Study on the synergistic effect and mechanism of curcumin combined with zerumbone on the biological behavior of non-small cell lung cancer cells / 中国药房

OBJECTIVE To investigate the synergistic effect and mechanism of curcumin （CUR） combined with zerumbone （ZER） on the biological behavior of non-small cell lung cancer （NSCLC） A549 cells. METHODS CCK-8 method and Gin’s formula were used to screen the optimal concentration combination for synergistic effect after the combination of CUR and ZER. The cells were divided into blank group， CUR group， ZER group， and CUR+ZER group. Flow cytometry was used to evaluate cell apoptosis， and clone formation experiment was used to evaluate cell proliferation ability， scratch experiment and Transwell migration experiment were used to evaluate cell migration ability， and Transwell invasion experiment was used to evaluate cell invasion ability. Western blot assay was used to detect the protein expressions of phosphorylated phosphatidylinositol-3-kinase （p- PI3K）， phosphorylated protein kinase B （p-Akt）， and vascular endothelial growth factor A （VEGF-A）. RESULTS The half inhibitory concentrations of CUR and ZER on A549 cells were approximately 16 and 12 μmol/L， respectively； the drug combination of CUR 8 μmol/L+ZER 6 μmol/L had the highest efficiency enhancement index， with the cell proliferation inhibition rate of （77.41±4.16）%， indicating the most significant synergistic effect. Compared with the CUR and ZER groups， the cell apoptosis rate in the CUR+ZER group was significantly increased （P＜0.01）， while the cell clone formation rate， cell migration rate， the number of migrating cells， the number of invading cells， and relative expression levels of p-PI3K， p-Akt， and VEGF-A proteins in the cells were significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS The combination of CUR and ZER has a synergistic effect， significantly promoting the apoptosis of NSCLC cells， and inhibiting cell proliferation， migration， and invasion. Its potential mechanism may be closely related to the inhibition of the PI3K/Akt signaling pathway， thereby down-regulating the protein expression of VEGF-A.

Advances on anti-tumor mechanisms of zerumbone / 中国中药杂志

Zerumbone(ZER), one of humulane-type sesquiterpenoids, showed its unique advantage against tumor activities. The main underlying mechanisms include inhibiting the growth and proliferation of cancer cells, inducing apoptosis of cancer cells and differentiation of cancer cells, regulating immune function, inhibiting invasion and metastasis of cancer cells, and reversing multidrug resistance of cancer cells. Studies on ZER focusing its cytotoxic or anti-tumor is one of hot topic. Currently, with the increasing studies on ZER, the clarified mechanisms are getting rich. The present paper describes a summary of its anti-tumor mechanism of action and helps to provide significant reference to more in-depth research.

Hepatoprotective Effects of Zerumbone against Paracetamol-Induced Acute Hepatotoxicity in Rats

Background: Zerumbone (ZER) is a major bioactive compound of Zingiber zerumbet,a wild ginger plant that has been documented to have anti-proliferative, anti-inflammatory andanti-oxidant properties. To investigate its hepatoprotective potential, this study was designed todetermine the treatment effects of ZER on acute hepatotoxicity induced by paracetamol (PCM) inrats.Methods: The control group was administered with phosphate buffer solution (PBS) whilethe other two groups received PCM alone (1000 mg/kg) and PCM + 25 mg/kg ZER, respectively,at 0 h and 4 h after PCM injection. After 24 h, the blood and liver were collected for differentialwhite blood cell count, liver histological observation and biochemical analysis including alanineaminotransferase (ALT), aspartate aminotransferase (AST), and total protein concentration inserum and liver.Results: Treatment with ZER was found to significantly reduce ALT (P = 0.041), AST (P =0.044) and total hepatic protein (P = 0.045) in comparison to PCM-induced rats. Rats treated withZER exhibited the normal structure of hepatocytes with no vacuolisation or necrosis and showedsignificantly reduced neutrophil count (P = 0.037). This finding suggests its ability to suppress theinflammatory processes caused by PCM overdosage and decrease the hepatocytes tendency to gothrough necrotic processes.Conclusion: ZER possessed protective activity against PCM-induced acute hepatotoxicityin a rat model.

Zerumbone attenuates MPP+-induced cytotoxicity in human neuroblasto-ma SH-SY5Y cells by inhibition of oxidative stress / 中国病理生理杂志

