ABSTRACT
Eight previously undescribed compounds, two quinones (1-2), one sesquiterpene (3), and five phenol compounds (4-8), including three enantiomers (6a, 7a, and 8a), along with three corresponding known enantiomers (6b-8b) were isolated from the aerial parts of Morinda umbellata L. Their structures were elucidated by 1D and 2D NMR spectroscopy, X-ray diffraction, and experimental and calculated ECD spectra, respectively. Compound 5 was found to have weak cytotoxity, which inhibited the growth of seven human cancer cell lines (A2780, HeLa, MCF-7, BGC-823, H7420, Ketr3 and SW 1990) with IC50 values from 13.3 to 15.1 µM.
Subject(s)
Cytotoxins/toxicity , Morinda/chemistry , Phenols/toxicity , Quinones/toxicity , Sesquiterpenes/toxicity , Cell Line, Tumor , Chromatography, High Pressure Liquid , Crystallography, X-Ray , Cytotoxins/isolation & purification , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Phenols/isolation & purification , Plant Components, Aerial/chemistry , Plant Extracts/isolation & purification , Plant Extracts/toxicity , Quinones/isolation & purification , Sesquiterpenes/isolation & purificationABSTRACT
Three novel norsesquiterpenoids, (2R,4S,8aR)-8,8a,1,2,3,4-hexahydro-2-hydroxy-4,8a-dimethyl-2(2H)-naphthalenone (1), (1S,3S,4S,4aS,8aR)-4,8a-dimethyloctahydronaphthalene-1,3,4a(3H)-triol(2), (4S,4aS,8aS)-octahydro-4a-hydroxy-4, 8a-dimethyl-1(2H)-naphthalenone (3), as well as six other known analogues (4-9), were isolated from the culture broth of Streptomyces sp. XM17, an actinobacterial strain inhabiting the fresh feces of the giant panda Ailuropoda melanoleuca. The chemical structures of 1-3 were elucidated comprehensively by NMR spectroscopic and MS analyses, furthermore, the stereochemical configurations were resolved by NOESY experiments, along with ECD spectral and single-crystal X-ray crystallographic analyses. These compounds were then tested for their antiviral activities using the "pretreatment of virus" approach, which showed that most of these compounds were potent in inhibiting the entry of influenza A virus, with IC50 values ranging from 5 to 49 nM and selectivity indices all above 500.
Subject(s)
Antiviral Agents/isolation & purification , Feces/microbiology , Influenza A virus/drug effects , Sesquiterpenes/isolation & purification , Streptomyces/chemistry , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/toxicity , Chick Embryo , Circular Dichroism , Crystallography, X-Ray , Dogs , Inhibitory Concentration 50 , Madin Darby Canine Kidney Cells , Magnetic Resonance Spectroscopy , Mass Spectrometry , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/toxicity , UrsidaeABSTRACT
A phytochemistry of the whole plant of Agrimonia pilosa led to the discovery of two new nortriterpenoids, agrimonorterpenes A and B (1 and 2), together with one known triterpenoid fupenzic acid (3) and seven known sesquiterpenoids (4-10). The new structures were determined as 19α-hydroxy-2-oxo-nor-A (3)-urs-11,12-dien-28-oic acid (1) and 2, 19ß-dihydroxy-3-oxo-23-noroleana-1, 4, 12-trien-28-oic acid (2) by the spectroscopic data of UV, IR, HR-ESI-MS, and NMR. Notably, the structure of 1 possessed a rare five-membered A- ring. And this is the first time to discover the sesquiterpenoids (4-10) from A. pilosa. Compound 3 displayed the selective cytotoxicity against HCT116, BGC823, and HepG2 cell lines with the IC50 values of 16.31 µM, 21.94 µM, and 23.40 µM, respectively.
