Curcuma zedoaria also known as Temu putih is traditionally used in food preparations and treatment of various ailments including cancer. The cytotoxic activity of hexane, dichloromethane, ethyl acetate, methanol, and the methanol-soxhlet extracts of Curcuma zedoaria rhizomes was tested on two human cancer cell lines (Ca Ski and MCF-7) and a noncancer cell line (HUVEC) using MTT assay. Investigation on the chemical components in the hexane and dichloromethane fractions gave 19 compounds, namely, labda-8(17),12 diene-15,16 dial (1), dehydrocurdione (2), curcumenone (3), comosone II (4), curcumenol (5), procurcumenol (6), germacrone (7), zerumbone epoxide (8), zederone (9), 9-isopropylidene-2,6-dimethyl-11-oxatricyclo[6.2.1.0(1,5)]undec-6-en-8-ol (10), furanodiene (11), germacrone-4,5-epoxide (12), calcaratarin A (13), isoprocurcumenol (14), germacrone-1,10-epoxide (15), zerumin A (16), curcumanolide A (17), curcuzedoalide (18), and gweicurculactone (19). Compounds (1-19) were evaluated for their antiproliferative effect using MTT assay against four cancer cell lines (Ca Ski, MCF-7, PC-3, and HT-29). Curcumenone (3) and curcumenol (5) displayed strong antiproliferative activity (IC50 = 8.3 ± 1.0 and 9.3 ± 0.3 μg/mL, resp.) and were found to induce apoptotic cell death on MCF-7 cells using phase contrast and Hoechst 33342/PI double-staining assay. Thus, the present study provides basis for the ethnomedical application of Curcuma zedoaria in the treatment of breast cancer.
Curcuma purpurascens BI. is a medicinal plant from the Zingiberaceae family, which is widely used as a spice and as folk medicine. The aim of the present study is to investigate the gastroprotective activity of C. purpurascens rhizome hexane extract (CPRHE) against ethanol- induced gastric ulcers in rats.
Different parts of the medicinal plant Zanthoxylum budrunga Wall enjoy a variety of uses in ethnobotanical practice in Bangladesh. In the present study, a number of phytochemical and pharmacological investigations were done on the ethanol extract of Z. budrunga seeds (ZBSE) to evaluate its antinociceptive and antioxidant potential. ZBSE was also subjected to HPLC analysis to detect the presence of some common antioxidants. In acetic acid induced writhing test in mice, ZBSE showed 65.28 and 74.30% inhibition of writhing at the doses of 250 and 500 mg/kg and the results were statistically significant (P < 0.001). In hot-plate test, ZBSE raised the pain threshold significantly (P < 0.001) throughout the entire observation period. In DPPH scavenging assay, the IC50 of ZBSE was observed at 82.60 μg/mL. The phenolic content was found to be 338.77 mg GAE/100 g of dried plant material. In reducing power assay, ZBSE showed a concentration dependent reducing ability. HPLC analysis indicated the presence of caffeic acid with a concentration of 75.45 mg/100 g ZBSE. Present investigation supported the use of Zanthoxylum budrunga seed in traditional medicine for pain management. Constituents including caffeic acid and other phenolics might have some role in the observed activity.
The ethanol extract of B. javanica seed was fractionated with solvents of different polarities and tested for antioxidant activities by several assays including DPPH radical scavenging activity, ferric reducing antioxidant power (FRAP), ferrous ion chelating activity (FCA), and nitric oxide radical scavenging activity (NORSA) along with their polyphenolic contents. Antidiabetic activity was evaluated both in vitro and in vivo using a glycogen phosphorylase α (GPα) inhibition assay and oral glucose tolerance test (OGTT) in nondiabetic rats. The ethyl acetate fraction (EAF), rich in tannin, exhibited the strongest antioxidant activities to DPPH, FRAP, and NORSA, except for FCA. The EAF also exerted a dose-depended inhibition of GPα (IC50 = 0.75 mg/ml). Further evaluation of hypoglycemic effect on OGGT indicated that rats treated with EAF (125 mg/kg bw) showed a 39.91% decrease (P < 0.05) in blood glucose levels at 30 min, and continuous fall (P < 0.05) of 28.89% and 20.29% was observed in the following hours (60 and 90 min) compared to the normal control during OGTT. The EAF was applied to polyamide column chromatography, and the resulting tannin-free fraction was tested for both GPα inhibition and antioxidant (DPPH only) activity. The GP α inhibitory activity was retained, while antioxidant activity was lost (4.6-fold) after tannin removal. These results concluded that the GPα inhibitory activity initially detected was primarily due to the compounds other than tannins, whereas antioxidant activity was mainly due to the tannins.
