Microneedles(MNs)have attracted increasing attention as a transdermal delivery system(TDDS)[1].However,traditional volatile Chinese medicines cannot be dissolved in conventional soluble MN materials,such as hyaluronic...Microneedles(MNs)have attracted increasing attention as a transdermal delivery system(TDDS)[1].However,traditional volatile Chinese medicines cannot be dissolved in conventional soluble MN materials,such as hyaluronic acid and chitosan,making it difficult for many traditional Chinese medicine ingredients to be applied to MN.Elemene(ELE)was successfully isolated from Curcuma longa,and has numerous antitumor and curative effects[2].展开更多
Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).Howev...Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Interestingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.展开更多
Objective： To explore the effect and possible mechanism in vitro of radiosensitization by β-Elemene in A549 cell line from adenocarcinoma of lung. Methods： The A549 cell line from adenocarcinoma of lung was chosen ...Objective： To explore the effect and possible mechanism in vitro of radiosensitization by β-Elemene in A549 cell line from adenocarcinoma of lung. Methods： The A549 cell line from adenocarcinoma of lung was chosen for the study to determine the inhibition ratio by using MTT assay. Morphologic change, growth curve, cloning efficiency, divisional index were observed. Change of cell cycle and apoptosis rate were analyzed by FCM and the expressions of gene P53 and Bcl-2 were detected. Results： Reproductive activity of the group which was under irradiation and β-Elemene was significantly suppressed and its cloning efficiency and divisional index also declined. The apoptosis rate of the group which was under irradiation and β-Elemene was significantly higher at 48 h and 72 h, which was analyzed by FCM. The expression of P53 without Bcl-2 was observed in the group under irradiation and β-Elemene and the group under β-Elemene only at the 48th hour point, while the expression of Bcl-2 without p53 was observed in the group under irradiation only and the control group. Conclusion： β-Elemene is good at radiosensitization and its mechanism may be relevant to the up-regulation of P53, down-regulation of Bcl-2 and inducing apoptosis.展开更多
Objective： To investigate the impact of beta-elemene injection on the growth and alpha-tubule of human hepatocarcinoma HepG2 cells. Methods： Cell proliferation was assessed by MTT assay. Cell cycle distribution was ...Objective： To investigate the impact of beta-elemene injection on the growth and alpha-tubule of human hepatocarcinoma HepG2 cells. Methods： Cell proliferation was assessed by MTT assay. Cell cycle distribution was detected by flow cytometry （FCM）. The mRNA expression of alpha-tubulin was measured by RT-PCR. Western blot analysis was used to determine protein expression of alpha-tubulin and the polymerization of tubulin. Results： Beta-elemene injection inhibited HepG2 cells proliferation in a dose- and time-dependent manner; FCM analysis indicated beta-elemene injection induced cell cycle arrested at S phase. RT-PCR and western- blot analysis showed that beta-elemene injection down-regulated alpha-tublin at both mRNA and protein levels, presenting a dose-dependent manner. Moreover, beta-elemene injection reduced the polymerization of microtubules in a dose-dependent manner. Conclusions： Beta-elemene injection can inhibit the proliferation of hepatoma HepG2 cells and induce cell apoptosis, the mechanism might be partly related to the down-regulation of alpha-tubulin and inhibition of microtubular polymerization.展开更多
AIM: To study the effects of elemene (Ele) on proliferation and cell cycle of human lens epithelial cells 63 (HLE-B3) and the mechanisms of its signal transduction. METHODS: Recombinant human basic fibroblast growth f...AIM: To study the effects of elemene (Ele) on proliferation and cell cycle of human lens epithelial cells 63 (HLE-B3) and the mechanisms of its signal transduction. METHODS: Recombinant human basic fibroblast growth factor (rhbFGF) was used to induce proliferation of HLE-B3 cells, which were incubated with 80mg/L Ele for 24 hours. The inhibitory effects of Ele on the proliferation of HLE-B3 cells were evaluated by MU method. The effect of Ele on HLE-B3 cell cycle was analyzed by flow cytometry (FCM). The expressions of protein kinase A (PKA) and protein kinase G (PKG) of HLE-B3 were also analyzed by FCM. RESULTS: Ele altered the cell cycle of HLE-B3 and effectively inhibited HLE-B3 cell proliferation induced by rhbFGF. Ele up-regulated PKA and down-regulated the expression of PKG in HLE-B3 cell. CONCLUSION: Ele inhibits HLE-B3 proliferation, making it an attractive potential agent in regimens to treat after-cataracts.展开更多
AIM:To explore the potential of β-elemene as a radiosensitizer for gastric cancer cells and the underlying mechanisms.METHODS:SGC7901,MKN45,MKN28,N87,and AGS human gastric cancer cell lines were used to screen for ra...AIM:To explore the potential of β-elemene as a radiosensitizer for gastric cancer cells and the underlying mechanisms.METHODS:SGC7901,MKN45,MKN28,N87,and AGS human gastric cancer cell lines were used to screen for radioresistant gastric cancer cell lines. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium(MTT) assay was used to determine the effects of β-elemene and IPA-3 on cell viability in MKN45 and SGC7901 gastric cancer cell lines. A clonogenic survival assay and annexin V-FITC/PI apoptosis detection assay were used to evaluate cellular radiosensitivity and radiation-induced cell death,respectively. A proteomic method,isobaric tags for relative and absolute quantitation(i TRAQ),was employed to screen the proteins regulated by β-elemene pretreatment prior to ionizing radiation(IR) in SGC7901 gastric cancer cell line. IPA-3 was used as a specific small molecule inhibitor of p21-activated protein kinase 1(Pak1) to target Pak1 signaling. Protein levels of PAK1IP1(p21-activated protein kinase-interacting protein 1),total Pak1(t-Pak1),phospho-Pak1(T423),phospho-ERK1/2( Thr202/Tyr204),and cleaved caspase-3(17 k Da) were assessed by western blotting.RESULTS:MKN45 and SGC7901 gastric cancer cell lines were relatively more resistant to IR. β-elemene pretreatment decreased clonogenic survival following IR in MKN45 and SGC7901 gastric cancer cell lines. Additionally,β-elemene pretreatment prior to IR increased radiation-induced cell death compared with IR alone in MKN45(10.4% ± 0.9% vs 34.8% ± 2.8%,P < 0.05) and SGC7901(11.6% ± 0.9% vs 