Subject(s)
Agrimonia/chemistry , Sesquiterpenes/isolation & purification , Triterpenes/isolation & purification , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Glycoside Hydrolase Inhibitors/toxicity , Magnetic Resonance Spectroscopy , Optical Rotation , Sesquiterpenes/chemistry , Sesquiterpenes/toxicity , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Triterpenes/chemistry , Triterpenes/toxicityABSTRACT
A. adenophora (Spreng.) R.M. King & H. Rob. is as invasive plant known to cause toxicity in humans and animals. The plant's toxic activities have been associated with some toxic phytochemicals present in the plant. One of the major phytochemicals that have been reported to induce toxicity in various organs is euptox A (9-oxo-10, 11-dehydroageraphorone). Previous studies have reported that the main target organs of euptox A are the liver and spleen. Although, many studies have reported on euptox A toxicity in rats and mice, the mechanism of action and the beneficial uses of this toxin as well as it potential uses have not been fully established in literatures. Therefore, this review firstly, aims at elaborating on the toxic effects and mechanism of action of euptox A to give basic knowledge to researchers to help in the development of strategies that will reduce its toxicity to the environment. Secondly, this paper will also report on some beneficial uses of euptox A in recent years as well as suggest some future potential applications of this toxin to help in the utilization of this plant resource.
Subject(s)
Campanulaceae , Sesquiterpenes , Animals , Campanulaceae/chemistry , Campanulaceae/toxicity , Introduced Species , Mice , Molecular Structure , Phytochemicals/pharmacology , Phytochemicals/toxicity , Rats , Sesquiterpenes/pharmacology , Sesquiterpenes/toxicityABSTRACT
Neglected tropical diseases such as leishmaniasis and American trypanosomiasis represent an increasing health problem. Current treatments are not satisfactory which remains an urgent need for novel, cheap and safe chemotherapies. In the course of our ongoing search for new potential anti-protozoal agents, this study aimed to perform a bio-guided fractionation of Inula viscosa (Asteraceae) using in vitro assays against three strains of Leishmania and Trypanosma genus. Eight known compounds were identified from the ethanolic extract of leaves, sesquiterpenoids (3 and 4) and flavonoids (5 and 6) were characterized as the main bioactive constituents. Sesquiterpene lactones 3 and 4 (IC50 values between 4.99 and 14.26⯵M) showed promising antiparasitic activity against promastigotes of L. donovani, L. amazonensis and epimastigotes of T. cruzi. Their structures were successfully characterized by spectroscopic techniques including 1D and 2D NMR experiments. Furthermore, the main bioactive compounds 4, 5 and 6 displayed higher potency (IC50 values between 0.64 and 2.13⯵M) against amastigotes of L. amazonensis than miltefosine (IC50 3.11⯵M), and a low toxicity on macrophages cell line (SIâ¯>â¯45). The analysis of structure-activity relationship (SAR) of the anti-protozoal activity revealed that lactonization or oxidation enhanced the biological proï¬le, suggesting that the hydrophobic moiety was presumably involved in the activity by increasing the aï¬nity and/or cell membrane permeability. In order to get an insight into the mechanism of action of these compounds, programmed cell death (PCD) experiments were performed, and the obtained results suggest that the reported compounds induced PCD in the treated parasites. These results highlight that sesquiterpenoids and flavonoids from I. viscosa could constitute an interesting scaffold for the development of novel antikinetoplastid agents.
Subject(s)
Antiprotozoal Agents/pharmacology , Apoptosis/drug effects , Flavonoids/pharmacology , Inula/chemistry , Sesquiterpenes/pharmacology , Animals , Cell Line , Flavonoids/toxicity , Leishmania/drug effects , Macrophages/drug effects , Oxidative Stress/drug effects , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/pharmacology , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Sesquiterpenes/toxicity , Structure-Activity Relationship , Trypanosoma/drug effectsABSTRACT
In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) initiated a program for the re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavor ingredients. This publication, fifth in the series, evaluates the safety of NFCs containing linalool and/or other characteristic mono- and sesquiterpenoid tertiary alcohols and esters using the safety evaluation procedure published by the FEMA Expert Panel in 2005 and updated in 2018. The procedure relies on a complete chemical characterization of the NFC intended for commerce and organization of the chemical constituents of each NFC into well-defined congeneric groups. The safety of each NFC is evaluated using the well-established and conservative threshold of toxicological concern (TTC) concept in addition to data on absorption, metabolism and toxicology of both the constituent congeneric groups and the NFCs. Sixteen NFCs, derived from the Lavandula, Aniba, Elettaria, Daucus, Salvia, Coriandrum, Ribes, Guaiacum/Bulnesia, Citrus, Pogostemon, Melaleuca and Michelia genera, were affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavor ingredients based on an evaluation of each NFC and the constituents and congeneric groups therein.
