Biochemistry and Biophysics Reports
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2021
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IF 0
Xiaomin Zhang,Yidan Chen,Ju Yao,Yingxin Zhang,Mengying Li,Bo Yu,Kaifeng Wang
Temozolomide (TMZ) is a widely used chemotherapeutic agent for malignant glioma. β-Elemene has been reported to have the ability of passing through the blood-brain barrier and reverse multidrug resistance. In the present study, transport of drugs through the in vitro blood-brain barrier (BBB) model also suggested that β-elemene can assist in TMZ transport to the brain. Plasma and brain pharmacokinetics demonstrated that when β-elemene is used in combination with TMZ, the metabolic rate of TMZ in plasma is slowed, and mean residence time (MRT) in brain is prolonged. The brain tissue distribution at 1 h indicated that the combination of TMZ and β-elemene promotes the distribution of β-elemene in the brain but slightly reduces the distribution of TMZ in the brain. Furthermore the antitumor effect and toxicity in vivo were also investigated. The combination of β-elemene and TMZ was well tolerated and significantly inhibited tumor growth in glioma xenografts. In summary, the present study indicates a synergistic antitumor effect of β-elemene and TMZ in glioma.
研究领域:
肿瘤学
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药理学
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神经科学
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DOI
PubMed
Synthetic and Systems Biotechnology
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2025
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IF 4.4
Mingyu Dai,Qingyi Cao,Shuanglong Jia,Jiang Chen,Hui-Ying Xu,Bang-Ce Ye,Wei-Bing Liu,Ying Zhou
β-Elemene, a pharmacologically active sesquiterpene derived from the traditional Chinese medicinal herb Curcuma wenyujin, exhibits broad-spectrum antitumor and anti-inflammatory activities. Currently, its commercial production relies heavily on plant extraction, a process associated with high costs and environmental burdens, limiting industrial scalability. To address these challenges, we developed a metabolically engineered Yarrowia lipolytica strain as an efficient microbial cell factory for de novo Germacrene A biosynthesis, the direct precursor of β-elemene. Through combinatorial optimization strategies—including (1) mevalonate (MVA) pathway enhancement, (2) copy number amplification of germacrene A synthase (GAS), (3) β-oxidation pathway reinforcement, and (4) introduction of the isopentenyl utilization pathway (IUP)—we significantly improved β-elemene production. The engineered strain achieved a titer of 3.08 ± 0.05 g/L in shake-flask cultures, with a yield of 51.27 ± 0.75 mg/g glucose, representing a 3.5-fold increase over the parental strain. Our work highlights the potential of Y. lipolytica as a sustainable and scalable platform for high-value sesquiterpene production, offering a viable alternative to plant-derived extraction.
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PubMed
高影响因子
IUBMB LIFE
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2022
·Vol. 74
·期 6
·508-518
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IF 4.709
Qin Guo,Yujia Li,Yuan Chen,Jin Ji,Shizhong Zheng,Xuefen Xu,Biyun Zhang,Jianzhou Ye
Hypertrophic scar (HS) is a condition characterized by excessive synthesis and deposition of collagen. There are many clinical methods to alleviate HS, but most of them are accompanied by many complications. To investigate the effects of β-Elemene, extracted from the ginger family plant Wenyujin, on human hypertrophic scar fibroblast (hHSFs). Cultured hHSFs and human normal fibroblasts, observed the effect of β-Elemene on apoptosis, extracellular matrix, and endoplasmic reticulum stress (ERS) by western blot, Real Time-Polymerase Chain Reaction (RT-PCR), and flow cytometry. Based on our findings, it is clear that β-Elemene could inhibit the expression of α-smooth muscle actin (α-SMA), collagen I, and fibronectin, reduced collagen deposition. Further studies had found that β-Elemene could increase the expression of ERS-related proteins CHOP and Calnexin in a dose-dependent manner, thereby promoting the aggregation of cleaved-caspase-3 and inducing hHSFs to undergo poptosis. This process may depend on the regulation of P53. The results of our study indicates that β-Elemene induced hHSFs to undergo apoptosis though ERS pathway in a P53-dependent manner, which means that our research provided a new strategy for the development of drugs for the treatment of HS.