46.7% ± 5.2%,P < 0.05) human gastric cancer cell lines,respectively,consistent with the level of cleaved caspase-3(17 k Da). Through i TRAQ analysis and western blot validation,we found that β-elemene upregulated PAK1IP1 and downregulated phospho-Pak1(T423) and phosphoERK1/2 in SGC7901 gastric cancer cells. IR increased the level of phospho-Pak1(T423). Pretreatment with β-elemene decreased radiation-induced Pak1 and ERK1/2 phosphorylation. Inhibition of Pak1 using IPA-3 decreased clonogenic survival following IR. In addition,IPA-3 increased radiation-induced cell death in MKN45(13.4% ± 0.3% vs 26.6% ± 1.0%,P < 0.05) and SGC7901(16.0% ± 0.6% vs 37.3% ± 1.7%,P < 0.05) gastric cancer cell lines,respectively,consistent with the level of cleaved caspase-3(17 k Da). Western blotting showed that IPA-3 decreased radiation-induced Pak1 and ERK1/2 phosphorylation.CONCLUSION:This is the first demonstration that β-elemene enhances radiosensitivity of gastric cancer cells,and that the mechanism involves inhibition of Pak1 signaling.展开更多
In the present study, a series of 13-β-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells(HUVECs). Among t...In the present study, a series of 13-β-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells(HUVECs). Among the test compounds, the dimer compounds 5v and 5w exhibited the most potent antioxidant activity with significant ROS suppression being observed. Both compounds markedly inhibited the H2O2-induced changes in various biochemical substances, such as superoxide dismutase(SOD), malonyldialdehyde(MDA), nitric oxide(NO), and lactic dehydrogenase(LDH), which were superior to that of the positive control vitamin E. Furthermore, they did not produce any obvious cytotoxicity, but increased the viability of HUVECs injured by H2O2 in a dose-dependent manner. Additionally, compound 5w, designed as a prodrug-like compound, showed improved stability relative to compound 4 in vitro.展开更多
AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced d...AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced diabetic SpragueDawley(SD) rat model.METHODS: SD rats were administered an abdominal injection of STZ and induced to a diabetic model. After 6 wk course of diabetes, the treatment groups were given β-elemene through periocular and intravitreous injection separately and the control groups were given blank emulsion injection. HE staining was used to observe the morphology of retina. The m RNA expressions of HIF-1α, VEGF and i NOS was assayed by real-time polymerase chain reaction(PCR) and the protein expression was measured by Western blot and immunocytochemistry methods.RESULTS: The results indicated that the protein and m RNA expressions of HIF-1α, VEGF and i NOS after treated by β-elemene periocularly and intravitreally injections were all found to be reduced compared with the levels in the diabetic rats group(P<0.05). The inhibitory effect of intravitreal injection was more remarkable.CONCLUSION: The results show β-elemene protect the retina of diabetic rats from high glucose damage by downregulating the expression of HIF-1α, VEGF and iNOS.展开更多
Elemene, isolated from the Chinese medicinal herbRhizoma Zedoariae was shown to exhibit antitumoractivity in vitro and in vivo to human and murine tumorcells. This novel antineoplastic agent has beendemonstrated to ha...Elemene, isolated from the Chinese medicinal herbRhizoma Zedoariae was shown to exhibit antitumoractivity in vitro and in vivo to human and murine tumorcells. This novel antineoplastic agent has beendemonstrated to have substantial clinical activity againstvarious tumors. In this paper, the mechanisms ofantitumor activity of elemene are reported. The in vitroeffect of elemene on the growth of leukemia cells wasevaluated by MTT assay. The IC50 values of elemene forpromyelocytic leukemia HL-60 cells and erythroleukemiaK562 cells were found to be 27.5 μg/ml and 81μg/ml,respectively, while IC50 for peripheral blood leukocytes(PBL) was 254.3 μg/ml. The inhibitory effect of elemeneon proliferation of HL-60 cells was associated with cellcycle arrest from S to G2M phase transition and withinduction of apoptosis. The apoptosis of tumor cells wasconfirmed by DNA ladder formation on gelelectrophoresis and characteristic ultrastructuralalternations. These results indicate that induction ofapoptosis contributes to the mechanisms of antitumoractivity of elemene.展开更多
Objective: To explore the therapeutic effect of elemene combined with S-1 / oxaliplatin (SOX) in the treatment of advanced metastatic gastric cancer, and to analyze and evaluate the safety of the chemotherapy, so as t...Objective: To explore the therapeutic effect of elemene combined with S-1 / oxaliplatin (SOX) in the treatment of advanced metastatic gastric cancer, and to analyze and evaluate the safety of the chemotherapy, so as to provide new ideas for clinical treatment. Methods: 71 patients with advanced metastatic gastric cancer from April 2015 to April 2018 were randomly divided into two groups: the control group treated with SOX alone and the observation group treated with elemene combined SOX. The short-term and long-term therapeutic effects of the two groups were compared by the RECIST1.1 score and survival curve, and the differences of tumor markers, serological indicators and adverse reactions between the two groups were compared. Results: the objective remission rate (ORR) and clinical benefit rate (CBR) of the observation group were significantly higher than those of the control group (χ2=5.161, P=0.031;χ2=5.124, P=0.037);after treatment, the serum CEA, CA-199, IGF-1, MMP-9, IL-2 and IFN-γ levels of the observation group were significantly improved compared with those of the control group (P<0.05);compared with the two groups, the incidence of leucopenia, anemia, asthenia, nausea and vomiting in the observation group were significantly lower than that in the control group (P<0.05);the median tumor progression time (7.1 months, 95%CI=4.037-10.248) and median total survival time (8.8 months, 95%CI=6.634-10.907) in the observation group were significantly higher than that in the control group (4.9 months, 95%CI=2.324-6.839) and median total survival time (6.5 months, 95%CI=5.007-7.638), and the difference was statistically significant (P=0.001, P=0.026). Conclusion: elemene combined with SOX has a high short-term and long-term efficacy in patients with advanced metastatic gastric cancer, and its side effects are less, and its safety is higher, which has a certain clinical significance.展开更多