AIM:To investigate the role of zerumbone ( ZER) in 1-methyl-4-phenylpyridinium ( MPP+)-in-duced cytotoxicity of human neuroblastoma SH-SY5Y cells. METHODS:Human neuroblastoma SH-SY5Y cells were cul-tured in vitro and the protective effect of ZER against MPP+-induced cytotoxicity was measured by CCK-8 assay. Flow cy-tometry was used to determine the apoptosis and reactive oxygen species (ROS). The expression of Parkinson disease pro-tein 7 (PARK7) was knocked-down by using PARK7-specific short hairpin RNA (shRNA). The protein levels of PARK7, nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined by Western blot. RESULTS:MMP+remarkably reduced the cell viability in a dose-dependent and time-dependent manner. The SH-SY5Y cell injury model was established by treatment with MPP+ at 600 μmol/L for 24 h. ZER up-regulated the protein levels of PARK7 and Nrf2 (P<0.05), alleviated apoptosis (P<0.05), and reduced ROS production (P<0.05) in the SH-SY5Y cell injury model. Meanwhile, N-acetyl-L-cysteine (NAC) had the similar functions. Moreover, significant reductions in the protein levels of Nrf2 and HO-1 ( P<0.05), and obvious increases in apoptosis ( P<0.05) and ROS level ( P<0.05) were demonstrated in PARK7-knockdown cells. CONCLUSION:ZER protects SH-SY5Y cells against MPP+-induced cytotoxi-city, which may be related to activation of PARK7/Nrf2/HO-1 pathway, and subsequent attenuation of oxidative stress and apoptosis.

Induction of apoptosis by zerumbone isolated from Zingiber zerumbet (L.) Smith in protozoan parasite Leishmania donovani due to oxidative stress

Abstract In the present context of emergence of resistance aligned with the conventional anti-leishmanial drugs and occasional treatment failure compelled us to continue the search for replaceable therapeutic leads against Leishmaniainfection. Various ginger spices of the Zingiberaceae family are widely used as spices, flavouring agents, and medicines in Southeast Asia because of their unique flavour as well as due to their medicinal properties. Zerumbone, a natural component of Zingiber zerumbet (L.) Smith, has been studied for its pharmacological potential as antiulcer, antioxidant, anticancer, and antimicrobial. In this study, we have shown that zerumbone could induce ROS mediated apoptosis in Leishmania donovani promastigotes and also found effective in reducing intracellular amastigotes in infected-macrophages. We emphasized the potential of zerumbone to be employed in the development of new therapeutic drugs against L. donovaniinfection and provided the basis for future research on the application of transitional medicinal plants.

Zerumbone, Sesquiterpene Photochemical from Ginger, Inhibits Angiogenesis

Here, we investigated the role of zerumbone, a natural cyclic sesquiterpene of Zingiber zerumbet Smith, on angiogenesis using human umbilical vein endothelial cells (HUVECs). Zerumbone inhibited HUVECs proliferation, migration and tubule formation, as well as angiogenic activity by rat aorta explants. In particular, zerumbone inhibited phosphorylation of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1, which are key regulators of endothelial cell function and angiogenesis. In vivo matrigel plug assay in mice demonstrated significant decrease in vascularization and hemoglobin content in the plugs from zerumbone-treated mice, compared with control mice. Overall, these results suggest that zerumbone inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects.

Antimicrobial activity of zerumbone from zingiber zurumbet against staphylococcus epidermidis and aspergillus spp.

Zingiber zerumbet belongs to the family Zingiberaceae and is generally known as bitter ginger. Zerumbone one of the major compound from Zingiber zerumbet rhizomes. Zerumbone finds its usage in medicinal applications, food flavoring, condiments, fragrances etc. Bioactive compound zerumbone was isolated from the column chromatography eluting with hexane and ethyl acetate mixture varying the polarity. The compound zerumbone exhibited strong antibacterial activity against Staphylococcus epidermidis, moderate activity against Escherichia coli, moderate antifungal activity against Aspergillus oryza and Aspergillus niger.

Effects of zerumbone on the proliferation and apoptosis of human pancreatic cancer cell line PANC1 / 中华胰腺病杂志

Objective To investigate the effect of zerumbone on the proliferation and apoptosis of human pancreatic cancer cell line PANC1 and its possible mechanism.Methods Zerumbone of various concentrations (3.75, 7.5, 15, 30, 60 μg/ml) were used to treat PANC1, and cells without treatment were used as control.CCK-8 assay was used to detect the inhibitory rate of cell proliferation.Cell apoptosis analysis was determined by using Hoechst 33342 staining and flow cytometry.Western blotting was performed to evaluate the phosphorylation Statl ( p-STAT1 ), and Bax and Bcl2 protein expression.Results Zerumbone caused a time- and dose-dependent reduction of cell viability in PANC1 cells.After 48h treatment of Zerumbone of 15 μg/ml, cells inhibitory rate was increased to (72.8 ± 2.72 )%, and classic apoptosis morphology was observed, with apoptosis rate was 14.2%.At the same time, p-STAT1, and Bax protein expression was significantly increased (0.654 ±0.048 vs 0.074 ±0.011, 0.577 ±0.044 vs 0.218 ±0.027,P＜0.05);Bcl-2 protein expression was significantly decreased (0.162 ± 0.029 vs 0.459 ± 0.034, P＜0.05).Conclusions Zerumbone may inhibit the proliferation of PANC1 cells and inducing cell apoptosis,which may be related to the up-regulation of STAT1's activity and Bcl-2/Bax ratio.