Zedoaria Rhizome Research Articles

Molecular Docking Simulation of Phenolics towards Tyrosinase, Phenolic Content, and Radical Scavenging Activity of Some Zingiberaceae Plant Extracts

In Indonesia, plants have been indigenously used to treat various diseases and as cosmetics. It is always challenging to explore the molecular interactions of phenolic compounds towards the levels of constituents that contribute to the biological activities of plants. This study aimed to select a plant of the Zingiberaceae family with the highest phenolics and flavonoids, the strongest radical scavenging activity, and the best interaction towards tyrosinase in terms of docking score and binding mode. Initially, the total phenolics and radical scavenging capacity of Zingiberaceae plants, namely, Hedychium coronarium, Curcuma zedoaria, Curcuma heyneana, and Alpinia galanga, were determined using the Folin–Ciocâlteu method and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The main phytoconstituents of plants with the highest phenolic levels were docked to the binding site of tyrosinase. Three anti-melanogenesis agents commonly used in cosmetics, namely, arbutin, hydroquinone, and kojic acid, were used as the standard. Our study revealed that all the tested plants contain polyphenolic compounds in the range of 17.92 (C. zedoaria rhizome extract) to 252.36 (A. galanga rhizome extract) mg GAE/g and have radical scavenging capacity, with IC50 values in the range of 66.67 (A. galanga rhizome extract) to 320.0 (C. heyneana rhizome extract) μg/mL. A molecular docking simulation demonstrated that four constituents, i.e., kaempferol, galangin, ethyl p-methoxycinnamate, and 6-gingerol, could occupy the binding site of tyrosinase with prominent affinity and interact with essential residues of the enzyme. This study confirms that Alpinia galanga possesses the potential to be further developed as a cosmetic with a radical scavenging and tyrosinase inhibitory activity. However, it may be interesting to carry out further studies of how the plant extract affects the melanogenesis signaling pathway.

Deeper insight into the volatile profile of essential oil of two Curcuma species and their antioxidant and antimicrobial activities

Essential oil of Curcuma angustifolia Roxb. and Curcuma zedoaria (Christm.) Rosc. are gaining increasing interest worldwide due to its medicinal and cosmetic application, however, the chemical constituents of their essential oil are not well explored. Therefore, the present research aims to obtain a deeper understanding of the volatile composition of two important Curcuma species viz. C. angustifolia and C. zedoaria using two-dimensional gas chromatography with time-of-flight mass spectrometry (GC × GC-TOFMS). A total of 206 different compounds were detected (139 in C. angustifolia and 147 in C. zedoaria), including alkanes, alkenes, aldehydes, alcohols, esters, ketones, monoterpenes, sesquiterpenes, diterpenes, phenylpropanoids, furans, and fatty acids. The major compounds were epicurzerenone (29.62 %), curzerenone (10.79 %), and trans-β-terpineol (6.12 %) in C. angustifolia and curzerenone (17.72 %), γ-Eudesmol acetate (15.85 %), and germacrone (6.50 %) in the C. zedoaria rhizome essential oil. Two-dimensional gas chromatography with time-of-flight mass spectrometry tentatively identified about three times more constituents than those identified by one dimensional gas chromatography with time-of-flight mass spectrometry (GC-TOFMS). The result showed the superiority of GC × GC-TOFMS to detect a higher no. of trace constituents and separate co-eluting components that remain unresolved on a single GC column. Both the essential oil exhibited promising antioxidant activity and were comparable to that of positive standard ascorbic acid and butylated hydroxytoluene (BHT). The essential oil of both the Curcuma species exhibited good antimicrobial activity against five bacterial, three fungal and yeast strains; however, C. zedoaria essential oil displayed a strong inhibitory effect against Candida albicans (6.25 μg/mL) and Staphylococcus aureus (6.25 μg/mL). The present study provides significant information on the chemical profile and bioactivity studies of rhizome essential oil of Curcuma angustifolia and Curcuma zedoaria.