Subject(s)
Flavoring Agents/toxicity , Monoterpenes/toxicity , Plants/chemistry , Sesquiterpenes/toxicity , Animals , Consumer Product Safety , Escherichia coli/drug effects , Female , Flavoring Agents/chemistry , Humans , Male , Mice , Monoterpenes/chemistry , Mutagenicity Tests , No-Observed-Adverse-Effect Level , Plant Oils/chemistry , Plant Oils/toxicity , Rats , Salmonella typhimurium/drug effects , Sesquiterpenes/chemistryABSTRACT
The genus Curcuma is part of the Zingiberaceae family, and many Curcuma species have been used as traditional medicine and cosmetics in Thailand. To find new cosmeceutical ingredients, the in vitro anti-inflammatory, anti-oxidant, and cytotoxic activities of four Curcuma species as well as the isolation of compounds from the most active crude extract (C. aromatica) were investigated. The crude extract of C. aromatica showed 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with an IC50 value of 102.3 µg/mL. The cytotoxicity effect of C. aeruginosa, C. comosa, C. aromatica, and C. longa extracts assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay at 200 µg/mL were 12.1 2.9, 14.4 4.1, 28.6 4.1, and 46.9 8.6, respectively. C. aeruginosa and C. comosa presented apoptosis cells (57.7 3.1% and 32.6 2.2%, respectively) using the CytoTox-ONE™ assay. Different crude extracts or phytochemicals purified from C. aromatica were evaluated for their anti-inflammatory properties. The crude extract of C. aromatica showed the highest potential to inhibit NF-κB activity, followed by C. aeruginosa, C. comosa, and C. longa, respectively. Among the various purified phytochemicals curcumin, germacrone, curdione, zederone, and curcumenol significantly inhibited NF-κB activation in tumor necrosis factor (TNF) stimulated HaCaT keratinocytes. Of all compounds, curcumin was the most potent anti-inflammatory.
Subject(s)
Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Curcuma/chemistry , Plant Extracts/chemistry , Curcuma/classification , HaCaT Cells , Humans , NF-kappa B/metabolism , Plant Extracts/toxicity , Sesquiterpenes/chemistry , Sesquiterpenes/classification , Sesquiterpenes/toxicity , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The research of natural products has allowed for the discovery of biologically relevant compounds inspired by plant secondary metabolites, which contributes to the development of many chemotherapeutic drugs used in cancer treatment. Psidium guajava leaves present a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids, and triterpenes as the major bioactive constituents. Guajadial, a caryophyllene-based meroterpenoid, has been studied for potential anticancer effects tested in tumor cells and animal experimental models. Moreover, guajadial has been reported to have a mechanism of action similar to tamoxifen, suggesting this compound as a promisor phytoestrogen-based therapeutic agent. Herein, the anti-estrogenic action and anti-proliferative activity of guajadial is reported. The enriched guajadial fraction was obtained by sequential chromatographic techniques from the crude P. guajava dichloromethane extract showing promising anti-proliferative activity in vitro with selectivity for human breast cancer cell lines MCF-7 and MCF-7 BUS (Total Growth Inhibition = 5.59 and 2.27 µg·mL-1, respectively). Furthermore, evaluation of anti-estrogenic activity in vivo was performed demonstrating that guajadial enriched fraction inhibited the proliferative effect of estradiol on the uterus of pre-pubescent rats. These results suggest a relationship between anti-proliferative and anti-estrogenic activity of guajadial, which possibly acts in tumor inhibition through estrogen receptors due to the compounds structural similarity to tamoxifen.
