Baicalin and ginsenoside Rb1 suppress the activation of cardiac fibroblasts via regulating the GRK2/AT1R/MasR network.

BACKGROUND

Obesity is a risk factor for cardiovascular diseases. Baicalin and ginsenoside Rb1 are the main components of the Scutellariae Radix-Ginseng Radix et Rhizoma herb pair. However, the effects on obesity-related cardiac fibrosis remain unclear.

PURPOSE: To evaluate the effects of baicalin, Rb1, and their combination on cardiac fibroblast (CF) activation in the background of obesity.

METHODS

The CFs were incubated with the conditioned medium derived from the visceral adipose tissue (T-CM) and angiotensin II (Ang II), and the high-fat diet (HFD)-fed mice received transverse aortic constriction (TAC) to induce pressure overload-mediated cardiac fibrosis.

RESULTS

Co-stimulation of T-CM and Ang II triggered a rippled change in the protein expression of GRK2, Ang II type 1 receptor (AT1R), and Ang 1-7 receptor Mas (MasR), leading to the activation of CFs, evidenced by the upregulation of α-SMA, TGF-β1, and Col-1. Baicalin, Rb1, combined treatment, and paroxetine decreased HFD-induced insulin resistance, reduced the upregulation of GRK2, and counterpoised the Ang II/AT1R and Ang 1-7/MasR axis, thereby suppressing CF activation and ameliorating cardiac fibrosis and cardiac function. The component combination showed a more potent effect. Inhibiting the phosphorylation of NF-κB and STAT3 through GRK2 downregulation contributed to the effect of baicalin and Rb1 on AT1R and MasR.

CONCLUSION

Baicalin, Rb1, and their combination suppress the CF activation and cardiac fibrosis in the background of obesity by regulating the expressions and activities of the GRK2/AT1R/MasR network. The finding might extend the understanding of their multifaceted effects and expand their potential applications.