Objective:The aim of this study was to observe the effects and adverse reactions of elemene emulsion added to the chemotherapy in the treatment of advanced gastric carcinoma (AGC).Methods:Forty-nine patients were divi...Objective:The aim of this study was to observe the effects and adverse reactions of elemene emulsion added to the chemotherapy in the treatment of advanced gastric carcinoma (AGC).Methods:Forty-nine patients were divided randomly into two groups,elemene emulsion group (25 cases,treated with chemotherapy and elemene emulsion) and chemotherapy group (24 cases,treated with chemotherapy only).All patients received chemotherapy.The clinical effects and adverse reactions were evaluated after four cycles.Results:The response rate (RR) were 60% in elemene emulsion group and 41.7% in chemotherapy group respectively (P < 0.05).The median time to progression and overall survival in elemene emulsion group and in chemotherapy group were 7.1 months and 11.0 months vs 5.2 months and 9.3 months (P < 0.05).A lower rate of neutropenia,nausea,vomiting and diarrhea occurred in elemene emulsion group compared with chemotherapy group (P < 0.05),and there was significant difference in the elevation of life quality as well (48% vs 25%;P < 0.05).Conclusion:Elemene emulsion in combination with FOLFOX4 regimen can improve the efficacy,decrease the incidence of side effects of chemotherapy and elevate the life quality and prolong the survival time in AGC.展开更多
To investigate the effects of β-elemene on the ANG Ⅱ-ATI receptor pathway in rats with liver fibrosis, a model of hepatic fibrosis was induced by hypodermical injection of carbon tetrachloride （CC14） into Wistar m...To investigate the effects of β-elemene on the ANG Ⅱ-ATI receptor pathway in rats with liver fibrosis, a model of hepatic fibrosis was induced by hypodermical injection of carbon tetrachloride （CC14） into Wistar male rats. D-elemene was intraperitonealy administered into the rats for 8 weeks （0.1 mL/100 g body weight per day）. Masson staining was used to observe the liver fibrosis of rats and liver functions were measured by enzymatic kinetic analysis. The content of hydroxyproline in liver tissues was detected by specimen alkaline hydrolysis. The level of plasma ANG Ⅱ in blood plasma was detected by radioimmunoassay. The expression of AT1R in rat liver were measured using reverse transcriptional-polymerase chain reaction and immunohistochemistry respectively. The results showed that β-elemene could reduce the collagen disposition in liver and inhibit the progression of liver fibrosis. In addition, the levels of plasma ANG Ⅱ and the expression of hepatic AT1R in rats with liver fibrosis were also suppressed by β-elemene. It is concluded that the ANG Ⅱ-AT1 receptor pathway plays an important role in the development of hepatic fibrosis and D-elemene could down-regulate the levels of plasma ANG Ⅱ and the expression of hepatic ATIR in rats with liver fibrosis.展开更多
The present study aimed at investigating the possible effects offl-elemene on the progression of atherosclerosis in a rabbit model. The rabbit atherosclerosis model was established by the combination of balloon angiop...The present study aimed at investigating the possible effects offl-elemene on the progression of atherosclerosis in a rabbit model. The rabbit atherosclerosis model was established by the combination of balloon angioplasty-induced endothelial injury and an atherogenic diet fed to the rabbits. New Zealand White rabbits were randomly divided into four groups （8/group）： the normal control group （fed with normal chow diet）, and three experimental groups, placebo group, atorvastatin group, and β-elemene group （received the atherogenic diet）. After two weeks on the diet, the three experimental groups underwent balloon injury at right common carotid artery and were treated with drugs or placebo for five weeks. Serum lipids were measured, Carotid artery lesions were isolated for histological and immunohistochemical analysis. In vitro, RAW264.7 macrophages were pretreated with β-elemene and ox-LDL for 24 h and the viability of macrophages was assayed using the MTT method. TNF-a and IL-6 were also determined. Compared with the control group, the thickness of the atherosclerosis lesion in the placebo group was significantly increased; The thickness the drug treatment groups were significantly decreased, compared with that of the placebo group. The infiltration of macrophage was markedly reduced in the β-elemene group compared with that of the placebo group,β-Elemene treatment also reduced the levels of TC, TC, and LDL-C, compared with the placebo group, β-elemene decreased the TNF-a and IL-6 levels in vitro. In conclusion, our results demonstrated that β-elemene retarded the progression of atherosclerosis in vivo and in vitro, which may be related to the capacity of β-elemene to reduce the infiltration of macrophages and suppress inflammatory factors.展开更多
Objective:To study the effect of bronchial arterial infusion chemotherapy combined with elemene on the malignant lesion molecules and systemic immune response in patients with advanced lung cancer.Methods:A total of 7...Objective:To study the effect of bronchial arterial infusion chemotherapy combined with elemene on the malignant lesion molecules and systemic immune response in patients with advanced lung cancer.Methods:A total of 78 patients diagnosed with advanced lung cancer in our hospital between April 2013 and March 2016 were selected as research subjects and randomly divided into observation group who accepted bronchial arterial infusion chemotherapy combined with elemene therapy and control group who accepted bronchial arterial infusion chemotherapy. After 4 weeks of treatment, tumor lesions were collected to determine the expression of proliferation and invasion molecule, and serum was collected to determine the levels of immune cell-related cytokines.Results:After 4 weeks of treatment, TCF3, Livin, Bcl-2, HOXB7, PTTG1, Vimentin, E-cadherin, Rap2a andβ-catenin protein expression in tumor lesions of observation group were significantly lower than those of control group;serum IFN-γ level of observation group was significantly higher than that of control group while IL-4, IL-9, IL-10 and TGF-β levels were significantly lower than those of control group.Conclusions:Bronchial arterial infusion chemotherapy combined with elemene can inhibit the expression of proliferation and invasion of molecules in tumor lesions and improve the systemic anti-tumor immune response in patients with advanced lung cancer.展开更多
