The effect of Danshen extract on lipoprotein-associated phospholipase A2 levels in patients with stable angina pectoris: study protocol for a randomized controlled trial - the DOLPHIN study.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2), a biomarker of oxidation and inflammation, has been associated with increased coronary artery disease risk. To date, very few studies have examined the Chinese herbal drug Danshen or its extract on Lp-PLA2 in patients with stable angina pectoris. In this study, we aim to investigate the effect of Danshen extract on Lp-PLA2 level in patients with stable angina. METHODS/DESIGN: This is a randomized, single-blind, placebo-controlled, adaptive clinical trial. A total of 156 patients meeting the eligibility criteria will be randomly assigned to either the Danshen extract (DanshenDuofensuanyan injection and Danshen drop spill) group or the placebo group in a 1:1 ratio. Participants will then undergo treatment with DanshenDuofensuanyan injection or placebo (glucose) during hospitalization, followed by open-label Danshen drop spill (30 pills/day) in Danshen extract group for 60 days after discharge. Because this is an adaptive trial, two interim analyses are prospectively planned. These will be performed after one-third and two-thirds of the patients, respectively, have completed the trial. On the basis of the results of these interim analyses, a data monitoring committee will determine how to modify aspects of the study without undermining the validity and integrity of the trial. The primary outcome measure is the serum level of Lp-PLA2 in the Danshen extract group and the placebo group. The secondary outcomes include the proportion of patients who show a clinically significant change, which is defined as at least a 20-point improvement in angina frequency score on the Seattle Angina Questionnaire and the carotid intima-media thickness, which will be measured using ultrasound. Other secondary efficacy and safety outcomes will also be assessed. DISCUSSION: This study will provide evidence that Danshen extract is beneficial for stable angina and may establish a possible mechanism of Danshen treatment effects on cardiovascular disease. This study may also validate an objective blood test (LP-PLA2 level) for assessing the effectiveness of Danshen therapy in patients with stable angina pectoris. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02870764 . Registered on 13 August 2016.

Immunomodulatory activity of macromolecular polysaccharide isolated from Grifola frondosa.

The present study was designed to evaluate the immune-modulating effects of the polysaccharide from Grifola frondosa (GFP) by using mouse peritoneal macrophage and cytoxan (CTX) induced immunosuppression models. Our results from the phagocytotic and mononuclear phagocytic system function assays showed that GFP-A (one component from GFP) stimulated the phagocytosis of the phagocytes. The splenocyte proliferation assay showed that GFP-A acted the effect combing ConA or LPS in splenocyte proliferation. The results showed that GFP-A increased indices of thymus and spleen, the levels of LDH and ACP in the spleen, the mRNA levels of IL-1ß, IL-2, IL-6 and IFN-γ in splenocyte. And GFP-A also significantly increased the expression of CD4(+) and CD8(+) splenic T lymphocytes, which were suppressed by the CTX in peripheral blood. In conclusion, our results indicate that the GFP-A is involved in immunomodulatory effects leading to its modulatory effects on immunosuppression.

[Protective effect of serum containing n-butanol fraction from Gynostemma pentaphyllum on NG108-15 cell apoptosis induced by Aß25.35 protein].

OBJECTIVE: To investigate the inhibition effect of serum containing n-butanol fractions from Gynostemma pentaphyllum on NG108-15 cell apoptosis induced by Aß25-35 protein in vitro. METHODS: The apoptosis of NG108-15 cells induced by Aß25-35 protein in vitro was evaluated by immunofluorescence and flow cytometry assay. The cellular Caspase-3 level during the apoptosis was determined by ELISA. RESULTS: The serum containing n-butanol fractions from Gynostemma pentaphyllum significantly inhibited the NG108-15 cells apoptosis induced by Aß25-35 protein in vitro,and decreased the cellular Caspase-3 level. CONCLUSION: The inhibition effect of n-butanol fractions from Gynostemma pentaphyllum on NG108-15 cell apoptosis induced by Aß25.35 protein is likely related to its potency on reducing of cellular Caspase-3 level.

Forty-six cases of vertebrobasilar insufficiency treated by acupuncture plus intravenous infusion of ligustrazine.

