Extracts of Celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating Epithelial-Mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells / 中国结合医学杂志

OBJECTIVE@#To evaluate the effects of Celastrus Orbiculatus extracts (COE) on metastasis in hypoxia-induced hepatocellular carcinoma cells (HepG2) and to explore the underlying molecular mechanisms.@*METHODS@#The effect of COE (160, 200 and 240 µ g/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. CoCl 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 immunofluorescence 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 1 α (Hif-1 α) and Twist1 were suppressed by COE. Additionally, the Hif-1 α 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 HepG2 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 HepG2 cells.@*CONCLUSIONS@#COE significantly inhibited the tumor metastasis and EMT by suppressing Hif-1 α/Twist1 signaling pathway in hypoxia-induced HepG2 cell. Thus, COE might have potential effect to inhibit the progression of HepG2 in the context of tumor hypoxia.

Chemical constituents from lipophilic parts of stems of Celastrus monospermus / 中国中药杂志

The chemical constituents from lipophilic parts of the stems of Celastrus monospermus were studied in this paper. The compounds were separated and purified by repeated column chromatographic methods including silica gel, ODS and Sephadex LH-20, and the structures of compounds were determined by spectral data analyses. Twenty six compounds were obtained and identified as 3-oxofriedelane(1), 3-oxofriedelan-28-al(2), 3,12-dioxofriedelane(3), 3β-hydroxyolean-12-en(4), 3-oxo-28-hydroxyfriedelane(5), 3-oxo-29-hydroxyfriedelane(6), 3-oxo-11β-hydroxyfriedel-ane(7), 3-oxo-16α-hydroxyfriedelane(8), 3,12-dioxo-28-hydroxyfriedelane(9), 1,3-dioxo-15α-hydroxyfriedelane(10), 3β,6α-dihydroxyolean-12-en(11), 3-oxo-7α,26-dihydroxyfriedel-ane(12), oleanolic acid(13), 3,15-dioxofriedelane(14), 3α-friedelinol(15), 3,12-dioxofriedelan-28-al(16), 3-oxo-12α-hydroxyfriedelane(17), 3,15-dioxo-12α-hydroxyfriedelane(18), 3β,11β-dihydroxyolean-12-en(19), 1β,3β-dihydroxylupan-20(29)-en(20), 3-oxo-12α,28-dihydroxyfriedelane(21), 3β,23-epoxyfriedelan-28-oic acid(22), salaquinone A(23), 2α,3β-dihydroxyfriedelan-28-oic acid(24), 23-nor-6-oxodemethylpristimerol(25) and 3-oxo-friedelan-27,28-dioic acid(26). Among them, compounds 8, 10-15, 18-20, 22-26 were obtained from this plant for the first time, and compounds 8, 10, 12, 14-15, 18, 22-24, 26 were separated from the genus Celastrus for the first time.

Behavioral and biochemical evidences for antidepressant-like activity of Celastrus paniculatus seed oil in mice

Introduction: Celastrus paniculatus seed oil, commonly known as Malkangni or Jyotishmati, was in use from time immemorial to treat brain related disorders. Celastrus paniculatus seed oil has significant antidepressant-like activity in chronic unpredictable stressed mice. The present study was undertaken to evaluate the antidepressant-like effect of Celastrus paniculatus seed oil in unstressed mice and to explore its mechanism of action

Methods: The seed oil [50, 100, and 200 mg/kg, PO] and fluoxetine per se were administered for 14 successive days to Swiss young albino mice. On the 14[th] day, 60 min after drug administration, animals were subjected to Tail Suspension Test [TST] and Forced Swim Test [FST]. The mechanism of action was also studied

Results: The oil significantly decreased immobility period of mice in both tail suspension test and forced swim test, indicating its significant antidepressant-like activity. The efficacy was found to be comparable to fluoxetine [P<0.0001]. ED50 value of celastrus seed oil using FST and TST were 17.38 and 31.62 mg/kg, respectively. The oil did not show any significant effect on locomotor activity. It significantly inhibited brain MAO-A activity and decreased plasma corticosterone levels. Sulpiride [selective D2-receptor antagonist], p-CPA [tryptophan hydroxylase inhibitor], and baclofen [GABAB agonist] significantly attenuated the oil-induced antidepressant-like effect, when assessed during TST