In this study, a new apoptotic monoterpenoid indole alkaloid, subditine (1), and four known compounds were isolated from the bark of Nauclea subdita. Complete (1)H- and (13)C- NMR data of the new compound were reported. The structures of isolated compounds were elucidated with various spectroscopic methods such as 1D- and 2D- NMR, IR, UV and LCMS. All five compounds were screened for cytotoxic activities on LNCaP and PC-3 human prostate cancer cell-lines. Among the five compounds, the new alkaloid, subditine (1), demonstrated the most potent cell growth inhibition activity and selective against LNCaP with an IC50 of 12.24±0.19 µM and PC-3 with an IC50 of 13.97±0.32 µM, compared to RWPE human normal epithelial cell line (IC50 = 30.48±0.08 µM). Subditine (1) treatment induced apoptosis in LNCaP and PC-3 as evidenced by increased cell permeability, disruption of cytoskeletal structures and increased nuclear fragmentation. In addition, subditine (1) enhanced intracellular reactive oxygen species (ROS) production, as reflected by increased expression of glutathione reductase (GR) to scavenge damaging free radicals in both prostate cancer cell-lines. Excessive ROS could lead to disruption of mitochondrial membrane potential (MMP), release of cytochrome c and subsequent caspase 9, 3/7 activation. Further Western blot analyses showed subditine (1) induced down-regulation of Bcl-2 and Bcl-xl expression, whereas p53 was up-regulated in LNCaP (p53-wild-type), but not in PC-3 (p53-null). Overall, our data demonstrated that the new compound subditine (1) exerts anti-proliferative effect on LNCaP and PC-3 human prostate cancer cells through induction of apoptosis.
A phytochemical investigation of the methanolic extract of the bark of Endiandra kingiana led to the isolation of seven new tetracyclic endiandric acid analogues, kingianic acids A-G (1-7), together with endiandric acid M (8), tsangibeilin B (9) and endiandric acid (10). Their structures were determined by 1D- and 2D-NMR analysis in combination with HRMS experiments. The structure of compounds 9 and 10 were confirmed by single-crystal X-ray diffraction analysis. These compounds were screened for Bcl-xL and Mcl-1 binding affinities and cytotoxic activity on various cancer cell lines. Compound 5 showed moderate cytotoxic activity against human colorectal adeno-carcinoma (HT-29) and lung adenocarcinoma epithelial (A549) cell lines, with IC50 values in the range 15-17 µM, and compounds 3, 6 and 9 exhibited weak binding affinity for the anti-apoptotic protein Mcl-1.
Our continuing research on the Aglaia genus (family Meliaceace) has led us to this first study on the chemical constituents of Aglaia lanuginose (bark). The dichloromethane extract from the bark of Aglaia lanuginose showed cytotoxicity against HL-60 leukaemia cell line (45% inhibition) at 20 µg/ml and was prioritised for further investigation. Repeated chromatography of the dichloromethane extract yielded the known dammarane triterpenes which were identified as cabralealactone (1), methyl eichlerianate (2), cabraleone (3), ocotillone (4), eichleriatone (5), eichlerianic acid (6) and shoreic acid (7) together with the known sterols, sitosterol (9) and stigmasterol (10). Another isolated compound was the aromatic 4-hydroxycinnamyl-acetate (8), which has not been reported to be present in a plant from the Meliaceae family. The structures of all the compounds were elucidated on the basis of spectroscopic methods (IR, MS and NMR). Cytotoxicity testing of 1-10 showed activity only for mixtures of (3, 4), and (5, 6).
