curcumin and germacrone

Germacrone, a kind of natural sesquiterpenoid compound, has been reported to exhibit many pharmacological properties, especially the anticancer effect. Many

Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Proliferation; Curcuma; Humans

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

Topics: Animals; Curcumin; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Humans; Microsomes, Liver; Rats; Sesquiterpenes, Germacrane; Tandem Mass Spectrometry

Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown.. Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay.. GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65.. GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.

Topics: Animals; Brain; Brain Edema; Brain Injuries, Traumatic; Curcuma; Cytokines; Disease Models, Animal; Drug Evaluation, Preclinical; Male; Memory; Mice, Inbred C57BL; Microglia; Nervous System Diseases; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Phytotherapy; Plant Extracts; Recovery of Function; Sesquiterpenes, Germacrane; Spatial Learning

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

Topics: Curcuma; Glucose; Hep G2 Cells; Humans; Molecular Structure; Plant Tubers; Polycyclic Sesquiterpenes; Sesquiterpenes; Sesquiterpenes, Germacrane; Terpenes

The essential oil extracted from rhizome and leaf of Curcuma angustifolia Roxb. (Zingiberaceae) was characterised by gas chromatography-mass spectrometry (GC-MS). The GC-MS analysis revealed the presence of 32 and 35 identified constituents, comprising 92.6% and 92% of total leaf and rhizome oil, respectively. Curzerenone (33.2%), 14-hydroxy-δ-cadinene (18.6%) and γ-eudesmol acetate (7.3%) were the main components in leaf oil. In rhizome oil, curzerenone (72.6%), camphor (3.3%) and germacrone (3.3%) were found to be the major constituents. Antioxidant capacities of oil were assessed by various methods, 2, 2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and reducing power ability (RPA). Based on the results, the leaf oil showed more antioxidant potential as compared to rhizome oil and reference standards (ascorbic acid and butylated hydroxytoluene (BHT)). Thus, the leaf essential oil of C. angustifolia can be used as an alternative source of natural antioxidant.

Topics: Antioxidants; Curcuma; Gas Chromatography-Mass Spectrometry; Oils, Volatile; Plant Leaves; Polycyclic Sesquiterpenes; Rhizome; Sesquiterpenes; Sesquiterpenes, Eudesmane; Sesquiterpenes, Germacrane

Germacrone is one of the major bioactive components in the Curcuma zedoaria oil product, which is extracted from Curcuma zedoaria Roscoe, known as zedoary. The present study designed some novel germacrone derivatives based on combination principles, synthesized these compounds, and investigated their inhibitions on Bel-7402, HepG2, A549 and HeLa cells. Meanwhile, the study evaluated inhibitions of these derivatives on c-Met kinase, which has been detected in a number of cancers. The results suggested that the majority of the compounds showed stronger inhibitory effect on cancers and c-Met kinase than germacrone. Furthermore, our docking experiments analyzed the results and explained the molecular mechanism. Molecular dynamics simulations were then applied to perform further evaluation of the binding stabilities between compounds and their receptors.

Topics: A549 Cells; Antineoplastic Agents; Apoptosis; Cell Proliferation; Curcuma; HeLa Cells; Hep G2 Cells; Humans; Molecular Docking Simulation; Molecular Dynamics Simulation; Neoplasms; Plant Extracts; Proto-Oncogene Proteins c-met; Sesquiterpenes, Germacrane

Anti-androgenic drugs are treatments for androgen-related disorders such as benign prostatic hyperplasia, acne, hirsutism, and androgenic alopecia. Germacrone (1), a sesquiterpene isolated from hexane extracts of Curcuma aeruginosa Roxb. rhizome, is an androgen inhibitor of steroid 5-alpha reductase in- vitro. Here, we used the similarity of germacrone's ,t,B-unsaturated carbonyl to testosterone's α,β-unsaturated carbonyl to find germacrene analogs obtained from this plant and by semi-synthesis that might be more potent steroid 5-alpha reductase inhibitors. 8-Hydroxy germacrene B (4) was -13-fold more potent than its parent, I and the most potent (ICso, 0.15 ± 0.022 mM) among 9 compounds tested. The conformation of its cyclodecadiene ring and the α,β-unsaturated ketone/hydroxy in the germacrene molecule might be crucial role for its anti-androgen activity. Moreover, I and 4 showed mild cytotoxic effect on prostate cancer cells. Neither compound was cytotoxic towards human dermal papilla cells at 100 μg/mL. We show that this SAR strategy created promising anti-androgenics for androgen dependent disorders and may create further analogues with further improvements in selectivity and clinical efficacy.

