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celastrus orbiculatus Extracts Inhibit Human Hepatocellular Carcinoma Growth by Targeting mTOR Signaling Pathways

Chinese Journal of Integrative Medicine 2019年第11期25卷 845-852页

作者： QIAN Ya-yun LI Wen-yuan YAN Yan ZHAO Xue-yu YANG Ting FANG Chuan-ci HOU Jing-jing LIU Yan-qing Institute of Traditional Chinese Medicine and Western Medicine School of MedicineYangzhou UniversityYangzhou (225009)Jiangsu ProvinceChina Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases Yangzhou (225001)Jiangsu ProvinceChina Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou (225009)Jiangsu ProvinceChina

Objective:To characterize the molecular mechanism underlying the antineoplastic activity of celastrus orbiculatus ***(COE).Methods:The human hepatocellular carcinoma HepG2 cells with mammalian target of rapamycin(mTOR)knockdown expressed(HepG2/mTOR-)were constructed using molecular biological *** vitro,the HepG2/mTOR-cells were treated with COE at various concentrations(10,20,40,80,160 and 320μg/mL).Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)*** to the half-maximal inhibitory concentration(IC50)value(140 mg/L),the concentrations of COE in the subsequent experiment was set to alleviate *** HepG2/mTOR-cells were divided into 5 groups:negative control(untreated),COE treatment groups(40,80,120 mg/L COE)and positive control group(cisplatin,DDP,2 mg/L),***-type HepG2 cells were used as a blank *** effects of COE on the cell apoptosis were analyzed by flow cytometry and transmission electronic microscopy(TEM),*** protein expression levels of mTOR signal pathways were determined by Western *** vivo,HepG2/mTOR-cells(2×106 cell/mice)were subcutaneously injected into the right flank of nude ***-six female nude mice were randomly assigned to 6 groups according to body weight(6 mice per group)as follows:solvent vehicle control,Banmao Capsule treated group(BM,195 mg/kg),Tegafur,Gimeracil and Oteracil Potassium Capsules(10 mg/kg)treated group,and different dosages of COE(10,20,40 mg/kg)*** growth was monitored and immunohistochemical staining was used to examine the expression of apoptosis-related proteins in tumor ***:COE inhibited the proliferation significantly in a concentration-dependent manner in HepG2/mTOR-cells(P<0.01).COE significantly induced the apoptosis of HepG2/mTOR-cells(P<0.01),and the apoptotic bodies can be observed under *** significantly inhibits the proteins expression of mTORrelate

关键词： celastrus orbiculatus hepatocellular carcinoma mammalian target of rapamycin apoptosis

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Extracts of celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating Epithelial-Mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells

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Chinese Journal of Integrative Medicine 2019年第5期25卷 334-341页

作者： QIAN Ya-yun SHI You-yang LU Song-hua YANG Ting ZHAO Xue-yu YAN Yan LI Wen-yuan LIU Yan-qing Institute of Traditional Chinese Medicine and Western Medicine School of MedicineYangzhou UniversityJiangsu Province(225009)China Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases YangzhouJiangsu Province(225001)China Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Jiangsu Province(225009)China

Objective: To evaluate the effects of celastrus Orbiculatus extracts(COE) on metastasis in hypoxiainduced hepatocellular carcinoma cells(Hep G2) and to explore the underlying molecular mechanisms. Methods:The effect of COE(160, 200 and 240 μg/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide(MTT), scratch-wound and transwell assays, respectively. Co Cl2 was used to establish a hypoxia model in vitro. Effects of COE on the expressions of E-cadherin, vimentin and N-cadherin were investigated with Western blot and immuno?uorescence analysis,respectively. Results: COE inhibited proliferation and metastasis of hypoxia-induced hepatocellular carcinoma cells in a dose-dependent manner(P<0.01). Furthermore, the expression of epithelial-mesenchymal transition(EMT) related markers were also remarkably suppressed in a dose-dependent manner(P<0.01). In addition, the upstream signaling pathways, including the hypoxia-inducible factor 1α(Hif-1α) and Twist1 were suppressed by COE. Additionally, the Hif-1α inhibitor 3-5'-hydroxymethyl-2'-furyl)-1-benzylindazole(YC-1), potently suppressed cell invasion and migration as well as expression of EMT in hypoxia-induced Hep G2 cells. Similarly, the combined treatment with COE and YC-1 showed a synergistic effect(P<0.01) compared with the treatment with COE or YC-1 alone in hypoxia-induced Hep G2 cells. Conclusions: COE signi?cantly inhibited the tumor metastasis and EMT by suppressing Hif-1α/Twist1 signaling pathway in hypoxia-induced Hep G2 cell. Thus, COE might have potential effect to inhibit the progression of Hep G2 in the context of tumor hypoxia.

