curcumin and elemene

Over the past decades curcuminoids have been extensively studied for their biological activities such as antiulcer, antifibrotic, antiviral, antibacterial, antiprotozoal, antimutagenic, antifertility, antidiabetic, anticoagulant, antivenom, antioxidant, antihypotensive, antihypocholesteremic, and anticancer activities. With the perception of limited toxicity and cost, these compounds forms an integral part of cancer research and is well established as a potential anticancer agent. However, only few studies have focused on the other bioactive molecules of turmeric, known as non-curcuminoids, which are also equally potent as curcuminoids. This review aims to explore the comprehensive potency including the identification, physicochemical properties, and anticancer mechanism inclusive of molecular docking studies of non-curcuminoids such as turmerones, elemene, furanodiene (FN), bisacurone, germacrone, calebin A (CA), curdione, and cyclocurcumin. An insight into the clinical studies of these curcumin-free compounds are also discussed which provides ample evidence that favors the therapeutic potential of these compounds. Like curcuminoids, limited solubility and bioavailability are the most fragile domain, which circumscribe further applications of these compounds. Thus, this review credits the encapsulation of non-curcuminoid components in diverse drug delivery systems such as co-crystals, solid lipid nanoparticles, liposomes, microspheres, polar-non-polar sandwich (PNS) technology, which help abolish their shortcomings and flaunt their ostentatious benefits as anticancer activities.

Topics: Antineoplastic Agents; Curcuma; Drug Carriers; Furans; Heterocyclic Compounds, 2-Ring; Microspheres; Nanoparticles; Neoplasms; Sesquiterpenes

Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Clinical Trials as Topic; Curcuma; Curcumin; Cyclohexanols; Disease Models, Animal; Furans; Heterocyclic Compounds, 2-Ring; Humans; Hypoglycemic Agents; Inflammation; Neoplasms; Sesquiterpenes; Sesquiterpenes, Germacrane

Resistance to anticancer drugs is a major problem in oncology, which causes the failure of antitumor treatment. A variety of factors contribute to drug resistance, including drug efflux and metabolism, tumor cell heterogeneity, tumor microenvironment stress-induced genetic or epigenetic alterations in the cancer cells and so on. However, how to circumvent this resistance to improve anticancer efficacy remains to be determined. To circumvent chemotherapeutic resistance, many reversal agents have been developed, but most of them fail in clinical trials due to severe adverse effects. Recently, several natural products have been reported to augment sensitivity or overcome resistance of anticancer chemotherapeutic drugs, including elemene, curcumin, Shenqi Fuzheng Injection (), PHY906, etc. Thus, understanding the novel function of Chinese medicine may allow us to develop a promising therapeutic approach to enhance the effects of anticancer strategies and prevent or overcome their resistance in the treatment of cancer patients.

Topics: Antineoplastic Agents; Curcumin; Drug Resistance, Neoplasm; Drugs, Chinese Herbal; Humans; Sesquiterpenes

Zedoary turmeric oil (ZTO), the steam extract of Curcuma zedoaria Rosc was researched for its chemical composition, antibacterial activity, and mechanism for countering two major food-borne pathogenic species, Listeria monocytogenes and Staphylococcus aureus.. Gas chromatography-mass spectrometry (GC-MS) was used to analyse and characterize the chemical composition of ZTO. Its MICs for the two bacterial species and growth curves were measured. Western blot and real-time reverse-transcription (RT)-PCR assays were utilized to elaborate the mechanism of the antibacterial effect of ZTO by examining the expression levels of virulence-related extracellular proteins. ELISA was used to explore the biological relevance.. Overall, L. monocytogenes and S. aureus were comparably susceptible to ZTO. These data demonstrated that ZTO's antimicrobial property was mediated by the repression of the production of virulence factors involved in L. monocytogenes and S. aureus pathogenesis, a finding that can potentially further progress in the development of new anti-virulence drugs.