Topics: 5-alpha Reductase Inhibitors; Androgen Antagonists; Cell Line, Tumor; Curcuma; Humans; Male; Molecular Structure; Prostatic Neoplasms; Rhizome; Sesquiterpenes, Germacrane; Testosterone

A simple, rapid and sensitive method was developed for the simultaneous quantification of curdione, furanodiene and germacrone in rabbit plasma using a LC-MS/MS analysis. The plasma sample preparation was a simple deproteinization by the addition of 3 vols of acetonitrile followed by centrifugation. The analytes and internal standard (IS) costunolide were separated on a Zorbax SB-C18 column (3.5 µm, 2.1 × 100 mm) with mobile phase of methanol-water (90:10, v/v) containing 0.1% formic acid at a flow rate of 0.3 mL/min with an operating temperature of 25°C. Detection was carried out by atmospheric pressure chemical ionization in positive ion selected reaction monitoring mode. Linear detection responses were obtained for the three test compounds ranging from 5 to 5000 ng/mL and the lower limits of quantitation were 5-10 ng/mL. The intra- and inter-day precisions (relative standard deviations) were within 9.4% for all analytes, while the deviation of assay accuracies was within ±10.0%. The average recoveries of analytes were >80.0%. All analytes were proved to be stable during all sample storage, preparation and analytical procedures. The method was successfully applied to the pharmacokinetic study of the three compounds after vaginal drug delivery of Baofukang suppository to rabbit.

Topics: Animals; Chromatography, High Pressure Liquid; Curcuma; Drugs, Chinese Herbal; Furans; Heterocyclic Compounds, 2-Ring; Rabbits; Sesquiterpenes, Germacrane; Tandem Mass Spectrometry

This study aims to develop a method for determination of beta-elemene, curcumol, germacrone and neocurdione in the volatile oil of Curcuma phaeocaulis, and to provide the basis of the quality control method for the volatile oil of C. phaeocaulis and the related preparations. Based on GC-MS, the 4 main compounds were simultaneously determined, with the internal standard n-tridecane. The Agilent 19091S-433 column (0.25 microm x 250 microm x 30 m) was adopted at the temperature of 250 degrees C, the programmed temperature method (60 degrees C for 1 min, 5 degrees C x min x to 110 degrees C for 5 min, 1 degrees C x min(-1) to 140 degrees C, 5 degrees C x min(-1) to 160 degrees C, 10 degrees C x min(-1) to 240 degrees C) was used. Helium gas was used as the carrier gas at a constant flow rat of 1 mL x min(-1), with an injection volume of 1 RL. Mass spectra were taken at 70 eV; the ion-source temperature was 200 degrees C. The relation time and character acteristic ions for each target compound were determined by full scan mode and SIM, and m/z 85.1, 93.1, 121.1, 107.1 and 180.1 were the detection ions of n-tridecane, beta-elemene, curcumol, germacrone and neocurdione. As a result, beta-elemene, curcumol, germacrone and neocurdione were all detected with good separation. They were all in a good linear relationship within each concentration scope. The average recovery rates were in the range of 98.2%-101%. So, the method can be used to control the quality of the volatile of C. phaeocaulis Val. and the preparations related.

Topics: Acetic Acid; Curcuma; Drugs, Chinese Herbal; Gas Chromatography-Mass Spectrometry; Oils, Volatile; Plant Oils; Sesquiterpenes; Sesquiterpenes, Germacrane