Discussion: Celastrus paniculatus seed oil produced significant antidepressant-like effect in mice possibly through interaction with dopamine D2, serotonergic, and GABAB receptors; as well as inhibition of MAO-A activity and decrease in plasma corticosterone levels

Celastrus orbiculatus extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in Vitro and in Vivo / 中国结合医学杂志

<p><b>OBJECTIVE</b>Celastrus orbiculatus Thunb. has been used for thousands of years in China as a remedy against cancer and inflammatory diseases. This study aims to investigate whether C. orbiculatus extract (COE) could inhibit angiogenesis, which is the pivotal step in tumor growth, invasiveness, and metastasis.</p><p><b>METHODS</b>In this study, the extract from the stem of C. orbiculatus was used. Mouse hepatic carcinoma cells (Hepa1-6) were treated with COE in different nontoxic concentrations (10, 20, 40, 80, and 160 μg/mL). The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively; the active fractions were further tested on C57BL/6 mice and human umbilical vein endothelial cells (HUVEC) for any antiangiogenic effects.</p><p><b>RESULTS</b>COE significantly inhibited proliferation and induced apoptosis in Hepa1-6 cells and inhibited VEGF expression at both mRNA and protein levels. Furthermore, this agent inhibited the formation of the capillary-like structure in primary cultured HUVEC in a dose-dependent manner. In vivo, COE significantly reduced the volume and weight of solid tumors with low adverse effects and decreased tumor angiogenesis.</p><p><b>CONCLUSIONS</b>In summary, COE could be used to treat hepatic carcinoma. The mechanisms of the antitumor activity of COE may be due to its effects against tumor angiogenesis by targeting the VEGF protein.</p>

Acetoacetate extract from Celastrus orbiculatus Thunb inhibits growth of RFP-xenografted human liver carcinoma / 中华肝脏病杂志

To investigate the inhibitory effect of acetoacetate extract from Celastrus orbiculatus Thumb (COT) on the growth of red fluorescent protein (RFP)-xenografted human hepatocellular carcinoma (HCC) in a nude mouse model. Human HCC HepG2 cells were transduced with RFP and inoculated into the liver of BALB/c nude mice. The tumor-bearing mice were randomly divided into five groups: control group (G1), oxaliplatin positive control group (G2; 25 mg/kg), COT low-dose group (G3; 20 mg/kg), COT high-dose group (G4; 40 mg/kg), and COT early treatment group (G5; 20 mg/kg). The early treatment group received oral COT from day 2 post-tumor implantation. All other mice were treated from day 20 post-tumor implantation. Growth of xenografted tumors was monitored weekly by in vivo real-time fluorescence imaging technology. At the end of the four-week treatment period, all mice were sacrificed and tumor tissues were collected and weighed. The two-sided t-test was used to evaluate intergroup differences in tumor volumes, final tumor weights, and final body weights. Mice treated with COT had significantly smaller xenografted tumors. On day 45 post-implantation, the mean tumor volumes (mm3) in the different groups were: G1, 803.1+/-512.3 ; G2, 83.8+/-23.5; G3, 852.7+/-502.6; G4, 410.0+/-231.6; and G5, 120.5+/-60.1. The mean tumor weights (g) were: G1, 0.95+/-0.49; G2, 0.36+/-0.09; G3, 0.67+/-0.29; G4, 0.48+/-0.15; and G5, 0.38+/-0.11. The differences in tumor weights from G2, G4 and G5 were significantly less than the weight in G1 (P less than 0.05); however, there was no significant differences between the tumor weights in G2, G4 and G5 (P more than 0.05). The tumor weight from the G2 group was significantly less than that of the G3 group (P less than 0.05). COT significantly inhibited the proliferation of human HCC in a nude mouse model. Early treatment with COT produced a more robust inhibitory effect, which was very similar to that achieved with oxaliplatin treatment.

