Pulmonary hypertension is a progressive disease characterized by marked pulmonary arterial remodeling and increased vascular resistance. Inflammation and oxidative stress promote the development of pulmonary hypertension. Oxymatrine, one of the main active components of the Chinese herb Sophora flavescens Ait. (Kushen), plays anti-inflammatory and antioxidant protective roles, which effects on pulmonary arteries remain unclear. This study aimed to investigate the effects of oxymatrine on pulmonary hypertension development. Sprague–Dawley rats were exposed to hypoxia for 28 days or injected with monocrotaline, to develop pulmonary hypertension, along with administration of oxymatrine (50 mg/kg/day). Hemodynamics and pulmonary arterial remodeling data from the rats were then obtained. The antiproliferative effect of oxymatrine was verified by in vitro assays. The inflammatory cytokine mRNA levels and leukocyte and T cell accumulation in lung tissue were detected. The antioxidative effects of oxymatrine were explored in vitro. Our study shows that oxymatrine treatment attenuated right-ventricular systolic pressure and pulmonary arterial remodeling induced by hypoxia or monocrotaline and inhibited proliferation of pulmonary arterial smooth muscle cells (PASMCs). Increased expression of inflammatory cytokine mRNA and accumulation of leukocytes and T cells around the pulmonary arteries were suppressed with oxymatrine administration. Under hypoxic conditions, oxymatrine significantly upregulated Nrf2 and antioxidant protein SOD1 and HO-1 expression, but downregulated hydroperoxide levels in PASMCs. In summary, this study indicates that oxymatrine may prevent pulmonary hypertension through its antiproliferative, anti-inflammatory, and antioxidant effects, thus providing a promising pharmacological avenue for treating pulmonary hypertension.

Inhibiting reactive oxygen species (ROS) has been viewed as a therapeutic target for the treatment of acute lung injury (ALI). Osthole, an active component in Chinese herbal medicine, has drawn increasing attention because of its various pharmacological functions, including anti-inflammatory and anti-oxidative activities. The aim of the present study was to examine the effects of osthole on ALI induced by lipopolysaccharide (LPS) through intratracheal instillation. The mRNA and protein expression levels of thioredoxin 1 (Trx1) and the nuclear factor erythroid-2 related factor 2 (Nrf2) were detected by real-time PCR, reverse transcription PCR (RT-PCR) and Western blot, respectively. ROS production was measured by flow cytometry. Our results showed that osthole treatment improved the mice survival rates in the middle and high dosage groups, compared with the untreated LPS group. Moreover, osthole treatment significantly improved LPS-induced lung pathological damage, and it decreased the lung injury scores, lung wet/dry ratios and the total protein level in Bronchoalveolar lavage fluid (BALF). Osthole treatment dramatically reduced the H2O2, MDA and OH levels in the lung homogenates. LDH and ROS were markedly reduced in the osthole + LPS group in vitro. Furthermore, osthole increased Nrf2 and Trx1 expression in terms of mRNA and protein in vivo and in vitro. Nrf2 siRNA (siNrf2) could suppress the beneficial effects of osthole on ALI. In conclusion, the current study demonstrates that osthole exerted protective effects on LPS-induced ALI by up-regulating the Nrf-2/Trx-1 pathway.

目的 探讨蛇床子素(Ost)预处理对脂多糖(LPS)引起的急性肺损伤的防治作用并初步研究其作用机制.方法 BALB/C小鼠随机分为生理盐水对照组(NS组)、蛇床子素对照组(Ost组)、模型组(LPS组)及蛇床子素处理组(Ost+LPS组).气管滴注LPS建立小鼠急性肺损伤模型.造模6 h后测定肺湿/干质量比值(W/D)、肺泡灌洗液(BALF)中蛋白含量及肿瘤坏死因子(TNF-α)浓度,同时观察肺组织病理学改变.结果 LPS可明显提高小鼠肺W/D、BALF中蛋白含量和TNF-α浓度(P<0.05),肺组织结构发生明显的病理改变;Ost处理组可有效减轻LPS引起的上述变化(P<0.05),组织损伤程度明显减轻.结论 Ost预处理对LPS导致的小鼠急性肺损伤有保护作用,其保护机制可能与抑制LPS诱导的肺通透性增加有关.

The renin–angiotensin–aldosterone system (RAAS) plays an important role in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Angiotensin converting enzyme 2 (ACE2) plays a protective role in acute lung injury. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to have anti-inflammatory effect, but the effect of osthole on the ALI is largely unknown. The aim of this study is to explore whether and by what mechanisms osthole protects lipopolysaccharide(LPS)-induced acute lung injury. Herein, we found that osthole had a beneficial effect on LPS-induced ALI in mice. As revealed by survival study, pretreatment with high doses of osthole reduced the mortality of mice from ALI. Osthole pretreatment significantly improved LPS-induced lung pathological changes, reduced lung wet/dry weight ratios and total protein in BALF. Osthole also inhibited the release of inflammatory mediators TNF-α and IL-6. Meanwhile, osthole markedly prevented the loss of ACE2 and Ang1-7 in lung tissue of ALI mice. ACE2 inhibitor blocked the protective effect of osthole in NR 8383 cell lines. Taken together, our study showed that osthole improved survival rate and attenuated LPS-induced ALI and ACE2 may play a role in it.

Objective: To investigate the effect of 5-hydroxytryptophane(5-HTP) on depression in mice.Methods: Mice received a gavage of 5-HTP(50,100 and 200 mg·kg-1) or foxtil(5 mg·kg-1) once a day for 7 days.Tail suspension test and forced swimming test were used to determine the behavioral effect of 5-HTP.For chronic stress-induced depression,5-HTP and foxtil were administered for 21 days,and then mice received the behavior test.Brain 5-HT levels and serum levels of TNF-α and IL-6 were detected by ELISA.Results: 5-HTP significantly decreased the immobility time in the tail suspension test and forced swimming test.It also increased brain 5-HT level,but decreased serum levels of TNF-α and IL-6.Conclusion: 5-HTP has an antidepressant effect.It can elevate the levels of 5-HT in the brain and reduce the production of cytokines,which may relate to its antidepressant effect.