PHENOLIC COMPOUNDS FROM INDONESIAN WHITE TURMERIC (CURCUMA ZEDOARIA) RHIZOMES

Objective: The aim of the present study is to isolate phenolic compounds from Curcuma zedoaria rhizomes grown in Bogor, West Java, Indonesia, which will enrich phytochemical information from this plant.
 Methods: C. zedoaria rhizomes were macerated in methanol then followed by increasing polarity partitions with n-hexane, ethyl acetate (EtOAc), and methanol, respectively. EtOAc fraction was further fractionated using various chromatography techniques to yield two isolated fractions, Z1 and Z2. These two isolated fractions were then characterized to determine their compound structures.
 Results: According to Fourier transform-infrared, ultraviolet-vis, and liquid chromatography–mass spectrometry (MS)/MS data, Z1 fraction was elucidated as curcuminoid derivative, that is, dimethoxycurcumin (DiMC, 1), while Z2 fraction was yielded as a mixture consisted of flavonoid and coumarin derivatives, that is, 3,5,7-trihydroxy-4’-methoxyflavon (kaempferide, 2) and 7-methoxy coumarin (herniarin, 3).
 Conclusion: This study reveals useful information regarding phenolic constituents of Indonesian C. zedoaria rhizomes. Further research needs to be carried out to purify other compounds contained and to conduct bioactivity assays.

Kinetin establish the volatile chemical profile after rhizome dormancy is released in Curcuma zedoaria (Christm.) Roscoe

The aim of this work was to provide information about kinetin effects on chemical volatile profile of Curcuma zedoaria (Christm.) Roscoe after several days of plant dormancy release. Rhizomes of C. zedoaria were immersed in four kinetin concentrations (0, 50, 100, 150 mg ml−1, n = 12 by each concentration) for 30 min. After 240 h of treatment, root length (mm), bud break (%) and bud speed index (BSI) were measured, and three rhizomes at 24 h and 240 h were collected for chemical volatile profile analysis by application of headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography–mass spectrometry (GC–MS). Kinetin does not alter morphological aspects of the bud dormancy releasing, but drastically changes metabolic aspects of volatile production on C. zedoaria rhizomes, by the selection of several monoterpenes, such as camphene, sabinene, isoborneol, borneol, 1,8-cineole. We assume that kinetin application maintain monoterpene production as a consequence of its signaling over dormancy release.

Sesquiterpenes from Curcuma zedoaria rhizomes and their cytotoxicity against human gastric cancer AGS cells

Curcuma zedoaria rhizome (Zingiberaceae) is a well-known traditional medicinal plant used in Ayurvedic and traditional Chinese medicine to treat various cancers. This study aimed to identify the cytotoxic components from C. zedoaria rhizomes that act against gastric cancer, which is the third leading cause of death from cancer worldwide because the MeOH extract of C. zedoaria rhizome was found to show a cytotoxic effect against gastric cancer AGS cells. Repeated column chromatography and semi-preparative HPLC purification were used to separate the components from the C. zedoaria MeOH extract. Two new sesquiterpenes, curcumenol-9,10-epoxide (1) and curcuzedoalide B (2), and 12 known related sesquiterpenes (3–14) were isolated from the C. zedoaria MeOH extract. The structures of new compounds were determined by 1D and 2D NMR spectroscopic experiments and HR-ESIMS, and quantum chemical ECD calculations. The cytotoxic effects of the isolated compounds were measured in human gastric cancer AGS cells using an MTT cell viability assay. Compounds 9, 10, and 12 exhibited cytotoxic effects against gastric cancer AGS cells, with IC50 values in the range of 212–392 μM. These findings provide further experimental scientific evidence to support the traditional use of C. zedoaria rhizomes for the treatment of cancer. Curcumenol (9), 4,8-dioxo-6β-methoxy-7α,11-epoxycarabrane (10), and zedoarofuran (12) were identified as the main cytotoxic components in C. zedoaria rhizomes.

Variations in the Volatile Compositions of Curcuma Species

Curcuma species have been cultivated in tropical and subtropical regions in Asia, Australia, and South America for culinary as well as medicinal applications. The biological activities of Curcuma have been attributed to the non-volatile curcuminoids as well as to volatile terpenoids. Curcuma essential oils have demonstrated a wide variety of pharmacological properties. The objective of this work was to examine the variation in the compositions of Curcuma rhizome essential oils. In this work, the volatile oils from C. longa and C. zedoaria were obtained and analyzed by gas chromatography-mass spectrometry. The chemical compositions of C. longa and C. zedoaria essential oils, including those reported in the literature, were analyzed by hierarchical cluster analysis. In addition, cluster analyses of the chemical compositions of C. aromatica and C. aeruginosa from the literature were also carried out. Curcuma longa volatiles were dominated by α-turmerone, curlone, ar-turmerone, β-sesquiphellandrene, α-zingiberene, germacrone, terpinolene, ar-curcumene, and α-phellandrene and showed four distinct chemical clusters. C. zedoaria rhizome oil contained 1,8-cineole, curzerenone/epi-curzerenone, α-copaene, camphor, β-caryophyllene, elemol, germacrone, curzerene, and β-elemene and showed two different chemical types. C. aromatica had three clearly defined clusters, and C. aeruginosa had three types.