Topics: Animals; Anti-Bacterial Agents; Curcuma; Exotoxins; Listeria monocytogenes; Mice; Microbial Sensitivity Tests; Oils, Volatile; Plant Extracts; Plant Oils; RAW 264.7 Cells; Sesquiterpenes; Sesquiterpenes, Germacrane; Staphylococcus aureus; Steam

To explore the effects of Elemene, the essential oil of Curcuma wenyujin, on Bone morphogenetic protein/drosophila mothers against decapentaplegic proteins (BMP/SMADs) signal pathway in ankylosing spondylitis (AS) fibroblasts.. Hip joint capsules were obtained from AS patients (n=10) receiving total hip replacement. Healthy hip joint capsules from patients with hip fracture (n=10) receiving surgery were included as a control. Primary fibroblast cell lines were established from these tissue samples. Fibroblasts were incubated with Elemene for 48 hours. The protein expression was detected by Western blot. The mRNA expression was detected by real-time fluorescent quantitative polymerase chain reaction (PCR).. The results showed that the expression of proteins including SMAD1, pSMAD1, SMAD4 and Runt-related transcription factor 2 (RUNX2), and mRNA of RUNX2, which were over-expressed in AS fibroblasts were decreased in the AS fibroblasts cultured in medium with Elemene.. Ele could have a hand in anti-osteogenic differentiation of AS fibroblasts by inhibiting the BMP/SMADs signal pathway and subsequently blocking expression of ossification marker genes RUNX2 that initiate the osteogenic differentiation.

Topics: Adult; Arthroplasty, Replacement, Hip; Bone Morphogenetic Proteins; Cell Differentiation; Cell Line; Core Binding Factor alpha Subunits; Curcuma; Fibroblasts; Hip Joint; Humans; Joint Capsule; Male; Middle Aged; Ossification, Heterotopic; Osteoblasts; Plant Oils; Sesquiterpenes; Signal Transduction; Smad Proteins; Spondylitis, Ankylosing; Young Adult

To investigate the effect of elemene on reversing chemoresistance to adriamycin (ADM) in human stomach cancer cell, and explore its possible mechanism.. SGC7901/ADM were divided imto two groups: control group and elemene treatment group. The cytotoxicity of ADM on SGC7901/ADM was determined by MTT assay. The activity of nuclear factor-kappa B (NF-kappaB) was measured by immunohistochemical staining. The apoptosis rate of stomach cancer cell line was determined by flow cyotometric analysis.. The immunohistochemical staining result showed that the activity of NF-kappaB in SGC7901/ADM was increased after treated with ADM for 9 - 12 h, while that of the elemene treatment group decreased with the increasing of the elemene concentration and the lowest level was 8 - 12%. The apoptosis rate of SGC7901/ADM stomach cancer cell line was increased with the increasing of elemene concentration. At the same elemene concentration, the apoptosis rate increased with ADM treatment time prolonged. MTT result showed that the non-cytotoxic dose of elemene had synergistic effect on rilling SGC7901/ADM stomach cancer cell line and was in a dose-dependant manner.. The inhibitory effect of elemene on reversing chemoresistance to ADM in human stomach cancer cell line maybe related to inhibiting NF-kappaB activity.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Curcuma; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance, Neoplasm; Flow Cytometry; Humans; Immunohistochemistry; NF-kappa B; Sesquiterpenes; Stomach Neoplasms

