作者机构：
[Wang, Ting; Xiao, Xiao-Qin] Hunan Univ Chinese Med, Inst Combinat Chinese Tradit Med & Western Med, Changsha 410208, Hunan, Peoples R China.;[Liu, Jian] Hunan Univ Chinese Med, Hosp 1, Dept Emergency, Changsha 410208, Hunan, Peoples R China.;[Xiao, Xiao-Qin] Hunan Univ Chinese Med, Inst Combinat Chinese Tradit Med & Western Med, Bachelor Rd, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Xiao, Xiao-Qin] H;Hunan Univ Chinese Med, Inst Combinat Chinese Tradit Med & Western Med, Bachelor Rd, Changsha 410208, Hunan, Peoples R China.
摘要：
Cantharidin (CTD), a chemical compound secreted by blister beetles, has been shown with anti-tumor property in many cancer cells. In this study, our data showed that CTD exerts potent anti-angiogenesis activity in a dose-dependent manner. CTD dose dependently suppressed human umbilical vascular endothelial cells proliferation, migration, and tube formation in vitro. Furthermore, CTD concentration dependently inhibited angiogenesis in chick embryo CAM model in vivo. At the molecular level, CTD abrogated VEGF-induced activation of STAT3 and suppressed the phosphorylation of JAK1 and ERK in a dose-dependent manner. Furthermore, CTD blocked the phosphorylation of AKT in a time-dependent manner. Taken together, these findings clearly demonstrate for the first time that CTD can inhibit angiogenesis and may have applications in the development of new anti-angiogenesis drugs.
摘要：
The expression of Ferroportin (Fpn) was examined at different time points in rats following focal cerebral ischemia treated with or without the traditional Chinese medicine Naotaifang. Initially, rats were randomly divided into 2, 6, 12, 24 and 72 h groups following middle cerebral artery occlusion (MCAO) and the mRNA and protein level of Fpn was detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) at the above time points. Secondly, the rats were randomly divided into five groups as follows: Sham surgery group, model group, low-dose group (3 g/kg NTE), medium dose group (9 g/kg NTE) and the high-dose group (27 g/kg NTE). After 3 days of corresponding therapy by intragastric administration once a day, the regional cerebral ischemia model was reproduced by the MCAO suture method. On the third day, the neurological behavior of the rats was analyzed by neurobehavioral assessment. Fpn in the hippocampal CA2 region was measured by immunohistochemistry and the mRNA level of Fpn was detected by RT-PCR. Expression of Fpn in the hippocampal CA2 region reached a peak 12 h after surgery (P<0.05, compared with the model group). The high-dose group (27 g/kg NTE) exhibited a lower neurological behavior score (P<0.05) and a higher level of expression of Fpn at the mRNA and protein level compared with the sham surgery group and model group (P<0.05). Dysregulation of intracellular iron balance is possibly a new mechanism underlying cerebral ischemia. NTE can protect the neuronal population in the hippocampal CA2 region by adjusting the expression of Fpn to balance iron levels following cerebral ischemia.
通讯机构：
[Deng, Chang-Qing] H;Hunan Univ Chinese Med, Mol Pathol Lab, Changsha 410208, Hunan, Peoples R China.