Subject(s)
Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , Estrogen Antagonists/pharmacology , Plant Extracts/chemistry , Plant Leaves/chemistry , Psidium/chemistry , Terpenes/pharmacology , Animals , Antineoplastic Agents/therapeutic use , Cell Cycle/drug effects , Cell Line, Tumor , Female , Gas Chromatography-Mass Spectrometry , Humans , Mice , Mice, Inbred BALB C , Ovary/drug effects , Rats , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/therapeutic use , Sesquiterpenes/toxicity , Terpenes/chemistry , Terpenes/therapeutic use , Terpenes/toxicity , Uterus/drug effects , Xenograft Model Antitumor AssaysABSTRACT
Aphanamoxene A-D (1-4), three new acyclic diterpene derivatives and one new acyclic norsesquiterpene were isolated from the seed of Aphanamixis polystachya. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D and 2D NMR and HRESIMS. And the absolute configuration of 1 was achieved by Mosher method. These acyclic terpenoids (1-4) showed obvious nitric oxide production inhibitory activity on lipopolysaccharide-Induced RAW264.7 macrophages with IC50 values of 17.6 ± 1.4, 9.8 ± 0.7, 16.6 ± 1.2, and 14.2 ± 0.9 µM, respectively.
Subject(s)
Diterpenes/isolation & purification , Meliaceae/chemistry , Sesquiterpenes/isolation & purification , Animals , Diterpenes/chemistry , Diterpenes/toxicity , Mice , RAW 264.7 Cells , Seeds/chemistry , Sesquiterpenes/chemistry , Sesquiterpenes/toxicityABSTRACT
Nerolidol is a sesquiterpene found in essential oils of several plant species. It is found commonly in human and animal diets and is approved by the US Food and Drug Administration as a flavoring agent. Nevertheless, recent studies have suggested that nerolidol has potent hepatotoxic effects. Because use of plant-based products in human and animal food has expanded considerably, it is essential to develop approaches such as nanotechnology to avoid or reduce hepatic toxic effects. Therefore, the aim of the study was to determine whether nerolidol dietary supplementation elicited hepatic damage associated with impairment of energy homeostasis, as well as whether supplementation with nerolidol-loaded in nanospheres prevented hepatotoxic effects in Nile tilapia (Oreochromis niloticus). Nile tilapia were divided into five groups (A-E, n = 10 per group) with four replicates each, as follows: group A received basal feed (without supplementation); group B received feed containing 0.5 mL free nerolidol/kg; group C received feed containing 1.0 mL free nerolidol/kg; group D received feed containing 0.5 mL nanospheres nerolidol/kg; and group E received feed containing 1.0 mL nanospheres nerolidol/kg. All groups received experimental feed once a day (10% total biomass) at 2 p.m. for 60 consecutive days. Hepatic liver weight and relative liver weight were significantly lower in fish fed 1.0 mL free nerolidol/kg feed than in fish given basal diet (control group). Hepatic pyruvate kinase (1.0 mL free nerolidol/kg) and adenylate kinase (0.5 and 1.0 mL free nerolidol/kg) activities were significantly lower than in the control group, while hepatic reactive oxygen species and lipid damage levels were significantly higher. Finally, the comet assay revealed significant increases in the frequency of damage and the damage index in fish given 0.5 and 1.0 mL free nerolidol/kg in a dose-dependent manner. Nerolidol-loaded in nanospheres prevented all alterations elicited by free nerolidol. Based on these data, we concluded that dietary supplementation with free nerolidol elicited severe impairment of hepatic bioenergetics homeostasis that appeared to be mediated by excessive ROS production and lipid damage, contributing to a genotoxic effect. Dietary supplementation with nerolidol-loaded in nanospheres did not elicit hepatic damage, and therefore, should be considered as a replacement so as to limit toxicity, permitting its continued use as a dietary supplement.