Nine monoterpenoid indole alkaloids; naucletine (1), angustidine (2), nauclefine (3), angustine (4), naucline (5), angustoline (6), harmane (7), 3,14-dihydroangustoline (8), strictosamide (9) and one quinoline alkaloid glycoside; pumiloside (10) from Nauclea officinalis were tested for cholinesterase inhibitory activity. All the alkaloids except for pumiloside (10) showed strong to weak BChE inhibitory effect with IC50 values ranging between 1.02-168.55 μM. Angustidine (2), nauclefine (3), angustine (4), angustoline (6) and harmane (7) showed higher BChE inhibiting potency compared to galanthamine. Angustidine (2) was the most potent inhibitor towards both AChE and BChE. Molecular docking (MD) studies showed that angustidine (2) docked deep into the bottom gorge of hBChE and formed hydrogen bonding with Ser 198 and His 438. Kinetic study of angustidine (2) on BChE suggested a mixed inhibition mode with an inhibition constant (Ki) of 6.12 μM.
An antiplasmodial screening of Phyllanthus debilis and Phyllanthus urinaria was carried out. The medicinal plants were extracted and evaluated for in vitro antiplasmodial activity against D10 (chloroquine-sensitive, CQS) and Gombak A (chloroquine-resistant, CQR) strains of Plasmodium falciparum. The methanolic crudes from the soxhlet extraction were active against both strains however, P. urinaria (IC50 8.9 μg/ml with CQR strain) exhibited better anti-malarial activity compared to P. debilis (IC50 12.2 μg/ml with CQR strain). Furthermore, the methanolic crude of P. urinaria obtained by the cold extraction has good anti-malarial activity towards CQS (IC50 4.1 μg/ml). The concentration of macronutrients (calcium and magnesium) and trace metals (copper, manganese, iron and zinc) from three Phyllanthus species i.e. P. debilis Klein ex Wild., Phyllanthus niruri L., P. urinaria L. and Alpinia conchigera Griff. were determined using microwave digestion method and analyzed by Flame Atomic Absorption Spectroscopy. Standard Reference Material 1547 (peach leaves) was used to validate the method throughout this study. The recovery values were in the range of 80% to 120% which were in very good agreement with the certified values. The three Phyllanthus species and leaves of A. conchigera showed the highest concentration of calcium compared to other metals and macronutrients studied. The significant presence of all the important macronutrients and trace metals which are essential for human health and well-being substantiate their use medicinally in traditional practices.
Vindogentianine, a new indole alkaloid together with six known alkaloids, vindoline, vindolidine, vindolicine, vindolinine, perivine and serpentine were isolated from leaf extract (DA) of Catharanthus roseus (L.) G. Don. Their structures were elucidated by spectroscopic methods; NMR, MS, UV and IR. Vindogentianine is a dimer containing a vindoline moiety coupled to a gentianine moiety. After 24h incubation, vindogentianine exhibited no cytotoxic effect in C2C12 mouse myoblast and β-TC6 mouse pancreatic cells (IC50>50μg/mL). Real-time cell proliferation monitoring also indicated vindogentianine had little or no effect on C2C12 mouse myoblast cell growth at the highest dose tested (200μg/mL), without inducing cell death. Vindogentianine exhibited potential hypoglycemic activity in β-TC6 and C2C12 cells by inducing higher glucose uptake and significant in vitro PTP-1B inhibition. However, in vitro α-amylase and α-glucosidase inhibition assay showed low inhibition under treatment of vindogentianine. This suggests that hypoglycemic activity of vindogentianine may be due to the enhancement of glucose uptake and PTP-1B inhibition, implying its therapeutic potential against type 2 diabetes.
