Efficacy of the wen dan decoction, a Chinese herbal formula, for metabolic syndrome.

CONTEXT: Metabolic syndrome (MS) refers to the clustering of metabolic derangements that include hyperglycemia, dyslipidemia, hypertension, and chronic kidney impairment. Those conditions are well known as being synergistically responsible for morbidity from cardiovascular disease as well as for driving the global epidemic of type 2 diabetes. It is still unknown whether an exact unifying pathogenesis of MS exists. OBJECTIVE: The meta-analysis intended to analyze the use of Chinese medicine (CM) as a therapeutic tool to explore indirectly the unifying pathogenesis of MS. METHODS: PubMed, the Chinese National Knowledge Infrastructure (CNKI), and the Wanfang databases were systematically searched from inception to November 2013 for randomized, controlled trials (RCTs) that compared treatment efficacy for MS patients using the Wen Dan decoction (WDD), a CM formula, versus Western conventional therapeutics. OUTCOME MEASURES: Measurements included tests of the overall therapeutic efficacy of WDD for hyperglycemia, hypertension, dyslipidemia, and renal functions, and the study also analyzed adverse events. Data were expressed as weighted mean differences (WMDs), with 95% confidence intervals (95% CIs) and the odds ratio (OR). RESULTS: A total of 31 RCTs were included for meta-analysis, involving 2512 patients and including 1282 participants in the intervention groups. The pooled data favored WDD over the control treatments as follows: (1) hyperglycemia, with a WMD of -0.95 mmol/L (95% CI: -1.19 to -0.71); (2) hypertension, with a WMD of -7.40 mm Hg (95% CI: -9.86 to -4.93); (3) dyslipidemia: (a) total cholesterol (TC), with a WMD of -0.62 mmol/L (95% CI: -0.90 to -0.33); (b) triglycerides (TGs), with a WMD of -0.32 mmol/L (95% CI: -0.52 to -0.13); (c) low-density lipoproteins (LDPs), with a WMD of -0.22 mmol/L (95% CI: -0.41 to -0.02); and (d) high-density lipoproteins (HDPs), with a WMD of 0.10 mmol/L (95% CI: 0.03 to 0.17); and (4) of renal functions: (a) urea, with a WMD of -3.41 mmol/L (95% CI: -5.50 to -1.32) and (b) creatinine, with a WMD of -68.81 µmol/L (95% CI: -132.63 to -4.98). No statistical significance was documented in creatinine clearance between the 2 treatments with a WMD of 15.47 mL/min (95% CI: -7.71 to 38.64). The overall efficacy rate was 91.4% for WDD and 66.9% for the control treatments (OR: 5.33; 95% CI: 4.06 to 6.99). Adverse events were rare and minor. CONCLUSIONS: The consistent improvements found in metabolic profiles by use of the single herbal formula may indirectly imply a common pathogenesis in MS.

Design, synthesis and biological evaluation of novel 1-hydroxyl-3-aminoalkoxy xanthone derivatives as potent anticancer agents.

A series of novel 1-hydroxyl-3-aminoalkoxy xanthone derivatives were designed, synthesized and evaluated for in vitro anticancer activity against four selected human cancer cell lines (nasopharyngeal neoplasm CNE, liver cancer BEL-7402, gastric cancer MGC-803, lung adenocarcinoma A549). Most of the synthesized compounds exhibit effective cytotoxic activity against the four tested cancer cell lines with the IC50 values at micromolar concentration level. Some preliminary structure-activity relationships were also discussed. In this series of derivatives, compound 3g shows excellent broad spectrum anticancer activity with IC50 values ranging from 3.57 to 20.07 µM. The in vitro anticancer activity effect and action mechanism of compound 3g on human gastric carcinoma MGC-803 cell were further investigated. The results showed that compound 3g exhibits dose- and time-dependent anticancer effects on MGC-803 cells through apoptosis, which might be associated with its decreasing intracellular calcium and the mitochondrial membrane potential.

Eight-year survival of AIDS patients treated with Chinese herbal medicine.