Objective:To explore the main factors of renal function injury caused by the combination of elemene emulsion injection in the real world.Methods:Based on the hospital information system medical database constructed by...Objective:To explore the main factors of renal function injury caused by the combination of elemene emulsion injection in the real world.Methods:Based on the hospital information system medical database constructed by the Institute of Clinical Basic Medicine of Chinese Academy of Traditional Chinese Medicine,taking the patient information of elemene emulsion injection used in 21 top three hospitals in China as the research object,the nested case control study method was used to compare the combined medication of patients with renal function injury group and control group,The main factors that may lead to renal function injury were screened by MCP variable selection method,and the above main factors were further analyzed by classical logistic regression and propensity score logistic regression method.Results:The analysis found that the combined use of potassium chloride within 7 d before the use of elemene emulsion injection or the combined use of furosemide during the use of elemene emulsion injection may be the main factor leading to renal function injury.Conclusion:The combination of elemene emulsion injection and the above main factors that may lead to renal injury should be avoided.If it must be used,clinical monitoring should be strengthened,and abnormal reactions should be treated immediately.The results of this study have certain clinical significance,and the clinical mechanism can be further studied and explored in the future.展开更多
Objective To investigate the effects of low dosage of β-elemene on the radiosensitivity of rabbit VX2 renal transplant carcinoma model. Methods We took the rabbit VX2 renal transplant carcinoma as the model. Experime...Objective To investigate the effects of low dosage of β-elemene on the radiosensitivity of rabbit VX2 renal transplant carcinoma model. Methods We took the rabbit VX2 renal transplant carcinoma as the model. Experimental rabbits were divided into three groups: the control group, the radiation group, and the radiation +β-elemene (radiosensitivity) group. The change of tumor was observed by Spiral CT and B ultrasound to compare its regrowth period. The tumor was measured by light microscopy and electron microscopy. Results The tumor in radiosensitivity group was restrained obviously and the sensitization enhancement ratio (SER) of β-elemene was 1.89. Different apoptosis was observed under transmission electron microscopy. Conclusion Low dosage β-elemene can enhance the radiosensitivity of rabbit VX2 renal transplant carcinoma model and induce the apoptosis of tumor cells, but the mechanism needs further study. It promotes apoptosis in mechanisms in vitro.展开更多
Objective: To observe and compare the differences in the clinical effect and the incidences of adverse reactions oftranscatheter arterial chemoembolization(TACE) combined with elemene injection and cinobufagin injecti...Objective: To observe and compare the differences in the clinical effect and the incidences of adverse reactions oftranscatheter arterial chemoembolization(TACE) combined with elemene injection and cinobufagin injection respectively for middleand advanced primary hepatic carcinoma. Methods: A total of 104 cases of patients with middle and advanced primary hepaticcarcinoma who were treated in the oncology department from August 2018 to January 2020 were included as the study objects, andwere randomly divided into two groups according to different treatment regimens, 52 cases in each group. Both groups were treatedwith TACE once;the cinobufagin injection group was given intravenous infusion with 500 mL of 5% glucose injection and 10 mLof cinobufagin injection once a day. The elemene injection group was given intravenous infusion with elemene injection of 0.4 geach time and once a day. Both groups were treated for two courses, 15 days of continuous treatment with a rest of 15 days beingone course. The clinical effect, the changes in the indexes of liver function including alanine amino transferase(ALT), aspartatetransaminase(AST) and total bilirubin(TBil), the scores of alpha-fetoprotein(AFP) and Karnofsky (KPS) and tumor volumes aswell as the difference in the incidences of adverse reactions between the two groups were observed and compared. Results: Thetotal clinical effective rate was 88.46% in the elemene injection group and 71.15% in the cinobufagin injection group, and thedifference was significant(P<0.05). After treatment, the levels of ALT, AST and TBil in serum in the two groups were significantlydecreased when compared with those before treatment, differences being significant(P<0.05). There was no significant differencebeing found in the comparison of the levels of ALT, AST and TBil in serum between the two groups (P>0.05). After treatment, thedecrease of AFP, tumor volume and the increase of KPS scores in the elemene injection group were significantly more than thosein the cinobufagin injection group, differences being significant (P<0.01). During treatment, there was no significant differencebeing found in the comparison of the total incidences of adverse reactions between the two groups(P>0.05). The adverse reactionsin the cinobufagin injection group were mainly nausea and vomiting, with higher incidence than that in the elemene injection group,the difference being significant (P<0.05). The adverse reactions in the elemene injection group were mainly pain at the injectionsite, with higher incidence than that in the cinobufagin injection group, the difference being significant (P<0.05). Conclusion: Thetherapy of elemene injection combined with TACE for middle and advanced primary hepatic carcinoma has better clinical effect thanthat of cinobufagin injection, but the occ.展开更多
基金supported by Shandong Provincial Natural Science Foundation Innovation and Development Joint Project,China(Grant No.:ZR2021LZY039)Zhejiang Provincial Traditional Chinese Medicine Science and Technology Plan,China(Grant No.:2021ZB184)。
文摘Microneedles(MNs)have attracted increasing attention as a transdermal delivery system(TDDS)[1].However,traditional volatile Chinese medicines cannot be dissolved in conventional soluble MN materials,such as hyaluronic acid and chitosan,making it difficult for many traditional Chinese medicine ingredients to be applied to MN.Elemene(ELE)was successfully isolated from Curcuma longa,and has numerous antitumor and curative effects[2].
