Yan Zhou

Xuzhou Medical College, Suchow, Jiangsu Sheng, China

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Publications (4)11.34 Total impact

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    ABSTRACT: Rabdosia rubescens, a commonly used traditional Chinese medicine, has increasingly gained attention for its use as an antitumor herb. Oridonin, a bioactive diterpenoid isolated from Rabdosia rubescens, has been reported to induce apoptosis in human laryngeal cancer HEp-2 cells by our group. Here, we made unexpected observations that the caspase-9 inhibitor (C9i) enhanced apoptosis in response to selected stimuli, and HEp-2 cells which were made deficient in caspase-9 using siRNA exhibited no resistance to apoptotic signals and actually demonstrated increased apoptotic sensitivity to oridonin. The results were reversed by the transfection of an exogenous caspase-9 expression vector. Caspase-9 reduced sensitivity to apoptotic stimuli through reactive oxygen species (ROS)-suppressing and autophagy-promoting methods. ROS triggered the progression of apoptosis through activation of both the caspase-9-independent mitochondrial pathway and death receptor pathways, and the autophagy had an anti-apoptotic function in oridonin-treated HEp-2 cells. These collective results suggest that oridonin targets caspase-9 to alter ROS production and autophagy situation to promote HEp-2 cell apoptosis. Therefore, oridonin has the potential to be developed as an anticancer agent, and the combination of oridonin with those agents leading to reduction of caspase-9 expression in tumor cells could represent a novel approach to human laryngeal cancer treatment.
    Preview · Article · Sep 2015 · International Journal of Oncology
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    ABSTRACT: Berberine (BBR) is an isoquinoline alkaloid isolated from several Chinese herbal medicines, such as Coptis chinensis, Berberis aristata, and Coptis japonica. It exhibits a lipid-lowering effect by up-regulating hepatic low density lipoprotein receptor (LDLR) expression. However, the plasma concentration of BBR is very low after oral administration for the reason that BBR is poorly absorbed and rapidly metabolized. Therefore, it is hard to explain the pharmacological effects of BBR in vivo. Here, RT-PCR, Western blotting and Oil Red O staining were used to investigate the effects of four BBR metabolites on LDLR expression and lipid accumulation in human hepatoma Hep G2 cells. Our results suggested that BBR increased LDLR mRNA and protein levels in a time- and dose-dependent manner. Four metabolites of BBR, Jatrorrhizin, Columbamine, Berberubine and Demethyleneberberine, were found to be able to up-regulate LDLR mRNA and protein expression. Moreover, almost all the metabolites had potent effects on inhibiting cellular lipid accumulation. These results suggest that both BBR and its metabolites exhibit lipid-lowering effects by up-regulating LDLR expression, and BBR and its metabolites might be the in vivo active forms of BBR produced after oral administration. This study provides information to help us understand the mechanisms underlying the hypolipidemic effects of BBR in vivo.
    Full-text · Article · Dec 2013 · Fitoterapia
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    ABSTRACT: Rhizoma Coptidis (Huanglian in Chinese) is commonly used in Chinese folk medicine to treat diarrhea, diabetes, hypertension, hyperlipidemia and tumours. This herb has increasingly gained attention because of its use as a hypolipidemic herb. Berberine (BBR) is the most important constituent of Rhizoma Coptidis that contribute to the pharmacological efficacy of the herb. Pharmacokinetic studies have indicated that BBR has poor oral bioavailability. Interestingly, several reports show that absorbed BBR is extensively metabolized in rats and humans. We speculate that the BBR metabolites might be responsible for the pharmacological effects. The aim of this study is to examine BBR metabolites for their triglyceride (TG)-lowering activities and the molecular mechanism to clarify BBR genuine effective forms in vivo. Four BBR metabolites were examined their TG-lowering effects with a commercial triglyceride assay kit. Real-time PCR and Western blotting were used to confirm genes and proteins of interest, respectively. Among those BBR metabolites, M2 exhibited the more potential effects on TG-lowering and AMP-activated protein kinase (AMPK) activation in Hep G2 cells as compared with BBR. Moreover, BBR and M2 inhibited gene expressions of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), glycerol-3-phosphate acyltransferase (GPAT) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), but motivated gene expression of medium chain acyl-CoA dehydrogenase (mCAD) significantly. The results suggested that the TG-lowering effects of BBR and M2 might be partially mediated by the up-regulation of lipolysis gene expressions and down-regulation of lipogenesis gene expressions through activation of the AMPK signaling pathway. BBR and its metabolites might be in vivo active forms of oral doses of BBR, and M2 might be a promising drug candidate against hyperlipidemia.
    No preview · Article · Jul 2013 · Journal of ethnopharmacology
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    ABSTRACT: Silibinin mostly has been used as hepatoprotectants, but it has other interesting activities, e.g. anti-cancer, cardial protective and brain-protective activities. A previous study demonstrated that silibinin protected amyloid β (Aβ)-induced mouse cognitive disorder by behavioural pharmacological observation. This study assessed the effect of silibinin on sodium nitroprusside (SNP)-treated rat pheochromocytoma PC12 cells. Subsequent morphologic observation, flow cytometric analysis and Western blot analysis indicated that treatment with SNP significantly induced apoptosis in PC12 cells. However, silibinin eliminated the apoptotic effect by reactive oxygen species (ROS) generation, especially hydroxyl free radical. Silibinin-induced autophagy through ROS generation when exerting a protective effect and silibinin-induced autophagy also enhanced the ROS generation since 3-methyladenine (3-MA), a specific autophagy inhibitor, decreased the ROS generation and rapamycin, an autophagy inducer, enhanced the ROS generation. Therefore, there exists a positive feedback loop between autophagy and ROS generation. Autophagy prevented SNP-induced apoptosis, since the addition of 3-MA significantly eliminated the protective effect of silibinin. This protective effect was attributed to the generation of ROS and its two downstream Ras/PI3K/NF-κB and Ras/Raf/MEK/ERK pathways. Both prevented PC12 cells from apoptosis. The PI3K/NF-κB pathway induced autophagy to protect PC12 cells, but the Raf/MEK/ERK pathway directly protected PC12 cells bypassing the autophagic effect.
    Full-text · Article · Jul 2011 · Free Radical Research

Publication Stats

33 Citations
11.34 Total Impact Points

Institutions

  • 2013
    • Xuzhou Medical College
      Suchow, Jiangsu Sheng, China
  • 2011-2013
    • Shenyang Pharmaceutical University
      • • Department of Natural Products Chemistry
      • • China-Japan Research Institute of Medical and Pharmaceutical Sciences
      Feng-t’ien, Liaoning, China