Treatment of acquired immunodeficiency syndrome (AIDS) currently relies on the use of antiretroviral drugs. Little is known about Chinese herbal medicine (CHM) outcomes in patients living with AIDS. We conducted a cohort study to investigate long-term survival among CHM-treated AIDS patients. Patients were poor farmers who contracted HIV-1 infection when selling blood in the 1990s. Symptoms of AIDS included recurring respiratory tract infections with a clinical diagnosis of pneumonia, swollen lymph nodes and weight loss. 385 patients with AIDS were included and 165 of them used a 16-herb formula for 14 days to 9 months. The eight-year survival rate was 87% for the CHM users and 34% for the non-users (increased survival probability for CHM user, 9.6; 95% CI = 6.0-15.4; p < 0.0001). Survival probability further increased 14.6-fold (95% CI = 8.2-26.1), when excluding the users who received CHM for less than three months. Zero deaths were found in patients who used CHM for six to nine months. All the survivors regained their body weight and none of them experienced a relapse of AIDS or any severe adverse events. After the CHM treatment for an average of 3.6 months, the plasma HIV load was 74.7% lower (paired t-test, p = 0.151) and the number of blood CD4+ lymphocytes increased from 253 to 314 (paired t-test, p = 0.021). Without life-long medication, CHM may be beneficial for long-term survival of AIDS patients.

Characterization of diethylnitrosamine-induced liver carcinogenesis in Syrian golden hamsters.

The aim of this study was to characterize hepatocarcinogenesis in diethylnitrosamine (DEN)-treated hamsters. Syrian golden hamsters (n=36) were administered DEN by hypodermic injection and addition to drinking water. Morphological analyses, including light microscopy and immunohistochemistry of α-fetal protein (AFP), were performed on liver and lung tissues. Primary cell culture and tumor transplantation were carried out to evaluate the potential application in hepatocellular carcinoma (HCC) research. From 25 to 50 weeks of treatment, liver tumors, including macronodular HCC and ascites, were found in one-third (4/12) of the animals treated with DEN. HCC was characterized by poor differentiation, frequent mitosis, AFP reaction, vessel invasion and potential application in primary cell culture and xenotransplantation. Pre-neoplastic lesions were hyperplastic nodules comprised of clear cells, bile duct proliferation, fatty metamorphosis and multilocular cysts. The DEN-treated hamsters also showed lung tumors consisting of AFP-negative, well-differentiated neoplastic cells. Characterization of DEN-induced HCC in hamsters provides insights into human hepatocarcinogenesis. This animal model has potential applications in HCC research.

Tanshinone IIA activates calcium-dependent apoptosis signaling pathway in human hepatoma cells.

Tanshinone IIA (Tan IIA), a natural product from herb Salvia miltiorrhiza Bunge, has potential anti-tumor activity. The aim of this study was to pinpoint the molecular mechanisms underlying Tan IIA-induced cancer cell apoptosis. Human hepatoma BEL-7402 cells treated with Tan IIA underwent assessment with MTT assay for cell viability, 10-day culture for colony formation, flow cytometry and fluorescence microscopy for apoptosis and cell cycle analysis. Changes in intracellular [Ca(2+)] and mitochondrial membrane potential (∆ψ) reflected the calcium-dependent apoptosis pathway. RT-PCR was used to detect gene expression of Bad and metallothionein 1A (MT 1A). Cytotoxicity of Tan IIA was tested in human amniotic mesenchymal stem cells (HAMCs). Tan IIA exhibited dose-dependent and time-dependent anticancer effects on BEL-7402 cells through apoptosis and G(0)/G(1) arrest. Cells treated with Tan IIA increased their intracellular calcium, decreased their mitochondrial membrane potential and induced Bad and MT 1A mRNA expression. No adverse effects of Tan IIA were found in HAMCs. In conclusion, these results indicate that Tan IIA-induced cancer cell apoptosis acts via activation of calcium-dependent apoptosis signaling pathways and upregulation of MT 1A expression.

[Anticancer effect of 5-fluorouracil combined with extract of Rosa roxburghii Tratt on human endometrial adenocarcinoma].

