Immunoregulation of Shenqi Fuzheng Injection Combined with Chemotherapy in Cancer Patients: A Systematic Review and Meta-Analysis

Background. Immunosuppression is a well-recognised complication of chemotherapy in cancer patients. We assemble the clinical evidence that SQI, an adjuvant drug for lung cancer and gastric cancer which was widely prescribed in China, interventions could increase objective tumour response and regulate immunity in cancer patients undergoing chemotherapy. Methods. We undertook a systemic review of the clinical data from randomised controlled trials up to September 2015 in which a SQI intervention was compared with a control arm in patients undergoing conventional chemotherapy. Revman 5.0 Software was used for the data analysis. Results. 49 randomised controlled trials were included in the systematic review. The meta-analysis results demonstrated that the SQI intervention with conventional chemotherapy exhibited better therapeutic efficacy than the conventional chemotherapy group with a statistically significant higher objective tumour response. Cotreatment with SQI could enhance NK, CD3+, CD4+ level, and CD4+/CD8+ ratio comparing with the conventional chemotherapy group. Conclusions. The conclusions of this review might suggest a high risk of bias due to the low quality and the limitation of cancer types in the included trials. A more reliable conclusion regarding the immunoregulation of SQI could be reached based on more trials of higher quality

New insight and potential therapy for NAFLD: CYP2E1 and flavonoids

Over the years, the prevalence of nonalcoholic fatty liver disease (NAFLD) has increased year by year; however, due to its complicated pathogenesis, there is no effective treatment so far. It is reported that Cytochrome P450 2E1 (CYP2E1) plays an indispensable role in the development of NAFLD, and numerous studies have shown that flavonoids have a hepatoprotective effect and can exert a beneficial effect on NAFLD by regulating the activity of CYP2E1. Therefore, flavonoids may become effective drugs for the treatment of NAFLD in the future. This prompted us to review the research progress of the pathological mechanism of NAFLD and the impact of CYP2E1 activity changes during the pathological process, and to summarize the protective effect of flavonoids against CYP2E1 activity

A Review of Danshen Combined with Clopidogrel in the Treatment of Coronary Heart Disease

Objective. Danshen, the root of Salvia miltiorrhiza Bunge, is a traditional herbal medicine in China, which has been used to treat irregular menstruation, cold hernia, and abdominal pain for thousands of years. Danshen is frequently used in combination with drugs to treat cardiovascular diseases. Clopidogrel is a commonly used drug for treating coronary heart disease, but clopidogrel resistance restricts its development. Therefore, the clinical efficacy of Danshen combined with clopidogrel treats coronary heart disease and the relationship between Danshen and clopidogrel metabolism enzymes is suggested for future investigations. Materials and Methods. The information was collected by searching online databases, and the RevMan 5.3 software was used to perform meta-analysis. Results. Twenty-two articles, including 2587 patients, were enrolled after the evaluation. Meta-analysis showed that Danshen combined with clopidogrel was more effective than clopidogrel alone in treating coronary heart disease by improving clinical curative effect, reducing the frequency of angina pectoris, improving electrocardiogram results, shortening the duration of angina pectoris, and easing adverse reactions. Danshen inhibited carboxylesterase 1 and most enzyme of cytochrome P450, especially cytochrome P450 1A2, which may affect the metabolism of clopidogrel. Conclusion. Danshen combined with clopidogrel may compensate for individual differences of clopidogrel resistance among individuals in the treatment of coronary heart disease. Meanwhile, the inhibitory effect of Danshen on cytochrome P450 and carboxylesterase 1 could be partly responsible for the synergistic and attenuating effects of Danshen combined with clopidogrel

Improvement of Endothelial Dysfunction of Berberine in Atherosclerotic Mice and Mechanism Exploring through TMT-Based Proteomics

Atherosclerosis is a multifactorial vascular disease triggered by disordered lipid metabolism, characterized by chronic inflammatory injury, and initiated by endothelial dysfunction. Berberine is the main active alkaloid of the herbal medicine Coptidis Rhizoma (Huanglian). Notably, berberine has been shown to have beneficial effects against atherosclerosis. However, the mechanisms of berberine in preventing atherosclerosis are still unclear. This study is aimed at investigating the effects and mechanisms of berberine in protecting the aorta and ameliorating atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. Here, we demonstrated that berberine reduced serum lipid levels, antagonized hepatic lipid accumulation, improved intima-media thickening, and alleviated atherosclerotic lesions in ApoE-/- mice fed a western-type diet for 12 weeks. Meanwhile, berberine reduced aortic reactive oxygen species (ROS) generation and reduced the serum levels of malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), and interleukin-6 (IL-6). In aortic ring assay, berberine restored aortic endothelium-dependent vasodilatation in vivo and in vitro. Furthermore, 4,956 proteins were identified by proteomic analysis, and 199 differentially expressed proteins regulated by berberine were found to be involved in many biological pathways, such as mitochondrial dysfunction, fatty acid β-oxidation I, and FXR/RXR activation. Summarily, these data suggested that berberine ameliorates endothelial dysfunction and protects against atherosclerosis, and thus may be a promising therapeutic candidate for atherosclerosis