δ-Elemene, an antitumor component, is a chemical compound isolated from Curcuma wenyujin, a Chinese traditional herb. We examined whether δ-elemene could affect apoptosis in human lung carcinoma mucoepidermoid NCI-H292 cells, and test whether and how the over-expression of B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma extra large (Bcl-xL) could off-set the effect of δ-elemene on cell growth. The result demonstrated that δ-elemene significantly induced apoptosis of NCI-H292, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, DNA fragmentation measurement, Annexin V (AnV) binding of externalized phosphatidylserine and the mitochondrial probe JC-1 using flow cytometry. Treatment of NCI-H292 with δ-elemene increased both p38 mitogen-activated protein kinase (MAPK) and inducible nitric oxide synthese (iNOS) levels, suggesting these two molecules maybe relate to the apoptotic effect of δ-elemene. The cells with Bcl-2 or Bcl-xL over-expression showed an elevation of nuclear factor kappa B (NF-kappa B) activity, accompanying a significant reduction of δ-elemene-induced apoptosis. Furthermore, inhibition of NF-kappa B by IkBαSR, which is a powerful inhibitor of NF-kappa B, restored the ability of δ-elemene to induce apoptosis in the cells transfected with Bcl-2. These data strongly indicated that the apoptotic effect of δ-elemene on NCI-H292 was closely associated with the activity of NF-kappa B, which was up-regulated by Bcl-2 and Bcl-xL. In conclusion, δ-elemene induced apoptosis in NCI-H292 cells. The apoptotic effect of δ-elemene could be significantly offset by over-expression of either Bcl-2 or Bcl-xL. Bcl-2 and Bcl-xL were able to increase the activity of NF-kappa B, which was a known anti-apoptotic molecule in human lung cancer cells.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; bcl-X Protein; Carcinoma, Mucoepidermoid; Cell Line, Tumor; Curcuma; DNA Fragmentation; Drugs, Chinese Herbal; Flow Cytometry; Humans; Lung Neoplasms; NF-kappa B; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Phytotherapy; Proto-Oncogene Proteins c-bcl-2; Sesquiterpenes; Signal Transduction

  δ-Elemene, an antitumor component, is a chemical compound isolated from Curcuma wenyujin, a Chinese traditional herb. We examined whether δ-elemene could inhibit cell growth and cell cycle progression and induce apoptosis in human leukemia HL-60 cells. The results demonstrated that δ-elemene induces significant apoptosis of HL-60 cells, as shown by MTT assay, annexin V (AnV) binding of externalized phosphatidylserine (PS), and the mitochondrial probe JC-1 using flow cytometry. HL-60 cells treated with δ-elemene showed high percentages in the early apoptotic and late apoptoctic/necrotic stages, as well as caspase-3 activation of HL-60 cells. By monitoring the changes in cell cycle profiles, we confirmed that δ-elemene could interfere with the cell cycle in the G2/M phase and induce apoptosis in HL-60 cells in a time-dependent manner. Caspase-3 plays a direct role in proteolytic cleavage of the cellular proteins responsible for progression to apoptosis. Therefore we examined apoptosis in HL-60 cells after exposure to δ-elemene and measured caspase-3 activities with or without Z-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk, a broad-spectrum caspase inhibitor) pretreatment using flow cytometric analysis. The results showed that δ-elemene could induce caspase-3 activation as detected by the decrease in δ-elemene-induced caspase-3 activities after treatment with z-VAD-fmk. In the present study, δ-elemene activated typical caspase-dependent apoptosis in HL-60 cells, as demonstrated by an inhibitory effect of z-VAD-fmk on this cell death. During δ-elemene-induced apoptosis, cytochrome c and apoptosis-inducing factor were released into the cytosol and BAX was translocated from the cytosol to mitochondria. However, these were not prevented by z-VAD-fmk. In conclusion, our study demonstrated that δ-elemene could induce G2/M cell cycle transition and trigger apoptosis through a caspase-3-dependent pathway.

Topics: Amino Acid Chloromethyl Ketones; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cell Division; Cell Line, Tumor; Curcuma; Cytochromes c; Cytosol; Dose-Response Relationship, Drug; G2 Phase; HL-60 Cells; Humans; Membrane Potential, Mitochondrial; Mitochondria; Sesquiterpenes; Time Factors

