Comparative study on short and long-term intervention impacts of six Chinese herbs with cold or heat property on lipid and energy metabolism in mice / 中国中药杂志

This study selected three typical Chinese herbs with cold property(Rhei Radix et Rhizoma, Scutellariae Radix, and Coptidis Rhizoma) and another three with heat property(Cinnamomi Cortex, Zingiberris Rhizoma, and Aconiti Lateralis Radix Praeparata) to observe their regulatory effects on metabolism in animal organism, especially on lipid and energy metabolism in mice after a short-(7 d) and long-term(35 d) intervention. The mRNA expression levels of lipid metabolism genes in epididymal adipose tissue and liver were determined by real-time PCR. The oxygen consumption, carbon dioxide production, and energy consumption were detected by metabolic system. After the short-term intervention, the Chinese herbs with heat property significantly reduced epididymal adipose tissue index and elevated the expression levels of acetyl-CoA carboxylase(ACC), lipoprotein lipase(LPL), and carnitine-palmityl transferase 1(CPT-1) in liver and epididymal adipose tissues. However, those with cold property promoted the expression of above-mentioned genes in epididymal adipose tissue. After the long-term intervention, cold and heat Chinese herbs had no significant effect on epididymal adipose tissue index of animals, while cold Chinese herbs could increase carbon dioxide production and energy consumption and reduce activity. These findings demonstrated that the short-term intervention effects of cold and heat Chinese herbs on animal metabolism were significantly stronger than the long-term intervention effects. Specifically, the short-term intervention with cold Chinese herbs enhanced the lipid metabolism in epididymal adipose tissue, while the heat Chinese herbs promoted lipid metabolism in epididymal adipose tissue and liver. The long-term intervention with cold and heat Chinese herbs resulted in no obvious change in lipid level, but long-term intervention with cold Chinese herbs accelerated energy consumption of the body. This study preliminarily observed the effects of cold and heat Chinese herbs on normal animal physiology from lipid and energy metabolism, which would provide reference for explaining the biological basis of Chinese herbs with cold or heat property based on biological response.

A four-component combination derived from Huang-Qin Decoction significantly enhances anticancer activity of irinotecan / 中国天然药物

Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index E

Aurone derivatives as Vps34 inhibitors that modulate autophagy

We report in this study the identification of a natural product-like antagonist () of Vps34 as a potent autophagy modulator structure-based virtual screening. Aurone derivative strongly inhibited Vps34 activity in cell-free and cell-based assays. Significantly, prevents autophagy in human cells induced either by starvation or by an mTOR inhibitor. modeling and kinetic data revealed that could function as an ATP-competitive inhibitor of Vps34. Moreover, it suppressed autophagy and without inducing heart or liver damage in mice. could be utilized as a new motif for more selective and efficacious antagonists of Vps34 for the potential treatment of autophagy-related human diseases.

Panax Notoginseng Flower Extracted by Methanol on Platelet Function in Healthy Human in Vitro / 中山大学学报(医学科学版)

@#【Objective】To evaluate the effects of methanol extract of Panax Notoginseng flower（PNFM）on platelet function in healthy human.【Methods】Platelet rich plasma were separated from venous blood of healthy volunteers and incubated with different concentrations（0，100，300 and 500 μg/mL）of PNFM for 20 min. After using ADP as agonist， granule-secretion were tested by CD62P expression and ATP release；integrin-αIIbβ3 activation was examined by PAC-1； Test platelet aggregation by turbidimetry ；Immunofluorescence examine platelet spreading on fibrinogen ；Changes in cytoplasmic calcium was studied using Fluo 3-AM，calcium ionophore. 【Results】After using ADP as agonist ，PNFM significantly inhibited platelet aggregation，compared to the control group（72.00±6.08），the 500μg/mL group decreased to 35.67±3.78（P<0.01）；Compared to the control group（30.05±6.48），PNFM reduced the CD62P expression on platelet surface，the 500 μg/mL group decreased to 2.66±0.90（P<0.001）；PNFM inhibited the expression of PAC-1 as a marker of the integrin- αIIbβ3 comformation，compared to the control group（33.37 ± 8.12），the 500 μg/mL group decreased to 11.89±6.12（P<0.01）；Compared to the control group（1.93±0.47），all dose groups attenuated platelet ATP release，the 500 μg/mL group decreased to 35.67±3.78（P<0.01）；Results demonstrated that 500 μg/mL PNFM markedly decreases the surface area of the spreading platelets（89.57±17.34 to 25.12±3.52，P<0.001），and all doses were affected；The Ca2 + mobilization was also reduced by all PNFM doses，compared to the control group（183.87 ± 11.59），the 500 μg/mL group was decreased to 71.25±5.33（P<0.001）.【Conclusions】PNFM attenuated platelet activation，spreading，and aggregation； Our results provided new ideas for prevention and treatment of cardiovascular and cerebrovascular diseases.