Subject(s)
Chemical and Drug Induced Liver Injury/prevention & control , Cichlids/metabolism , Dietary Supplements/toxicity , Energy Metabolism/drug effects , Liver/drug effects , Nanospheres , Sesquiterpenes/toxicity , Adenosine Triphosphate/metabolism , Animal Feed , Animals , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , DNA Damage , Lipid Peroxidation/drug effects , Liver/metabolism , Liver/pathology , Oxidative Stress/drug effectsABSTRACT
Skin contact or exposure to sensitizers often occurs as a consequence of occupational exposures (e.g. poison ivy in forestry), wearing jewelry (e.g. nickel), or use of cosmetics (e.g. fragrances). However, many of the known skin sensitizers or their chemical variants are also consumed orally through foods or other sources. Since oral exposure to antigenic substances can lead to tolerance, consumption of sensitizers may impact the development and potency of skin sensitization, especially if the sensitizer is consumed early in life, prior to the first skin contact. To address this issue, we have reviewed human clinical and epidemiological literature relevant to this subject and evaluated whether early oral exposures to relevant sensitizers, or their chemical variants, are associated with reduced prevalence of skin sensitization to three main allergic sensitizers - nickel, urushiols of poison ivy, and sesquiterpene lactones of chrysanthemum and other plants.
Subject(s)
Dermatitis, Allergic Contact/immunology , Lactones/toxicity , Nickel/toxicity , Plant Extracts/toxicity , Sesquiterpenes/toxicity , Skin/immunology , Toxicodendron/toxicity , Dermatitis, Allergic Contact/etiology , Diet , Humans , Skin/drug effects , Toxicodendron/immunologyABSTRACT
BACKGROUND: The current drugs for Chagas disease treatment present several limitations. METHODS: The sesquiterpene lactone goyazensolide (GZL) was evaluated regarding to cytotoxicity and trypanocidal activity against amastigotes, selectivity index (SI) in vitro, acute toxicity and anti-Trypanosoma cruzi activity in vivo. RESULTS: The in vitro cytotoxicity in H9c2 cells was observed at doses >250 ng mL-1 of GZL and the SI were of 52.82 and 4.85 (24 h) and of 915.00 and 41.00 (48 h) for GZL and BZ, respectively. Nephrotoxicity and hepatotoxicity were not verified. Treatment with GZL of mice infected with CL strain led to a significant decrease of parasitaemia and total survival at doses of 1 and 3 mg kg-1 day-1 by oral and IV, respectively. This last group cured 12.5% of the animals (negativation of HC, PCR, qPCR and ELISA). Animals infected with Y strain showed significant decrease of parasitaemia and higher negativation in all parasitological tests in comparison to BZ and control groups, but were ELISA reactive, as well as the BZ group, but mice treated with 5.0 mg kg-1 day-1 by oral were negative in parasitological tests and survived. CONCLUSION: GZL was more active against T. cruzi than benznidazole in vitro and presented important therapeutic activity in vivo in both T. cruzi strains.
Subject(s)
Bridged-Ring Compounds/pharmacology , Bridged-Ring Compounds/therapeutic use , Chagas Disease/drug therapy , Furans/pharmacology , Furans/therapeutic use , Sesquiterpenes/pharmacology , Sesquiterpenes/therapeutic use , Sesterterpenes/pharmacology , Sesterterpenes/therapeutic use , Trypanosoma cruzi/drug effects , Animals , Bridged-Ring Compounds/toxicity , Cell Line , Cell Survival/drug effects , Disease Models, Animal , Furans/toxicity , Mice , Nitroimidazoles/pharmacology , Nitroimidazoles/therapeutic use , Sesquiterpenes/toxicity , Sesterterpenes/toxicity , Survival Analysis , Trypanocidal Agents/pharmacology , Trypanocidal Agents/therapeutic use , Trypanocidal Agents/toxicityABSTRACT
Euptox A, from Ageratina adenophora juice, is a toxin associated with the plant's resistance to infections, invasiveness and traditional use in cancer treatment. We used FTIR spectroscopy and protein profiling of cell lines to study the impact of euptox A on human cells, to clarify its mechanism of action in a top-down approach. Euptox A was extracted from the juice of A. adenophora. Its stability in the gastrointestinal tract was evaluated, as the compound/juice is generally taken orally. Cytotoxicity was determined in HeLa, Caco-2 and MCF7 cells, and the mechanism of action analyzed by protein and metabolite profiles using electrophoresis and FTIR spectroscopy. Euptox A resisted gastrointestinal digestion and was the most cytotoxic component of the extract for all cell lines tests. Euptox A-treated HeLa cells showed changes in protein profile, especially on 40S ribosomal protein S8 (RP), generally associated with cancer cells. FTIR profiles of treated cells diverged in the same metabolites as cells treated with cisplatin, both in metabolite directed analysis and in multivariate analysis (principal component analysis). In conclusion, euptox A in this top-down study showed a cellular impact that suggests a strong potential against cancer, acting on cancer targeted cellular characteristics.