The chemical compound delta-elemene, isolated from the Chinese herbal medicine plant Curcuma Wenyujin, has been known to exert antitumor activity. In this study we demonstrated that apoptotic cell death induced by delta-elemene in DLD-1 cells was concentration-and time-dependent, and had little inhibition of the normal human liver cell line WRL-68. Apoptosis was further confirmed and quantified by DNA fragmentation ELISA, Annexin V (AnV) binding of externalized phosphatidylserine and the mitochondrial probe JC-1 using flow cytometry. The rapid increase in intracellular reactive oxygen species (ROS) levels was involved in the mechanism of cell death. Western blot analysis demonstrated that delta-elemene activated the caspase-signaling pathway, leading to the proteolysis conversion of pro-caspase-3 to activate caspase-3, and the subsequent cleavage of the caspase substrate PARP. In the process of the induction of apoptotic cell death, Bax translocated into mitochondria, a reduction in Deltapsim was observed and a release of cytochrome c and apoptosis inducing factor (AIF) from mitochondria into the cytosol occurred, indicating that cell death induced by delta-elemene was through a mitochondrial-mediated pathway.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Apoptosis; Caspase 3; Cell Line, Tumor; Colorectal Neoplasms; Curcuma; Dose-Response Relationship, Drug; Humans; Mitochondria; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species; Sesquiterpenes; Time Factors

Elemene is a chemical extracted from plants. It has demonstrated anti-tumour capability. Although widely studied, there has been little reported regarding its tissue distribution. Our aim was to rectify this.. The tissue distribution of elemene was studied after intragastric or intravenous administration in rats. The effectiveness of elemene in treating brain tumours was studied using the G-422 tumour cell model in mice.. Elemene had a higher concentration in the lungs, spleen and livers than other tissues of normal rats after intragastric and intravenous administration, while the concentration in the gastrointestinal tract was greater after intragastric administration. Elemene molecules were also detected in the rats' brain tissue. Elemene had a therapeutic effect on mice inoculated with G-422 cells both intracranially and subcutaneously. The best life-extending rate and the best tumour-inhibiting rate of elemene were 64.43% and 34.46%, respectively, when 80 mg/kg elemene was used for treatment.. The results from the tissue distribution study showed that elemene can pass through the blood-brain barrier. The therapeutic experiments showed that elemene is effective in treating cerebral malignancy.

Topics: Animals; Antineoplastic Agents, Phytogenic; Blood-Brain Barrier; Brain; Brain Neoplasms; Carcinoma; Cell Line, Tumor; Curcuma; Gastrointestinal Tract; Humans; Liver; Lung; Mice; Mice, Nude; Models, Animal; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Sesquiterpenes; Spleen; Tissue Distribution; Xenograft Model Antitumor Assays

In this paper, GC-MS and pressurized liquid extraction (PLE) was developed for identification and quantitative determination/estimation 11 sesquiterpenes including germacrene D, curzerene, gamma-elemene, furanodienone, curcumol, isocurcumenol, furanodiene, germacrone, curdione, curcumenol and neocurdione in Ezhu which are derived from three species of Curcuma, i.e., Curcuma phaeocaulis, Curcuma wenyujin and Curcuma kwangsiensis by using an analogue as standard. The results showed the methodology could quantitatively compare the quality of three species of Curcuma. The contents of investigated sesquiterpenes in three species of Curcuma were high variant. Hierarchical clustering analysis based on characteristics of 11 identified peaks in GC profiles showed that 18 samples were divided into two main clusters, C. phaeocaulis and C. wenyujin, respectively. C. kwangsiensis showed the characters closed to C. phaeocaulis or C. wenyujin based on its location. Five components such as furanodienone, germacrone, curdione, curcumenol and neocurdione were optimized as markers for quality control of Ezhu.

Topics: Chemistry, Pharmaceutical; Chromatography; Chromatography, Ion Exchange; Chromatography, Liquid; Curcuma; Drug Industry; Furans; Gas Chromatography-Mass Spectrometry; Heterocyclic Compounds, 2-Ring; Magnetic Resonance Spectroscopy; Models, Chemical; Phylogeny; Quality Control; Sesquiterpenes; Sesquiterpenes, Germacrane