研究领域:
药理学
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细胞生物学
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皮肤科
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DOI
PubMed
高影响因子
PLANT CELL AND ENVIRONMENT
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2025
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IF 6.3
Lanxin Luo,Ting Gao,Yanni Deng,Mengyao Chai,Bo Li,Hao Ni,Kai Wang,Mengting Zhang,Yaojia Liu,Hao Jiang,Chuankui Song,Tingting Jing
Herbivore-induced plant volatiles play a crucial role in enhancing plant resistance and adaptability. However, the key volatiles triggering this response and their activation mechanisms remain largely unknown. Although tea aphids ( Toxoptera aurantii ) are common tea plantation pests, the underlying biochemical pathways by which aphid-induced volatiles in Camellia sinensis contribute to aphid resistance are not well understood. In this study, we measured jasmonic acid (JA) accumulation induced by aphid feeding using LC-MS and DESI-IMS analysis. We also identified a diverse array of aphid-induced volatiles through GC-MS. Notably, tea aphids stimulated β-Elemene accumulation, enhancing ‘Shuchazao’ resistance to tea aphids. We also evaluated the insecticidal activity of β-Elemene through contact toxicity and repellent bioassays. For the first time, we identified aphid-induced CsELE as a terpene synthase enzyme catalyzing the final step in β-Elemene biosynthesis from farnesyl pyrophosphate. Transient overexpression and gene silencing of CsELE affected β-Elemene accumulation, thereby influencing tea plant resistance to aphids. Furthermore, Dual-Luciferase and Y1H assays revealed that MYC2a, a core transcription factor in the JA signaling pathway, positively regulates CsELE expression. Overall, this study advances our understanding of the transcriptional regulation of tea volatiles in response to pest attacks, providing new insights into the ecological significance of terpene volatiles under biotic stress.
研究领域:
植物学
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分子生物学
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生态学
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PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
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2024
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IF 5.8
Sihan Shen,Ran Xie,Yiqun Wang,Lingyu Jia,Zhangran Zhu,Hai Ma,Lifang Wang,Feng Sui,Yu Zhao,Qinghe Zhao,Yanjun Chen
Ferroptosis represents a novel procedure of programmed cell death driven by iron-dependent lipid peroxidation, and may offer a promising strategy for cancer therapy. In this study, we developed poly (2-ethyl-2-oxazoline)-poly (lactic acid)-SS-poly (β-amino ester) (PEOz-PLA-SS-PBAE) loaded with β-elemene. The disulfide bond mediated depletion of glutathione (GSH) and inactivation of glutathione peroxidase 4 (GPX4) will lead to inactivation of the antioxidant system of the tumor cell, and β-elemene has the capacity to generate reactive oxygen species (ROS), and the above changes would induce a disruption of the redox balance within the tumor cell, resulting in ferroptosis of the tumor cell. In conclusion, in this study, water insoluble β-elemene was solubilized by the triblock copolymer to construct a pH/GSH dual-responsive nano-delivery system, and combined with iron death and chemotherapy to exert combinatory inhibition effect on breast cancer cells, which provides a new idea for the potential clinical application of β-elemene
研究领域:
肿瘤学
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药学
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纳米技术
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DOI
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
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2022
·Vol. 106
·期 24
·8053-8066
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IF 5.56
Li Meijie,Wen Qifeng,Lv Shuzhe,Yang Rumeng,Cheng Tao,Wang Zhaobao,Yang Jianming
Abstract
β-Elemene is the major component of a traditional Chinese medicine ( Rhizoma Curcumae ) for cancer treatment, and plant extraction is the major methods currently. Biosynthesis of β-elemene is a promising and attractive route due to its advantages, including environmentally friendly processes, renewable resources, and sustainable development. In this research, biosynthesis of germacrene A, direct precursor of β-elemene, in Escherichia coli was successfully performed and 11.99 mg/L germacrene A was obtained. Thereafter, a cobiosynthesis system for germacrene A and lycopene, another kind of isoprenoid, was constructed. Furthermore, the cultivation conditions were optimized. The germacrene A production was increased to the highest level reported to date, 364.26 mg/L, threefold increase to the strain with only germacrene A production. The cobiosynthesis system was suggested to promote the metabolic flux for germacrene A production. This research enabled germacrene A production in E. coli , and it highlights the promoting mechanism of the cobiosynthesis system for two chemicals which are both belonging to isoprenoids. Key points
• Co-production of germacrene A and lycopene in E. coli. • Promoting mechanism of cobiosynthesis of two isoprenoid compounds in E. coli. • Shake-flask production of germacrene A reached to the highest 364.26 mg/L in E. coli.
