Quercetin, Perillyl Alcohol, and Berberine Ameliorate Right Ventricular Disorders in Experimental Pulmonary Arterial Hypertension: Effects on miR-204, miR-27a, Fibrotic, Apoptotic, and Inflammatory Factors.
Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease causing right ventricular (RV) hypertrophy, failure, and death. Some miRNAs are involved in the pathophysiology of PAH. As the current treatments cannot prevent the progression of the disease, we investigated whether 3 plant derivatives, namely perillyl alcohol (PA), quercetin (QS), and berberine (BBR), can improve RV function and affect the expression of miR-204, miR-27a, and biochemical factors in monocrotaline-induced PAH (MCT-PAH). Thirty-six rats were divided into control (CTL), MCT, MCT+Veh (vehicle), MCT+PA, MCT+QS, and MCT + BBR groups (n = 6 each). After inducing PAH using MCT (60 mg/kg), PA (50 mg/kg), QS (30 mg/kg), and BBR (30 mg/kg) were administrated daily for 3 weeks. miR-204 expression, total antioxidant capacity, and antiapoptotic protein Bcl-2 significantly declined in the RV of PAH rats, and PA, QS, and BBR treatment significantly compensated for these decreases. Proapoptotic protein Bax and p21 cell cycle inhibitor increased in the RV. All 3 herbal derivatives compensated for Bax increase, and BBR caused a decrease in p21. TNFα, IL-6, and malondialdehyde increased in the RV, and PA, QS, and BBR significantly counterbalanced these increases. miR-27a expression was not affected by MCT and plant derivatives. Overall, PA, QS, and BBR improved ventricular disorders in rats with PAH by decreasing inflammation, apoptosis, and fibrosis and increasing the antioxidant-to-oxidant ratio. Therefore, these herbal derivatives may be considered as target therapeutic goals for this disease either alone or in combination with current medications.
Rajabi S
，Najafipour H
，Jafarinejad-Farsangi S
，Joukar S
，Beik A
，Askaripour M
，Jafari E
，Safi Z
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Baicalein attenuates monocrotaline-induced pulmonary arterial hypertension by inhibiting vascular remodeling in rats.
Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder characterized by elevated pulmonary arterial pressure (PAP) and right ventricular hypertrophy (RVH) driven by progressive vascular remodeling. Reversing adverse vascular remodeling is an important concept in the treatment of PAH. Endothelial injury, inflammation, and oxidative stress are three main contributors to pulmonary vascular remodeling. Baicalein is a natural flavonoid that has been shown to possess anti-proliferative, anti-inflammatory, anti-oxidative, and cardioprotective properties. We hypothesized that baicalein may prevent the progression of PAH and preserve the right heart function by inhibiting pulmonary arterial remodeling.
Male Sprague-Dawley rats were distributed randomly into 4 groups: control, monocrotaline (MCT)-exposed, and MCT-exposed plus baicalein treated rats (50 and 100 mg/kg/day for 2 weeks). Hemodynamic changes, RVH, and lung morphological features were examined on day 28. Apoptosis was determined by TUNEL staining, and the mRNA levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 were detected by qRT-PCR. The changes in oxidative indicators, including malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured using corresponding commercial kits. The levels of Bax, Bcl-2, and cleaved caspase-3, and the activation of mitogen-activated protein kinase (MAPK) and NF-κB were assessed by western blotting.
MCT induced an increase in hemodynamic parameters and RVH, which were attenuated by baicalein treatment. Baicalein also blocked MCT-induced pulmonary arterial remodeling. The levels of apoptotic (Bax/Bcl-2 ratio and cleaved caspase-3) and inflammatory (IL-6, TNF-α, and IL-1β) biomarkers in lung tissue were lower in baicalein-treated groups. Baicalein also decreased MDA level, and increased SOD and GSH-Px activity in rat pulmonary tissue. Furthermore, baicalein inhibited MCT-induced activation of the MAPK and NF-κB pathways.
Baicalein ameliorates MCT-induced PAH by inhibiting pulmonary arterial remodeling at least partially via the MAPK and NF-κB pathways in rats.
Shi R
，Wei Z
，Zhu D
，Fu N
，Wang C
，Yin S
，Liang Y
，Xing J
，Wang X
，Wang Y
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