OBJECTIVE: To investigate anticancer effects of 5-fluorouracil (5-FU) combined with CL, extract of Rosa roxburghii Tratt on human endometrial adenocarcinoma cell line (JEC). METHODS: JEC cells cultured in vitro in the logarithmic growth phase were seeded in the culture plate and divided into the control group (RPMI 1640), the positive group (10(-4) mol/L 5-FU), the CL groups (at the dose of 0.01, 0.1, 1, 10, and 100 microg/mL), and the CL (0.01, 0.1, 1, 10, and 100 microg/mL) combined with 5-FU groups. Effects of 5-FU combined with CL on JEC cell growth were drawn and measured by MTT and growth curves. Effects of CL combined with 5-FU on the JEC cell differentiation was analyzed by detecting the reduction capability of nitrobenzene thiocyanate (NBT) and lactate dehydrogenase (LDH) contents in the cultured medium. Effects of CL combined with 5-FU on the JEC cell apoptosis and cell proliferation cycle were detected by acridine orange (AO)/ethidium bromide (EB) fluorescent staining and flow cytometry (FCM). RESULTS: The proliferation inhibitory effect of CL combined with 5-FU on JEC cells was enhanced when compared with that of CL or 5-FU alone (P<0.05). The percentages of NBT positive JEC cells and apoptotic JEC cells increased in the 5-FU combined with CL groups when compared with 5-FU group or the CL group alone (P<0.05). The LDH concentration of the JEC cell culture supernate decreased in 5-FU combined with CL groups (P<0.05). Furthermore, the percentage of G0-G1 phase JEC cells treated by 5-FU combined with CL was higher than that of 5-FU or CL alone (P<0.05). CONCLUSION: CL could enhance anticancer effects of 5-FU. Its mechanisms might be correlated with reinforcing the cytotoxicity of 5-FU, inducing cell differentiation and apoptosis, and inhibiting cell proliferation and division.

[Study on the constituents of petroleum ether fraction of Buxus microphylla].

OBJECTIVE: To study the chemical constituents from the petroleum ether fraction of Buxus microphylla. METHODS: The petroleum ether fraction of Buxus microphylla was isolated and identified by silica gel column chromatography. And the anticancer activity of different chemical constituents was measured by MTT reduction test. RESULTS: Eight compounds were isolated and identified as lupeol (1), butulin (3), beta-sitosterol (4), stigmasterol (5), dibutyl phthalate (6), 3beta, 30-dihydroxy-lup-20 (29) ene (7), daucosterol (8). Compound 7 inhibited KB cells' proliferation in a dose-dependent manner. CONCLUSION: Compounds 2 - 5, 7, 8 are isolated from this genus for the first time. Compound 7 has certainly anticancer effects.

[The effects of extracts from Arenaria kansuensis on the levels of HBsAG and HBeAg in HepG2.2.15 cells].

OBJECTIVE: To investigate the anti-HBV effects of the extracts with alcohol and water from Arenaria kansuensis in vitro. METHODS: HepG2.2.15 cells were used to estimate the effects of the extracts with alcohol and water from Arenaria kansuensis on the levels of HBsAg and HBeAg in medium by ELISA. RESULTS: Incubation of HepG2.2.15 cells with both the extracts with alcohol and water from Arenaria kansuensis (50-400 mg/L) for 72 and 96h significantly inhibited the levels of HBsAg and HBeAg. The maximum inhibiting rate of HBeAg from the Arenaria kansuensis extracts with alcohol was 63.2% and 90. 8% at 72h and 96h, respectively. Meanwhile, the Arenaria kansuensis extracts with water had obvious inhibitory effects on the levels of HBsAg and HBeAg in HepG2.2.15 cells at 96 h, compared with that of the control group (P < 0.01). The maximum inhibiting rates were 52.5% and 72.8%, respectively. CONCLUSION: The extracts with water from Arenaria kansuensis has obvious anti-HBV effects in vitro.

[Anticancer effect of CL extract of Rosa roxburghii].

OBJECTIVE: To investigate anticancer effects and potential mechanisms of CL, extract of Rosa roxburghii. METHOD: In vitro anticancer effect was observed in Ehrlich's ascites carcinoma (EAC) mice model. Cell toxicity of CL on human endometrial adenocarcinoma cell line JEC (JEC) cells was measured by MTT reduction test and growth curves drawing by trypan blue dye exclusion method. Lactate dehydrogenase (LDH) concentration of cultured medium was detected by auto-biochemistry-meter. Cell differentiation was showed by detection of NBT reduction ability. Apoptosis was showed by AO/EB fluorescent staining and flow cytometer detection. Cell proliferation cycle was detected by flow cytometer. RESULT: Comparing with the negative group, life span of EAC mice treated with CL was prolonged (P <0.05), and thymus index and spleen index of them were raised (P <0.05). The inhibitory effect of CL on JEC cells was in concentration-and time-dependent manner. IC50 of CL on JEC cells was 0.05 microg mL(-1) in 96 hours. Growth curves showed right-shift with CL concentration increasing. The number of NBT positive JEC cells increased and the LDH concentration of cultured medium declined with CL increasing. Apoptosis of JEC cells with CL treated was induced in concentration-dependent manner, apoptotic percentage of CL 10 microg mL(-1) on JEC cells was 25.59% in 24 hours. CL arrested JEC cells in G2-M phase (P <0.05). CONCLUSION: CL has certainly anticancer effects in vivo and in vitro. Anticancer effect of CL in vivo was in relation to enhancing immune function of EAC mice; anticancer mechanisms of CL on JEC cells may be its direct cytotoxic effect, inducing cell apoptosis and inhibiting cell segmentation.