A series of 21 compounds isolated from Curcuma zedoaria was subjected to cytotoxicity test against MCF7; Ca Ski; PC3 and HT-29 cancer cell lines; and a normal HUVEC cell line. To rationalize the structure-activity relationships of the isolated compounds; a set of electronic; steric and hydrophobic descriptors were calculated using density functional theory (DFT) method. Statistical analyses were carried out using simple and multiple linear regressions (SLR; MLR); principal component analysis (PCA); and hierarchical cluster analysis (HCA). SLR analyses showed that the cytotoxicity of the isolated compounds against a given cell line depend on certain descriptors; and the corresponding correlation coefficients (R2) vary from 0%-55%. MLR results revealed that the best models can be achieved with a limited number of specific descriptors applicable for compounds having a similar basic skeleton. Based on PCA; HCA and MLR analyses; active compounds were classified into subgroups; which was in agreement with the cell based cytotoxicity assay.
A large-scale in vitro screening of tropical plants using an antibacterial assay permitted the selection of several species with significant antibacterial activities. Bioassay-guided purification of the dichloromethane extract of the leaves of the Malaysian species Vitex vestita, led to the isolation of six new labdane-type diterpenoids, namely, 12-epivitexolide A (2), vitexolides B and C (3 and 4), vitexolide E (8), and vitexolins A and B (5 and 6), along with six known compounds, vitexolides A (1) and D (7), acuminolide (9), 3β-hydroxyanticopalic acid (10), 8α-hydroxyanticopalic acid (11), and 6α-hydroxyanticopalic acid (12). Their structures were elucidated on the basis of 1D and 2D NMR analyses and HRMS experiments. Both variable-temperature NMR spectroscopic studies and chemical modifications were performed to investigate the dynamic epimerization of the γ-hydroxybutenolide moiety of compounds 1-4. Compounds were assayed against a panel of 46 Gram-positive strains. Vitexolide A (1) exhibited the most potent antibacterial activity with minimal inhibitory concentration values ranging from 6 to 96 μM, whereas compounds 2 and 6-9 showed moderate antibacterial activity. The presence of a β-hydroxyalkyl-γ-hydroxybutenolide subunit contributed significantly to antibacterial activity. Compounds 1-4 and 6-9 showed cytotoxic activities against the HCT-116 cancer cell line (1 < IC50s < 10 μM) and human fetal lung fibroblast MRC5 cell line (1 < IC50s < 10 μM for compounds 1, 2, 7, 8, and 9).
Previous in vitro and in vivo studies have reported that 1'-S-1'-acetoxychavicol acetate (ACA) isolated from rhizomes of the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) induces apoptosis-mediated cell death in tumour cells via dysregulation of the NF-κB pathway. However there were some clinical development drawbacks such as poor in vivo solubility, depreciation of biological activity upon exposure to an aqueous environment and non-specific targeting of tumour cells. In the present study, all the problems above were addressed using the novel drug complex formulation involving recombinant human alpha fetoprotein (rhAFP) and ACA.
Phytochemical investigation on the fruits of Mesua lepidota (Calophyllaceae) led to the isolation of seven new phenylcoumarin derivatives named lepidotols A-E (1-5) and lepidotins A and B (6, 7). These structures were elucidated by spectroscopic and spectrometric methods including UV, NMR, and HRMS. Lepidotol A (1), the major compound, was evaluated for its inhibitory effect on inflammation and immunity using endothelial cell-based cellular assays. At 10 μM, 1 exhibited an anti-inflammatory activity, with a significant inhibition of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 expression induced by tumor necrosis factor-α. Lepidotol A also showed a mild immunosuppressive effect, with inhibition of the major histocompatibility complex molecules, namely, human leukocyte antigen (HLA)-DR and HLA-E.