Simple gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) methods were developed for quantifying eight volatile compounds and 10 sesquiterpenoids, respectively. GC-MS analysis was performed on an HP-5MS capillary column (30 m×0.25 mm i.d.) coated with 0.25 μm film 5% phenyl-95% methylpolysiloxane and selected ion monitoring was used for quantification. Four volatile and previously unquantified monoterpenoids were determined. HPLC analysis was performed on a C18 column with water and acetonitrile as mobile phase. The proposed method, determined 10 non-polar and polar sesquiterpenoids simultaneously, which covered a wider polar range of analytes and had a more perfect resolution. Among them, five sesquiterpenoids were not determined before and some specific components, (4S,5S)-germacrone-4,5-epoxide, curcumenone and dehydrocurdione were completely separated for the first time. Both methods were validated for linearity, limit of detection and quantification, precision, accuracy, recovery and system suitability. The methods were simple, effective, reliable and successfully applied to global detection and analysis of volatile and non-volatile components of steamed and non-steamed rhizomes of Curcuma wenyujin (Wen-E-Zhu (WEZ) and Pian-Jiang-Huang (PJH)). Multivariate statistical analysis was employed to distinguish PJH and WEZ and seven chemical components, including (4S,5S)-germacrone-4,5-epoxide, curcumenone, β-elemene, curzerene, borneol, isoborneol and camphor, were screened as chemical markers. The present study provided a promising method for accurate discrimination of the herbal medicines with the same origin.

Topics: Chromatography, High Pressure Liquid; Curcuma; Drugs, Chinese Herbal; Gas Chromatography-Mass Spectrometry; Multivariate Analysis; Plant Extracts; Principal Component Analysis; Quality Control; Reproducibility of Results; Rhizome; Sesquiterpenes; Sesquiterpenes, Germacrane; Steam

Germacrone is one of the major bioactive components of the traditional Chinese Medicinal plant Curcuma aromatica Salisb. and has been shown to possess anti‑tumor properties. In the present study, the anti‑proliferative effect of germacrone on human glioma cells and the molecular mechanism underlying its cytotoxicity were investigated. Treatment of the U87 and U251 human glioma cell lines with germacrone inhibited the cell proliferation in a dose‑ and time‑dependent manner as assessed by MTT assay, while significantly lower effects were observed on normal human astrocytes. Flow cytometric analysis and DNA fragmentation revealed that germacrone promoted apoptosis of glioma cells, associated with an increased expression of p53 and bax and decreased expression of bcl‑2. Furthermore, flow cytometric cell cycle analysis revealed that germacrone induced G1 phase arrest, associated with an obvious decrease in the expression of cyclin D1 and CDK2 and an increased expression of p21. In conclusion, the present study suggested that germacrone may be a novel potent chemopreventive drug candidate for gliomas via regulating the expression of proteins associated with apoptosis and G1 cell cycle arrest.

Topics: Apoptosis; bcl-2-Associated X Protein; Cell Line, Tumor; Cell Proliferation; Curcuma; Cyclin D1; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase Inhibitor p21; DNA Fragmentation; G1 Phase Cell Cycle Checkpoints; Glioma; Humans; Proto-Oncogene Proteins c-bcl-2; Sesquiterpenes, Germacrane; Tumor Suppressor Protein p53

Curcuma aeruginosa Roxb. extract is a 5α-reductase antagonist that can be used to treat hair loss. We aimed to study the stability of antiandrogenic constituents, germacrone and other sesquiterpene components in the extract.. Germacrone and the extract were analyzed as solid forms or solublized with polyethylene glycol-40 (PEG-40) or methanol using high-performance liquid chromatography and gas chromatography with flame ionization detector. The effects of pH, temperature and light on their stability were studied.. Degradation of antiandrogenic compounds in C. aeruginosa was highly sensitive to temperature especially pure anhydrous germacrone, which was completely lost within 3 days at 45°C. Curiously, degradation was slower than as a dried extract. Paradoxically, when solubilized with PEG-40, it was largely intact even after 90 days at 45°C. The MS spectrum of a major degradation product suggested that it was elemenone probably produced by Cope rearrangement. Two other putative degradation products were germacrone-1,10-epoxide and germacrone-4,5-epoxide suggesting that oxidation of double bonds was an important mechanism. Germacrone stability was unaffected by pH (2.0-9.0) but only as dried extract it was slightly degraded by light.. Antiandrogenic constituents of C. aeruginosa were instable at high temperature and in solid form. Thus, the extract would be optimately stored as a solution or otherwise as solid form at low temperature.