Inhibitory effect of ginsenoside Rb1 on cardiac hypertrophy induced by monocrotaline in rat.

Ginseng, the root of Panax ginseng, has been used as folk medicine in the treatment of various diseases for thousands of years in China. Ginsenoside Rb1 (Rb1), one of the effective components of ginseng, has been reported to release nitric oxide and decrease intracellular free Ca2+ in cardiac myocytes, both of which play important roles in antihypertrophic effect. This study was to investigate the potential effect of Rb1 on right ventricular hypertrophy (RVH) induced by monocrotaline (MCT) and its possible influence on calcineurin (CaN) signal trasnsduction pathway. MCT-treated animals were administered with Rb1 (10 and 40 mg /kg) from day 1 to day 14 (preventive administration) or from day 15 to day 28 (therapeutic administration), or with vehicle as corresponding controls. After 2 weeks, significantly hypertrophic reactions, including RVH index and the expressions of atrial natriuretic peptide mRNA, appeared in right ventricle of all MCT-treated animals (p < 0.05), which were significantly decreased with some improvements of myocardial pathomorphology in both Rb1 prevention- and therapy-groups (p < 0.05). Similarly, MCT-treatment caused the high expressions of mRNA and/or proteins of CaN, NFAT3 and GATA4 from cardiocytes (p < 0.05) and Rb1 could alleviate the expressions of these factors above (p < 0.05). These results suggest that Rb1 treatment can inhibit the RVH induced by MCT, which may be involved in its inhibitory effects on CaN signal transduction pathway.

Cardiac hypertrophy induced by prostaglandin F(2alpha) may be mediated by calcineurin signal transduction pathway in rats.

In this paper, we studied the relationship between the prostaglandin F(2alpha) (PGF(2alpha))-induced cardiac hypertrophy and calcineurin (CaN) signal transduction pathway in vivo and in vitro. Male Sprague-Dawley rats were given a single i.p. injection with monocrotaline (MCT) (60 mg/kg) and then given orally with celecoxib (20 mg/kg) or vehicle once a day for 14 d before (from d 1 to d 14) or after (from d 15 to d 28) right ventricular hypertrophy (RVH) was formed. Body weight (BW), right ventricular weight (RV), left ventricular with septum weight (LV), as well as lung weight were determined. RVH index (RVHI=RV/LV), RV/BW, and lung weight/BW were calculated and histological changes were observed with transmission electron microscope. PGF(2alpha) level, atrial natriuretic peptide (ANP) and CaN mRNA expressions, expression of CaN and its downstream effectors, NFAT(3) and GATA(4) protein were assayed by EIA kit, RT-PCR, and Western blotting, respectively. The cardiomyocyte hypertrophy in primary culture induced by PGF(2alpha) (0.1 micromol/L) was evaluated by measuring the cell diameter, protein content, and ANP mRNA as well as CaN mRNA expressions. It was found that 14 d or 28 d after MCT was given, the RVHI, RV/BW, and lung weight/BW were significantly increased by 47%, 53% and 118%, and by 64%, 94% and 156%, respectively; at the same time PGF(2alpha) levels in RV tissue were increased by 44% and by 51% with increasing RVHI, and elevated expressions of ANP and CaN mRNA, as well as CaN, NFAT(3) and GATA(4) proteins in a positive correlation manner. Furthermore, some histological injuries were found in RV tissue. Celecoxib, a cyclooxygenase inhibitor, obviously blunted the elevation of RVHI, RV/BW, and lung weight/BW no matter it was given before or after RVH. In vitro experiments showed that 0.1 micromol/L PGF(2alpha) significantly increased the cardiomyocyte diameter and protein content, and promoted ANP and CaN mRNA expressions, which was blocked by cyclosporin A, a CaN inhibitor. Our results indicate that PGF(2alpha) may be involved in cardiac hypertrophy induced by MCT in rats through CaN signal transduction pathway.