role of herbal drugs in psychiatry

The therapeutic uses of various herbal drugs for psychiatric disorders have a long tradition in India, China and other Asian cultures. The unwanted side effects of synthetic psychotropics have contributed to the increasing interest in phytotherapeutic agents. Improved understanding of appropriate and safe uses of naturally occurring substances as psychotropic agents will greatly contribute to global mental care. An important objective of this paper is to stress the scientific evidence, supporting the use of natural products in psychiatry. Traditional Ayurvedic drugs used in psychiatry is briefly discussed. Knowledge of the properties of these therapies supported by clinical evidence, efficacy and safety profile can improve the care of psychiatric patients

Chemical constituents from leaves of Celastrus gemmatus Loes / 药学学报

To study the chemical constituents from the leaves of Celastrus gemmatus Loes., chromatographic methods were used to isolate and purify the chemical constituents, their structures were elucidated by the physiochemical characteristics and spectral data. Nine compounds were obtained and identified as (-)-massoniresinol 3a-O-beta-D-glucopyranoside (1), ambrosidine (2), isolariciresinol 9-O-beta-D-glucopyranoside (3), kaempferol 3-O-beta-D-glucopyranoside (astragalin) (4), kaempferol 3-O-rutinoside (5), kaempferol 3-O-neohesperidoside (6), apigenin 7-O-beta-D-glucuronide (7), apigenin 7-O-beta-D-glucuronide methyl ester (8) and D-sorbitol (9). Compound 1 is a new compound, the others are isolated from this genus for the first time, and this is the first time to report lignan compounds from genus Celastrus.

Methanol extract of Celastrus orbiculatu suppresses synovial hyperplasia and cartilage erosion and degradation in rheumatoid arthritis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of methanol extract of Celastrus orbiculatu (MECO) on synovial hyperplasia and cartilage erosion and degradation in rheumatoid arthritis (RA), and explore the possible mechanisms to provide clues for new drug development for RA treatment.</p><p><b>METHODS</b>The articular synovium from patients with RA and normal articular cartilage were co-implanted into the back of severe combined immunodeficient (SCID)mice to establish the chimeric model SCID- HuRAg. Four weeks later, the mice were given MECO intragastrically at 30 mg/day, leflunomide at 500 microg/day or distilled water, respectively, for 4 consecutive weeks. After completion of the treatments, the histological scores of the grafts for synovial hyperplasia, cartilage invasion by synoviocyte and cartilage degradation around the chondrocytes were evaluated, and serum level of tumor necrosis factor-alpha (TNF-alpha) was measured with radioimmunoassay. The expression of TNF-alpha mRNA and the cell apoptosis in the synovium were detected with in situ hybridization (ISH) and TUNEL, respectively, and the results were analyzed with the image analysis system.</p><p><b>RESULTS</b>The grafts survived in the mice till the end of experiment. MECO and leflunomide, in comparison with distilled water, significantly lowered the scores for synovial hyperlasia (2.00+/-0.76 and 2.25+/-0.89 vs 3.63+/-0.52), cartilage erosion (1.69+/-0.80 and 2.00+/-1.36 vs 3.75+/-0.53), cartilage degradation (1.88+/-0.83 and 2.13+/-0.83 vs 3.63+/-0.74) and serum TNF-alpha level (0.84+/-0.09 and 0.83+/-0.12 vs 0.99+/-0.11 ng/ml). Cell apoptosis of the synovium increased significantly with MECO and leflunomide treatments, but the expression of TNF-alpha mRNA in the synovium decreased significantly in MECO group.</p><p><b>CONCLUSION</b>MECO can effectively suppress synovial hyperplasia and cartilage erosion and degradation SCID-HuRAg mice by reducing TNF-alpha production in the synovium and promoting synovial apoptosis. MECO can be comparable with leflunomide in their effect, but the former is more effective in suppressing TNF-alpha expression in the synovium.</p>