关键词：
Active Component Combination;Apoptosis;Astragalus;Cerebral I/R;Inflammation;Panax notoginseng
摘要：
Astragalus and Panax notoginseng are commonly used to treat cardio-cerebrovascular diseases in China and are often combined together to promote curative effect. We speculate that the enhancement of the combination on anticerebral ischemia injury may come from the main active components. The purpose of this work was to probe the effects and mechanisms of Astragaloside IV (the active component of Astragalus) combined with Ginsenoside Rg1, Ginsenoside Rb1, and Notoginsenoside R1 (the active components of P. notoginseng) to antagonize ischemia/reperfusion (I/R) injury via inflammation and apoptosis. C57BL/6 mice were randomly divided into sham, model, Astragaloside IV, Ginsenoside Rg1, Ginsenoside Rb1, Notoginsenoside R1, four active components combination, and Edaravone groups. After administration for 3 days, bilateral common carotid arteries (CCA) were occluded with artery clip for 20[Formula: see text]min followed by reperfusion for 24[Formula: see text]h. Our results showed that the survival rate of nerve cell in hippocampal CA1 decreased while the apoptotic rate increased, and the level of caspase-3 protein in brain tissues was elevated, the expressions of TNF-a, IL-1, and ICAM-1 mRNA as well as phosphorylated nuclear factor kappa B (NF-kappaB) inhibitor protein alpha (p-IkappaBa) in brain tissues were up-regulated, and the nuclear translocation rate of NF-kappaB was raised. Additionally, the protein expressions of phosphorylated tyrosine kinase 1 (p-JAK1), phosphorylated signal transducer and activator of transcription-1 (p-STAT1), glucose regulated protein 78 (GRP78), caspase-12, and phosphorylated c-Jun N-terminal kinases 1/2 (p-JNK1/2) in brain tissues were also significantly strengthened after I/R for 24 h. All drugs could increase neurocyte survival rate in hippocampal CA1, decrease the apoptotic rate, and inhibit caspase-3 protein expression, in contrast, the effects of four active components combination were better than those of active components alone. In addition, Astragaloside IV and Ginsenoside Rg1 could down-regulate the level of TNF-alpha, and ICAM-1 mRNA, respectively, Notoginsenoside R1 reduced both TNF-alpha and ICAM-1 mRNA, and the combination of the 4 effective components had inhibitory effects on the expressions of TNF-alpha, IL-1beta, and ICAM-1 mRNA. Astragaloside IV, Ginsenoside Rg1, Notoginsenoside R1, and 4 effective components combination were able to restrain the phosphorylation of IkappaBalpha, and relieve the nuclear translocation rate of NF-kappaB. Moreover, the effects of the combination are greater than those of active components alone. All drugs could suppress the phosphorylation of JAK1 induced by I/R; meanwhile the expression of p-STAT1 exhibited a decrease in Ginsenoside Rg1 and four active components combination groups. The decreases of p-JAK1 and p-STAT1 in the four active components combination group were more obvious than those in active components alone groups. Astragaloside IV, Ginsenoside Rg1, and Notoginsenoside R1 further augmented GRP78 expression caused by I/R, Notoginsenoside R1 attenuated caspase-12 protein expression, Astragaloside IV and Ginsenoside Rg1 lessened the phosphorylation of JNK1/2, and the four active components combination was capable of up-regulating GRP78 protein while down-regulating the expressions of caspase-12 and p-JNK1/2. Similarly, the effects of the four active components combination were greater than those of effective components alone. These suggested that the combination of the main active components of Astragalus and Panax notoginseng could strengthen protective effects on cerebral ischemia injury via anti-apoptosis and anti-inflammation, and the mechanisms might be associated with restraining the activation of NF-kappaB and JAK1/STAT1 signal pathways and regulating endoplasmic reticulum stress (ERS) after cerebral ischemia.
摘要：
BACKGROUND: Astragalus and Panax notoginseng are traditional Chinese Medicines used for the treatments of ischemic cerebrovascular disease, being often combined together in China and achieving a good effect. OBJECTIVE: The objective of this study is to investigate the effects of astragaloside-IV (AST-IV) (the effective component of Astragalus) combined with ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1 (the effective components of P. notoginseng) on oxidative stress injury after cerebral ischemia-reperfusion in mice, and to explore the mechanisms through nuclear factor-erythroid 2-related factor-2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. MATERIALS AND METHODS: C57BL/6 mice were randomly grouped after treated for 3 days, the model of cerebral ischemia-reperfusion injury was established, and the brain tissues were detected. RESULTS: AST-IV combined with ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1 could increase significantly the survival rate of nerve cell; decrease the contents of malondialdehyde, nitric oxide, increase the activity of superoxide dismutase and the level of glutathione; Nrf2 was down-regulated in the cytoplasm while up-regulated in nucleus, nuclear translocation rate raised as well as HO-1 messenger ribonucleic acid and protein expressions increased. The effects of four active components combination were better than those of the active components alone. CONCLUSION: Active components of Astragalus and P. notoginseng had the effects against cerebral ischemia-reperfusion injury, which were related to the antioxidative stress after cerebral ischemia-reperfusion. AST-IV combined with ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1 could strengthen the antagonism effects on ischemia-reperfusion and oxidative stress injury, the mechanism underlying might be associated with jointly activating Nrf2/HO-1 signaling pathway after cerebral ischemia-reperfusion.