基金supported by the National Natural Science Foundation of China(Grant No.:82225048)the Dalian Science and Technology Leading Talents Project,China(Grant No.:2019RD15)Sanming Project of Medicine in Shenzhen,China(Grant No.:SZZYSM202106004).
文摘Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Interestingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.
文摘Objective： To explore the effect and possible mechanism in vitro of radiosensitization by β-Elemene in A549 cell line from adenocarcinoma of lung. Methods： The A549 cell line from adenocarcinoma of lung was chosen for the study to determine the inhibition ratio by using MTT assay. Morphologic change, growth curve, cloning efficiency, divisional index were observed. Change of cell cycle and apoptosis rate were analyzed by FCM and the expressions of gene P53 and Bcl-2 were detected. Results： Reproductive activity of the group which was under irradiation and β-Elemene was significantly suppressed and its cloning efficiency and divisional index also declined. The apoptosis rate of the group which was under irradiation and β-Elemene was significantly higher at 48 h and 72 h, which was analyzed by FCM. The expression of P53 without Bcl-2 was observed in the group under irradiation and β-Elemene and the group under β-Elemene only at the 48th hour point, while the expression of Bcl-2 without p53 was observed in the group under irradiation only and the control group. Conclusion： β-Elemene is good at radiosensitization and its mechanism may be relevant to the up-regulation of P53, down-regulation of Bcl-2 and inducing apoptosis.
基金The General Program of National Natural Science Foundation of China:Research Fund for the mechanism of Arenobufagin space isomer inhibits lymphatic metastasis of mouse hepatocarcinomaThe Project Sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education MinistrySpecialized Research Fund for the Doctoral Program of Higher Education(NO.20102105120002)
文摘Objective： To investigate the impact of beta-elemene injection on the growth and alpha-tubule of human hepatocarcinoma HepG2 cells. Methods： Cell proliferation was assessed by MTT assay. Cell cycle distribution was detected by flow cytometry （FCM）. The mRNA expression of alpha-tubulin was measured by RT-PCR. Western blot analysis was used to determine protein expression of alpha-tubulin and the polymerization of tubulin. Results： Beta-elemene injection inhibited HepG2 cells proliferation in a dose- and time-dependent manner; FCM analysis indicated beta-elemene injection induced cell cycle arrested at S phase. RT-PCR and western- blot analysis showed that beta-elemene injection down-regulated alpha-tublin at both mRNA and protein levels, presenting a dose-dependent manner. Moreover, beta-elemene injection reduced the polymerization of microtubules in a dose-dependent manner. Conclusions： Beta-elemene injection can inhibit the proliferation of hepatoma HepG2 cells and induce cell apoptosis, the mechanism might be partly related to the down-regulation of alpha-tubulin and inhibition of microtubular polymerization.
基金Youth Foundation of Fujian Scientific Committee, China (No.2008F3050)
文摘AIM: To study the effects of elemene (Ele) on proliferation and cell cycle of human lens epithelial cells 63 (HLE-B3) and the mechanisms of its signal transduction. METHODS: Recombinant human basic fibroblast growth factor (rhbFGF) was used to induce proliferation of HLE-B3 cells, which were incubated with 80mg/L Ele for 24 hours. The inhibitory effects of Ele on the proliferation of HLE-B3 cells were evaluated by MU method. The effect of Ele on HLE-B3 cell cycle was analyzed by flow cytometry (FCM). The expressions of protein kinase A (PKA) and protein kinase G (PKG) of HLE-B3 were also analyzed by FCM. RESULTS: Ele altered the cell cycle of HLE-B3 and effectively inhibited HLE-B3 cell proliferation induced by rhbFGF. Ele up-regulated PKA and down-regulated the expression of PKG in HLE-B3 cell. CONCLUSION: Ele inhibits HLE-B3 proliferation, making it an attractive potential agent in regimens to treat after-cataracts.