Bioactivity-based analysis and chemical characterization of anti-inflammatory compounds from Curcuma zedoaria rhizomes using LPS-stimulated RAW264.7 cells

Inflammation is not only a self-defense response of the innate immune system, but also the pathogenesis mechanism of multiple diseases such as arthritis, neurodegeneration, and cancer. Curcuma zedoaria Roscoe (Zingiberaceae), an indigenous plant of India, has been used traditionally in Ayurveda and folk medicine. As part of our ongoing efforts to screen traditional medicinal plants exhibiting pharmacological potential and to characterize the compounds involved, we examined the anti-inflammatory effects of the MeOH extract of C. zedoaria rhizomes using lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells and found that MeOH extract inhibited the synthesis of nitric oxide (NO) in a dose-dependent manner (IC50: 23.44 ± 0.77 μg/mL). In our efforts to characterize the compounds responsible for these anti-inflammatory effects, bioactivity-guided fractionation of the MeOH extract and chemical investigation of its active hexane-soluble fraction led to the successful isolation of five sesquiterpenes (1–5), the structures of which were elucidated by NMR spectroscopic analysis and LC/MS analysis. Among them, curcuzedoalide (5) exhibited potent inhibitory effects on NO synthesis (IC50: 12.21 ± 1.67 μM) and also suppressed pre-inflammatory protein expression of iNOS and COX-2. Curcuzedoalide (5) was thus determined to be a contributor to the anti-inflammatory effect of C. zedoaria rhizomes and could be a potential candidate for therapeutic applications.

In vivo assessment of plant extracts for control of plant diseases: A sesquiterpene ketolactone isolated from Curcuma zedoaria suppresses wheat leaf rust

ABSTRACTAs an alternative to synthetic pesticides, natural materials such as plant extracts and microbes have been considered to control plant diseases. In this study, methanol extracts of 120 plants were explored for in vivo antifungal activity against Rhizoctonia solani, Botrytis cinerea, Phytophthora infestans, Puccinia triticina, and Blumeria graminis f. sp. hordei. Of the 120 plant extracts, eight plant extracts exhibited a disease control efficacy of more than 90% against at least one of five plant diseases. In particular, a methanol extract of Curcuma zedoaria rhizomes exhibited strong activity against wheat leaf rust caused by P. triticina. When the C. zedoaria methanol extracts were partitioned with various solvents, the layers of n-hexane, methylene chloride, and ethyl acetate showed disease control values of 100, 80, and 43%, respectively, against wheat leaf rust. From the C. zedoaria rhizome extracts, an antifungal substance was isolated and identified as a sesquiterpene ketolactone based on the mass and nuclear magnetic resonance spectral data. The active compound controlled the development of rice sheath blight, wheat leaf rust, and tomato late blight. Considering the in vivo antifungal activities of the sesquiterpene ketolactone and the C. zedoaria extracts, these results suggest that C. zedoaria can be used as a potent fungicide in organic agriculture.

Curcuzedoalide contributes to the cytotoxicity of Curcuma zedoaria rhizomes against human gastric cancer AGS cells through induction of apoptosis

Ethnopharmacological relevanceCurcuma zedoaria Roscoe (Zingiberaceae), also known as white turmeric or zedoaria, has been used in Ayurveda and traditional Chinese medicine to treat various cancers, and it possesses several sesquiterpenoid compounds. ObjectiveThis study aimed to evaluate the therapeutic effects of a methanolic (MeOH) extract of C. zedoaria rhizomes, as well as its active constituents, against gastric cancer, which is a frequently diagnosed cancer in South Korea. Materials and methodsRepeated column chromatography, together with semi-preparative HPLC purification, was used to separate the bioactive constituents from the C. zedoaria MeOH extract. The cytotoxic effects of the C. zedoaria MeOH extract and its active compounds were measured in human gastric cancer AGS cells. Expression of proteins related to apoptosis was evaluated using Western blotting analysis. ResultsThe MeOH extract of C. zedoaria rhizomes exerted a cytotoxic effect on AGS cells (IC50: 96.60 ± 4.87μg/mL). Based on the bioactivity-guided fractionation for antiproliferative activity, a chemical investigation of the MeOH extract led to the isolation of five sesquiterpenes including isoprocurcumenol (1), germacrone (2), curzerenone (3), curcumenol (4), and curcuzedoalide (5). Among these, curcuzedoalide demonstrated the strongest effect in suppressing gastric cancer cell proliferation in a dose-dependent manner with an IC50 value of 125.11±2.77μM. Western blotting analysis showed that curcuzedoalide inhibited AGS human gastric cancer cell viability by activating caspase-8, caspase-9, caspase-3, and PARP, which contributed to apoptotic cell death in AGS human gastric cancer cells. ConclusionThese data indicate that curcuzedoalide contributed to the cytotoxicity of C. zedoaria by activating the cleavage of caspases and PARP, which are representative markers for apoptosis. Therefore, curcuzedoalide is a positive candidate for the development of novel chemotherapeutics.