Curcumenol, a sesquiterpene isolated from Curcuma zedoaria is known to possess a variety of health and medicinal values which includes neuroprotection, anti-inflammatory, anti-tumor and hepatoprotective activities. The current study aim is to investigate the modulatory effects of curcumenol towards the lipopolysaccharides (LPS)-induced inflammation in BV-2 microglia. Curcumenol markedly decreased LPS-induced production of nitric oxide (NO), pro-inflammatory cytokines [(IL-6) and (TNF-α)] and pro-inflammatory proteins expression, iNOS and COX-2. Moreover, curcumenol inhibited NF-κB activation by suppressing the nuclear translocation of the NF-κB p65 subunit and blocking IκBα phosphorylation and degradation. Furthermore, an NF-κB inhibitor, ethyl 3,4-dihydroxycinnamate also known as caffeic acid ethyl ester (CAEE), attenuated LPS-stimulated iNOS and COX-2 expression, suggesting that NF-κB inhibition is a regulator in the expression of iNOS and COX-2 proteins. Further mechanistic study with an Akt inhibitor, triciribine hydrate (API-2), revealed that curcumenol acted through Akt-dependent NF-κB activation. Moreover, curcumenol inhibition on LPS-induced phosphorylation of p38 MAPK is confirmed by its inhibitor (SB 202190). These results indicate that curcumenol diminishes the proinflammatory mediators and the expression of the regulatory genes in LPS-stimulated BV-2 by inhibiting Akt-dependent NF-κB activation and downregulation of Akt and p38 MAPKs signaling.
Curcuma purpurascens BI. is a member of Zingiberaceae family. The purpose of this study is to investigate the wound healing properties of hexane extract of C. purpurascens rhizome (HECP) against excisional wound healing in rats.
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.
BACKGROUND: Curcuma purpurascens BI. (Zingiberaceae) commonly known as 'Koneng Tinggang' and 'Temu Tis' is a Javanese medicinal plant which has been used for numerous ailments and diseases in rural Javanese communities. In the present study, the apoptogenic activity of dichloromethane extract of Curcuma purpurascens BI. rhizome (DECPR) was investigated against HT-29 human colon cancer cells.
METHODS: Acute toxicity study of DECPR was performed in Sprague-Dawley rats. Compounds of DECPR were analyzed by the gas chromatography-mass spectrometry-time of flight (GC-MS-TOF) analysis. Cytotoxic effect of DECPR on HT-29 cells was analyzed by MTT and lactate dehydrogenase (LDH) assays. Effects of DECPR on reactive oxygen species (ROS) formation and mitochondrial-initiated events were investigated using a high content screening system. The activities of the caspases were also measured using a fluorometric assay. The quantitative PCR analysis was carried out to examine the gene expression of Bax, Bcl-2 and Bcl-xl proteins.
RESULTS: The in vivo acute toxicity study of DECPR on rats showed the safety of this extract at the highest dose of 5 g/kg. The GC-MS-TOF analysis of DECPR detected turmerone as the major compound in dichloromethane extract. IC50 value of DECPR towards HT-29 cells after 24 h treatment was found to be 7.79 ± 0.54 μg/mL. In addition, DECPR induced LDH release and ROS generation in HT-29 cells through a mechanism involving nuclear fragmentation and cytoskeletal rearrangement. The mitochondrial-initiated events, including collapse in mitochondrial membrane potential and cytochrome c leakage was also triggered by DECPR treatment. Initiator caspase-9 and executioner caspase-3 was dose-dependently activated by DECPR. The quantitative PCR analysis on the mRNA expression of Bcl-2 family of proteins showed a significant up-regulation of Bax associated with down-regulation in Bcl-2 and Bcl-xl mRNA expression.
CONCLUSIONS: The findings presented in the current study showed that DECP suppressed the proliferation of HT-29 colon cancer cells and triggered the induction of apoptosis through mitochondrial-dependent pathway.
Garo Hills represents one of earliest human habitation in Bangladesh preserving its ancient cultures due to the geographic location. It is situated in the most northern part of Durgapur sub-district having border with Meghalaya of India. Durgapur is rich in ethnic diversity with Garo and Hajong as the major ethnic groups along with Bangalee settlers from the mainstream population. Thus the ethnomedicinal practice in Garo Hills is considered rich as it encompasses three different groups. Present survey was undertaken to compile the medicinal plant usage among the various communities of the Garo Hills.
A new pyranoxanthone, venuloxanthone (1), was isolated from the stem bark of Calophyllum venulosum, together with three other xanthones, tovopyrifolin C (2), ananixanthone (3) and caloxanthone I (4), along with two common triterpenes, friedelin (5) and lupeol (6). The structures of these compounds were identified using several spectroscopic analyses which are NMR, GCMS and FTIR experiments.