Subject(s)
Sesquiterpenes/toxicity , Ageratina , Caco-2 Cells , Cell Survival/drug effects , Chromatography, Liquid , Gastric Juice/chemistry , HeLa Cells , Humans , MCF-7 Cells , Mass Spectrometry , Pancreatic Juice/chemistry , Plant Extracts , Proteome/drug effects , Sesquiterpenes/chemistry , Spectroscopy, Fourier Transform InfraredABSTRACT
In this study, we developed an intravenously injectable, transferrin-functionalised microemulsion that simultaneously carries ß-elemene and celastrol (called Tf-EC-MEs) for enhanced anti-lung cancer treatment and reduced systemic toxicity. These dual-drug-loaded Tf-EC-MEs not only displayed synergistic antiproliferative effects on cultured cells in vitro, but also showed enhanced efficacy in vivo via active tumour targeting. In preparatory experiments, we found that ß-elemene was capable of being used as oil phase, which enhanced drug-loading efficiency and allowed the mass ratio of ß-elemene and celastrol to be optimised. In cellular studies, Tf-EC-MEs exhibited significantly improved A549 cellular uptake compared with ß-elemene+celastrol (conventional combination treatment) and EC-MEs (non-active targeted treatment), demonstrating remarkable synergistic antiproliferative effects and higher rates of cell apoptosis. In A549-bearing xenograft mouse tumour models, Tf-EC-MEs exhibited enhanced antitumour activity compared to all other treatments. More importantly, Tf-EC-MEs did not cause the obvious systemic toxicity commonly found with mono-celastrol treatment. Collectively, these findings suggest that Tf-EC-MEs are a promising strategy for the combination drug treatment of lung cancer.
Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Lung Neoplasms/drug therapy , Sesquiterpenes/administration & dosage , Transferrin/administration & dosage , Triterpenes/administration & dosage , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/toxicity , Apoptosis/drug effects , Cell Line, Tumor , Drug Synergism , Emulsions , Female , Humans , Lung Neoplasms/pathology , Male , Mice, Inbred BALB C , Mice, Nude , Pentacyclic Triterpenes , Sesquiterpenes/chemistry , Sesquiterpenes/toxicity , Transferrin/chemistry , Triterpenes/chemistry , Triterpenes/toxicityABSTRACT
A new cadinane sesquiterpenoid glucoside, 2ß,7,3-trihydroxycalamenene 3-O-ß-d-glucoside (1) together with six known compounds, N-(p-trans-coumaroyl)-N-methyl tyramine (2), Cleomiscosin A (3), 9,12,13-trihydroxy-10,15-heptadecadienoic acid (4), Cytochalasin B (5), Marmesinin (6) and N-(p-trans-coumaroyl) tyramine (7) were obtained from the stem bark of Abelmoschus sagittifolius. The new structure of compound 1 was elucidated by analysing its 1H and 13C-NMR, 1H-1H COSY, HSQC, HMBC, NOESY and HR-ESI-MS spectra. Compounds 1-7 showed moderate cytotoxicity against Hela and HepG-2 human cancer cell lines.
