Danshen, the dried root of Salvia miltiorrhiza, is widely used in clinics in China for treating various diseases, including cardiovascular diseases. Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA isolated as the major active component from Danshen, was recently reported to be effective in attenuating the characteristic pulmonary vascular changes associated with chronically hypoxic pulmonary hypertension (CHPH); however, the underlying detailed mechanisms are poorly understood. In this study, we investigated the effects of STS on basal intracellular Ca 21 concentration ([Ca 21 ] i ) and store-operated Ca 21 entry (SOCE) in distal pulmonary arterial smooth muscle cells (PASMCs) exposed to prolonged hypoxia or isolated from CHPH rats. SOCE measured by Mn 21 quenching of Fura-2 fluorescence in PASMCs from rats exposed to chronic hypoxia (10% O 2 , 21 d) was increased by 59%, and basal [Ca 21 ] i was increased by 119%; this effect was inhibited by intraperitoneal injection of STS. These inhibitory effects of STS on hypoxic increases of SOCE and basal [Ca 21 ] i were associated with reduced expression of canonical transient receptor potential (TRPC)1 and TRPC6 in distal pulmonary arterial smooth muscle and decreases on right ventricular pressure, right ventricular hypertrophy, and peripheral pulmonary vessel thickening. In ex vivo cultured distal PASMCs from normoxic rats, STS (0-25 mM) dose-dependently inhibited hypoxiainduced cell proliferation and migration, paralleled with attenuation in increases of basal [Ca 21 ] i , SOCE, mRNA, and protein expression of TRPC1 and TRPC6. STS also relieved right ventricular systolic pressure, right ventricular hypertrophy, and TRPC1 and TRPC6 protein expression in distal pulmonary arteries in a monocrotaline-induced rat model of pulmonary arterial hypertension. These results indicate that STS prevents pulmonary arterial hypertension development likely by inhibiting TRPC1 and TRPC6 expression, resulting in normalized basal [Ca 21 ] i and attenuated proliferation and migration of PASMCs.Keywords: STS; TRPC; SOCE; pulmonary hypertension Pulmonary arterial hypertension (PAH) is a rare yet life-threatening disease that affects 15 per 1 million adults, according to the most recent estimation in 2008 (1). It is physiologically defined by mean pulmonary arterial pressure of 25 mm Hg or greater at rest and is pathologically characterized by pulmonary vascular remodeling, including smooth muscle hypertrophy and intima thickening. Although significant progress has been made in the past decades in our understanding of PAH and in disease management, the prognosis is still poor, with a 1-year survival rate of 91.0% (2) and 3-year survival rate of 77% or less according to recent investigations (3-5). The principal treatments for PAH rely on approaches targeting the prostacyclin, endothelin, or NO pathways (phosphodiesterase inhibition) or, increasingly, on a combination of them (6-11). Few patients show indication for treatment with calcium channel...
Acute lung injury (ALI) is a life-threatening syndrome which causes a high mortality rate worldwide. In traditional medicine, lots of aromatic plants-such as some Thymus species-are used for treatment of various lung diseases including pertussis, bronchitis, and asthma. Thymol, one of the primary active constituent derived from Thymus vulgaris (thyme), has been reported to exhibit potent anti-microbial, anti-oxidant, and anti-inflammatory activities in vivo and in vitro. The present study aims to investigate the protective effects of thymol in lipopolysaccharide (LPS)-induced lung injury mice model. In LPS-challenged mice, treatment with thymol (100 mg/kg) before or after LPS challenge significantly improved pathological changes in lung tissues. Thymol also inhibited the LPS-induced inflammatory cells influx, TNF-α and IL-6 releases, and protein concentration in bronchoalveolar lavage fluid (BALF). Additionally, thymol markedly inhibited LPS-induced elevation of MDA and MPO levels, as well as reduction of SOD activity. Further study demonstrated that thymol effectively inhibited the NF-κB activation in the lung. Taken together, these results suggested that thymol might be useful in the therapy of acute lung injury.
The aim of this study is to investigate the effects of dexpanthenol in a model of acute lung injury (ALI) induced by lipopolysaccharides (LPS). Lung injury was induced by exposure to atomized LPS. Mice were randomly divided into four groups: control group; Dxp (500 mg/kg) group; LPS group; LPS + Dxp (500 mg/kg) group. The effects of dexpanthenol on LPS-induced neutrophil recruitment, cytokine levels, total protein concentration, myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) contents were examined. Additionally, lung tissue was examined by histology to investigate the changes in pathology in the presence and absence of dexpanthenol. In LPS-challenged mice, dexpanthenol significantly improved lung edema. Dexpanthenol also markedly inhibited the LPS-induced neutrophiles influx, protein leakage, and release of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). Furthermore, dexpanthenol attenuated MPO activity and MDA contents and increased SOD and GSH activity in the LPS-challenged lung tissue. These data suggest that dexpanthenol protects mice from LPS-induced acute lung injury by its anti-inflammatory and anti-oxidative activities.
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