Topics: Androgens; Chromatography, High Pressure Liquid; Curcuma; Drug Stability; Hot Temperature; Plant Extracts; Polyethylene Glycols; Sesquiterpenes; Sesquiterpenes, Germacrane; Solubility

Curcuma purpurascens Bl., belonging to the Zingiberaceae family, is known as temu tis in Yogyakarta, Indonesia. In this study, the hydrodistilled dried ground rhizome oil was investigated for its chemical content and antiproliferative activity against selected human carcinoma cell lines (MCF7, Ca Ski, A549, HT29, and HCT116) and a normal human lung fibroblast cell line (MRC5). Results from GC-MS and GC-FID analysis of the rhizome oil of temu tis showed turmerone as the major component, followed by germacrone, ar-turmerone, germacrene-B, and curlone. The rhizome oil of temu tis exhibited strong cytotoxicity against HT29 cells (IC50 value of 4.9 ± 0.4 μg/mL), weak cytotoxicity against A549, Ca Ski, and HCT116 cells (with IC50 values of 46.3 ± 0.7, 32.5 ± 1.1, and 35.0 ± 0.3 μg/mL, resp.), and no inhibitory effect against MCF7 cells. It exhibited mild cytotoxicity against a noncancerous human lung fibroblast cell line (MRC5), with an IC50 value of 25.2 ± 2.7 μg/mL. This is the first report on the chemical composition of this rhizome's oil and its selective antiproliferative effect on HT29. The obtained data provided a basis for further investigation of the mode of cell death.

Topics: Cell Proliferation; Curcuma; Cytostatic Agents; HCT116 Cells; HT29 Cells; Humans; MCF-7 Cells; Oils, Volatile; Plant Extracts; Rhizome; Sesquiterpenes, Germacrane

Germacrone is one of the main bioactive components in the traditional Chinese medicine Rhizoma curcuma and has been shown to possess an anti-inflammatory activity. Our present study aimed to investigate the protective effects of germacrone on lipopolysaccharide (LPS)-induced acute lung injury in neonatal rats. Results showed that germacrone treatment significantly decreased the expression of pro-inflammatory cytokines IL-6 and TNF-α. Meanwhile, the expression of anti-inflammatory mediators TGF-β1 and IL-10 was obviously increased following germacrone administration. The LPS-induced pathological changes in neonatal rats were also attenuated by germacrone treatment. In vitro, MTT and EdU incorporation assay indicated that germacrone administration significantly increased the A549 cell viabilities in a dose-dependent manner. Besides, flow cytometry and TUNEL analysis showed that the cell apoptosis rate was significantly reduced in a concentration-dependent manner after germacrone injection. At the molecular level, we found that germacrone treatment promoted the expression of claudin-4 both in vivo and in vitro as shown by real time PCR and western blot. Collectively, our study demonstrated that germacrone protected neonatal rats against LPS-induced ALI partially by modulation of claudin-4.

Topics: Acute Lung Injury; Animals; Animals, Newborn; Anti-Inflammatory Agents; Apoptosis; Cell Line; Claudin-4; Curcuma; Humans; Interleukin-10; Interleukin-6; Lipopolysaccharides; Lung; Rats; Rats, Wistar; RNA, Messenger; Sesquiterpenes, Germacrane; Tumor Necrosis Factor-alpha; Up-Regulation

To study zedoary turmeric oil (ZTO) and the pharmacokinetics of its homemade compound antiviral preparation in New Zealand rabbits.. RP-HPLC was used to determinate the content of germacrone in rabbit plasma after oral administration.. After oral administration of ZTO and its homemade compound antiviral preparation, the plasma concentration-time curve of germacrone is in conformity to two-compartment open model. The pharmacokinetic parameters of ZTO: t1/2alpha, t1/2beta, Vd, CL, AUC and Ka were (1.52 +/- 0.59), (1.97 +/- 0.27) h, (47.59 +/- 2.29) L x kg(-1), (176.77 +/- 7.65) L x h(-1) x kg(-1), (5.70 +/- 0.70) mg x h x L(-1) and (0.97 +/- 0.11) h(-1), respectively, while those of compound preparation were (0.41 +/- 0.03), (1.47 +/- 0.35) h, (75.21 +/- 5.21) L x kg(-1), (287.79 +/- 6.39) L x h(-1) x kg(-1), (3.91 +/- 0.53) mg x h x L(-1) and (5.14 +/- 1.26) h(-1), respectively. There was no significant difference between the above two groups of pharmacokinetic parameters, expect that Ka of compound preparation was significantly higher than that of ZTO (P < 0.05).. Hypericum perforatum in compound preparation doesn't impact the distribution and elimination of active ingredients of ZTO in New Zealand rabbits, but it improves the absorption speed, and shortens the time of drug absorption, which contributes to rapid efficacy of ZTO in rabbits.