Subject(s)
Abelmoschus/chemistry , Sesquiterpenes/isolation & purification , Cell Line, Tumor , Glucosides/chemistry , Glucosides/isolation & purification , HeLa Cells , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Structure , Plant Extracts/chemistry , Polycyclic Sesquiterpenes , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/toxicityABSTRACT
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⯱â¯0.77⯵g/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⯱â¯1.67⯵M) 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.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Curcuma/chemistry , Rhizome/chemistry , Sesquiterpenes/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/toxicity , Cyclooxygenase 2/metabolism , Mice , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/toxicity , RAW 264.7 Cells , Sesquiterpenes/isolation & purification , Sesquiterpenes/toxicityABSTRACT
Two new stilbenoids, named 2,3 -dimethoxyl-7-hydroxyl-1,4-phenanthrenedione (1) and 2-methoxyl-3-methyl-7-hydroxyl-9,10-dihydro-1,4-phenanthrenedione (2), together with two known stilbenoids including densiflorol B (3) and ephemeranthoquinone (4), were isolated from aerial parts of Flickingeria fimbriata (Bl.) Hawkes. The structures of two new compounds were elucidated by extensive spectroscopic analysis, including HRESIMS, 1H and 13C NMR, DEPT, HMBC, COSY, HMQC, NOESY. All the compounds were obtained from this genus for the first time. In addition, they all exhibited moderate cytotoxic activities against HepG2 cell lines.
Subject(s)
Orchidaceae/chemistry , Plant Components, Aerial/chemistry , Sesquiterpenes/isolation & purification , Stilbenes/isolation & purification , Drugs, Chinese Herbal , Hep G2 Cells/drug effects , Humans , Molecular Structure , Polycyclic Sesquiterpenes , Sesquiterpenes/chemistry , Sesquiterpenes/toxicity , Stilbenes/chemistry , Stilbenes/toxicityABSTRACT
Treatment of drug resistant protozoa, bacteria, and viruses requires new drugs with alternative chemotypes. Such compounds could be found from Southeast Asian medicinal plants. The present study examines the cytotoxic, antileishmanial, and antiplasmodial effects of 11 ethnopharmacologically important plant species in Malaysia. Chloroform extracts were tested for their toxicity against MRC-5â¯cells and Leishmania donovani by MTT, and chloroquine-resistant Plasmodium falciparum K1 strain by Histidine-Rich Protein II ELISA assays. None of the extract tested was cytotoxic to MRC-5â¯cells. Extracts of Uvaria grandiflora, Chilocarpus costatus, Tabernaemontana peduncularis, and Leuconotis eugenifolius had good activities against L. donovani with IC50â¯<â¯50⯵g/mL. Extracts of U. grandiflora, C. costatus, T. peduncularis, L. eugenifolius, A. subulatum, and C. aeruginosa had good activities against P. falciparum K1 with IC50â¯<â¯10⯵g/mL. Pinoresinol isolated from C. costatus was inactive against L. donovani and P. falciparum. C. costatus extract and pinoresinol increased the sensitivity of Staphylococcus epidermidis to cefotaxime. Pinoresinol demonstrated moderate activity against influenza virus (IC50â¯=â¯30.4⯱â¯11⯵g/mL) and was active against Coxsackie virus B3 (IC50â¯=â¯7.1⯱â¯3.0⯵g/mL). ß-Amyrin from L. eugenifolius inhibited L. donovani with IC50 value of 15.4⯱â¯0.01⯵M. Furanodienone from C. aeruginosa inhibited L. donovani and P. falciparum K1 with IC50 value of 39.5⯱â¯0.2 and 17.0⯱â¯0.05⯵M, respectively. Furanodienone also inhibited the replication of influenza and Coxsackie virus B3 with IC50 value of 4.0⯱â¯0.5 and 7.2⯱â¯1.4⯵g/mL (Ribavirin: IC50: 15.6⯱â¯2.0⯵g/mL), respectively. Our study provides evidence that medicinal plants in Malaysia have potentials as a source of chemotypes for the development of anti-infective leads.