研究领域:
生物技术
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代谢工程
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药学
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植物化学
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微生物学
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DOI
PubMed
高影响因子
ACTA HISTOCHEMICA
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2020
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IF 2.107
Yufei Liang,Shengmian Li,Guoqi Zheng,Lan Zhang
Background Esophageal cancer is a digestive tract malignancy, ranking sixth among the world's deadliest tumor incidence. However, the pathogenesis of esophageal cancer is complex and the prognosis remains poor. Therefore, in-depth study of the pathogenesis and developing effective treatments are of great value for esophageal cancer. β-elemene is a natural monomeric compound derived from the Chinese herbal Curcuma wenyujin . β-elemene has been reported to have anti-tumor effects and used as an adjunct to clinical therapy for multiple cancers. This study aims to explore the effects of β-elemene on esophageal cancer and its related molecular mechanisms. Methods TE-1 and KYSE-150 cells were used to evaluate the activity of β-elemene on esophageal cancer in vitro and in vivo . Western blot was performed for protein expression assessment. CCK8 assay and cell cycle analysis were used for proliferation testing. Flow cytometry was performed for apoptosis detection. Wound healing assay was subjected to assess the migration ability. Transwell chamber assay was applied to assess the invasion ability. HE staining, TUNEL staining and immunohistochemical staining were used to evaluate the changes in tumor tissues. Results We found that β-elemene treatment suppressed proliferation, as well as induced apoptosis of esophageal cancer cells. In addition, β-elemene inhibited the migration and invasion ability of esophageal cancer cells. Furthermore, β-elemene exerted its effects against esophageal cancer by specifically regulating AKT signaling, thereby controlling the expression of PD-L1. Conclusion β-elemene inhibits proliferation and metastasis of esophageal cancer cells by regulating the phosphorylation of AKT.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
DRUG DELIVERY
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2019
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IF 3.829
Xiaorong Zhou,Chuanpei Cao,Nan Li,Shaofei Yuan
The aim of this study is to construct a SYL3C aptamer-anchored microemulsion based on β-elemene and PTX (SYL3C/EP-MEs) for enhancement on colorectal cancer therapy. Such microemulsion is consist of encapsulated drugs (β-elemene and PTX), tumor targeting ligand (3’-end thiolated SYL3C aptamer), thiol conjugated site (maleimide-modified PEGylated 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, mal-DOPE-PEG), pH-sensitive component (DOPE) and other necessary excipients. SYL3C/EP-MEs showed a spherical particle with an average particle size around 30 nm and a high encapsulation efficiency (>80%) for both drugs. β-elemene and PTX could be released controllably from SYL3C/EP-MEs as pH values changed. SYL3C/EP-MEs displayed a selective affinity to HT-29 cells, leading to an obvious increase in cellular uptake, cell apoptosis and cytotoxicity. In the HT-29 tumor xenograft-bearing nude mice model studies, SYL3C/EP-MEs showed an overwhelming tumor growth inhibition, the longest survival time and the lowest systemic toxicity among all the treatments. The potential mechanism of enhanced anti-cancer ability was probably associated with the induction of M1 macrophage polarization, the downregulation of mutant p53 protein and the reduction of bcl-2 protein expression. Collectively, the microemulsion codelivery of β-elemene and PTX using functionalization with SYL3C aptamer provides a novel approach for combinational colorectal cancer-targeted treatment.
