Article

Terpenoids from Stinking toe (Hymneae courbaril) fruits with cyclooxygenase and lipid peroxidation inhibitory activities

December 2007
Food Chemistry 105(2):485-490

DOI:10.1016/j.foodchem.2007.04.004

Authors:

Bolleddula Jayaprakasam

Ruby Lisa Alexander-Lindo

University of the West Indies

Deborah Dewitt

University of Maryland, Baltimore

Muraleedharan Gopalan Nair

Michigan State University

Stinking toe (Hymenaea courbaril), also called Jatoba and Kerosene tree, is a medicinal plant commonly found in the central and South American countries. In the Caribbean, Mexico and Brazil, the powdery sweet dust of its fruit is consumed for energy. The chemical examination of the yellowish sweet powder of the fruit yielded sucrose and linolenic acid as major compounds. The pods yielded the labdane diterpenoids crotomachlin (1), labd-13E-en-8-ol-15-oic acid (2), labdanolic acid (4), (13E)-labda 7, 13 dien-15-oic acid (5) and labd-8 (17), 13E- dien-15-oic acid (6), along with the sesquiterpene, spathulenol (7), as confirmed by 1H and 13C NMR spectral studies. The methyl ester of labd-13E-en-8-ol-15-oic acid (3) was also characterized during the purification of compound 5. The total amount of these terpenoids in the fruit was about 0.1% (w/w) of the dried fruit. Compounds 1–5 and 7 were assayed for anti-inflammatory activity using cyclooxygenase-1 (COX-1) and -2 (COX-2) enzymes. At 100 ppm, compounds 3 and 4 showed selective COX-2 enzyme inhibition. Also, compounds 1, 2 and 5 inhibited lipid peroxidation by 46%, 48% and 75%, respectively, at 100 ppm. These compounds were isolated from this fruit and their COX and lipid peroxidation inhibitory activities are reported for the first time in this paper.

Chemical, Botanical and Pharmacological Aspects of the Leguminosae

Article

Full-text available

Dec 2020

In Vitro and In Silico Anticyclooxygenase and Antitopoisomerase Activity of Anonna cherimola Ent-Kaurenes

Article

Full-text available

Sep 2024

Annona cherimola is noted for its bioactive compounds, particularly diterpenes called ent-kaurenes, which exhibit various biological activities. This study focused on evaluating the ability of ent-kaurenes from Annona cherimola to inhibit cyclooxygenase (COX) and topoisomerase (TOP) enzymes. Researchers used solvent-free lipophilic eluates (SFLEs) from the plant in enzymatic assays and a yeast model. The major compounds in SFLE were identified using gas chromatography–mass spectrometry (GC-MS), and in silico studies explored their inhibition mechanisms. SFLE showed significant inhibition of COX-II (95.44%) and COX-I (75.78%) enzymes and fully inhibited the yeast strain. The effectiveness of inhibition is attributed to the compounds’ structural diversity, lipophilicity, and molecular weight. Two main compounds, kauran-16-ol and isopimaral, were identified, with in silico results suggesting that they inhibit COX-II by blocking peroxidase activity and COX-I by interacting with the membrane-binding region. Additionally, these compounds allosterically and synergistically inhibit TOP-II and potentially sensitize cancer cells by interacting with key amino acids. This research is the first to identify and evaluate kauran-16-ol and isopimaral in silico, suggesting their potential as anti-inflammatory and anticancer agents.

Crude extract of Jatobá leaves promotes canine osteosarcoma cell D17 proliferation

Article

Full-text available

May 2022
Vet. World

Background and Aim: New substances for neoplasm treatment have to be carefully studied to minimize adverse effects and prevent disease progression stimulation. Jatobá is a typical tree of the Cerrado and Caatinga biome, with antifungal, antimicrobial, larvicide, antioxidant, and antiproliferative properties. This study aimed to investigate the action of the crude extract of Jatobá leaves (EBFJ) on canine osteosarcoma (CO) cells and analyze the expression of biomarkers in neoplasm progression. Materials and Methods: D17 cells were cultured and subjected to treatment with EBFJ at different concentrations (10 μg/ mL; 100 μg/mL; 1000 μg/mL; 2000 μg/mL; and 5000 μg/mL) and exposure times (24 h, 48 h, and 72 h). The tetrazolium reduction assay and the immunocytochemistry technique, with anti-Bcl2, anti-p53, and anti-Ki-67 antibodies, were used to observe the effect of the extract on cell proliferation. Results: Doses of 2000 µg and 5000 µg had cell viability of 300.80% and 361.84%, respectively. The extract did not show significant cytotoxicity of samples with the control group. The confluence of cells, the number of labeled cells, and the expression of Bcl2, Ki-67, and p53 were higher in the groups treated with EBFJ, with a statistical difference from the group without treatment. Conclusion: EBFJ was not cytotoxic and had a proliferative effect on CO D17 cells. The confluence of cells, the number of labeled cells, and the expression of Bcl2, Ki-67, and p53 were higher in the groups treated with the extract.

STITCH, Physicochemical, ADMET, and In Silico Analysis of Selected Mikania Constituents as Anti-Inflammatory Agents

Article

Full-text available

Jun 2023

The Mikania genus has been known to possess numerous pharmacological activities. In the present study, we aimed to evaluate the interaction of 26 selected constituents of Mikania species with (i) cyclooxygenase 2 (COX 2), (ii) human neutrophil elastase (HNE), (iii) lipoxygenase (LOX), matrix metalloproteinase ((iv) MMP 2 and (v) MMP 9), and (vi) microsomal prostaglandin E synthase 2 (mPGES 2) inhibitors using an in silico approach. The 26 selected constituents of Mikania species, namely mikamicranolide, kaurenoic acid, stigmasterol, grandifloric acid, kaurenol, spathulenol, caryophyllene oxide, syringaldehyde, dihydrocoumarin, o-coumaric acid, taraxerol, melilotoside, patuletin, methyl-3,5-di-O-caffeoyl quinate, 3,3′,5-trihydroxy-4′,6,7-trimethoxyflavone, psoralen, curcumene, herniarin, 2,6-dimethoxy quinone, bicyclogermacrene, α-bisabolol, γ-elemene, provincialin, dehydrocostus lactone, mikanin-3-O-sulfate, and nepetin, were assessed based on the docking action with COX 2, HNE, LOX, MMP 2, MMP 9, and mPGES 2 using Discovery Studio (in the case of LOX, the Autodock method was utilized). Moreover, STITCH (Search Tool for Interacting Chemicals), physicochemical, drug-likeness, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analyses were conducted utilizing the STITCH web server, the Mol-inspiration web server, and Discovery Studio, respectively. In the present study, STITCH analysis revealed only six ligands (dihydrocoumarin, patuletin, kaurenol, psoralen, curcumene, and nepetin) that showed interactions with human proteins. Physicochemical analysis showed that seventeen ligands complied well with Lipinski’s rule. ADMET analysis showed eleven ligands to possess hepatotoxic effects. Significantly, the binding free energy estimation displayed that the ligand methyl-3, 5-di-O-caffeoyl quinate revealed the highest binding energy for all the target enzymes, excluding LOX, suggesting that this may have efficacy as a non-steroidal anti-inflammatory drug (NSAID). The current study presents a better understanding of how Mikania is used as a traditional medicinal plant. Specifically, the 26 ligands of the Mikania plant are potential inhibitor against COX 2, HNE, LOX, MMP 2, MMP 9, and mPGES 2 for treatments for acute and/or chronic inflammatory diseases.

Cerrado and Pantanal fruit flours affect gut microbiota composition in healthy and post‐COVID‐19 individuals: an in vitro pilot fermentation study

Article

Full-text available

Jan 2023
INT J FOOD SCI TECH

Cerrado and Pantanal plants can provide fruits with high nutritional value and antioxidants. This study aims to evaluate four fruit flours (from jatobá pulp, cumbaru almond, bocaiuva pulp and bocaiuva almond) and their effects on the gut microbiota in healthy (HD) and post‐COVID‐19 individuals (PC). An in vitro batch system was carried out, the microbiota was analysed by 16S rRNA amplicon sequencing and the short‐chain fatty acids ratio was determined. Furthermore, the effect of jatobá pulp flour oil (JAO) on cell viability, oxidative stress and DNA damage was investigated in a myelo‐monocytic cell line. Beyond confirming a microbiota imbalance in PC, we identified flour‐specific effects: (i) reduction of Veillonellaceae with jatobá extract in PC samples; (ii) decrease in Akkermansia with jatoba and cumbaru flours; (iii) decreasing trend of Faecalibacterium and Ruminococcus with all flours tested, with the exception of the bocaiuva almond in HD samples for Ruminococcus and (iv) increase in Lactobacillus and Bifidobacterium in PC samples with bocaiuva almond flour. JAO displayed antioxidant properties protecting cells from daunorubicin‐induced cytotoxicity, oxidative stress and DNA damage. The promising microbiota‐modulating abilities of some flours and the chemopreventive effects of JAO deserve to be further explored in human intervention studies.

Potential of Phytomolecules in Sync with Nanotechnology to Surmount the Limitations of Current Treatment Options in the Management of Osteoarthritis

Article

May 2022
MINI-REV MED CHEM

Osteoarthritis (OA), a chronic degenerative musculoskeletal disorder, progressively increases with old age. It is characterized by progressive loss of hyaline cartilage followed by subchondral bone remodelling and inflammaging. To counteract the inflammation, synovium pours various inflammatory and immune mediators along with metabolic intermediates which further worsen the condition. However, even after recognizing the key molecular and cellular factors involved in the progression of OA, only disease-modifying therapies are available such as oral and topical NSAIDs (Non-steroidal anti-inflammatory drugs), Opioids, SNRIs (Serotonin-norepinephrine reuptake inhibitors), etc addressing symptomatic treatment and functional improvement in lieu of suppressing OA progression. Long term use of these therapies leads to various life-threatening complications. Interestingly, mother nature has numerous medicinal plants containing active phytochemicals that can act on various targets involved in the development and progression of OA. Phytochemicals have been used for millennia in traditional herbalism and are promising alternatives with a lower rate of adverse events and efficiency frequently comparable to synthetic molecules. Nevertheless, their mechanism of action in many cases are elusive and/or uncertain. Even though many in vitro and in vivo studies show promising results, clinical evidence is scarce. Studies suggests that, presence of carbonyl group at 2nd, chloro at 6th along with electron withdrawing group at the 7th position exhibited enhanced COX-2 (Cyclo-oxygenase-2) inhibition activity in OA. On the other hand, the presence of a double bond at C2-C3 position of C ring in flavonoids plays an important role in Nrf2 activation. Moreover, with the advancements in the understanding of OA progression, SARs (Structure activity relationships) of phytochemicals and integration with nanotechnology have given great opportunities to develop phytopharmaceuticals. Therefore, in the present review, we have discussed various promising phytomolecules, SAR as well as their nano-based delivery systems for the treatment of OA to motivate the future investigation of phytochemical based drug therapy.

The edible seaweed Laminaria japonica contains cholesterol analogues that inhibit lipid peroxidation and cyclooxygenase enzymes

Article

Full-text available

Jan 2022
PLOS ONE

In this study, 5 sterols were isolated and purified from Laminaria japonica, commonly known as edible brown seaweed, and their structures were identified based on detailed chemical methods and spectroscopic analyses. Spectroscopic analyses characterized 5 sterols as 29-Hydroperoxy-stigmasta-5,24(28)-dien-3β-ol, saringosterol (24-vinyl-cholest-5-ene-3β,24-diol), 24-methylenecholesterol, fucosterol (stigmasta-5,24-diene-3β-ol), and 24-Hydroperoxy-24-vinyl-cholesterol. The bioactivities of these sterols were tested using lipid peroxidation (LPO) and cyclooxygenase (COX-1 and -2) enzyme inhibitory assays. Fucosterol exhibited the highest COX-1 and -2 enzyme inhibitory activities at 59 and 47%, respectively. Saringosterol, 24-methylenecholesterol and fucosterol showed higher LPO inhibitory activity at >50% than the other compounds. In addition, the results of molecular docking revealed that the 5 sterols were located in different pocket of COX-1 and -2 and fucosterol with tetracyclic skeletons and olefin methine achieved the highest binding energy (-7.85 and -9.02 kcal/mol) through hydrophobic interactions and hydrogen bond. Our results confirm the presence of 5 sterols in L. japonica and its significant anti-inflammatory and antioxidant activity.

In vivo evaluation of the toxic activity and genotoxicity of the Hymenaea courbaril L.’s resin in Drosophila melanogaster

Article

Full-text available

Sep 2021

Due to the negative consequences carried by the usage of synthetic insecticides, a global interest into finding substitutes for these chemical compounds through natural products has arisen. When yielded to external attacks, plants generally produce metabolites to defend themselves. The physicochemical characteristics of this kind of compounds have allowed their usage as potential bioinsecticides. The Hymenaea courbaril L. (algarrobo) has proven to be a plant rich in metabolites with outstanding biological activity, in such a way that some of its extracts have been tested as insecticides. The goal of this study was to know the phytochemical composition of Hymenaea courbaril L.’s resin and perform evaluations in vivo of its toxic and genotoxic effects in the biological model Drosophila melanogaster. For this, two resin extracts were prepared and both a phytochemical analysis were carried out on them, having found in the ethanolic total extract the presence of terpenes, flavonoids and coumarins, while in the partial ethanolic extract only presence of terpenes and flavonoids was found. Drosophila larvae were submitted to different concentrations of the extracts and both the survival and the sexual ratio were evaluated, finding that larvae are more sensitive to the partial ethanolic extract. Subsequently, the induction of somatic mutation and mitotic recombination (SMART) was evaluated in the flies’ eyes. The most significant affectations at a genotoxic level were found when larvae were tested with the partial extract, indicating that possibly the coumarins absence makes this insect more susceptible to damages at a genetic material level.

Stevia Genus: Phytochemistry and Biological Activities Update

Article

Full-text available

May 2021
MOLECULES

The Stevia genus (Asteraceae) comprises around 230 species, distributed from the southern United States to the South American Andean region. Stevia rebaudiana, a Paraguayan herb that produces an intensely sweet diterpene glycoside called stevioside, is the most relevant member of this genus. Apart from S. rebaudiana, many other species belonging to the Stevia genus are considered medicinal and have been popularly used to treat different ailments. The members from this genus produce sesquiterpene lactones, diterpenes, longipinanes, and flavonoids as the main types of phytochemicals. Many pharmacological activities have been described for Stevia extracts and isolated compounds, antioxidant, antiparasitic, antiviral, anti-inflammatory, and antiproliferative activities being the most frequently mentioned. This review aims to present an update of the Stevia genus covering ethnobotanical aspects and traditional uses, phytochemistry, and biological activities of the extracts and isolated compounds.

Óleo essencial das cascas descartadas do fruto de Hymenaea courbaril L. como larvicida frente Aedes aegypti

Article

Full-text available

Sep 2020

Este estudo objetivou avaliar a atividade larvicida do óleo essencial (OE) extraído das cascas do fruto comumente descartadas de Hymenaea coubaril L. Para extração do OE foi utilizada a técnica de hidrodestilação em um sistema extrator de Clevenger modificado. Os constituintes químicos foram obtidos por Cromatografia Gasosa acoplada a espectrometria de massas (CG/EM). Para atividade larvicida submeteu-se larvas de Aedes aegypti a soluções do OE em concentrações de 10-100 mg L-1, onde avaliou-se a mortalidade das larvas e determinou-se a CL50. O β-ocimeno foi quantificado como majoritário no OE. Observou-se ação do OE como larvicida onde foi determinada a CL50 de 16,6 mg L-1. Os resultados obtidos permitiram concluir que o OE estudado apresentou atividade larvicida eficiente contra as larvas de Aedes aegypti, sendo importante e incentivado seu uso e aplicação.

Natural Product Inhibitors of Cyclooxygenase (COX) Enzyme: A Review on Current Status and Future Perspectives

Article

Jun 2020

Background Several clinically used COX-1 and COX-2 inhibitor drugs were reported to possess severe side effects like GI ulcers and cardiovascular disturbances, respectively. Natural products being structurally diverse always attracted the attention of chemists/medicinal chemists as a potential source of lead molecules in drug discovery process. COX-2 inhibitory natural products also possess potential cancer chemopreventive property against various cancers including that of colon, breast, and prostate. Methods Various in vitro, in vivo, in silico standardized methods were used to evaluate COX inhibition property of different secondary metabolites isolated from plant, microbial and marine origin. Results We had earlier reported a detailed account of natural product inhibitors of COX reported during 1995-2005 in 2006. In the proposed review we report 158 natural product inhibitors of COX during 2006 to 2019 belonging to various secondary metabolite classes such as alkaloids, terpenoids, polyphenols as flavonoids, chromones, coumarins, lignans, anthraquinones, naphthalenes, curcuminoids, diarylheptanoids and miscellaneous compounds of plant and marine origin. Further structure activity relationship (SAR) studies of possible leads are also included in the article. Conclusion COX inhibitors served as a potential source of lead molecules for discovery and development of anti-inflammatory drugs. Compilation of natural product and semi-synthetic inhibitors of COX may serve as valuable information to the researchers who are looking for possible lead molecules from natural source to conduct further preclinical and clinical studies.

Genotoxicity, anti-melanoma and antioxidant activities of Hymenaea courbaril L. seed extract

Article

Full-text available

Dec 2019
AN ACAD BRAS CIENC

Hymenaea courbaril has been used to treat different diseases, although its properties are yet to be scientifically validated. The objective of this study was to determine the cytotoxicity, genotoxicity, antigenotoxicity and antioxidant potentials of hydroethanolic extract from H. courbaril seeds. Therefore, for the cytotoxicity test an anti-melanoma assay was performed in B16F10 strain cells. The genotoxicity and antigenotoxicity was evaluated in bone marrow cells (Permit number: 002/2010) of mice, the antioxidant activity was determined by the DPPH test and the total flavonoid content was also determined. The hydroethanolic extract showed antigenotoxic effect and antioxidant activity. It was verified that total flavonoid content was 442.25±18.03 mg RE/g dry extract. HPLC-PAD chromatogram revealed presence of flavones as majority compound in evaluated extract. The results allowed us to also infer that the hydroethanolic extract from seeds shows cytotoxic activity against B16F10 melanoma cells line and it has dose-and-time-dependency.

Fabaceae medicinal flora with therapeutic potential in Savanna areas in the Chapada do Araripe, Northeastern Brazil

Article

Full-text available

Sep 2018
REV BRAS FARMACOGN

Fabaceae is one of the largest families of ethnopharmacological importance. From this botanical group, important chemical constituents that act in the treatment and/or healing of various bodily systems arise. The objective of this study was to evaluate the most versatile Fabaceae species and the agreement of use among the informants, in the Chapada do Araripe Savanna. The research included five rural communities located in the municipalities of Nova Olinda, Crato, Barbalha, Moreilândia and Exu, covering the states of Ceará and Pernambuco. We conducted semi-structured interviews with 126 informants, adopting the snowball technique and using a standardized form. The relative importance and the Informant Consensus Factor were analyzed for the selection of species with therapeutic potential. Twenty-six medicinal species, distributed across 22 genera, were associated with seventy therapeutic purposes. As for the habitat of the species, the arboreal habitat predominated (76.92%). In relation to the plant parts, the bark (28.57%) and stem inner bark (26.53%) were the most used structures. Among the species, four showed great versatility in relation to their uses, with relative importance (RI¯>1), these being: Copaifera langsdorffii Desf. (1.70), Stryphnodendron rotundifolium Mart. (1.52), Bowdichia virgiloides Kunth (1.10) and Amburana cearenses (Allemand) A. C. Sm. (1.02). These species had eight to thirty curative properties and ranged from five to twelve body systems. The therapeutic indications cited were grouped into sixteen categories of body systems, of which Sensory System Disorders and Mental and Behavioral Diseases presented maximum values for the Informant Consensus Factor. For the Sexual Impotence category there was no agreement, whereas for the remaining systems the Informant Consensus Factor ranged from 0.33 to 0.91. The study evidences that the information of use and/or knowledge are shared among the people within the community, proving the great importance of Fabaceae in the use of medicinal plants.

Proteomic Insights on the Metabolism of Penicillium janczewskii during the Biotransformation of the Plant Terpenoid Labdanolic Acid

Article

Full-text available

Jul 2017

Plant terpenoids compose a natural source of chemodiversity of exceptional value. Many of these compounds own biological/pharmacological activity, others are regarded as unique chemical skeletons for the synthesis of derivatives with improved properties. Functional chemical modification of terpenoids through biotransformation frequently relies on the use of Ascomycota strains, but information on major cellular responses is still largely lacking. Penicillium janczewskii mediates a stereo-selective hydroxylation of labdanolic acid (LA)—terpenoid found abundantly in Cistus ladanifer—producing 3β-hydroxy-labdanolic acid with yields >90%. Herein, combined analyses of mycelial and extracellular differential proteomes demonstrated that the plant terpenoid increased stress responses, especially against oxidative stress (e.g., accumulation of superoxide dismutase) and apparently altered mitochondria functioning. One putative cytochrome P450 monooxygenase differentially accumulated in the secretome and the terpenoid bioconversion was inhibited in vivo in the presence of a P450 inhibitor. The stereo-selective hydroxylation of the plant terpenoid is likely mediated by P450 enzymes, yet its unequivocal identity remains unclear. To the best of our knowledge, this is the first time that proteomics was used to investigate how a plant terpenoid impacts the metabolism of a filamentous fungus during its efficiently biotransformation. Our findings may encourage the development of new strategies for the valorization of plant natural resources through biotechnology.

Efeito antimicrobiano e modulador do óleo essencial extraído da casca de frutos da Hymenaea courbaril L

Article

Full-text available

Aug 2014

RESUMO O Jatobá (Hymenaea courbaril L.) possui um amplo histórico de utilização, seus frutos são compostos por óleos essenciais, taninos, substâncias amargas, matérias resinosas e pécticas, amido e açúcares. O objetivo deste estudo foi avaliar a atividade antimicrobiana e moduladora do óleo essencial extraído da casca de frutos da Hymenaea courbaril L. (OEHc) sobre cepas de S. aureus oxacilina sensíveis (OSSA) de referência. Para a avaliação da atividade antimicrobiana foram determinadas as Concentrações Inibitória (CIM) e Letal Mínimas (CLM) do OEHc e o efeito do tempo de exposição a concentrações do OEHc, o efeito modulador do OEHc sobre antibióticos de uso clínico foi avaliado pelo teste de difusão em ágar modificado. OEHc inibiu o crescimento das cepas de S. aureus ATCC 6538P (CIM = CLM = 0,28% v/v) e S. aureus ATCC 14458 (CIM = 0,28% v/v; CLM = 0,56% v/v). A CLM do OEHc foi capaz de inviabilizar as cepas OSSA testadas em 8 horas (S. aureus ATCC 6538P) e 24 horas (S. aureus ATCC 14458) e a CIM inibiu o crescimento de S. aureus ATCC 14458 até 48h de exposição. A ação moduladora do OEHc na atividade de antibióticos de uso clínico variou com o ATM e com a cepa testada. Os resultados encontrados mostram que o OEHc possui uma boa atividade antimicrobiana sobre a espécie Gram-positivo S. aureus, revelando seu efeito modulador sinérgico quando associado a antibióticos de uso clínico, demonstrando ser o OEHc um forte candidato para o desenvolvimento de fármacos com atividade antimicrobiana. Palavras-chave: Hymenaea. Planta medicinal. Óleo essencial. Testes de sensibilidade bacteriana. Potencialização da ação de fármacos. Staphylococcus aureus.

Atividade Anti-inflamatória de Produtos de Origem Vegetal

Article

Full-text available

Apr 2015

Normal 0 false false false PT-BR JA X-NONE A inflamacao e um dos primeiros e o mais importante componente da resposta imune a infeccao e que pode desencadear uma serie de doencas como artrite, câncer, diabetes e hepatite. Durante o processo inflamatorio ocorre a liberacao de compostos inflamatorios os quais podem ser inibidos por substâncias com propriedades antiinflamatorias que podem ser obtidos atraves da alimentacao. Os vegetais sao fontes destes compostos antiinflamatorios, e por isso, seu consumo deve ser incluido na dieta. Diante do exposto, o presente trabalho tem como objetivo trazer informacoes sobre a importância do consumo de uma dieta rica em frutas na prevencao de doencas inflamatorias. O trabalho esta dividido em quatro secoes: a primeira aborda a recomendacao da ingesta de frutas; a segunda apresenta como se desenvolve os processos inflamatorios; a terceira aborda as propriedades antiinflamatorias presentes nos vegetais; e a quarta contempla as frutas ricas em compostos que podem inibir estagios inflamatorios.

Partial purification of trypsin/papain inhibitors from Hymenaea courbaril L. seeds and antibacterial effect of protein fractions

Article

Full-text available

Mar 2016

The crude extract and protein fractions of Hymenaea courbaril L. seeds were investigated for the presence of trypsin and papain inhibitors and antimicrobial activity against Vibrio parahaemolyticus, Staphylococcus aureus, and Escherichia coli. Protein fractions were obtained from the crude extract after precipitation with ammonium sulfate into three saturation ranges (0-30%, 30-60%, and 60-90%), called Hc030, Hc3060, and Hc6090, respectively. The crude extract and protein fractions inhibited trypsin and papain activity, but to different degrees. Antimicrobial activity was observed in Hc030 and Hc3060 fractions, but only against V. parahaemolyticus.The inhibitor isolated from the Hc3060 fraction was more effective in inhibiting trypsin (100% inhibition) than papain (54% inhibition), and showed an apparent molecular mass of 20 kDa. This study shows that H. courbaril seeds contain proteins with protease-inhibiting and antibacterial activity, indicating that this species is a source of bioactive compounds.

Antimicrobial effect and modulator of essential oil extracted from the fruits peel of Hymenaea courbaril L.

Article

Full-text available

Aug 2014

Jatobá (Hymenaea courbaril L.) has an extensive history of use, its fruits are composed of essential oils, tannins, bitter substances, resinous and pectic materials, starch and sugars. The objective of this study was to evaluate antimicrobial activity and effect of essential oil extracted from the rind of fruits of Hymenaea courbaril l. (OEHc) about reference strains of S. aureus oxacillin susceptible (OSSA). For the evaluation of antimicrobial activity were determined Inhibitory (MIC) and Lethal (CLM) Minimum Concentrations from OEHc and the effect of time of exposure to concentrations of OEHc, OEHc modulator effect on antibiotics of clinical use was assessed by modified agar diffusion test. OEHc inhibited the growth of S. aureus strains ATCC 6538P (CIM = CLM = 0,28% v/v) and S. aureus ATCC 14458 (CIM = 0,28% v/v; CLM = 0,56% v/v). The CLM from OEHc was able to derail the OSSA strains tested in 8 hours (S. aureus ATCC 6538P) and 24 hours (S. aureus ATCC 14458) and the CIM inhibited the growth of S. aureus ATCC 14458 until 48 hours of exposure. The modulatory action of the antibiotic activity of OEHc clinical use ranged with the ATM and with the strain tested. The results show that the OEHc has a good antimicrobial activity on the species Gram-positive S. aureus, revealing its synergistic modulator effect when associated with antibiotics of clinical use, demonstrating the OEHc a strong candidate for the development of drugs with antimicrobial activity. © 2014, Universidade Estadual Paulista (UNESP). All rights reserved.

New glycosylated biscoumarins from Hymenaea coubaril L. seeds

Article

Sep 2015
PHYTOCHEM LETT

Hymenaea coubaril L. seeds are widely used by the population for the treatment of several ailments. Despite its popular use, no other phytochemical studies had been carried out about "Jatobá" seeds. For this reason, this is the first study on the matter and it was carried out with the purpose of finding and identifying the molecules that constitute this seed. This work presented the isolation and elucidation of two new biscoumarins from H. coubaril L. seeds. The new compounds: hymenain 7-O-β-glucopyranosyl-(1′′′ → 2′′)-O-α-apiofuranosyl-(1′′′′ → 2′′′)-O-α-galactopyranoside (1) and hymenain 7-O-β-glucopyranosyl-(1′′′ → 2′′)-O-α-apiofuranoside (2). Their structures were elucidated by extensive 1D and 2D NMR experiments, IR and electrospray high resolution mass spectrometry (ESI-HRMS). © 2015 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.

Sáude em Revista

Article

Full-text available

Jun 2015

Isabella Montenegro Brasil

Resumo A inflamação é um dos primeiros componentes da resposta imune à infecção e que pode estar envolvida em uma série de doenças como artrite, câncer, diabetes e hepatite. Durante o processo inflamató-rio ocorre à liberação de compostos inflamatórios os quais podem ser inibidos por substâncias com propriedades antiinflamatórias que po-dem ser obtidos através da alimentação, dentre estes os produtos de ori-gem vegetal. Os vegetais são fontes destes compostos antiinflamatórios, e por isso, seu consumo deve ser incluído na dieta. Diante do exposto, o presente trabalho teve como objetivo trazer informações sobre a im-portância de uma dieta rica em vegetais no controle de doenças infla-matórias. O trabalho está dividido em quatro seções: a primeira aborda a recomendação da ingestão de frutas; a segunda apresenta como se desenvolve o processo inflamatório; a terceira aborda as propriedades antiinflamatórias presentes nos vegetais; e a quarta contempla as frutas ricas em compostos que podem inibir estágios inflamatórios. Palavras-chave: saúde; anti-inflamatórios; vegetais. Abstract Inflammation is one of the first components of the immune response to infection and that may be involved in a variety of diseases such as arthritis, cancer, diabetes and hepatitis. During inflammation occurs the release of inflammatory compounds which can be inhibited by substances with anti-inflammatory properties which may be obtained from food, such as plants products. The vegetables are sources of these anti-inflammatory compounds, and therefore, their consumption should be included in the diet. Given the above, the present work aims to bring information about the importance of a diet rich in plants products in in-flammatory diseases control. This work is divided into four sections: the first discusses the recommended intake of fruit; the second shows how to develop inflammatory process; the third discusses the anti-inflammatory properties present in plants products; and the section considers the fruits rich in compounds that can inhibit inflammatory stages.

Prasaplai: An essential Thai traditional formulation for primary dysmenorrhea treatment

Article

Full-text available

May 2014

Affecting more than half of menstruating women, dysmenorrhea is a cramp which causes abdominal or lower back pain just before or during a menstruation. In western medicine, non-steroidal anti-inflammatory drugs (NSAIDs) are normally used to treat primary dysmenorrheal symptoms. Despite their rapidity in relieving pain, NSAIDs have many serious side effects on the liver, kidney, and gastrointestinal tract. Thai traditional medicines comprise many preparations for treating dysmenorrhea, especially Prasaplai preparation which has been listed in the Thai traditional common household drug list since 2006. The use of Prasaplai was originated about 100 years ago and is still being used in the present time to treat dysmenorrhea. This review focuses on the history of the preparation, active ingredients, and biological activities especially on cyclooxygenase inhibitor, artifacts occurred in the preparation, quantitative analysis, and clinical trial of Prasaplai formulation.

A Perspective on Natural Products Research and Ethnopharmacology in Mexico: The Eagle and the Serpent on the Prickly Pear Cactus

Article

Feb 2014
J NAT PROD

Native foods from Brazilian biodiversity as a source of bioactive compounds

Article

Aug 2012
FOOD RES INT

The interest in South American native plant species has been growing in recent years due to their health benefits. Brazil is one of the world's mega-diverse locations with over 40,000 different plant species representing 20% of the world's flora. The country was visited in the 19th century by European travelers and naturalists, who described the use of native plant species as food. In this study, data on 67 species was recovered from historical documents and bibliographies. Several of the recorded species show potential as functional food in laboratory studies. Other species are unknown or not yet submitted to any study, in order to verify their health benefits.

An ethnopharmacological survey of the traditional medicine utilized in the community of Porvenir, Bajo Paraguá Indian Reservation, Bolivia

Article

Feb 2012

Porvenir is a semi-isolated Indian community in the Bajo Paraguá Indian Reservation in Bolivian Amazon, one of the two communities of people from the Guarasug'we indigenous nation now close to extinction. The aim of our study was the collection of data on the traditional medicine utilized in the community, and to identify new subjects for further investigation by comparison of the folk-medicinal use with the available scientific literature data. Field work was conducted for 5 months, which included participant observation, semi-structured interviews with 16 individuals, and the collection of voucher specimens for botanical identification. The knowledge of the inhabitants relating to medicinal plants was analysed by means of the modified method of Gentry and Phillips (1993a,b), which assesses the frequency and the variety of use of plants. Scientific data were gathered on selected species, and the correlations of the traditional uses of the herbs with scientific evidence were assessed. The lifestyle and beliefs in Porvenir, botanical data on the plants used, the frequency and variety of medicinal use, diseases that occur and their possible treatment, and methods of plant application are discussed in detail. 145 plant species were registered with 451 recorded uses. The majority of the plants were utilized to treat gastrointestinal complaints (60 species), followed by diseases of the central nervous system, pain and fever (37 species), diseases of the genitourinary tract (35 species), dermatological disorders (34 species) and diseases of the respiratory system (32 species). One fifth of the species are also applied in traditional medicine in other areas of Bolivia or in other countries. The majority of the 145 species used in the community have not been extensively investigated from phytochemical and pharmacological aspects. There are no data in the scientific literature on one fifth of the species. The medicine applied in Porvenir and the contemporary knowledge of the people interviewed concerning plants reflect the local traditions and their changes very well, clearly demonstrating the influence exerted by conventional medicine, and how the ancestral knowledge is progressively being forgotten. The present ethnopharmacological survey indicates that 24 species that are frequently and consistently used in the community of Porvenir are perspective for further research, as their chemistry and pharmacology have not been published to date.

Toxicological profile of the Hymenaea courbaril stem bark hydroalcoholic extract using in vitro bioassays and an alternative in vivo Caenorhabditis elegans model

Article

Jul 2023

Hymenaea genus has been used in folk medicine in Brazil, but few studies investigated its toxicity profile. Thus, the aim of this study was to determine toxicological parameters of Hymenaea courbaril stem bark hydroalcoholic extract by utilizing three cell lines including murine macrophages (RAW 264.7), mouse fibroblast cells (L929) and human lung fibroblast (MRC-5), as well as Salmonella/microsome assay, and in vivo Caenorhabditis elegans model. The predominant detected phytoconstituents in the extract were coumarins, flavonoids, phenolics, tannins and saponins and by HPLC analysis, astilbin (AST) was found to be the main component. The DPPH assay demonstrated that H. courbaril hydroalcoholic extract exhibited potent antioxidant activity, with an IC50 of 3.12 μg/ml. The extract at concentrations of 400 and 800 μg/ml decreased cell viability 48 hr after treatment in L929 and MRC-5 cell lines. In the Raw 264.7 strain, just the highest concentration (800 μg/ml) lowered cell viability within 48 hr following exposure. The concentration of 100 μg/ml did not markedly affect cell viability in the trypan blue assay. In the alkaline comet assay the extract was found to be non-genotoxic. In the Ames test, the extract exhibited low mutagenic potential without metabolic activation, since only the highest concentrations produced an effect. H. courbaril extract only affected the survival of C. elegans at concentrations of 800 and 1600 μl/ml. These findings demonstrate that H. courbaril extract appears to exert low toxicity as evidenced in vitro and mutagenicity assays; however, the biological relevance of the response of C. elegans survival to safety assessments needs further studies.

Jatobá ( Hymenaea courbaril L.)

Chapter

Oct 2022

Étude chimique et valorisation pharmacologique d'espèces du genre Psiadia endémiques de La Réunion et de Madagascar

Thesis

Full-text available

Nov 2021

Elsa Razafindrabenja

Les travaux de thèse exposés dans ce manuscrit portent sur l'étude chimique de plantes du genre Psiadia. Deux axes de recherche ont été menés parallèlement. Le premier a été consacré aux criblages chimique et biologique de cinq espèces du genre Psiadia endémiques de Madagascar. Le criblage chimique avait pour objectif d’identifier les biomarqueurs de ces espèces. Il comprend, d’une part, des analyses par CCM, CLHP-UV-CAD et RMN 1H, pour l’étude du métabolome non volatil, et d’autre part, des analyses par CG-SM et CG-DIF pour l’étude des composés volatils. Le criblage biologique a permis, quant à lui, de déceler les espèces présentant des propriétés biologiques prometteuses. Les cibles biologiques choisies étaient le parasite Plasmodium falciparum, pour l’activité anti-paludique, les macrophages de souris stimulés par un composé pro-inflammatoire pour l’activité anti-inflammatoire et les lignées cellulaires cancéreuses HepG2 (cancer de foie humain) et HT 29 (cancer du côlon) pour l’activité cytotoxique. À l'issue de ce criblage, l’ensemble des extraits, riches en métabolites, a révélé un potentiel antipaludique, anti-inflammatoire et cytotoxique. Le deuxième axe de recherche a été consacré à l’étude phytochimique détaillée d’une espèce endémique de La Réunion (P. dentata) et d’une espèce endémique de Madagascar (P. lucida), sélectionnées en raison de leurs fortes activités biologiques. L'extraction, l'isolement et l'élucidation structurale de leurs métabolites ont été entrepris par différentes techniques chromatographiques (CLMP, CLHP…) et spectroscopiques (UV, IRTF, SMHR, RMN 1D et 2D). Trente-quatre métabolites spécialisés appartenant à la famille des acides hydroxycinnamiques, des polyacétylènes, des flavonoïdes, des diterpènes et des coumarines ont été isolés de ces deux plantes. Seize sont de structures nouvelles. La valorisation des molécules isolées a ensuite été envisagée via l'évaluation de leurs activités biologiques. Vingt-sept composés se sont montrés actifs contre le parasite P. falciparum (isokaempféride,3α-angéoyloxy-19,16(R)-dihydroxy-ent-labda-8(17),13-dién-15,16-olide, … ), dix ont montré une activité anti-inflammatoire et se sont révélés en même temps être non toxiques pour les cellules saines (3α-angéoyloxy-19,15(R)-dihydroxy-ent-andrograpanine, 3(R),8(R)-déhydrofalcarindiol, …) et sept ont manifesté une cytotoxicité prometteuse sur cellules HepG2 et HT 29 (11-hydroxy-3(R),8(R)-déhydrofalcarindiol, ermanine, …). Par ailleurs, une approche bio-informatique par génération de réseaux moléculaires à partir des analyses CLUHP-SM2 des fractions issues des deux espèces a permis de supposer la présence de 28 autres composés tels que le falcarinol et l’acide labdanolique, connus pour être bioactifs.