Subject(s)
Anti-Infective Agents/pharmacology , Leishmania donovani/drug effects , Medicine, East Asian Traditional/methods , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Plasmodium falciparum/drug effects , Anti-Infective Agents/toxicity , Apocynaceae/chemistry , Cell Line , Drug Synergism , Enterovirus B, Human/drug effects , Ethnopharmacology/methods , Furans/chemistry , Furans/isolation & purification , Furans/pharmacology , Furans/toxicity , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Influenza A Virus, H1N1 Subtype/drug effects , Inhibitory Concentration 50 , Lignans/chemistry , Lignans/isolation & purification , Lignans/pharmacology , Lignans/toxicity , Malaysia , Plant Extracts/chemistry , Plant Extracts/toxicity , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Sesquiterpenes/toxicity , Tabernaemontana/chemistry , Uvaria/chemistryABSTRACT
Stem barks of Drimys brasiliensis (Winteraceae) are consumed by the population in the form of a condiment. It is widely used to treat gastric and stomach problems and also to treat cancer. The extracts have demonstrated antiproliferative, antileishmanial and antimicrobial activities assigned to drimane sesquiterpenes. This study aimed to optimize the extraction conditions of the drimanes sesquiterpenes identified as 1-ß-(p-coumaroyloxy)-polygodial 1, drimanial 2 and 1-ß-(p-methoxycinnamoyl)-polygodial 3 in stem bark extracts. The HPLC-DAD method was developed and validated for the quantification of drimanes 1-3. The cytotoxic activity of these drimanes in human cancer cells, and the toxicological effects of the hydroethanolic extract, were determined. The extracts were prepared using different extractive conditions (solvents, plant: solvent ratio and time). The cytotoxicity effect was evaluated against leukemia, lymphomas, carcinomas and sarcomas cells using the tetrazolium assay (MTT). Furthermore, the acute toxicity was determined by measuring the biochemical parameters and by histopathological analysis. The hemolytic activity and micronucleus test were also performed. The method was linear, sensitive, precise and accurate for both drimanes 1-3. The best condition for extraction was using dichloromethane with plant: solvent proportion 1:10 (w/v) for six hours under dynamic maceration. Isolated drimanes exhibited cytotoxic effects with IC50 values ââranging from 0.13 to 112.67 µM. Compound 1 demonstrated significant results for acute promyelocytic leukemia (NB4) and Burkitt's lymphoma (RAMOS) cells while driamane 3 for Burkitt's lymphoma (RAJI) and acute T cell leukemia (MOLT4) cells. No signs of toxicity was observed and neither was mutagenicity or hemolytic activity.
Subject(s)
Drimys/chemistry , Plant Bark/chemistry , Plant Stems/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/toxicity , Toxicity Tests, Acute , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Ethanol/chemistry , Hemolysis/drug effects , Humans , Limit of Detection , Micronucleus Tests , Organ Size/drug effects , Plant Extracts/pharmacology , Plant Extracts/toxicity , Polycyclic Sesquiterpenes , Rats, Wistar , Reproducibility of Results , Sesquiterpenes/chemistryABSTRACT
Public interest in natural therapies has increased significantly over past decades. Herbs and herbal products are extensively consumed worldwide and they are generally considered as safe. However, this may not always be true as many cases of herb-induced liver injury are reported every year. The liver is a frequent target tissue of toxicity from all classes of toxicants as liver structure and function predispose it to high sensitivity to xenobiotics. The present review is focused on the hepatotoxic properties of monoterpenes and sesquiterpenes, plant secondary metabolites that represent the major components of essential oils wildly used in folk medicines, pharmaceutical industry and cosmetics. Most of these terpenes easily enter the human body by oral absorption, penetration through the skin, or inhalation leading to measurable blood concentrations. Several studies showed that some monoterpenes (e.g., pulegone, menthofuran, camphor, and limonene) and sesquiterpenes (e.g., zederone, germacrone) exhibited liver toxicity, which is mainly based on reactive metabolites formation, increased concentration of reactive oxygen species and impaired antioxidant defense. There is a high probability that many other terpenes, without sufficiently known metabolism and effects in human liver, could also exert hepatotoxicity. Especially terpenes, that are important components of essential oils with proved hepatotoxicity, should deserve more attention. Intensive research in terpenes metabolism and toxicity represent the only way to reduce the risk of liver injury induced by essential oils and other terpenes-containing products.