Chemical Constituents and Evaluation of Cytotoxic Activities of Curcuma zedoaria (Christm.) Roscoe Oils from Malaysia and Indonesia

The essential oils obtained by hydrodistillation of the rhizomes of Curcuma zedoaria (Christm.) Roscoe collected from Malaysia and Indonesia were analyzed by capillary GC and GC-MS. Both the oils were principally sesquiterpenic in nature and were characterized by zerumbone (17.14% and 12.07%, respectively). Camphor (17.56% and 19.69%, respectively) was also abundant in both oils. The cytotoxic effects of both the oils on human breast (MCF-7 and MDA-MB 231), lung (A549 and SK-LU-1) and cervical (HeLa S3 and SiHa) cancer cell lines were examined using the MTT assay. The Malaysian C. zedoaria rhizome oil was found to be cytotoxic against the MCF-7, SK-LU-1, HeLa S3 and SiHa cell lines, with IC50 values being less than 10 μg/mL. Our findings support the use of the Malaysian C. zedoaria rhizome oil as a potential chemopreventive agent towards a wide spectrum of cancer in particular cervical cancer.

Rhizome extracts of Curcuma zedoaria Rosc induce caspase dependant apoptosis via generation of reactive oxygen species in filarial parasite Setaria digitata in vitro

Human lymphatic filariasis (LF) is mainly caused by filarial parasite Wuchereria bancrofti and is the second leading cause of long term and permanent disability in tropical countries. To date, incapability to eliminate long lived adult parasites by current drugs remains the major challenge in the elimination of LF. Hence, in the current study, the efficacy of rhizome extracts of Curcuma zedoaria (a plant traditionally used in Sri Lanka in the management of LF) was evaluated as an effective filaricide in vitro. Sequential solvent extracts of C. zedoaria rhizomes were screened for in vitro antifilarial activity at 0.01–1 mg/mL concentrations by motility inhibition assay and 3-(4, 5 dimethylthiazol-2-yl)-2, 5 diphenyl tetrazolium bromide (MTT) reduction assay using cattle parasite Setaria digitata as a model organism. Exposure of parasites to hexane and chloroform extracts of C. zedoaria caused a dose dependant reduction in motility and viability of microfilariae (IC50 = 72.42 μg/mL for hexane extract, 191.14 μg/mL for chloroform extract) and adult parasites (IC50 = 77.07 μg/mL for hexane extract, 259.87 μg/mL for chloroform extract). Both extracts were less toxic to human peripheral blood mononuclear cells when compared to filariae. A dose dependant increase in caspase 3/CED 3 and a decrease in total protein content, cyclooxygenase (COX) and protein tyrosine phosphatase (PTP) activities were observed in adult parasites treated with hexane or chloroform extract. A significant degree of chromatin condensation and apoptotic body formation were also observed in these worms by Hoechst 33342 and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) staining respectively. Dose dependant chromosomal DNA laddering was observed in treated adult worms but not in microfilariae in response to both extracts. Oxidative stress parameters such as reduction in reduced glutathione (GSH) levels and increase in glutathione s transferase (GST), superoxide dismutase (SOD) and catalase activities, increased reactive oxygen levels (ROS) and lipid peroxidation were also observed indicating that an apoptotic event is induced by reactive oxygen species.

Spectrofluorometric and molecular docking studies on the binding of curcumenol and curcumenone to human serum albumin.