基金Supported by National Nature Science Foundation of China,No.81172357
文摘AIM:To explore the potential of β-elemene as a radiosensitizer for gastric cancer cells and the underlying mechanisms.METHODS:SGC7901,MKN45,MKN28,N87,and AGS human gastric cancer cell lines were used to screen for radioresistant gastric cancer cell lines. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium(MTT) assay was used to determine the effects of β-elemene and IPA-3 on cell viability in MKN45 and SGC7901 gastric cancer cell lines. A clonogenic survival assay and annexin V-FITC/PI apoptosis detection assay were used to evaluate cellular radiosensitivity and radiation-induced cell death,respectively. A proteomic method,isobaric tags for relative and absolute quantitation(i TRAQ),was employed to screen the proteins regulated by β-elemene pretreatment prior to ionizing radiation(IR) in SGC7901 gastric cancer cell line. IPA-3 was used as a specific small molecule inhibitor of p21-activated protein kinase 1(Pak1) to target Pak1 signaling. Protein levels of PAK1IP1(p21-activated protein kinase-interacting protein 1),total Pak1(t-Pak1),phospho-Pak1(T423),phospho-ERK1/2( Thr202/Tyr204),and cleaved caspase-3(17 k Da) were assessed by western blotting.RESULTS:MKN45 and SGC7901 gastric cancer cell lines were relatively more resistant to IR. β-elemene pretreatment decreased clonogenic survival following IR in MKN45 and SGC7901 gastric cancer cell lines. Additionally,β-elemene pretreatment prior to IR increased radiation-induced cell death compared with IR alone in MKN45(10.4% ± 0.9% vs 34.8% ± 2.8%,P < 0.05) and SGC7901(11.6% ± 0.9% vs 46.7% ± 5.2%,P < 0.05) human gastric cancer cell lines,respectively,consistent with the level of cleaved caspase-3(17 k Da). Through i TRAQ analysis and western blot validation,we found that β-elemene upregulated PAK1IP1 and downregulated phospho-Pak1(T423) and phosphoERK1/2 in SGC7901 gastric cancer cells. IR increased the level of phospho-Pak1(T423). Pretreatment with β-elemene decreased radiation-induced Pak1 and ERK1/2 phosphorylation. Inhibition of Pak1 using IPA-3 decreased clonogenic survival following IR. In addition,IPA-3 increased radiation-induced cell death in MKN45(13.4% ± 0.3% vs 26.6% ± 1.0%,P < 0.05) and SGC7901(16.0% ± 0.6% vs 37.3% ± 1.7%,P < 0.05) gastric cancer cell lines,respectively,consistent with the level of cleaved caspase-3(17 k Da). Western blotting showed that IPA-3 decreased radiation-induced Pak1 and ERK1/2 phosphorylation.CONCLUSION:This is the first demonstration that β-elemene enhances radiosensitivity of gastric cancer cells,and that the mechanism involves inhibition of Pak1 signaling.
基金supported by the National Natural Science Foundation of China(Nos.81001358,30873156,and 30672524)the New Century Excellent Talents in University(NCET-07-0851)the Project Program of State Key Laboratory of Natural Medicines,China Pharmaceutical University(No.SKLNMZZCX201404)
文摘In the present study, a series of 13-β-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells(HUVECs). Among the test compounds, the dimer compounds 5v and 5w exhibited the most potent antioxidant activity with significant ROS suppression being observed. Both compounds markedly inhibited the H2O2-induced changes in various biochemical substances, such as superoxide dismutase(SOD), malonyldialdehyde(MDA), nitric oxide(NO), and lactic dehydrogenase(LDH), which were superior to that of the positive control vitamin E. Furthermore, they did not produce any obvious cytotoxicity, but increased the viability of HUVECs injured by H2O2 in a dose-dependent manner. Additionally, compound 5w, designed as a prodrug-like compound, showed improved stability relative to compound 4 in vitro.
文摘AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced diabetic SpragueDawley(SD) rat model.METHODS: SD rats were administered an abdominal injection of STZ and induced to a diabetic model. After 6 wk course of diabetes, the treatment groups were given β-elemene through periocular and intravitreous injection separately and the control groups were given blank emulsion injection. HE staining was used to observe the morphology of retina. The m RNA expressions of HIF-1α, VEGF and i NOS was assayed by real-time polymerase chain reaction(PCR) and the protein expression was measured by Western blot and immunocytochemistry methods.RESULTS: The results indicated that the protein and m RNA expressions of HIF-1α, VEGF and i NOS after treated by β-elemene periocularly and intravitreally injections were all found to be reduced compared with the levels in the diabetic rats group(P<0.05). The inhibitory effect of intravitreal injection was more remarkable.CONCLUSION: The results show β-elemene protect the retina of diabetic rats from high glucose damage by downregulating the expression of HIF-1α, VEGF and iNOS.
文摘Elemene, isolated from the Chinese medicinal herbRhizoma Zedoariae was shown to exhibit antitumoractivity in vitro and in vivo to human and murine tumorcells. This novel antineoplastic agent has beendemonstrated to have substantial clinical activity againstvarious tumors. In this paper, the mechanisms ofantitumor activity of elemene are reported. The in vitroeffect of elemene on the growth of leukemia cells wasevaluated by MTT assay. The IC50 values of elemene forpromyelocytic leukemia HL-60 cells and erythroleukemiaK562 cells were found to be 27.5 μg/ml and 81μg/ml,respectively, while IC50 for peripheral blood leukocytes(PBL) was 254.3 μg/ml. The inhibitory effect of elemeneon proliferation of HL-60 cells was associated with cellcycle arrest from S to G2M phase transition and withinduction of apoptosis. The apoptosis of tumor cells wasconfirmed by DNA ladder formation on gelelectrophoresis and characteristic ultrastructuralalternations. These results indicate that induction ofapoptosis contributes to the mechanisms of antitumoractivity of elemene.