关键词： celastrus Orbiculatus hepatocellular carcinoma antimetastasis epithelial-mesenchymal transition Hif-1α/Twist1 signaling pathway

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THE STRUCTURE OF CELAGLAUMIN——ANTITUMOR PRINCIPLE OF celastrus glaucophyllus

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Chinese Science Bulletin 1989年第19期34卷 1639-1642页

作者：刘吉开贾忠建吴大刚周俊朱子清 Institute of Organic Chemistry Lanzhou University Kunming Institute of Botany Academia Sinica

Since pronounced antitumor activity displayed by maytansine and triptolide from the plants of Celastraceae was discovered, scientists investigated and screened the plants of Celastraceae phytochemically and pharmacologically, hoping to discover new antitumor compounds. Four sesquiterpene esters were isolated from the acetone extract of the root barks

关键词： celastrus sesquiterpene esters β-dihydroagarofurane derivatives antitumor activity

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celastrus orbiculatus extract induces mitochondrial-mediated apoptosis in human hepatocellular carcinoma cells

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Journal of Traditional Chinese Medicine 2012年第4期32卷 621-626页

作者： Hua Zhang Yayun Qian Yanqing Liu Guoqing Li Pingfang Cui Yaodong Zhu Hui Ma Xue Ji Shiyu Guo Hisamits Tadashi Department of Nursing School of MedicineYangzhou University Institute of Traditional Chinese Medicine and Western Medicine School of MedicineYangzhou University Traditional Chinese Medicine Division Clinical Medical SchoolYangzhou University Department of Physiology School of MedicineShowa University1-5-8 HatanodaiTokyo 142-8555Japan

OBJECTIVE： To investigate the apoptotic effects and underlying molecular mechanisms of celastrus orbiculatus （C. orbiculatus） extract in human hepa- tocellular carcinoma cells. METHODS： Human hepatocellular carcinoma cells （HCCLM6） were treated with C. orbiculatus extract （COE） at different nontoxic concentrations （10, 20, 40, 80, and 160 IJg/mL）. The effect of COE on HC-CLM6 viability was examined using 3-（4,5-dimethyl- thiazol-2-yl）-2,5-diphenyl tetrazolium bromide （MTT） assays. Cellular apoptosis following COE treatment was assessed by flow cytometry and western blot analysis. RESULTS： COE significantly inhibited cell viability and induced apoptosis of HCCLM6 cells in a dose-dependent manner. Apoptosis was accompa- nied by increased Bax expression and decreased Bcl-2 expression. In addition, COE treatment led to the release of cytochrome c, activation of cas- pase-3, and cleavage of poly （ADP-ribose） poly- merase （PARP）. Furthermore, activation of extracel- lular signal-regulated kinase （ERK）, p38 kinase, and c-Jun N-terminal kinase （JNK） phosphorylation, and down-regulation of Akt phosphorylation was ob- served. CONCLUSION： COE induces mitochondrial-mediat- ed, caspase-dependent apoptosis in HCCLM6 cells, which might be attributed to the activation of mito- gen-activated protein kinase （MAPK） and inhibition of Akt signaling pathways. These data suggest that COE may be a potential treatment for human hepa- tocellular carcinoma.

关键词： celastrus Apoptosis Carcinoma, hepa-tocellular Mitochondria Caspases Mitogen-activat-ed protein kinase

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FOUR NEW ALKALOIDS FROM celastrus angulatus

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Chinese Science Bulletin 1989年第12期34卷 1041-1043页

作者：刘吉开贾忠建吴大刚周俊朱子清 Institute of Organic Chemistry Lanzhou University Kunming Institute of Botany Academia Sinica

The roots of celastrus angulatus Maxim. are used in folk medicine for antipycetic and anti-wandering arthritis purpose. It also has been used as insecticide. The seven alkaloids were isolated from the root-bark of thi... 详细信息

关键词： celastrus angulatus insecticidal plants sesquiterpene alkaloids.

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Study on effect and mechanism of celastrus Orbiculatus total terpenoids in regulating lipid metabolism

Study on effect and mechanism of Celastrus Orbiculatus total...

