RESUMO
Chrysin (CH) is the main ingredient of many medicinal plants. Our previous study showed that CH could suppress hypoxia-induced pulmonary arterial smooth muscle cells proliferation and alleviate chronic hypoxia-induced pulmonary hypertension by targeting store-operated Ca entry (SOCE)-[Ca]i pathway. In this study, we investigated the effect of CH on monocrotaline-induced pulmonary hypertension (MCTPH) and the mechanism behind it. Results show that, in MCTPH model rats, (1) CH significantly reduced the enhancement of right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling; (2) CH markedly suppressed the promotion of SOCE and [Ca]i in pulmonary arterial smooth muscle cells; and (3) CH obviously inhibited the MCT-upregulated proliferating cell nuclear antigen, TRPC1, TRPC4, and TRPC6 expression in distal pulmonary arteries. These results demonstrate that CH likely alleviates MCTPH by targeting TRPC1,4,6-SOCE-[Ca]i pathway.
Assuntos
Anti-Hipertensivos/farmacologia , Pressão Arterial/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Flavonoides/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Monocrotalina , Músculo Liso Vascular/efeitos dos fármacos , Remodelação Vascular/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/fisiopatologia , Hipertrofia Ventricular Direita/prevenção & controle , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Ratos Sprague-Dawley , Canais de Cátion TRPC/antagonistas & inibidores , Canais de Cátion TRPC/metabolismo , Função Ventricular Direita/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacosRESUMO
BACKGROUND: Acute lung injury (ALI) is an inflammatory disorder. Semen Cassiae has potent anti-inflammatory activities. The aim of our study was to investigate whether Semen Cassiae plays a protective effect on lipopolysaccharide (LPS)-induced ALI and, if so, to elucidate its potential mechanism. METHODS: Male Sprague-Dawley rat lungs were injured by intratracheal instillation of LPS. Rats were treated with Semen Cassiae or vehicle 3 h after LPS challenge. Samples were harvested 24 h post-LPS administration. We also investigated the effects of Semen Cassiae on LPS stimulation in RAW 264.7 cells. RESULTS: LPS administration markedly induced pulmonary edema and polymorphonuclear neutrophil influxes. These changes were significantly attenuated in Semen Cassiae treated group. Moreover, Semen Cassiae markedly reduced pulmonary interleukin (IL)-6, tumor necrosis factor (TNF)-α, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. The pulmonary soluble epoxide hydrolase (sEH) activity and the DNA binding activity of Nuclear factor (NF)-κB were significantly inhibited in Semen Cassiae treated group. Furthermore, Semen Cassiae treatment significantly increased epoxyeicosatrienoic acids (EETs), and heme oxygenase-1 (HO-1) activity. Our in vitro study demonstrates that Semen Cassiae treatment may inhibit LPS induced IκBα phosphorylation and NF-κB p65 nucleus translocation. CONCLUSION: Semen Cassiae protects LPS-induced ALI in rats. Semen Cassiae can be developed as a novel treatment for ALI.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Cassia , Citocinas/metabolismo , Pulmão/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , 8-Hidroxi-2'-Desoxiguanosina , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animais de Doenças , Epóxido Hidrolases/metabolismo , Heme Oxigenase-1/metabolismo , Lipopolissacarídeos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Neutrófilos/metabolismo , Extratos Vegetais/farmacologia , Edema Pulmonar/prevenção & controle , Células RAW 264.7 , Ratos Sprague-Dawley , SementesRESUMO
BACKGROUND: Pulmonary hypertension (PH) is a lethal disease with no cure currently available. Sodium Tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the major active component from salvia miltiorrhiza, a kind of Chinese herbal medicine. We investigate the efficacy of STS towards treatment of PH patients. METHODS AND RESULTS: Five hospitalized patients were randomly enrolled for this study. These patients were suffering from various types of serious PH without getting sufficient benefits from sildenafil treatment (20 mg tid) for at least three months. The efficacy of STS on PH was evaluated by measuring the pulmonary arterial systolic pressure (PASP), RV size by echocardiography, 6-minute walking distance (6MWD), Borg dyspnea score, and WHO functional class of PH. Patients aged from 17 to 46 (average 33±11) years old, pulmonary arterial systolic pressure (PASP) ranged from 60 to 140 mmHg, RV size ranged from 25 to 39 mm were included in study. At the endpoint of observation for 8 weeks of STS infusion, they obtained reduction of PASP in the range of 14-45 (average 28.6±12.5) mmHg, RV size in the range of 0-10 (average 4.2±1.6). All patients exhibited improved exercise capacity with an increase of 6MWD from 63 to 268 (average 138.4±40.7) meters, significantly reduced Borg dyspnea score from maximum 9 down to 1 or 0, and reduced WHO functional class of PH from III or IV down to II. CONCLUSIONS: These results indicate that STS exhibits remarkable beneficiary effects on treating PH patients either alone or in concert with sildenafil.