beta-Elemene

Beta-Elemene, a natural sesquiterpene, is a novel anti-tumor agent. The pharmacokinetics of beta-elemene after single i.v. administration have been investigated in male SD rats. beta-Elemene was administered at three doses (50, 75 and 100 mg/kg) and a full pharmacokinetic profile was obtained. beta-Elemene was metabolized extensively and eliminated rapidly. High permeability of beta-elemene through the blood-brain barrier was found following i.v. administration based on the brain/plasma ratio. Following i.v. administration, the drug was eliminated primarily as metabolite and minimally as unchanged drug. Cumulative fecal, biliary and urinary excretion of beta-elemene in rats was 0.61%, 0.06% and 0.003% of the administered dose (75 mg/kg) at 32 h after administration, respectively. These results indicate that biotransformation may be the main elimination passage of beta-elemene. The metabolism of beta-elemene was extensive and the structure of the metabolite (M1) in rat bile was determined by GS/MS and NMR analysis.

Whereas the purified form is generally not used as a dietary supplement because of poor absorption, many patients consume herbs high in beta-elemene in belief that they help cure cancer.

In vitro studies show anti-proliferative effects of beta-elemene in various cancer cells through cell-cycle arrest and induction of apoptosis . It also enhanced the activity of cisplatin against prostate cancer cells. The parenteral form of beta-elemene isolated from Rhizoma zedoariae, a species of ginger, has been studied in Asia and is reported to relieve pain, decrease the side effects of chemotherapy, and increase the quality of life in cancer patients. However, human trials conducted so far are of poor quality 

A systematic review indicates that beta-elemene injection may improve effectiveness of chemotherapy for the treatment of lung cancer . However, controlled trials are needed to confirm this observation.

Mechanism of Action

In an erythroleukemic cell line, beta-elemene inhibited telomerase activity, which was enhanced in combination with cyclophosphamide. It also demonstrated anti-fibrotic effects, inducing decreases in plasma angiotensin II levels and angiotensin II receptor type 1 expression, reducing collagen formation in a liver fibrosis rat model. Beta-elemene also exhibits anti-inflammatory effects, with reduction in LPS-induced nitric oxide production and prostaglandin E2 by rat peritoneal macrophages .

Beta-elemene has been shown to affect cancer cells via different mechanisms. In an in vitro study, following administration of beta-elemene, leukemia cells were arrested in S/G2 phase and underwent apoptosis . The antiproliferative effects were dependent on p38 MAPK activation/phosphorylation, cell cycle arrest in G0/G1, and inhibition of tumor growth of glioblastoma cells . Beta-elemene also induced G2/M arrest in lung carcinoma cells and ovarian cancer cells by combined reduction of cell-cycle promoters Cdc2 and cyclin B1, and elevated cell cycle regulators p53 and p27. Derivatives of beta-elemene showed antiproliferative activity in human cervical carcinoma cells through a decrease in cell cycle protein Cyclin D1 and thus cell cycle suppression. Furthermore, beta-elemene may enhance the effects of chemotherapy and radiation. In non-small cell lung cancer cells, apoptosis was induced by increased expression of Bax and p-Bcl-2, decreased Bcl-2 and XIAP, and augmented cisplatin-induced increases in caspase activity. In another study, apoptosis response to the taxanes paclitaxel and docetaxel in lung carcinoma cells was enhanced with beta-elemene, through increases in cytochrome c, caspase activity, downregulation of Bcl-2, and altered cell membrane permeability. Beta-elemene combined with radiation induced apoptosis in lung adenocarcinoma cells, possibly by sensitizing cancer cells to radiation.

