Tetramethylpyrazine Improves Monocrotaline-Induced Pulmonary Hypertension through the ROS/iNOS/PKG-1 Axis.

Background: Tetramethylpyrazine (TMP), a potent anti-free radical and anti-inflammations substance, has been demonstrated to possess a direct vessel relaxation property. This study aimed to evaluate the effect of TMP treatment in pulmonary hypertension (PH) and test the hypothesis that TMP prevents or reverses the process of PH. Methods: Rats (n = 36) injected with 50 mg/kg of monocrotaline (MCT) subcutaneously 4 weeks to develop PH were then randomized to TMP (5 mg/kg per day) for another 4 weeks. Hemodynamics was evaluated via the right ventricle. Pulmonary vessels structural remodeling and inflammation were examined by histologic and transmission electron microscopy observation. The expression of inducible nitric oxide synthase (iNOS) and cGMP-dependent protein kinases 1 (PKG-1) was detected by immunohistochemical staining and Western blot. Generation of reactive oxygen species (ROS) and antioxidation species was measured by biochemical analyses. Results: MCT increased PH and right ventricle hypertrophy. TMP alleviated pulmonary arterial pressure elevation, leukocyte infiltration, and structural remodeling of pulmonary arterials induced by MCT successfully. TMP treatment significantly increased the PKG-1 expression and suppressed the iNOS expression. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT) was significantly higher than control group, while malondialdehyde (MDA) levels were lower compared with MCT group. Conclusion: TMP can suppress established MCT-induced PH through the ROS/iNOS/PKG axis. The underlying mechanisms may be associated with its anti-inflammatory, antioxidant, and antiproliferative properties in pulmonary arterial.

[Protective effects of high-dose ulinastatin on vital organs in patients receiving total arch replacement for type A aortic dissection].

OBJECTIVE: To investigate the protective effects of high-dose ulinastatin on the vital organs in patients undergoing total arch replacement for type A aortic dissection. METHODS: Between September 2014 and March 2016, 66 patients with type A aortic dissection underwent total arch replacement at our center. Thirty-six of the patients received ulinastatin treatment at 300 000 U/8 h from admission to 3 days postoperatively and at 300 000 U/2 h during cardiopulmonary bypass surgery (UTI group), and the other 30 patients did not receive perioperative ulinastatin treatment (control group). The surgical data and blood biochemistry profiles on days 1, 3, and 5 postoperatively were compared between the two groups, and the postoperative ICU stay, re-operation for bleeding, ventilation for over 7 days, ultrafiltration for postoperative renal failure, tracheotomy, incidences of pulmonary and neurological complications and hospital death were also compared. RESULTS: s The operating time, cardiopulmonary bypass time, ACP time, cardiac arrest time, the lowest rectal temperature and frequency of bilateral and unilateral antegrade selective cerebral perfusion were similar between the two groups (P>0.05). Compared with those in the control group, patients in UTI group had lower lactate, S-100 and neuron specific enolase levels on the first postoperative day and higher OI on the 1st, 3rd, and 5th postoperative days (P<0.05), but serum creatinine, blood urea nitrogen, total bilirubin, and alanine aminotransferase levels were comparable between the two groups (P>0.05). No significant differences were found in the frequency of re-operation for bleeding, ultrafiltration for renal failure, tracheotomy, neurological complications or hospital death after the operation between the two groups, but the patients in UTI group had a shorter ICU time, a less frequent long-term ventilation and a lower incidence of pulmonary infection (P<0.05). CONCLUSION: High-dose ulinastatin offers protection on pulmonary function and lowers the specific brain injury markers in patients with type A aortic dissection after total arch replacement, but its protective effects on brain is uncertain.

Review of Herbal Traditional Chinese Medicine for the Treatment of Diabetic Nephropathy.

Diabetic nephropathy (DN) is the most serious chronic complications of diabetes; 20-40% of diabetic patients develop into end stage renal disease (ESRD). However, exact pathogenesis of DN is not fully clear and we have great difficulties in curing DN; poor treatment of DN led to high chances of mortality worldwide. A lot of western medicines such as ACEI and ARB have been demonstrated to protect renal function of DN but are not enough to delay or retard the progression of DN; therefore, exploring exact and feasible drug is current research hotspot in medicine. Traditional Chinese medicine (TCM) has been widely used to treat and control diabetes and its complications such as DN in a lot of scientific researches, which will give insights into the mechanism of DN, but they are not enough to reveal all the details. In this paper, we summarize the applications of herbal TCM preparations, single herbal TCM, and/or monomers from herbal TCM in the treatment of DN in the recent 10 years, depicting the renal protective effects and the corresponding mechanism, through which we shed light on the renal protective roles of TCM in DN with a particular focus on the molecular basis of the effect and provide a beneficial supplement to the drug therapy for DN.

Protective effects of osthole against myocardial ischemia/reperfusion injury in rats.

Osthole, a bioactive simple coumarin derivative extracted from a number of medicinal plants, such as Cnidium monnieri and Angelica pubescens, has been shown to exert a variety of pharmacological activities and is considered to have potential therapeutic applications. In this study, we investigated the protective effects of osthole against myocardial ischemia/reperfusion (I/R) injury in rats. Male Sprague-Dawley rats were randomly assigned to 1 of 5 groups: the sham-oeprated control group (control), the vehicle group (vehicle), and 3 treatment groups, which were treated with osthole at the concentration of 1, 10 or 50 mg/kg (intraperitoneally), respectively, upon the initiation of myocardial ischemia. Treatment with osthole suppressed the formation of lipid peroxidation products, enhanced the capacities of antioxidant enzymes and inhibited the expression of inflammatory cytokines following myocardial I/R injury. Moreover, treatment with osthole reduced high-mobility group box protein 1 (HMGB1) and phosphorylated nuclear factor (NF)-κB expression in ischemic myocardial tissue. These results demonstrate the protective effects of osthole against myocardial I/R injury in rats and suggest that these effects may be associated with its antioxidant and anti-inflammatory activities.

Apoptosis induced by ardipusilloside III through BAD dephosphorylation and cleavage in human glioblastoma U251MG cells.

Ardipusilloside III is a saponin newly isolated from Ardisia pusilla A.DC. Since saponins have exhibited broad anti-cancer and pro-apoptotic activity, we investigated the ability of ardipusilloside III to induce apoptosis in human glioblastoma U251MG cells, as well as the involvement of apoptotic signaling pathways. Ardipusilloside III markedly suppressed proliferation of U251MG cells in a time- and dose-dependent manner (P < 0.05, IC50 = 8.2 microg/ml), but did not affect the growth of primary cultures of human astrocytes. Ardipusilloside III-treated U251MG cells underwent typical apoptotic changes. Exposure to a low dose of ardipusilloside III provoked G2/M-phase cell cycle arrest, which preceded apoptosis characterized by the appearance of cells with sub-G1 DNA content. However, a higher dose of ardipusilloside III induced apoptosis without first causing cell cycle arrest. In addition, ardipusilloside III exposure resulted in time-dependent BAD dephosphorylation and cleavage as well as activation of caspase-8 and caspase-3. Therefore, both the intrinsic pathway of apoptosis, mediated by BAD dephosphorylation and cleavage, and the extrinisic pathway of apoptosis, mediated by caspase-8 and caspase-3 activation, were involved in ardipusilloside III-induced apoptosis. These data suggest that ardipusilloside III is a reliable candidate for chemotherapeutic treatment of human glioblastomas, and should be investigated further.