OBJECTIVE: To observe the therapeutic effect of acupuncture plus Ligustrazine on vertebrobasilar insufficiency (VBI) by transcranial Doppler (TCD) sonography. METHODS: 86 VBI patients including 56 cases of low flow rate velocity type (LFVT) and 30 cases of high flow velocity type (HFVT) were randomly divided into Ligustrazine group (26 LFRT and 14 HFVT) and acupuncture plus Ligustrazine group (30 LFVT and 16 HFVT). The blood flow velocity (BFV) of vertebral artery (VA) and basilar artery (BA) in systole before and after treatment was measured with TCD and therapeutic effects were evaluated after 10 days' treatment in the two groups. RESULTS: In the acupuncture plus Ligustrazine group, the total effective rate was 93.3% and 88.5% in cases of LFVT and HFVT respectively, and BFV of VA and BA increased in LFVT patients while that in HFVT patients decreased significantly (P<0.05 or P<0.01). CONCLUSION: Owing to its dual regulation on blood flow of VA and BA, the therapeutic effect of acupuncture plus Ligustrazine was better than that of simple Ligustrazine.

[Experimental study on effect of Huaxian Decoction treating bleomycin-induced pulmonary fibrosis in mice].

OBJECTIVE: To study the preventive and therapeutic effect of Huaxian Decoction (HXD) on bleomycin-induced pulmonary fibrosis in mice by taking treatment of ligustrazin and prednisone as controls, for investigate the clinical value and possible mechanism in treatment of pulmonary fibrosis by traditional Chinese herbs. METHODS: A total of 96 male ICR mice, aged 6 to 8 weeks, were randomly divided into 8 groups. Pulmonary fibrosis was induced in the model group by intranasal instillation of bleomycin 5 mg/kg. HXD were given via gastrogavage to the HXD prevention group and treatment group respectively at 48 h before and 14 days after they were modeled with the same method, and the groups of ligustrazin and prednisone, treatment and prevention, were managed the same as for HXD groups, but with ligustazin and prednisone instead of HXD respectively. Bronchoalveolar lavage fluid (BALF) and lung tissue of animals were gathered on day 28. Cellular ultrastructural changes of lung was examined under electron microscope by HE, Masson stain; Content of hydroxyproline (HYP) in lung tissue was assessed by acidolysis method; and concentration of transforming growth factor-beta1 (TGF-beta1) in BALF was assessed by ELISA. RESULTS: Pulmonary coefficient was significantly lower in all the drug intervening groups than that in the model group (P < 0.05), improvement on alveolitis and pulmonary fibrosis were alsonaged the safter intervention, especially in the HXD prevention group (Pinstead < 0.05). HYP content in lung tissue and TGF-beta1 content in BALF lowered at the same time. CONCLUSION: Early stage application of HXD can alleviate bleomycin-induced alveolitis and pulmonary fibrosis in mice to certain degree, suggesting that Chinese herbs with supplementing qi and activating blood circulation effect could play a definite preventive action on pulmonary fibrosis, and the inhibition on expressions of TGF-beta1 in lung tissues may be one of the mechanisms.

[Effects of cordyceps sinensi on bleomycin-induced pulmonary fibrosis in mice].

OBJECTIVE: To study the prevention & treatment effect of cordyceps sinensi on bleomycin-induced pulmonary fibrosis (PF) in mice. METHOD: Rats were divided into 4 groups. In BM group (model), pulmonary interstitial fibrosis model was established through nasal dripping of 5 mg x kg(-1) bleomycin. In PCT group (prevention & treatment with cordyceps sinensi), cordyceps sinensi was orally administered 48 h before bleomycin dripping. In CT group (treatment with cordyceps sinensi), cordyceps sinensi was orally administered at 14 d after bleomycin dripping, and NC group (normal mice, control). At 28 d, bronchoalveolar lavage fluid (BALF) and lung tissue were collected, right lung received HE staining and masson staining, the change in cell micro-structure was observed under electron microscope, the hydroxyproline (HYP) content in lung tissue of left lung was detected through acidolysis method, and TGF-beta1, IFN-gamma and IL-4 concentration in BALF was detected through ELISA. RESULT: Compared with those in BM group, mouse lung coefficient decreased significantly (P < 0.05), alveolitis and fibrosis degree improved significantly in PCT and CT groups (P < 0.05), HYP content in lung decreased (P < 0.05). TGF-beta1 and 1L-4 content in BALF decreased significantly in each drug intervention group, IFN-gamma content increased significantly (P < 0.05). CONCLUSION: The cordyceps sinensi can alleviate bleomycin-induced alveolitis and fibrosis degree in a certain degree. The mechanism of the alleviation is possibly due to its inhibition of TGF-beta1 expression and its regulation of imbalance of the type I and II cytokine in lung tissue.