Efficacy and Safety of Chinese Herbal Medicine Compared With Losartan for Mild Essential Hypertension: A Randomized, Multicenter, Double-Blind, Noninferiority Trial.

BACKGROUND: Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Songling Xuemaikang capsule (SXC)-a Chinese herbal formula-was effective for essential hypertension. However, the efficacy of SXC monotherapy for hypertension remains unclear. We aimed to compare the blood pressure (BP)-lowering efficacy and safety of SXC versus losartan in patients with essential hypertension. METHODS: In this multicenter, randomized, double-blind, noninferiority trial in China, patients 18 to 65 years of age with mild essential hypertension were randomly allocated to receive either SXC or losartan for 8 weeks. The primary outcome was the change in sitting diastolic BP from baseline to 8 weeks, with a predefined noninferiority margin of -2.5 mm Hg. RESULTS: Of the 755 patients who entered a 2-week run-in period, 628 patients (327 women and 301 men; mean [SD] age, 52.6 [9.2] years) were randomly assigned to the SXC (n=314) or losartan (n=314) group. The primary analysis based on the intention-to-treat principle showed that the change in diastolic BP from baseline to 8 weeks was similar between the SXC and losartan groups (-7.9 [8.0] versus -8.1 [7.9]). The lower boundary of 95% CI (mean difference, -0.24 [95% CI, -1.51 to 1.03]) was above the margin of -2.5 mm Hg, showing noninferiority. Results were consistent with per-protocol analysis. SXC produced greater improvements in total hypertension symptom score (-5.7 [4.2] versus -5.0 [4.0]; P=0.020) and total cholesterol (-0.1 [1.0] versus 0.1 [1.2]; P=0.025). There were no differences between groups in the other BP and patient-reported outcomes. Incidence and severity of adverse events were similar between groups. CONCLUSIONS: SXC was well tolerated and demonstrated noninferior to losartan in BP lowering in patients with mild hypertension. SXC might be an alternative for mild hypertension, particularly for patients with a preference for natural medicine. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR-IPR-16008108.

Pretreatment with the active fraction of Rhodiola tangutica (Maxim.) S.H. Fu rescues hypoxia-induced potassium channel inhibition in rat pulmonary artery smooth muscle cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have shown that the active fraction of Rhodiola tangutica (Maxim.) S.H. Fu (ACRT) dilates pulmonary arteries and thwarts pulmonary artery remodelling. The dilatation effect of ACRT on pulmonary artery vascular rings could be reduced by potassium (K+) channel blockers. However the exact mechanisms of ACRT on ion channels are still unclear. AIM OF THE STUDY: This study aimed to investigate whether the effect of ACRT on K+ channels inhibits cell proliferation after pulmonary artery smooth muscle cells (PASMCs) are exposed to hypoxia. MATERIALS AND METHODS: The whole-cell patch-clamp method was used to clarify the effect of ACRT on the K+ current (IK) of rat PASMCs exposed to hypoxia. The mRNA and protein expression levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. The intracellular calcium (Ca2+) concentration ([Ca2+]i) values in rat PASMCs were detected by laser scanning confocal microscopy. The cell cycle and cell proliferation were assessed using flow cytometry analysis and CCK-8 and EdU assays. RESULTS: ACRT pretreatment alleviated the inhibition of IK induced by hypoxia in rat PASMCs. Compared with hypoxia, ACRT upregulated voltage-dependent K+ channel (Kv) 1.5 and big-conductance calcium-activated K+ channel (BKCa) mRNA and protein expression and downregulated voltage-dependent Ca2+ channel (Cav) 1.2 mRNA and protein expression. ACRT decreased [Ca2+]i, inhibited the promotion of cyclin D1 and proliferating cell nuclear antigen (PCNA) expression, and prevented the proliferation of rat PASMCs exposed to hypoxia. CONCLUSION: In conclusion, the present study demonstrated that ACRT plays a key role in restoring ion channel function and then inhibiting the proliferation of PASMCs under hypoxia, ACRT has preventive and therapeutic potential in hypoxic pulmonary hypertension.

Total saponins extracted from Abrus cantoniensis Hance suppress hepatitis B virus replication in vitro and in rAAV8-1.3HBV transfected mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatitis B, an infectious disease caused by hepatitis B virus (HBV), is still a serious problem affecting global public health. Abrus cantoniensis Hance (AC), a traditional Chinese medicinal herb, has been used as a folk medicine for treating hepatitis in China from ancient times. However, its active ingredients are still unclear. AIM OF STUDY: Our previous study indicated that saponins extracted from AC (ACS) were the active anti-HBV ingredients in AC. This study aimed to further investigate the anti-HBV effect of ACS in vitro and in vivo. MATERIALS AND METHODS: HepG2.2.15 cells which consecutively produce HBV DNA and HBV antigens were used for in vitro test, and C57BL/6 mice infected by a recombinant adeno-associated virus 8 vector carrying 1.3 copies of HBV genome (rAAV8-HBV1.3) were used for in vivo test. The histopathological changes and the immune indices were evaluated in mice model. Genechip was conducted to identify genes and pathways regulated by ACS in HepG2.2.15 cells. RESULTS: In this study, we confirmed that ACS treatment prominently inhibited production of HBV DNA, Hepatitis Be Antigen (HBeAg), and Hepatitis B surface antigen (HBsAg) in HepG2.2.15 cells. ACS treatment also decreased serum HBsAg, HBeAg, and HBV DNA level in rAAV8-1.3HBV transfected mice, which is in accordance with the in vitro results. Moreover, HBV infection-induced liver inflammation was significantly relieved by ACS, which could be observed in H&E staining and immunohistochemistry of HBcAg. ACS treatment elevated IFN-γ level in mice serum and increased CD4+ T cell percentage in splenocytes. KEGG pathway analysis showed that phenylalanine metabolism pathway and tyrosine metabolism pathway were greatly regulated by ACS treatment. CONCLUSION: ACS exerted potent inhibitory effects on HBV replication both in vivo and in vitro, which may provide basis for its potential clinical usage.

Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes.

OBJECTIVE: To investigate whether ginsenoside-Rb1 (Gs-Rb1) inhibits the apoptosis of hypoxia cardiomyocytes by up-regulating apelin-APJ system and whether the system is affected by hypoxia-induced factor 1α (Hif-1α). METHODS: Neonatal rat cardiomyocytes were randomly divided into 6 groups: a control group, a simple CoCl group, a simple Gs-Rb1 group, a CoCl and Gs-Rb1 hypoxia group, a CoCl and 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) group, a CoCl and YC-1 group and a Gs-Rb1 group, in which YC-1 inhibits the synthesis and accelerates the degradation of Hif-1a. The concentration of CoCl, Gs-Rb1 and YC-1 was 500 µmol/L, 200 µmol/L and 5 µmol/L, respectively; the apoptosis ratio was analyzed with a flow cytometer; and apelin, APJ and Hif-1α were assayed with immunocytochemistry, Western blot assays and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: (1) The anti-apoptosis effect of Gs-Rb1 on hypoxia cardiomyocytes was significantly inhibited by YC-1; (2) Hypoxia significantly up-graded the expression of mRNA and protein of apelin; this effect was further reinforced by Gs-Rb1 and significantly inhibited by YC-1; (3) Gs-Rb1 further strengthened the expression of APJ mRNA and APJ proteins once hypoxia occurred, which was significantly inhibited by YC-1; (4) Gs-Rb1 significantly increased the expression of Hif-1α, which was completely abolished by YC-1; (5) There was a negative relationship between AR and apelin (or APJ, including mRNA and protein), a positive correlation between apelin (or APJ) protein and Hif-1a protein, in hypoxia cardiomyocytes. CONCLUSION: The apelin-APJ system plays an important role in the anti-apoptosis effect of Gs-Rb1 on hypoxia neonatal cardiomyocytes, which was partly adjusted by Hif-1α.

The clinical study of autologous peripheral blood stem cell transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI).

PURPOSE: To investigate the effects and safety of autologous peripheral blood stem cell (PBSCs) transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI). METHODS: 70 patients with AMI were allocated to two groups, one was PBSCs transplantation group (n=35) that received optimal post-infarction medical treatment (standard drug and coronary artery intervention therapy) and intracoronary transplantation of PBSCs; the other was control group (n=35) that received optimum post-infarction medical treatment (standard drug and coronary artery intervention therapy). The PBSCs transplantation group received granulocyte colony-stimulating factor (G-CSF: Filgrastim, 300 microg) with the dose of 300-600 microg/day to mobilize the stem cell, and the duration of administration G-CSF was 5 days. On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then, the suspend liquid was transferred into the infarct-related artery (IRA) by occluding the over-the-wire balloon and infusing artery through balloon center lumen. In the process of the mobilization, separation and intracoronary infusion of PBSCs, the complications have been investigated. Changes in left ventricular function were assessed at 6-month follow-up. RESULTS: 35 cases had finished follow-up in the treated group, while 23 cases in control group. After 6 months, within the treated group, there was a significant improvement in global left ventricular function ejection fraction (EF) from a baseline of 50.0+/-8.2% to 57.1+/-7.8% (P<0.0001), wall motion score index (WMSI) from 1.219+/-0.190 to 1.101+/-0.118 (P<0.0001), left end-systolic volume (ESV) from 63.8+/-23.9 ml to 52.6+/-20.3 ml (P=0.01) and left end-diastolic volume (EDV) from 134.2+/-36.7 ml to 119.2+/-30.3 ml (P=0.07); in the control group, there was no significant improvement in EF, WISM, EDV and ESV (P=0.490, 0.259, 0.117, 0.395). After 6-month follow-up, according to treatment group vs. control group, there was a significant improvement in EF from 57.1+/-7.8 to 52.6+/-5.7 (P=0.041) and WISM from 1.101+/-0.118 to 1.184+/-0.138 (P=0.034). There were a total of 25 cases with complications during the mobilization, separating and infusion of PBSC. The incidence of complications relating to mobilization was 37.1% (13/35), relating to separating was 14.3% (5/35) and relating to intracoronary infusion was 20.0% (7/35). No death was observed. CONCLUSION: Autologous PBSCs transplantation by intracoronary infusion is feasible and safe, and it can improve left ventricular function in the 6-month follow-up.