Pro-angiogenic activity of notoginsenoside R1 in human umbilical vein endothelial cells in vitro and in a chemical-induced blood vessel loss model of zebrafish in vivo / 中国结合医学杂志

<p><b>OBJECTIVE</b>This study aimed at investigating whether notoginsenoside R1 (R1), a unique saponin found in Panax notoginseng could promote angiogenic activity on human umbilical vein endothelial cells (HUVECs) and elucidate their potential molecular mechanisms. In addition, vascular restorative activities of R1 was assessed in a chemically-induced blood vessel loss model in zebrafish.</p><p><b>METHODS</b>The in vitro angiogenic effect of R1 was compared with other previously reported angiogenic saponins Rg1 and Re. The HUVECs proliferation in the presence of R1 was determined by cell proliferation kit II (XTT) assay. R1, Rg1 and Re-induced HUVECs invasion across polycarbonate membrane was stained with Hoechst-33342 and quantified microscopically. Tube formation assay using matrigelcoated wells was performed to evaluate the pro-angiogenic actions of R1. In order to understand the mechanism underlying the pro-angiogenic effect, various pathway inhibitors such as SU5416, wortmannin (wort) or L-Nω-nitro- L-arginine methyl ester hydrochloride (L-NAME), SH-6 were used to probe the possible involvement of signaling pathway in the R1 mediated HUVECs proliferation. In in vivo assays, zebrafish embryos at 21 hpf were pre-treated with vascular endothelial growth factor (VEGF) receptor kinase inhibitor II (VRI) for 3 h only and subsequently post-treated with R1 for 48 h, respectively. The intersegmental vessels (ISVs) in zebrafish were assessed for the restorative effect of R1 on defective blood vessels.</p><p><b>RESULTS</b>R1 could stimulate the proliferation of HUVECs. In the chemoinvasion assay, R1 significantly increased the number of cross-membrane HUVECs. In addition, R1 markedly enhanced the tube formation ability of HUVECs. The proliferative effects of these saponins on HUVECs were effectively blocked by the addition of SU5416 (a VEGF-KDR/Flk-1 inhibitor). Similarly, pre-treatment with wort [a phosphatidylinositol 3-kinase (PI3K)-kinase inhibitor], L-NAME [an endothelial nitric oxide synthase (eNOS) inhibitor] or SH-6 (an Akt pathway inhibitor) significantly abrogated the R1 induced proliferation of HUVECs. In chemicallyinduced blood vessel loss model in zebrafish, R1 significantly rescue the damaged ISVs.</p><p><b>CONCLUSION</b>R1, similar to Rg1 and Re, had been showed pro-angiogenic action, possibly via the activation of the VEGF-KDR/Flk-1 and PI3K-Akt-eNOS signaling pathways. Our findings also shed light on intriguing pro-angiogenic effect of R1 under deficient angiogenesis condition in a pharmacologic-induced blood vessels loss model in zebrafish. The present study in vivo and in vitro provided scientific evidence to explain the ethnomedical use of Panax notoginseng in the treatment of cardiovascular diseases, traumatic injuries and wound healing.</p>

RP-HPLC characteristics of Panax notoginseng / 药学学报

<p><b>AIM</b>To develop the chemical characteristics of Panax notoginseng in order to control its quality.</p><p><b>METHODS</b>The samples was extracted using pressurized liquid extraction (PLE) and analyzed by HPLC-DAD. The data were evaluated using the "similarity evaluation system for chromatographic fingerprint of TCM" software (version 2004A).</p><p><b>RESULTS</b>The chromatographic characteristics of 28 Panax notoginseng from different places were established using HPLC-DAD, and 8 peaks among 13 typical ones in the chromatograms were identified by comparing with their reference compounds. The similarity of different samples was high (0.982 +/- 0.008, RSD = 0.78%).</p><p><b>CONCLUSION</b>The chromatographic characteristics are useful to control the quality of Panax notoginseng.</p>