An in vivo study showed that beta-elemene inhibits growth of lung cancer cells, and up-regulates the expression of the tumor suppressor, P53, and the release of exosome . Another proposed mechanism is that beta-elemene reverses the resistance of lung cancer cells to cisplatin via the mitochondrial apoptosis pathway.  Source

Herb/Drug Interactions

• Chemotherapy: Beta-elemene may increase the activity of cisplatin and taxanes
• Radiation: Beta-elemene may increase the effects of radiation

Articles/Studies

β-elemene regulates endoplasmic reticulum stress to induce the apoptosis of NSCLC cells through PERK/IRE1α/ATF6 pathway

Anti-fibrotic

ANG II-AT1 receptor pathway is involved in the anti-fibrotic effect of beta-elemene. 

Cancer

• The antitumor efficacy of β-elemene by changing tumor inflammatory environment and tumor microenvironment
• The pharmacokinetics of a novel anti-tumor agent, beta-elemene, in Sprague-Dawley rats
• Assessing the quality of RCTs on the effect of beta-elemene, one ingredient of a Chinese herb, against malignant tumors. 
• The synthesis and anti-proliferative effects of beta-elemene derivatives with mTOR inhibition activity. 
• Synthesis and in vitro anti-proliferative activity of beta-elemene monosubstituted derivatives in HeLa cells mediated through arrest of cell cycle at the G1 phase. 
• The pharmacokinetics of a novel anti-tumor agent, beta-elemene, in Sprague-Dawley rats. 
• β-Elemene induces apoptosis and autophagy in **colorectal cancer** cells through regulating the ROS/AMPK/mTOR pathway.
• β-elemene suppresses the malignant behavior of **esophageal cancer** cells by regulating the phosphorylation of AKT.
• β-elemene suppresses migration of **esophageal squamous cell** carcinoma.
• β-Elemene inhibits the metastasis of **multidrug-resistant gastric cancer** cells through miR-1323/Cbl-b/EGFR pathway.
• β-elemene combined with temozolomide in treatment of brain **glioma**.
• Beta-elemene inhibits proliferation of human **glioblastoma** cells through the activation of glia maturation factor â and induces sensitization to cisplatin.
• Anti-tumor effect of beta-elemene in **glioblastoma** cells depends on p38 MAPK activation. 
• Beta-elemene may be used as a potential drug in combination with the radiotherapy and chemotherapy of **glioblastoma multiforme.**
• Beta-Elemene piperazine derivatives induce apoptosis in human **leukemia** cells through downregulation of c-FLIP and generation of ROS. *PLoS One.*
• Systematic review of β-elemene injection as adjunctive treatment for **lung cancer**. 
• Elemene for the treatment of **lung cancer**.
• FBP1 induced by β-elemene enhances the sensitivity of **gefitinib in lung cancer**.
• β-elemene restrains PTEN mRNA degradation to restrain the growth of **lung cancer** cells.
• In vitro combination characterization of the new anticancer plant drug beta-elemene with taxanes against human **lung carcinoma**. 
• Elemene induces cell apoptosis via inhibiting glutathione synthesis in **lung adenocarcinoma**.
• Antitumor effect of beta-elemene in **non-small-cell lung cancer** cells is mediated via induction of cell cycle arrest and apoptotic cell death. 
• beta-Elemene, a novel plant-derived antineoplastic agent, increases cisplatin chemosensitivity of **lung tumor cells** by triggering apoptosis. 
• Beta-elemene inhibits **melanoma** growth and metastasis via suppressing vascular endothelial growth factor-mediated angiogenesis. 
• Effects of arsenic trioxide, ginseng saponin and beta-elemene on telomere-telomerase system in K562 cell line].  (myelogenous leukemia cell line)
• Antiproliferative effect of beta-elemene in chemoresistant **ovarian carcinoma** cells is mediated through arrest of the cell cycle at the G2-M phase.
• Antineoplastic effect of beta-elemene on **prostate cancer** cells and other types of solid tumour cells. 
• Evaluation of Cisplatin in Combination with beta-Elemene as a Regimen for **Prostate Cancer** Chemotherapy. 

Pain

β-elemene relieves neuropathic pain in mice through the regulation on C-X-C motif chemokine receptor 3 and GABAA receptor.

From Duke's DAtabase

Biological ActivityAnticancer

Plants with the Highest Levels: