Search

The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT2ULN) and early liver fibrosis (F ≤ 2).We aimed to investigate whether monotherapy with AHP improves liver histology in these patients.In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment.Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients.Treatment of CHB patients who had ALT2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.

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 (50mg/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.

Insulin is a main glucose homeostatic hormone in the body. Previous reports showed that insulin also exerted anti-inflammatory actions and attenuated systemic inflammatory response. Here, we observed the effects and the underlying mechanisms of insulin on lipopolysaccharide (LPS)-induced acute lung injury (ALI). As revealed by survival study, insulin reduced mortality of rats and prolonged their survival time. Meanwhile, insulin significantly reduced the levels of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and high mobility group box 1 (HMGB1) in bronchoalveolar lavage fluid (BALF). Besides, insulin markedly inhibited the expression of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB). Taken together, these data provided information that insulin attenuated LPS-induced ALI may attribute partly to the inhibition of the production of cytokines, and the expression of TLR2, TLR4 and NF-κB.

The present study was designed to investigate the vascular effects and underlying mechanisms of tanshinone IIA on isolated rat pulmonary artery. Isometric tension was recorded in the arteries from normal and hypoxic pulmonary hypertension rats under normoxia or hypoxia condition. The results showed that tanshinone IIA exerted a biphasic effect on rat pulmonary artery. The constriction was attenuated by endothelium-denudation but was enhanced by inhibition of nitric oxide synthase. Pretreatment with tetraethylammonium (Ca2+-activated K+ channel inhibitor) upward shifted the concentration-response curve without affecting the maximum dilatation. Pretreatment with zinc protoporphyrin IX (heme oxygenase-1 inhibitor), 4-aminopyridine (KV channel inhibitor), glibenclamide (KATP channel inhibitor) or BaCl2 (inwardly rectifying K+ channel inhibitor) did not affect the vasoreactivity. Meanwhile, tanshinone IIA almost abolished vasoconstriction induced by extracellular Ca2+. Under hypoxia condition, tanshinone IIA eliminated acute hypoxia-induced initial contraction, potentiated following vasorelaxation, attenuated and reversed sustained contraction to relaxation in pulmonary artery from normal rats, and reversed phenylephrine-induced sustained constriction to sustained relaxation in remodeled pulmonary artery from hypoxic pulmonary hypertension rats. We concluded that the mild constrictive effect induced by tanshinone IIA was affected by integrity of endothelium and production of nitric oxide, while the potent dilative effect was endothelium-independent and produced primarily by inhibiting extracellular Ca2+ influx and partially by inhibiting intracellular Ca2+ release, as well as activating Ca2+-activated K+ channels. The modulation of tanshinone IIA on pulmonary vasoreactivity under both acute and chronic hypoxia condition may provide a new insight for curing hypoxic pulmonary hypertension.