基金Wu Jieping medical foundation project (320.3750.18075)
文摘Objective: To explore the therapeutic effect of elemene combined with S-1 / oxaliplatin (SOX) in the treatment of advanced metastatic gastric cancer, and to analyze and evaluate the safety of the chemotherapy, so as to provide new ideas for clinical treatment. Methods: 71 patients with advanced metastatic gastric cancer from April 2015 to April 2018 were randomly divided into two groups: the control group treated with SOX alone and the observation group treated with elemene combined SOX. The short-term and long-term therapeutic effects of the two groups were compared by the RECIST1.1 score and survival curve, and the differences of tumor markers, serological indicators and adverse reactions between the two groups were compared. Results: the objective remission rate (ORR) and clinical benefit rate (CBR) of the observation group were significantly higher than those of the control group (χ2=5.161, P=0.031;χ2=5.124, P=0.037);after treatment, the serum CEA, CA-199, IGF-1, MMP-9, IL-2 and IFN-γ levels of the observation group were significantly improved compared with those of the control group (P<0.05);compared with the two groups, the incidence of leucopenia, anemia, asthenia, nausea and vomiting in the observation group were significantly lower than that in the control group (P<0.05);the median tumor progression time (7.1 months, 95%CI=4.037-10.248) and median total survival time (8.8 months, 95%CI=6.634-10.907) in the observation group were significantly higher than that in the control group (4.9 months, 95%CI=2.324-6.839) and median total survival time (6.5 months, 95%CI=5.007-7.638), and the difference was statistically significant (P=0.001, P=0.026). Conclusion: elemene combined with SOX has a high short-term and long-term efficacy in patients with advanced metastatic gastric cancer, and its side effects are less, and its safety is higher, which has a certain clinical significance.
文摘Objective:The aim of this study was to observe the effects and adverse reactions of elemene emulsion added to the chemotherapy in the treatment of advanced gastric carcinoma (AGC).Methods:Forty-nine patients were divided randomly into two groups,elemene emulsion group (25 cases,treated with chemotherapy and elemene emulsion) and chemotherapy group (24 cases,treated with chemotherapy only).All patients received chemotherapy.The clinical effects and adverse reactions were evaluated after four cycles.Results:The response rate (RR) were 60% in elemene emulsion group and 41.7% in chemotherapy group respectively (P < 0.05).The median time to progression and overall survival in elemene emulsion group and in chemotherapy group were 7.1 months and 11.0 months vs 5.2 months and 9.3 months (P < 0.05).A lower rate of neutropenia,nausea,vomiting and diarrhea occurred in elemene emulsion group compared with chemotherapy group (P < 0.05),and there was significant difference in the elevation of life quality as well (48% vs 25%;P < 0.05).Conclusion:Elemene emulsion in combination with FOLFOX4 regimen can improve the efficacy,decrease the incidence of side effects of chemotherapy and elevate the life quality and prolong the survival time in AGC.
基金supported by a grant from the National Natural Sciences Foundation of China (No.30500658)
文摘To investigate the effects of β-elemene on the ANG Ⅱ-ATI receptor pathway in rats with liver fibrosis, a model of hepatic fibrosis was induced by hypodermical injection of carbon tetrachloride （CC14） into Wistar male rats. D-elemene was intraperitonealy administered into the rats for 8 weeks （0.1 mL/100 g body weight per day）. Masson staining was used to observe the liver fibrosis of rats and liver functions were measured by enzymatic kinetic analysis. The content of hydroxyproline in liver tissues was detected by specimen alkaline hydrolysis. The level of plasma ANG Ⅱ in blood plasma was detected by radioimmunoassay. The expression of AT1R in rat liver were measured using reverse transcriptional-polymerase chain reaction and immunohistochemistry respectively. The results showed that β-elemene could reduce the collagen disposition in liver and inhibit the progression of liver fibrosis. In addition, the levels of plasma ANG Ⅱ and the expression of hepatic AT1R in rats with liver fibrosis were also suppressed by β-elemene. It is concluded that the ANG Ⅱ-AT1 receptor pathway plays an important role in the development of hepatic fibrosis and D-elemene could down-regulate the levels of plasma ANG Ⅱ and the expression of hepatic ATIR in rats with liver fibrosis.
基金supported by National Science and Technology Infrastructure Program(No.2012BAI30B001)Mega-projects of Science Research for the 12th Five-Year Plan of China(No.2011ZX09401-007)
文摘The present study aimed at investigating the possible effects offl-elemene on the progression of atherosclerosis in a rabbit model. The rabbit atherosclerosis model was established by the combination of balloon angioplasty-induced endothelial injury and an atherogenic diet fed to the rabbits. New Zealand White rabbits were randomly divided into four groups （8/group）： the normal control group （fed with normal chow diet）, and three experimental groups, placebo group, atorvastatin group, and β-elemene group （received the atherogenic diet）. After two weeks on the diet, the three experimental groups underwent balloon injury at right common carotid artery and were treated with drugs or placebo for five weeks. Serum lipids were measured, Carotid artery lesions were isolated for histological and immunohistochemical analysis. In vitro, RAW264.7 macrophages were pretreated with β-elemene and ox-LDL for 24 h and the viability of macrophages was assayed using the MTT method. TNF-a and IL-6 were also determined. Compared with the control group, the thickness of the atherosclerosis lesion in the placebo group was significantly increased; The thickness the drug treatment groups were significantly decreased, compared with that of the placebo group. The infiltration of macrophage was markedly reduced in the β-elemene group compared with that of the placebo group,β-Elemene treatment also reduced the levels of TC, TC, and LDL-C, compared with the placebo group, β-elemene decreased the TNF-a and IL-6 levels in vitro. In conclusion, our results demonstrated that β-elemene retarded the progression of atherosclerosis in vivo and in vitro, which may be related to the capacity of β-elemene to reduce the infiltration of macrophages and suppress inflammatory factors.