The Effects of Growth Inhibition and Quinone Reductase Activity Stimulation of Celastrus Orbiculatus Fractions in Various Cancer Cells

Celastrus orbiculatus (CO) has been used as a traditional herb medicine to treat fever, chill, joint pain, edema, rheumatoid arthritis and bacterial infection in China and Korea. In this study, we investigated anticarcinogenic effects of Celastrus orbiculatus (CO). CO was extracted with methanol (COM), and then further fractionated into four different types: methanol (COMM), hexane (COMH), butanol (COMB) and aqueous (COMA) partition layers. We determined the cytotoxicity of these four partitions in four kind of cancer cell lines, such as HepG2, MCF-7, HT29 and B16F10 Cells by MTT assay. Among various partition layers of CO, the COMM showed the strongest cytotoxic effects on cancer cell lines we used. We also observed quinone reductase (QR) induced effects in all partition layers of CO on HepG2 cells. The QR induced effects of COMM on HepG2 cells at 80 microgram/mL concentration indicated 3.28 to a control value of 1.0. The COMM showed the highest induction activity of quinone reductase on HepG2 cells among the other partition layers. Although further studies are needed, the present work suggests that CO may be a chemopreventive agent for the treatment of human cells.

Antitumor effects of novel triterpene from Celastrus hypoleucus on human colorectal cancer cell line RKO in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effects of novel triterpene (12-oleanene-3beta, 6alpha-diol) from Celastrus hypoleucus on the proliferation and apoptosis of human colorectal cancer cell line RKO.</p><p><b>METHOD</b>The inhibitory effect of the novel triterpene on RKO cell proliferation was assayed by MTT dye reduction. The morphology of apoptotic cells was observed with AO/EB double fluorescence staining and HE staining, DNA fragment with electrophoresis on agarose gels, sub-diploid peak and cell cycle with flow cytometer (FCM).</p><p><b>RESULT</b>Novel triterpene (12-oleanene-3beta, 6alpha-diol) from C. hypoleucus significantly inhibited proliferation of RKO cells in dose-dependent and time-dependent manner, the IC50 was (12.20 +/- 0.79) microg x mL(-1) at 48 h. Typical apoptotic changes were observed in RKO cells under the fluorescence microscope and the light microscope. DNA ladder was detected on agarose gels at concentrations from 10 microg x mL(-1) to 20 microg x mL(-1) at 48 h. With FCM methods, dose-dependent apoptosis-induced effect was observed in RKO cell line after treatment of triterpene for 48 h, and the apoptotic rates were increased from(2.93 +/- 0.84) % to (50.79 +/- 6.61) % at concentrations from 2.5 microg x mL(-1) to 20 microg x mL(-1). DNA histograms data from FCM analysis showed that the number of cells was obviously reduced during G0-G1 phase and G2-M phase, but not during S phase for RKO cell line after treatment with various concentrations of the triterpene for 48 hours.</p><p><b>CONCLUSION</b>Novel triterpene (12-oleanene-3beta, 6alpha-diol) from C. hypoleucus can induce apoptosis and has inhibition effect on the proliferation in RKO cell line.</p>

Experimental study on anti-tumor effect of extractive from Celastrus orbiculatus in vivo / 中国中药杂志

<p><b>OBJECTIVE</b>To study the anti-tumor activity of extractive from Celastrus orbiculatus in vivo.</p><p><b>METHOD</b>Mice bearing transplanted tumor S180 and Heps were used to study the effects of acetoacetate and n-butanol extractive from C. orbiculatus. The changes in serum contents of SOD and malondialdehyde (MDA) content were assayed.</p><p><b>RESULT</b>Acetoacetate and n-butanol extractive from C. orbiculatus significantly inhibited the growth of S180 and Heps tumor in mice. SOD content was obviously increased, MDA content obviously decreased in the serum after extractive treatment.</p><p><b>CONCLUSION</b>Acetoacetate and n-butanol extractive from C. orbiculatus have anti-tumor effects and anti-oxidative capacity.</p>