Puerarin mitigated transverse aorta constriction-induced cardiac fibrosis and suppressed endothelial-to-mesenchymal transition via upregulation of PPAR-γ and inhibition of TGF-β1/Smad2 signaling.
Does puerarin reduce cardiac fibrosis in a mouse model of transverse aorta constriction?
Puerarin protects against pressure overload-induced cardiac fibrosis by upregulating PPAR-γ and inhibiting TGF-β1/Smad2-mediated endothelial-to-mesenchymal transition in preclinical models.
Background . Puerarin is a kind of flavonoids and is extracted from Chinese herb Kudzu root. Puerarin is widely used as an adjuvant therapy in Chinese clinics. But little is known about its effects on regulating cardiac fibrosis. Methods . Mice were subjected to transverse aorta constriction (TAC) for 8 weeks; meanwhile puerarin was given 1 week after TAC. Cardiac fibrosis was assessed by pathological staining. The mRNA and protein changes of CD31 and vimentin in both animal and human umbilical vein endothelial cells (HUVECs) models were detected. Immunofluorescence colocalization of CD31 and vimentin and scratch test were carried out to examine TGF- β 1-induced changes in HUVECs. The agonist and antagonist of peroxisome proliferator-activated receptor- γ (PPAR- γ ) were used to explore the underlying mechanism. Results . Puerarin mitigated TAC-induced cardiac fibrosis, accompanied with suppressed endothelial-to-mesenchymal transition (EndMT). The consistent results were achieved in HUVECs model. TGF- β 1/Smad2 signaling pathway was blunted and PPAR- γ expression was upregulated in puerarin-treated mice and HUVECs. Pioglitazone could reproduce the protective effect in HUVECs, while GW9662 reversed this effect imposed by puerarin. Conclusion . Puerarin protected against TAC-induced cardiac fibrosis, and this protective effect may be attributed to the upregulation of PPAR- γ and the inhibition of TGF- β 1/Smad2-mediated EndMT.
Jin et al. (2017) studied Cardiac fibrosis. Puerarin vs. Control/Vehicle was evaluated on Cardiac fibrosis and endothelial-to-mesenchymal transition. Puerarin mitigated transverse aorta constriction-induced cardiac fibrosis and suppressed endothelial-to-mesenchymal transition via upregulation of PPAR-γ and inhibition of TGF-β1/Smad2 signaling.