研究领域:
药学
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肿瘤学
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药物递送系统
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2023
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IF 7.9
Jiong Wang,Chenchen Qian,Yue Chen,Tianyang Jin,Yongsheng Jiang,Lijiang Huang,Xinyan Fu,Dong Yang,Leiming Jin,Bo Jin,Yi Wang
ABSTRACT Background Hyperglycemic induced cardiac hypertrophy and cardiac inflammation are important pathological processes in diabetic cardiomyopathy. β-elemene (Ele) is a natural compound extracted from Curcuma Rhizoma and has anti-tumor effects. It also has therapeutic effects in some inflammatory diseases. However, the therapeutic effect of Ele on diabetic cardiomyopathy is not clear. The purpose of this study was to evaluate the effect of Ele on hyperglycemia-caused cardiac remodeling and heart failure. Methods C57BL/6 mice were intraperitoneally injected with streptozotocin to induce DCM, and Ele was administered intragastric after 8 weeks to investigate the effect of Ele. RNA sequencing of cardiac tissue was performed to investigate the mechanism. Results Ele markedly inhibited cardiac inflammation, fibrosis and hypertrophy in diabetic mice, as well as in high glucose-induced H9c2 cells. RNA sequencing showed that cardioprotective effect of Ele involved the JAK/STAT3-NF-κB signaling pathway. Ele alleviated heart and cardiomyocyte inflammation in mice by blocking diabetes-induced JAK2 and STAT3 phosphorylation and NF-κB activation. Conclusions The study found that Ele preserved the hearts of diabetic mice by inhibiting JAK/STAT3 and NF-κB mediated inflammatory responses, suggesting that Ele is an effective therapy for DCM.
研究领域:
药理学
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心脏病学
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糖尿病
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DOI
PubMed
高影响因子
Pharmaceutics
·
2020
·Vol. 12
·期 2
·191
·
IF 4.421
Kambere Amerigos Daddy J.C.,Minglei Chen,Faisal Raza,Yanyu Xiao,Zhigui Su,Qineng Ping
Multidrug resistance (MDR) due to P-glycoprotein (P-gp) overexpression is a major obstacle to successful leukemia chemotherapy. The combination of anticancer chemotherapy with a chemosensitizer of P-gp inhibitor is promising to overcome MDR, generate synergistic effects, and maximize the treatment effect. Herein, we co-encapsulated a chemotherapeutic drug of mitoxantrone (MTO) and a P-gp inhibitor of β-elemene (βE) in solid lipid nanoparticles (MTO/βE-SLNs) for reversing MDR in leukemia. The MTO/βE-SLNs with about 120 nm particle size possessed good colloidal stability and sustained release behavior. For the cellular uptake study, doxorubicin (DOX) was used as a fluorescence probe to construct SLNs. The results revealed that MTO/βE-SLNs could be effectively internalized by both K562/DOX and K562 cells through the pathway of caveolate-mediated endocytosis. Under the optimized combination ratio of MTO and βE, the in vitro cytotoxicity study indicated that MTO/βE-SLNs showed a better antitumor efficacy in both K562/DOX and K562 cells than other MTO formulations. The enhanced cytotoxicity of MTO/βE-SLNs was due to the increased cellular uptake and blockage of intracellular ATP production and P-gp efflux by βE. More importantly, the in vivo studies revealed that MTO/βE-SLNs could significantly prolong the circulation time and increase plasma half-life of both MTO and βE, accumulate into tumor and exhibit a much higher anti-leukemia effect with MDR than other MTO formulations. These findings suggest MTO/βE-SLNs as a potential combined therapeutic strategy for overcoming MDR in leukemia.Keywords:multidrug resistance;mitoxantrone;β-elemene;solid lipid nanoparticles;leukemia;P-glycoprotein
研究领域:
药理学
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肿瘤学
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纳米技术
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2025
