Hydroxysafflor yellow A improves established monocrotaline-induced pulmonary arterial hypertension in rats.

To evaluate the beneficial effects of hydroxysafflor yellow A (HSYA) on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats, and to investigate the main pathophysiological mechanism of HSYA in preventing development of MCT-induced PAH. Four groups (control, control with HSYA treatment, MCT-exposed, and MCT-exposed with HSYA treatment) were evaluated at day 28 following MCT exposure. Haemodynamic measurements, right ventricular hypertrophy, morphometry, inflammatory cytokines and oxidant expression were assessed. HSYA significantly reduced haemodynamic changes, right ventricular hypertrophy and morphometric changes induced by exposure to MCT. HYSA also suppressed MCT-induced inflammation and oxidative stress in rat pulmonary tissue. Experimental MCT-induced PAH may be reduced by HSYA treatment, and the mechanism may involve suppression of inflammation and oxidative stress.

Han X ，Zhang Y ，Zhou Z ，Zhang X ，Long Y ... -  《-》

Hydroxysafflor yellow A (HSYA) attenuates hypoxic pulmonary arterial remodelling and reverses right ventricular hypertrophy in rats.

Carthamus tinctorius L. is a traditional herbal medicine native to China with properties of promoting blood circulation and removing blood stasis, which is used for the treatment of cerebrovascular and cardiovascular diseases. Hydroxysafflor yellow A (HSYA) is the main constituent isolated from the flower of Carthamus tinctorius L. which is used as a marker substance in the quality control of Carthamus tinctorius L. in Chinese Pharmacopeia. This study is to investigate the hypertension attenuating effect of HSYA on hypoxia-induced pulmonary artery hypertension model rats, and the possible mechanism. The animal models were made by treating adult male Wistar rats (of the same age with the same weight of 200±25g) under hypoxia 24h per day for 9 days with or without administration of HSYA. The pulmonary arterial pressure of rats was measured after anesthetization; The right ventricular hypotrophy was evaluated by the right ventricular hypotrophy index (RVHI=[RV/(LV+S)]) as well as histomorphology assay with Hematoxylin and Eosin (HE) staining; The reducing of pulmonary artery remodelling was evaluated by histomorphology assay with HE staining; The proliferation of pulmonary artery smooth muscle cells (PASMCs) was evaluated by immunohistochemistry assays (PCNA and Ki67) and MTT assay. Cell cycle analysis and Weston-blot analysis were also performed in the study. HSYA reduced the mean right ventricular systolic pressure (RVSP) of rats with hypoxic pulmonary arterial hypertension (HPH) in a manner of concentration dependency. It significantly inhibited the PASMCs proliferation and attenuated the remodelling of the pulmonary artery and right ventricular hypertrophy. These findings suggested that HSYA protected against hypoxic induced pulmonary hypertension by reversing the remodelling of the pulmonary artery through inhibiting the proliferation and hypertrophy of PASMCs. This is in accordance with our previous finding that HSYA protects against the pulmonary artery vascular constriction. All these results suggest that HSYA may be a promising candidate for HPH treatment.

Li L ，Dong P ，Hou C ，Cao F ，Sun S ，He F ，Song Y ，Li S ，Bai Y ，Zhu D ... -  《-》

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 ... -  《-》

Perillyl alcohol suppresses monocrotaline-induced pulmonary arterial hypertension in rats via anti-remodeling, anti-oxidant, and anti-inflammatory effects.

Beik A ，Najafipour H ，Joukar S ，Rajabi S ，Iranpour M ，Kordestani Z ... -  《-》

Tetrandrine prevents monocrotaline-induced pulmonary arterial hypertension in rats through regulation of the protein expression of inducible nitric oxide synthase and cyclic guanosine monophosphate-dependent protein kinase type 1.

Wang X ，Yang Y ，Yang D ，Tong G ，Lv S ，Lin X ，Chen C ，Dong W ... -  《-》