Topics: Animals; Antiviral Agents; Curcuma; Drug Compounding; Drug Interactions; Drugs, Chinese Herbal; Hypericum; Male; Plant Oils; Rabbits; Sesquiterpenes, Germacrane

Misclassification of Curcuma species (family Zingiberaceae) may lead to unwanted human exposure to Curcuma elata sesquiterpenes zederone and germacrone which have caused hepatotoxicity and changes in CYP expression in laboratory animals. We investigated how these compounds interact with the human cytochrome P450 (CYP) system, in order to evaluate their potential for human liver toxicity and herb-drug interactions. We found that both sesquiterpenes (1-30 μM) greatly induced expression of CYP2B6 and CYP3A4 but not CYP1A2 mRNAs in human primary hepatocytes (HPHs). This induction profile correlated with activation of constitutive androstane and pregnane X receptors. Cytotoxicity was also observed in exposed HPHs. CYP inhibition studies with pooled human liver microsomes (HLMs) indicated that zederone and germacrone moderately inhibited CYP2B6 and CYP3A4 activities in vitro, with IC50 values below 10 μM. When zederone was incubated with HLMs and NADPH, one di-epoxide metabolite was formed and by using glutathione trapping, five epoxide-derived conjugates were detected. Germacrone produced two oxidized metabolites and four glutathione conjugates. The results suggest that enzymes in HLMs convert sesquiterpenes into reactive, electrophilic compounds which may be causative for the reported liver injuries. These findings provide insight on the safety and drug-herb interactions of the Curcuma species.

Topics: Animals; Cell Line, Tumor; Cell Survival; Cells, Cultured; Constitutive Androstane Receptor; Curcuma; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Hepatocytes; Herb-Drug Interactions; Humans; Mice; Microsomes, Liver; Pregnane X Receptor; Receptors, Aryl Hydrocarbon; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; Recombinant Proteins; RNA, Messenger; Sesquiterpenes; Sesquiterpenes, Germacrane

Six sesquiterpenes: germacrone (1), zederone (2), dehydrocurdione (3), curcumenol (4), zedoarondiol (5) and isocurcumenol (6) were isolated from rhizomes of Curcuma aeruginosa Roxb. (Zingiberaceae). They inhibited 5α-reductase which converts testosterone to dihydrotestosterone (DHT). Germacrone (1) was the most potent (IC(50)=0.42±0.05 mg/mL). Compound 1 was anti-androgenic in LNCaP cells when proliferation was testosterone-induced. The growth of flank gland of male Syrian hamsters is dependent on circulating androgen and when maintained with testosterone, 1 (3, 30, 100μg) inhibited growth but was ineffective against DHT. The similar activity profile was observed on the 5α-reductase inhibitor, finasteride (100 μg) treatment group. The androgen receptor binding assay showed that 1 did not bind to the androgen receptor. In conclusion, 1 showed anti-androgenic effect on in vitro and in vivo assays. One of the possible mechanisms was inhibition 5α-reductase activity. Thus, 1 is a potential lead compound for treatment of androgen-dependent disorders.

Topics: 5-alpha Reductase Inhibitors; Androgen Antagonists; Animals; Cell Line; Cricetinae; Curcuma; Finasteride; Humans; Inhibitory Concentration 50; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Receptors, Androgen; Rhizome; Sesquiterpenes; Sesquiterpenes, Germacrane; Testosterone

Germacrone (1) and (4S,5S)-germacrone-4,5-epoxide (2) were isolated, along with guaiane and secoguaiane-type sesquiterpenes, from Curcuma aromatica plants. Compound 2 was derived from 1 and cyclized through transannular (T-A) reactions into various guaiane and secoguaiane-type sesquiterpenes in C. aromatica. The cyclization reaction of 2 was initiated by protonation at an epoxide oxygen atom, followed by cleavage of the epoxide ring and the formation of a C-C bond between C-1 and C-5 to give guaiane-type derivatives. Acidic and thermal treatments of 2 produced twelve sesquiterpenes having guaiane and secoguaiane skeletons. The structures of these products were elucidated by spectral methods, including 2D-NMR spectroscopy. Most were identified as sesquiterpenes isolated from C. aromatica as natural products. The T-A cyclization of 2 occurred via two transition states, a cross conformation and a parallel conformation. The mechanism of the T-A cyclization reaction of 2 is discussed.

