Baicalin Attenuates Hypoxia‐Induced Pulmonary Arterial Hypertension to Improve Hypoxic Cor Pulmonale by Reducing the Activity of the p38 MAPK Signaling Pathway and MMP‐9

Abstract

Baicalin has a protective effect on hypoxia-induced pulmonary hypertension in rats, but the mechanism of this effect remains unclear. Thus, investigating the potential mechanism of this effect was the aim of the present study. Model rats that display hypoxic pulmonary hypertension and cor pulmonale under control conditions were successfully generated. We measured a series of indicators to observe the levels of pulmonary arterial hypertension, pulmonary arteriole remodeling, and right ventricular remodeling. We assessed the activation of p38 mitogen-activated protein kinase (MAPK) in the pulmonary arteriole walls and pulmonary tissue homogenates using immunohistochemistry and western blot analyses, respectively. The matrix metalloproteinase- (MMP-) 9 protein and mRNA levels in the pulmonary arteriole walls were measured using immunohistochemistry and in situ hybridization. Our results demonstrated that baicalin not only reduced p38 MAPK activation in both the pulmonary arteriole walls and tissue homogenates but also downregulated the protein and mRNA expression levels of MMP-9 in the pulmonary arteriole walls. This downregulation was accompanied by the attenuation of pulmonary hypertension, arteriole remodeling, and right ventricular remodeling. These results suggest that baicalin may attenuate pulmonary hypertension and cor pulmonale, which are induced by chronic hypoxia, by downregulating the p38 MAPK/MMP-9 pathway.

Retracted: Baicalin relieves TNF‐α‐evoked injury in human aortic endothelial cells by up‐regulation of miR‐145

“…A number of earlier investigations elucidated that BAI exerted its roles in various diseases through regulating JNK and p38MAPK pathways. For instance, Yan et al pointed out that BAI alleviated hypoxia‐evoked pulmonary arterial hypertension by suppressing p38MAPK activation in both tissue homogenates and the pulmonary arteriole walls (Yan, Wang, & Liu, ). Besides, Wu et al proved that BAI alleviated atherosclerosis through attenuating inflammatory response and oxidative stress via repressing p38MAPK pathway (Wu et al, ).…”

Baicalin Attenuates Cardiac Dysfunction and Myocardial Remodeling in a Chronic Pressure-Overload Mice Model

“…In an acute myocardial infarction rats model, baicalin presented cardioprotective effests by modulating p38 MAPK cascades [16, 38]. Additionally, baicalin may attenuate chronic hypoxia-induced pulmonary hypertension and cor pulmonale by downregulating the p38 MAPK/MMP-9 pathway [39]. Besides, evidence showed that baicalin attenuated HFD-induced obesity and liver dysfunction, with dose-dependently inhibited hepatic CaMKKβ/AMPK/ACC pathway [40].…”

Protective effect of baicalin against severe burn‑induced remote acute lung injury in rats

“…In the present study, treatment with baicalin significantly suppressed NF-κB and MMP-9 protein expression in rats with burn-induced remote ALI. Yan et al (9) suggested that baicalin may attenuate pulmonary hypertension by downregulating the p38 mitogen-activated protein kinase/MMP-9 pathway.…”

“…Since the oral absorption of baicalin is challenging, it translocates into the blood via the intestinal tract, aided by enzymatic hydrolysis into baicalein, and is rapidly transformed into baicalinin in vivo. Baicalein has been receiving an increased amount of attention from researchers due to its versatility (9). In the present study, a possible mechanism underlying the neuroprotective effects of baicalin against ALI was investigated.…”