Effect of Shenmai injection on preventing the development of nitroglycerin-induced tolerance in rats

<div><p>Long-term nitroglycerin (NTG) therapy causes tolerance to its effects attributing to increased oxidative stress and endothelial dysfunction. Shenmai injection (SMI), which is clinically used to treat cardiovascular diseases, consists of two herbal medicines, <i>Ginseng Rubra</i> and <i>Ophiopogonjaponicas</i>, and is reported to have antioxidant effects. The present study was designed to investigate the potential preventive effects of Shenmai injection on development of nitroglycerin-induced tolerance. The present study involves both in vivo and in vitro experiments to investigate nitroglycerin-induced tolerance. We examined the effect of Shenmai injection on the cardiovascular oxidative stress by measuring the serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Endothelial dysfunction was determined by an endothelium-dependent vasorelaxation method in aortic rings and NOS activity. Inhibition of the cGMP/cGK-I signalling pathway was determined from released serum levels of cGMP and the protein expression levels of sGC, cGK-I, PDE1A and P-VASP by western blot. Here, we showed that SMI ameliorated the decrease in AV Peak Vel, the attenuation in the vasodilation response to nitroglycerin and endothelial dysfunction. SMI also reduced the cardiovascular oxidative stress by reducing the release of MDA and increasing the activity of SOD. Shenmai injection further ameliorated inhibition of the cGMP/cGK-I signalling pathway triggered by nitroglycerin-induced tolerance through up-regulating the protein expression of sGC, cGK-I, and P-VASP and down- regulating the proteins expression of PDE1A. In vitro studies showed that Shenmai injection could recover the attenuated vasodilation response to nitroglycerin following incubation (of aortic rings) with nitroglycerin via activating the enzymes of sGC and cGK-I. Therefore, we conclude that Shenmai injection could prevent NTG nitroglycerin-induced tolerance at least in part by decreasing the cardiovascular oxidative stress, meliorating the endothelial dysfunction and ameliorating the inhibition of the cGMP/cGK-I signalling pathway. These findings indicate the potential of Shenmai injection (SMI) as a promising medicine for preventing the development of nitroglycerin-induced tolerance.</p></div

SMI improved the injury of the cGMP/cGK-I signalling pathway occurring due to NTG-induced tolerance.

<p>(A) Detection of the release of cGMP. <b>(B)</b> Protein expression of sGCα1. <b>(C)</b> Protein expression of sGCβ1. <b>(D)</b> Protein expression of PDE1A. <b>(E)</b> Protein expression of cGK-I. <b>(F)</b> Protein expression of serin239 phosphorylated VASP (P-VASP). The data are expressed as the mean ± SEM; n = 9 in each group; ^#P < 0.05 versus control, *P < 0.05 versus the NTG-induced tolerance group; ^##P < 0.01 versus control, **P < 0.01 versus the NTG-induced tolerance group.</p

The activator of sGC and cGK-I reduce NTG-induced tolerance in rat aortic rings.

<p><b>(A)</b> The activator of sGC reduce NTG-induced tolerance in rat aortic rings. <b>(B)</b> The activator of cGK-I reduce NTG-induced tolerance in rat aortic rings. The data are expressed as the mean ± SEM; n = 9 in each group; ^##P < 0.01 versus control, **P < 0.01 versus the NTG-induced tolerance group.</p

SMI reduced endothelial dysfunction of NTG-induced tolerance.

<p>(A) Maximal constriction and dilation by NE and Ach. <b>(B)</b> The maximal vasodilatation of Ach by NE-induced constriction. <b>(C)</b> Detection of the activity of TNOS. <b>(D)</b> Detection of the activity of nNOS. <b>(E)</b> Detection of the activity of iNOS. <b>(F)</b> Detection of the activity of nNOS. The data are expressed as the mean ± SEM; n = 9 in each group; ^#P < 0.05 versus control, *P < 0.05 versus the NTG-induced tolerance group; ^##P < 0.01 versus control, **P < 0.01 versus the NTG-induced tolerance group.</p

SMI reduced NTG-induced tolerance in rat aortic rings.

<p>The data are expressed as the mean ± SEM; n = 15 in each group; ^##P < 0.01 versus control, **P < 0.01 versus the NTG-induced tolerance group.</p

SMI reduced oxidative stress of NTG-induced tolerance.

<p>(A) Detection of ROS production. <b>(B)</b> Detection of MDA production. <b>(C)</b> Detection of H2O2 production. <b>(D)</b> Detection of GSH-PX activity. <b>(E)</b> Detection of SOD activity. (F) Detection of CAT activity. The data are expressed as the mean ± SEM; n = 9 in each group; ^##P < 0.01 versus control, **P < 0.01 versus the NTG -induced tolerance group.</p