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两岸三地药理学与临床药理学术会议

作者： LIU Hui YAN Yan SUN Yun (Medical College of Yangzhou University, Yangzhou 225001, China)

Objective To investigate the effect and mechanism of celastrus Orbiculatus total terpenoids on lipid metabolism in hyperlipidemia *** ICR mice were selected as investigated *** hy- perlipemia mice models were made with feeding high-fat forage and were randomly divided into six groups: the normal group,the model group,the positive control group (treated with simvastatin) and the three groups treated with celastrus Orbiculatus total terpenoids with low,medium and high dosage,respectively. Each group included eight *** control group was fed normal forage,but other groups were fed high fat *** groups were allowed to drink water *** the first day when the models were made,in- tragastric administration had been *** normal group was fed normal forage without intragastrie administration;the model group was received physiological saline 20 mL·kg·d with intragastric admin- istration;the positive control group received simvastatin 2.6 mg·kg·d with intragastric administration;the three treated groups received celastrus Orbiculatus total terpenoids 60 mg·kg·d,120 mg·kg. d,200 mg·kg·d with intragastric administration *** group was weighed once a week. On the basis of establishing hyperlipidemia mice model,blood lipids,lipid metabolic enzyme,antioxidative capacity were investigated after 21 days feeding of high-fat *** Compared with model group,TC and TG in mice treated with celastrus Orbiculatus total terpenoids all reduced and HDL-C raised obviously (Pcelastrus orbiculatus total terpenoids was shown to decreased MDA content in both serum and liver,increased serum SOD activity and inhibited the activity of the cholesteryl ester transfer protein (CETP).Conclusions celastrus Orbiculatus total terpenoids could remarkably modulate the lipid metabolic disorder in hyperlipidemia mice,and has a certain regulating function on lipoprotein,inferring that it could reduce the occur of *** mechanism

关键词： celastrus Orbiculatus total terpenoids hyperlipidemia CETP antioxidation

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Study on effect and mechanism of celastrus Orbiculatus total terpenoids in regulating lipid metabolism

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沈阳药科大学学报 2008年第S1期25卷 92-92页

作者： LIU Hui,YAN Yan,SUN Yun(Medical College of Yangzhou University,Yangzhou 225001,China)

Objective To investigate the effect and mechanism of celastrus Orbiculatus total terpenoids on lipid metabolism in hyperlipidemia *** ICR mice were selected as investigated *** hyperlipemia mice models were made with feeding high-fat forage and were randomly divided into six groups:the normal group,the model group,the positive control group(treated with simvastatin)and the three groups treated with celastrus Orbiculatus total terpenoids with low,medium and high dosage,*** group included eight *** control group was fed normal forage,but other groups were fed high fat *** groups were allowed to drink water *** the first day when the models were made,intragastric administration had been *** normal group was fed normal forage without intragastric administration;the model group was received physiological saline 20 mL·kg-1·d-1 with intragastric administration;the positive control group received simvastatin 2.6 mg·kg-1·d-1 with intragastric administration;the three treated groups received celastrus Orbiculatus total terpenoids 60 mg·kg-1·d-1,120 mg·kg-1·d-1,200 mg·kg-1·d-1 with intragastric administration *** group was weighed once a *** the basis of establishing hyperlipidemia mice model,blood lipids,lipid metabolic enzyme,antioxidative capacity were investigated after 21 days feeding of high-fat *** Compared with model group,TC and TG in mice treated with celastrus Orbiculatus total terpenoids all reduced and HDL-C raised obviously(Pcelastrus orbiculatus total terpenoids was shown to decreased MDA content in both serum and liver,increased serum SOD activity and inhibited the activity of the cholesteryl ester transfer protein(CETP).Conclusions celastrus Orbiculatus total terpenoids could remarkably modulate the lipid metabolic disorder in hyperlipidemia mice,and has a certain regulating function on lipoprotein,inferring that it could reduce the occur of *** mech

关键词： celastrus Orbiculatus total terpenoids hyperlipidemia CETP antioxidation

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Erratum to "celastrus paniculatus oil ameliorates synaptic plasticity in a rat model of attention deficit hyperactivity disorder"

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Asian Pacific Journal of Tropical Biomedicine 2023年第4期13卷 184-184页

In the article“celastrus paniculatus oil ameliorates synaptic plasticity in a rat model of attention deficit hyperactivity disorder”published on pages 105-114,Issue 3,Volume 11 of Asian Pacific Journal of Tropical B... 详细信息

关键词： plasticity Figure celastrus

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CHEMICAL CONSTITUENTS AND BIOLOGICAL ACTIVITY OF CELASTRACEAE PLANTS

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Chinese Science Bulletin 1992年第14期37卷 1212-1215页

作者：涂永强吴大刚 Department of Chemistry Lanzhou University Lanzhou 730000 PRC Kunming Institute of Botany Academia Sinica Kunming 650204 PRC

Ⅰ. INTRODUCTIONDihydroagarofuran sesquiterpenoids are the main chemical constituents of Celastraceae plants. Since the Celastraceae plants were used as agricultural insecticides, we are quite interested in the investigation on the insecticidal activity of this kind of compound. Our previous note reported that three sesquiterpenoids (1—3) were isolated

关键词： Celastraceae celastrus sesquiterpenoid Herisrapae biological activity

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