Curcumenol and curcumenone are two major constituents of the plants of medicinally important genus of Curcuma, and often govern the pharmacological effect of these plant extracts. These two compounds, isolated from C. zedoaria rhizomes were studied for their binding to human serum albumin (HSA) using the fluorescence quench titration method. Molecular docking was also performed to get a more detailed insight into their interaction with HSA at the binding site. Additions of these sesquiterpenes to HSA produced significant fluorescence quenching and blue shifts in the emission spectra of HSA. Analysis of the fluorescence data pointed toward moderate binding affinity between the ligands and HSA, with curcumenone showing a relatively higher binding constant (2.46 × 105 M−1) in comparison to curcumenol (1.97 × 104 M−1). Cluster analyses revealed that site I is the preferred binding site for both molecules with a minimum binding energy of −6.77 kcal·mol−1. However, binding of these two molecules to site II cannot be ruled out as the binding energies were found to be −5.72 and −5.74 kcal·mol−1 for curcumenol and curcumenone, respectively. The interactions of both ligands with HSA involved hydrophobic interactions as well as hydrogen bonding.

Effects of the extracts and an active compound curcumenone isolated from Curcuma zedoaria rhizomes on alcohol-induced drunkenness in mice

The Curcuma zedoaria rhizome has been used traditionally to treat gastrointestinal diseases as an aromatic stomachic drug, and this is currently used to treat alcohol-induced loss of appetite and nausea in Japan. We examined the effects of various fractions and isolated compounds on alcohol-induced drunkenness and blood alcohol concentrations in mice. The 30% ethanol-extract (1000mg/kg) of C. zedoaria rhizome prevented drunkenness 60 and 120min after 40% alcohol administration. The n-hexane-soluble fraction (300mg/kg) and an isolated compound (3, 10 or 30mg/kg) prevented drunkenness at 30, 60 or 120min. The extract, n-hexane-soluble fraction and isolated compound reduced the elevation in blood alcohol concentrations 30 and 60min after 40% alcohol administration. The isolated compound (10 and 30mg/kg) enhanced liver ADH activity 30 and 60min after 40% alcohol administration. The compound was identified as curcumenone by a direct comparison of 1H- and 13C-NMR spectral data. In conclusion, the protective effect of the C. zedoaria extract on drunkenness might be due to an active substance, curcumenone, and decreases in the elevation of blood alcohol concentrations through increased liver alcohol dehydrogenase activity.

A curcuminoid and two sesquiterpenoids fromCurcuma zedoaria as Inhibitors of nitric oxide synthesis in activated macrophages

The overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) is known to be responsible for vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of iNOS, thus, may be useful candidates for the treatment of inflammatory diseases accompanied by overproduction of NO. In the course of screening oriental anti-inflammatory herbs for the inhibitory activity of NO synthesis, a crude methanolic extract of Curcuma zedoaria exhibited significant activity. The activity-guided fractionation and repetitive chromatographic procedures with the EtOAc soluble fraction allowed us to isolate three active compounds. They were identified as 1,7-bis (4-hydroxyphenyl)-1,4,6-heptatrien-3-one (1), procurcumenol (2) and epiprocurcumenol (3) by spectral data analyses. Their concentrations for the 50% inhibition of NO production (IC50) in lipopolysaccharide (LPS)-activated macrophages were 8, 75, 77 microM, respectively. Compound 1 showed the most potent inhibitory activity for NO production in LPS-activated macrophages, while the epimeric isomers, compound 2 and 3 showed weak and similar potency. Inhibition of NO synthesis by compound 1 was very weak when activated macrophages were treated with 1 after iNOS induction. In the immunoblot analysis, compound 1 suppressed the expression of iNOS in a dose-dependent manner. In summary, 1,7-bis (4-hydroxyphenyl)-1,4,6-heptatrien-3-one from Curcuma zedoaria inhibited NO production in LPS-activated macrophages through suppression of iNOS expression. These results imply that the traditional use of C. zedoaria rhizome as anti-inflammatory drug may be explained at least in part, by inhibition of NO production.

The vapour action of essential oils and monoterpenoids against pathogenic fungi

The vapour action of pure monoterpenoids and volatile oils has been screened for their antifungal activity against four sugarcane pathogenic fungi using inverted petriplate method. Among tested monoterpenoids, menthol caused complete mycelial inhibition againstCurvularia pallescens at 2000 ppm, geraniol againstColletotrichum falcatum at 3000 ppm, linalool againstC. pallescens at 3000 ppm concentrations. Among tested essential oils, seed oil ofDaucus carota showed complete mycelial inhibition ofC. falcatum at 3000 ppm,Sugandh kokila oil againstC. falcatum at 3000 ppm,Curcuma aromatica againstC. falcatum at 3000 ppm andCurcuma zedoaria rhizome oil againstC. falcatum at 2000 ppm concentrations. Other doses of oils and monoterpenoids exhibited lower antifungal activity.