppressing	Li et al. (2021b)
	Silymarin	TGF-β1、Smad2/3、Smad7	Decreasing MF and collagen deposition	Meng et al. (2019)
	Baicalin	TGF-β、Smad2/3、Smad4	Anti-fibrosis effect	Xiao et al. (2018)
Saponins	Astragaloside IV	TGF-β1、Smad3、Smad7	Anti-fibrosis effect	Wei et al. (2020)
	Saikosaponin A	smad2、smad3、smad4	Attenuate the cardiac fibrosis and inhibiting the EndMT process	Fu et al. (2015)
				Liu et al. (2018b)
Polyphenols	Resveratrol	TGF-β1、Smad2、Smad3	Reducing ECM deposition and alleviating HG-induced cardiac fibrosis	Gambini et al. (2015)
				Zhu et al. (2022)
Others	Emodin	SMAD2/3、Erk1/2	Anti-cardiac fibrosis	Carver et al. (2021)
	Higenamine	TGF-β1、Smad	Improving cardiac fibrosis and dysfunction	Zhu et al. (2021)