文摘Objective:To study the effect of bronchial arterial infusion chemotherapy combined with elemene on the malignant lesion molecules and systemic immune response in patients with advanced lung cancer.Methods:A total of 78 patients diagnosed with advanced lung cancer in our hospital between April 2013 and March 2016 were selected as research subjects and randomly divided into observation group who accepted bronchial arterial infusion chemotherapy combined with elemene therapy and control group who accepted bronchial arterial infusion chemotherapy. After 4 weeks of treatment, tumor lesions were collected to determine the expression of proliferation and invasion molecule, and serum was collected to determine the levels of immune cell-related cytokines.Results:After 4 weeks of treatment, TCF3, Livin, Bcl-2, HOXB7, PTTG1, Vimentin, E-cadherin, Rap2a andβ-catenin protein expression in tumor lesions of observation group were significantly lower than those of control group;serum IFN-γ level of observation group was significantly higher than that of control group while IL-4, IL-9, IL-10 and TGF-β levels were significantly lower than those of control group.Conclusions:Bronchial arterial infusion chemotherapy combined with elemene can inhibit the expression of proliferation and invasion of molecules in tumor lesions and improve the systemic anti-tumor immune response in patients with advanced lung cancer.
基金Key project of Science and Technology Innovation Project of China Academy of Chinese Medical Sciences(NO.CI2021A00702)the National Key Research and Development Program(NO.2018YFC1707410)。
文摘Objective:To explore the main factors of renal function injury caused by the combination of elemene emulsion injection in the real world.Methods:Based on the hospital information system medical database constructed by the Institute of Clinical Basic Medicine of Chinese Academy of Traditional Chinese Medicine,taking the patient information of elemene emulsion injection used in 21 top three hospitals in China as the research object,the nested case control study method was used to compare the combined medication of patients with renal function injury group and control group,The main factors that may lead to renal function injury were screened by MCP variable selection method,and the above main factors were further analyzed by classical logistic regression and propensity score logistic regression method.Results:The analysis found that the combined use of potassium chloride within 7 d before the use of elemene emulsion injection or the combined use of furosemide during the use of elemene emulsion injection may be the main factor leading to renal function injury.Conclusion:The combination of elemene emulsion injection and the above main factors that may lead to renal injury should be avoided.If it must be used,clinical monitoring should be strengthened,and abnormal reactions should be treated immediately.The results of this study have certain clinical significance,and the clinical mechanism can be further studied and explored in the future.
基金This work was supported by the National Natural Science Foundation of China (No30371831)
文摘Objective To investigate the effects of low dosage of β-elemene on the radiosensitivity of rabbit VX2 renal transplant carcinoma model. Methods We took the rabbit VX2 renal transplant carcinoma as the model. Experimental rabbits were divided into three groups: the control group, the radiation group, and the radiation +β-elemene (radiosensitivity) group. The change of tumor was observed by Spiral CT and B ultrasound to compare its regrowth period. The tumor was measured by light microscopy and electron microscopy. Results The tumor in radiosensitivity group was restrained obviously and the sensitization enhancement ratio (SER) of β-elemene was 1.89. Different apoptosis was observed under transmission electron microscopy. Conclusion Low dosage β-elemene can enhance the radiosensitivity of rabbit VX2 renal transplant carcinoma model and induce the apoptosis of tumor cells, but the mechanism needs further study. It promotes apoptosis in mechanisms in vitro.
文摘Objective: To observe and compare the differences in the clinical effect and the incidences of adverse reactions oftranscatheter arterial chemoembolization(TACE) combined with elemene injection and cinobufagin injection respectively for middleand advanced primary hepatic carcinoma. Methods: A total of 104 cases of patients with middle and advanced primary hepaticcarcinoma who were treated in the oncology department from August 2018 to January 2020 were included as the study objects, andwere randomly divided into two groups according to different treatment regimens, 52 cases in each group. Both groups were treatedwith TACE once;the cinobufagin injection group was given intravenous infusion with 500 mL of 5% glucose injection and 10 mLof cinobufagin injection once a day. The elemene injection group was given intravenous infusion with elemene injection of 0.4 geach time and once a day. Both groups were treated for two courses, 15 days of continuous treatment with a rest of 15 days beingone course. The clinical effect, the changes in the indexes of liver function including alanine amino transferase(ALT), aspartatetransaminase(AST) and total bilirubin(TBil), the scores of alpha-fetoprotein(AFP) and Karnofsky (KPS) and tumor volumes aswell as the difference in the incidences of adverse reactions between the two groups were observed and compared. Results: Thetotal clinical effective rate was 88.46% in the elemene injection group and 71.15% in the cinobufagin injection group, and thedifference was significant(P<0.05). After treatment, the levels of ALT, AST and TBil in serum in the two groups were significantlydecreased when compared with those before treatment, differences being significant(P<0.05). There was no significant differencebeing found in the comparison of the levels of ALT, AST and TBil in serum between the two groups (P>0.05). After treatment, thedecrease of AFP, tumor volume and the increase of KPS scores in the elemene injection group were significantly more than thosein the cinobufagin injection group, differences being significant (P<0.01). During treatment, there was no significant differencebeing found in the comparison of the total incidences of adverse reactions between the two groups(P>0.05). The adverse reactionsin the cinobufagin injection group were mainly nausea and vomiting, with higher incidence than that in the elemene injection group,the difference being significant (P<0.05). The adverse reactions in the elemene injection group were mainly pain at the injectionsite, with higher incidence than that in the cinobufagin injection group, the difference being significant (P<0.05). Conclusion: Thetherapy of elemene injection combined with TACE for middle and advanced primary hepatic carcinoma has better clinical effect thanthat of cinobufagin injection, but the occ.