作者机构：
[Wu, Lu] Hunan Univ Tradit Chinese Med, Affiliated Tradit & Western Med Hosp 2, Changsha, Hunan, Peoples R China.;[Deng, Chang-Qing] Hunan Univ Tradit Chinese Med, Sch Integrated Chinese & Western Med, Pathophysiol Lab, Changsha, Hunan, Peoples R China.;[Tang, Ying-Hong] Hunan Univ Tradit Chinese Med, Dept Pharmacol, Changsha, Hunan, Peoples R China.;[Li, Hua; Zhang, Guo-Min; Chen, Bei-Yang] Hunan Univ Tradit Chinese Med, Dept Pathol, Changsha, Hunan, Peoples R China.;[Deng, Chang-Qing] Hunan Univ Tradit Chinese Med, Sch Integrated Chinese & Western Med, Pathophysiol Lab, Xiangzui Rd, Changsha, Hunan, Peoples R China.
通讯机构：
[Deng, Chang-Qing] H;Hunan Univ Tradit Chinese Med, Sch Integrated Chinese & Western Med, Pathophysiol Lab, Xiangzui Rd, Changsha, Hunan, Peoples R China.
关键词：
Total saponins of "panax notoginseng root";Atorvastatin;Vascular smooth muscle cell;Proliferating cell nuclear antigen;Cyclind D-1;Cycline;Extracellular matrix;Collagen I;Fibronectin;Matrix metalloproteinase-9;Tissue inhibitor metalloproteinase-1
摘要：
Aim of the study: the effect of total saponins of "panax notoginseng root" on aortic intimal hyperplasia and the expressions of cell cycle protein and extracellular matrix in rats Materials and methods: Sprague-Dawley rats were randomly divided into sham-operated, control, TSPN and atorvastatin group. Rat aorta intima in all groups were injured by insertion of domestic balloon catheter into the aortae except sham-operated rats. Drugs were administrated orally from the second day after vascular injury and continued for 14 days. The injured segments of aortae were collected on the sixteenth day after operation to observe the morphological changes of vascular structure and to examine the expressions of proliferating cell nuclear antigen(PCNA), cyclinD1, cyclinE, collagen I(Col-I), fibronect(FN), matrix metalloproteinase-9(MMP-9) and tissue inhibitor metalloproteinase-1(TIMP-1). Results: TPNS significantly inhibited the vascular intimal hyperplasia. TPNS significantly lowered the expression of PCNA, cyclinE, cyclinD1, FN and MMP-9. TPNS had no significant impacts on the expression of Col-I and TIMP-1. Conclusions: Our studies indicated that TSPN could inhibit vessel restenosis after vascular intimal injury, and its mechanisms may be related to the blockage of the excessive proliferation of VSMC, the reduction of ECM protein deposition in the endometrium, and the degradation of ECM protein. (C) 2009 Elsevier GmbH. All rights reserved.
期刊：
Journal of Zhejiang University. Science. B,2009年10(3):172-179 ISSN：1673-1581
通讯作者：
He, Ying-chun
作者机构：
[Tian, Dao-fa; He, Ying-chun] Chinese Med Univ Hunan, Fac Integrat Med, Changsha 410007, Peoples R China.;[Lu, Fang-guo] Chinese Med Univ Hunan, Fac Basic Med, Changsha 410007, Peoples R China.;[Tang, Fa-qing] Cent S Univ, Dept Clin Lab, Xiangya Hosp 1, Changsha 410008, Peoples R China.
通讯机构：
[He, Ying-chun] C;Chinese Med Univ Hunan, Fac Integrat Med, Changsha 410007, Peoples R China.