Topics: Curcuma; Molecular Structure; Sesquiterpenes, Germacrane; Sesquiterpenes, Guaiane

To establish a HPLC method for determination of 4 components in different varieties of vinegar backed Rhizoma Curcuma.. The method was established by using an Elite Hypersil ODS2 column (4.6 mm x 250 mm, 5 microm). The mobile phase comprising acetonitrile (A) and water (B) was used to elute the targets in gradient elution mode. Flow rate and detection wavelength were set at 1 mL x min(-1) and 214 nm, respectively. The column temperature was 25 degrees C and the injection volume was 10 microL.. All calibration curves showed good linearity with r > 0.999 5. Recoveries measured at three concentrations were in the range of 97.27% - 99.27% with RSD < 3%.. The validated method is simple, reliable, and successfully applied to determine the contents of the selected compounds in vinegar backed Rhizoma Curcuma. The results of the determination showed that contents of the four components in vinegar backed Curcuma wenyujin were relatively high.

Topics: China; Chromatography, High Pressure Liquid; Curcuma; Drugs, Chinese Herbal; Rhizome; Sesquiterpenes; Sesquiterpenes, Germacrane

From the dried rhizomes of Curcuma comosa cultivating in Thailand, 26 known sesquiterpenes were isolated: zederone, zederone epoxide, furanodienone, isofuranodienone, 1(10)Z,4Z-furanodiene-6-one, glechomanolide, dehydrocurdione, neocurdione, curdione, 7 alpha-hydroxyneocurdione, 7 beta-hydroxycurdione, germacrone-1(10),4-diepoxide, germacrone, 13-hydroxygermacrone, curzerenone, curcolonol, alismol, alismoxide, zedoarondiol, isozedoarondiol, procurcumenol, isoprocurcumenol, aerugidiol, zedoalactone B, curcumenone, and curcumadione. Their structures were elucidated on the basis of physicochemical evidence. Among them, glechomanolide, curzerenone, curcolonol, alismol, alismoxide, and zedoarondiol showed no significant optical activities, so they may be artifact products during the isolation or drying process.

Topics: Curcuma; Furans; Heterocyclic Compounds, 2-Ring; Plant Extracts; Sesquiterpenes; Sesquiterpenes, Germacrane

To provide the scientific basis for the reasonable development and use of the leaves of Rhizoma Curcumae.. To extract the volatile oil from roots and leaves of three species Rhizoma Curcumae by steam distillation and isolate these products with the method of gas chromatography-mass spectrum. Taking Nist98 standard mass spectrometer database and contrast as control, the structure of the mass spectrogram was identified, and the relative contents of the components were determined with area normalization method.. The anti-tumor active constituents such as curdione and germacrone in the leaves had the greater content than in its rhizome.. The varieties of volatile components in different parts of three species of Rhizoma Curcumae are similar, but their contents are obviously various. We can make the leaves of Rhizoma Curcumae for recycling use.

Topics: Curcuma; Gas Chromatography-Mass Spectrometry; Oils, Volatile; Plant Leaves; Plants, Medicinal; Rhizome; Sesquiterpenes; Sesquiterpenes, Germacrane

Eight transformed sesquiterpenes of germacrone by Mucor alternata were obtained. Their structures were characterized on the basis of spectral methods including 2D NMR. Among them, (1S, 4S, 5S, 10R)-isozedoarondiol (2) and (1R, 4S, 5S, 10R)-diepoxy-12-hydroxygermacrone (3) are new compounds.

Topics: Biotransformation; Curcuma; Drugs, Chinese Herbal; Molecular Conformation; Mucor; Nuclear Magnetic Resonance, Biomolecular; Sesquiterpenes, Germacrane

Volatile components of Curcuma sichuanensis X. X. Chen growing in Sichuan, China, were extracted by steam distillation and analyzed by using gas chromatography and gas chromatography-mass spectrometry. A total of 44 volatile essential oil components were identified in the extract of C. sichuanensis X. X. Chen, representing 87.1% of the total integrated chromatographic peaks. The major compounds were found to be epi-curzerenone (26.9%), germacrone (12.4%), isocurcumenol (9.7%), beta-elemene (6.4%) and curzerene (6.2%). The results of semi-quantitative analysis indicated that levels of total sesquiterpene fraction (85.4%) were more than 55 times higher than those of monoterpene components (1.5%).