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IF 4.8
Xiaoli Deng,Chunjie Hu,Lin Li,Guixian Yang,Chikun Li,Wanxun Zhang,Guangyu Cheng
Background Lung cancer is a leading cause of cancer-related deaths, with cisplatin being a cornerstone of treatment. However, resistance to cisplatin presents a significant challenge. β-elemene, a natural compound, has demonstrated potential to reverse cisplatin resistance. LncRNA LINC00511 has been implicated in cisplatin resistance through its role in activating the PI3K/AKT/mTOR pathway, which supports tumor survival and proliferation. Purpose This study aims to investigate the mechanism by which β-elemene overcomes cisplatin resistance in lung cancer by regulating LINC00511. Methods Human lung adenocarcinoma cells (A549 and A549/DDP) were treated with β-elemene and cisplatin. Cell proliferation and apoptosis were assessed using CCK-8, EdU staining, and flow cytometry. LINC00511 expression was measured by qRT-PCR, and protein levels of PI3K, AKT, and mTOR were evaluated via Western blot. A xenograft model was used to confirm in vivo effects. Results β-elemene significantly enhanced cisplatin-induced apoptosis in A549/DDP cells, reduced LINC00511 expression, and inhibited the PI3K/AKT/mTOR pathway. LINC00511 knockdown further potentiated these effects, both in vitro and in vivo . Xenograft models confirmed the enhanced anti-tumor effects of the combination treatment. Conclusion β-elemene overcomes cisplatin resistance in lung cancer by downregulating LINC00511 and inhibiting the PI3K/AKT/mTOR pathway. These findings propose a promising therapeutic strategy for treating cisplatin-resistant lung cancer.
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PubMed
高影响因子
Frontiers in Pharmacology
·
2025
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IF 4.8
Qian Feng,Cai-Zhi Li,Yi-Hua Zou,Xue-Yu Wang,Xia Yang,Rong Zhang*,Zhong-Qiu Liu*,Rong-Rong Zhang
Introduction: Brain metastasis (BM) is the most common and serious complication of breast cancer (BC). There is significant interest in investigating the crosstalk between BC cells and immune cells. β-elemene is the main pharmacodynamic component of Curcumae Rhizoma, a traditional Chinese medicine that is commonly used for the clinical treatment and prevention of various tumors. However, the specific underlying mechanism of β-elemene in BC-BM is still unclear.Methods: An intracardiac (ICT) injection model was used to establish specific BC-BM cells, then an intracarotid (ICD) injection model was used to verify the inhibitory effect of β-elemene in BC-BM. Tumor-cell-conditioned media, a primary microglia co-culture model, and an in vitro recruitment experiment were used to explore crosstalk between BC cells and immune cells. TMT-based quantitative proteomic, ELISA, IF, and other molecular biotechnologies were used to investigate the mechanisms.Results: The BC-BM cells established in our study not only increased BM rates but also exhibit mesenchymal phenotype and activated the JAK–STAT signaling pathway. Microglia, particularly M2 microglia, were enriched in BM lesions and secreted high levels of both IL6 and CCL2. Hypersecretory IL6 reversed the MET process of BC cells by regulating the JAK2/STAT3 signaling pathway to promote colonization in the brain. Increased levels of CCL2 significantly recruited monocytic myeloid-derived suppressor cells (M-MDSCs) to induce an immunosuppressive brain microenvironment. β-elemene could significantly inhibit BC-BM in mice by regulating the IL6/STAT3 signaling pathway and suppressing the M-MDSC recruitment.Conclusion: Our work first demonstrated that β-elemene regulated the IL6/STAT3 axis and M-MDSC recruitment to reconstruct immunosuppressive brain microenvironment to suppress BC-BM.
研究领域:
肿瘤学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
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