摘要：
OBJECTIVE: To investigate the enhancive effect of N,N'-dinitrosopiperazine (DNP) on induced carcinogenesis in nasal and/or nasopharyngeal epithelia among TgN(p53mt-LMP1)/HT transgenic mice to examine the underlying mechanism for the development of nasopharyngeal carcinoma (NPC). METHODS: TgN(p53mt-LMP1)/HT transgenic mice and the same strain of C(57)BL/6J wild-type mice both at the age of 5 months were randomly divided into 2 groups in parallel, respectively, i.e., TgN(p53mt-LMP1)/HT cancerous lesion-inducing group (TI), TgN(p53mt-LMP1)/HT control group (TC), C57BL/6J cancerous lesion-inducing group (CI), and C57BL/6J control group (CC). TI and CI mice were treated only with DNP for 16 weeks, twice each week, while TC and CC mice were given the same volume of saline as controls. At the end of treatment, animals were sacrificed to collect epithelial tissue samples from nasal cavity and nasopharynx for pathohistological evaluation by haematoxylin and eosin (HE) staining and for determination on the expression of TRAF2, c-Jun, and p16 by immunohistochemistry. RESULTS: Atypical hyperplasia was more significant in the samples of TI than in those of TC, CI, and CC, with the rates of lesions being 90%, 10%, 0, and 0 (P<0.01) respectively, though DNP was used alone in a much shortened inducing period at less dosage and without the use of carcinogenic promoter 12-O-tetradecanoylphorbol-13-acetate as usual. The expressions of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and c-Jun in these samples were significantly up-regulated in TI (P<0.01), while the expression of p16 was significantly lower in TI than in the other groups (P<0.01). CONCLUSION: TgN(p53mt-LMP1)/HT mice hold inherited constitutional defect in immune surveillance function, which can be aggravated by environmental carcinogens, such as DNP used even though in a much less strength. The enhanced carcinogenesis-inducing effect of DNP on TgN(p53mt-LMP1)/HT mice should be closely associated with abnormal signaling of activator protein-1 (AP-1) pathway, especially up-regulated expressions of TRAF2 and c-Jun, and down-regulated expression of p16.
作者机构：
[Tian, D. F.; Liu, S. J.; He, Y. C.] Tradit Chinese Med Univ Hunan, Fac Integrat Med, Changsha 410007, Peoples R China.;[Ling, C. Q.; Liu, S. J.] Changhai Hosp, Dept Tradit Chinese Med, Shanghai, Peoples R China.;[Sun, Y. M.] Chinese Acad Sci, Inst Genet & Dev Biol, Beijing, Peoples R China.;[Zeng, L.] Huan Provincial Tumor Hosp, Dept Pathol, Changsha, Peoples R China.;[Sun, S. H.; He, Y.] Second Mil Med Univ, Dept Med Genet, Shanghai, Peoples R China.
通讯机构：
[Tian, D. F.] T;Tradit Chinese Med Univ Hunan, Fac Integrat Med, 113 Shaoshan Middle Rd, Changsha 410007, Peoples R China.
摘要：
Because the focus of nasopharyngeal carcinoma (NPC) is very close to intracranial organs, it often makes incursions into cranial cavity. Identification of intracranial invasion-associated indicators will provide potential therapeutic targets for NPC patients with intracranial invasion. In this regard, Human Xpro(TM) HC-plus cancer-related gene chip was utilised to screen intracranial invasion-associated genes for NPC from the biopsied primary focus tissue samples. In all, 8 upregulated and 23 downregulated genes were obtained. VEGF165 and MMP-9, the two upregulated genes, and NM23-H1, the downregulated one, were further confirmed by immunohistochemistry, quantitative real-time PCR and western blot. Invasion-associated cellular and nude mouse models were subsequently employed to study the biological properties of NM23-H1. NM23-H1 expression was significantly lower in 5-8F cells compared with that in 6-10B cells. Moreover, patch-clamp and transwell chamber were adopted to investigate the invading potential-associated biological dynamic mechanisms in the two cell lines, and Ca2+ current and motility were significantly elevated in 5-8F cells compared with that in 6-10B cells. Berberine, an inhibitor of Ca2+ current, could substantially increase the expression of NM23-H1 and decrease 5-8F cell motility. The specificity of berberine on NM23-H1 and cell motility was confirmed by RNAi assay.