Topics: China; Curcuma; Flame Ionization; Gas Chromatography-Mass Spectrometry; Oils, Volatile; Plant Oils; Plant Roots; Sesquiterpenes; Sesquiterpenes, Germacrane; Steam; Volatilization

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

A validated new, simple and highly sensitive reversed-phase HPLC method is developed for studying the pharmacokinetics of germacrone after intravenous administration of zedoary turmeric oil (ZTO) oil-in-water microemulsion. The method did not require a complex and expensive equipment. A high extraction recovery (>80%) of germacrone was obtained. Linear calibration curves obtained with the peak-area ratio (y) of germacrone to internal standard (tanshinoneIIA) versus drug concentration (x) were found to be linear between 8.08 and 808 ng/ml. The limit of quantitation was 8.08 ng/ml. The monitored compounds were completely separated from others in ZTO and from endogenous species in plasma by HPLC. Pharmacokinetic investigations were performed on 18 male rabbits after intravenous administration of ZTO microemulsion via the ear vein at germacrone doses of 3.2, 6.4 and 9.6 mg/kg. The plasma concentration-time data fit to a two-compartment intravenous model with a weight of 1/C(2) (C: germacrone concentration in plasma). Germacrone exhibited linear pharmacokinetics after intravenous administration of ZTO microemulsion to rabbits over the germacrone dose range 3.2-9.6 mg/ml.

Topics: Animals; Area Under Curve; Chromatography, High Pressure Liquid; Curcuma; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Injections, Intravenous; Male; Metabolic Clearance Rate; Plant Oils; Rabbits; Reproducibility of Results; Sesquiterpenes, Germacrane

To study the fingerprint of Ezhu by GC-MS.. GC-MS analysis was performed for 18 samples of three species of Curcuma used as Ezhu. TIC profiles were evaluated by "Computer Aided Similarity Evaluation System" (MATLAB5.3 based, Ver. 1.240, developed by Research Center for Modernization of Chinese Medicine, Central South University). The characteristic peaks in chromatograms were identified by comparing mass data with literatures. Hierarchical clustering analysis was performed by SPSS based on the relative peak area (RPA) of identified peak to germacrone in 18 samples.. Resemblance values of 18 samples of Ezhu were pretty low. The mutual mode fingerprint plots of Ezhu were failed to develop. However, 18 samples were divided into two main clusters based on hierarchical clustering analysis, Curcuma wenyujin cluster and Curcuma phaeocaulis cluster, but the samples of Curcuma kwangsiensis were dispersive. Therefore, based on hierarchical clustering analysis, two mutual mode fingerprint plots of Curcuma wenyujin and Curcuma phaeocaulis were developed. But that of Curcuma kwangsiensis was failed because of low resemblance among samples.. The mutual mode fingerprint is the basis for quality control of Chinese materia medica from multi-origins. Development of GC-MS fingerprint of Ezhu was failed, which indicates that the chemical components in different species of herbs used as one Chinese materia medica may be significantly different. The relationship of chemical components and pharmacological activities should be further studied so as to elucidate the rationality of Chinese materia medica from multi-origins.

Topics: Cluster Analysis; Curcuma; Gas Chromatography-Mass Spectrometry; Phylogeny; Plant Roots; Plants, Medicinal; Quality Control; Reproducibility of Results; Sesquiterpenes; Sesquiterpenes, Germacrane

To study the absorption of zedoary oil in intestine of rat.. In situ single pass perfusion model was used and the concentrations of three components in perfusate were determined by HPLC in combination with diode array detection.. The P(app) s of curcumol, curdione and germacrone were all low and had no significant difference (P > 0.05) at zedoary oil concentration of 0.4, 0.8 and 1.2 mg x mL(-1) in transmucosal fluid or in four different regions of intestine of rat [duodenum, jejunum, ileum, colon]. The absorption rates of germacrone and curdione were faster than curcumol's in this study.. The zedoary oil concentration in transmucosal fluid had no significant effect on the P(app) s within the scope of 0.4-1.2 mg x mL(-1). The absorption of curcumol, curdione and germacrone showed the passive diffusion process, and didn't contain a special absorption window.

Topics: Animals; Biological Transport; Colon; Curcuma; Duodenum; Ileum; In Vitro Techniques; Intestinal Absorption; Jejunum; Male; Perfusion; Plant Oils; Plants, Medicinal; Rats; Rats, Wistar; Sesquiterpenes; Sesquiterpenes, Germacrane