Culture matters: A systematic review of antioxidant potential of tree legumes in the semiarid region of Brazil and local processing techniques as a driver of bioaccessibility

Article

Full-text available

Mar 2022
PLOS ONE

Ethnobotanical studies report that human populations from the Brazilian Caatinga biome use tree legumes (Fabaceae) with medicinal and food purposes. Our study provides a systematic review of the available published information concerning the antioxidant potential of Hymenaea courbaril L. (jatobá), Libidibia ferrea (Mart. Ex Tul.) L.P.Queiroz (jucá), and Dioclea grandiflora Mart. Ex Benth. (mucunã). Furthermore, in this paper, we infer the possible effects of local processing techniques applied to these plants on their antioxidant potential. In order to achieve these goals, we reviewed 52 articles, including studies from ethnobiology (n = 17), chemistry (n = 32), and food studies testing antioxidant activity (n = 17), excluding 14 repetitions. We found that these legume species can inhibit the formation of free radicals and this potential action varies among different parts of the plant. Probably, the presence of phenolic compounds such as phenolic acids and flavonoids, which are not uniformly distributed in the plants, explain their antioxidant activity. Local processing techniques (i.e., roasting, milling) affect the bioaccessibility of antioxidant components of tree legumes, inducing both positive and negative effects. However, studies about the antioxidant potential did not consider local processing techniques in their analyses. Our study highlights that culture is a fundamental driver of nutritional and pharmacological outcomes related to edible resources since it determines which parts of the plant people consume and how they prepare them. Hence, ignoring cultural variables in the analysis of antioxidant activity will produce inaccurate or wrong scientific conclusions.

IMPACTO CAUSADO PELO EXTRATIVISMO DA CASCA DE ESPÉCIES DE JATOBÁ NA ESTAÇÃO ECOLÓGICA SERRA DAS ARARAS E ZONAS ADJACENTES, MT

Chapter

Full-text available

Jan 2021

The Genus Hymenaea (Fabaceae): A Chemical and Pharmacological Review

Chapter

Aug 2018

Hymenaea (Fabaceae) is a genus greatly spread out from Central to South America. Plants of this genus are known as “jatobá,” “jetaí,” “jataí-uva,” and “jetaíba,” and are commonly used in traditional medicine. The tree trunks exude a resin, used in folk medicine for the treatment of several disorders. The aim of this study was to review the main publications on the genus Hymenaea, focusing on the pharmacological and chemical approaches. The biological activity and chemical research of the Hymenaea species were run through the main data banks available. The specific names of the genus and the species were used as keywords. There are some important ethnopharmaceutical studies on the Hymenaea species, reporting its use either as a decoction or as a syrup for coughing, anemia, bronchitis, inflammation, antioxidant, sinusitis, abdominal spasms, prostate, asthma, common cold, and lung problems, and the resin in a patch for healing wounds. In some ethnopharmacological articles, the genus was one of the most cited by the population. The parts of the plants cited are the barks, resin, stem, and epicarp. This genus was tested for several activities, and many results were positive. A main chemical characteristic of Hymenaea species is the essential content of diterpenoids in the bark extracts and resin. Flavonoids, amino acids, fatty acids, carbohydrates, coumarins, sesquiterpenes, steroids, misc lactones, chromones, and diterpenes were found in its composition. Important studies were developed with Hymenaea plants, and the research showed in this review justifies its traditional use for the treatment of several health problems. Among important medicinal plants, Hymenaea is a genus with a great chemical and pharmacological potential. New research data would improve the knowledge and the application of this genus, contributing to its safe use and the development of new medicinal alternatives.

Labdane diterpenoids as potential anti-inflammatory agents

Article

Jul 2017
PHARMACOL RES

The search for new anti-inflammatory agents is challenging due to the complexity of the inflammatory process and its role in host defense. Over the past few decades, a significant body of evidence has emerged, supporting the prominent role of labdane diterpenoids in therapeutic interventions of various inflammatory diseases. The anti-inflammatory activity of labdane diterpenoids has been attributed mainly to the inhibition of nuclear factor-κB (NF-κB) activity, the modulation of arachidonic acid (AA) metabolism and the reduction of nitric oxide (NO) production. This article provides extensive coverage of naturally occurring labdane diterpenes, discovered between 1981 and 2016, which have been verified as NF-κB, NO, or AA modulators. Herein, we also discuss the role of Michael acceptor, a common structural feature present in most of the active labdane diterpenes, and its association with NF-κB signaling inhibition. In the cases where a sufficient amount of data exists, structure-activity relationship (SAR) studies and clinical studies performed on the anti-inflammatory labdane diterpenoids are also discussed.

Current state of knowledge on the traditional uses, phytochemistry, and pharmacology of the genus Hymenaea

Article

May 2017

Ethnopharmacological relevance Plants of the genus Hymenaea (Fabaceae) are used in South American and Asian traditional medicines to treat a multitude of disorders, like cough, diarrhea, dysentery, intestinal colic, pulmonary weakness, asthma, anemia, sore throat, and for the treatment of kidney problems, viral related disorders, chronic cystitis, bronchitis, and bladder infections. Some Hymenaea species are also used as vermifuge, and for the treatment of arthritis, and inflammation conditions. This review deals with updated information on the traditional uses, phytochemistry and pharmacology of ethnomedicinally important Hymenaea species in order to provide an input for the future research prospects. Methods Literature available in various recognized databases including Google Scholar, PubMed, SciFinder, Scopus, Springer, Wiley, ACS, Scielo and Web of Science, as well as from theses, dissertations, books, reports, and other relevant websites (www.theplantlist.org), are surveyed, analysed, and included in this review. Herein, the literature related to chemical constituents and pharmacological activities were searched in November 2016. Results The literature provided information on ethnopharmacological uses of the South American and African species of the genus Hymenaea (e.g., H. courbaril, H. stigonocarpa, H. onblogifolia, H. martiana, H. parvifolia (South America) and H. verrucosa (African species)) for the treatment of multi-factorial diseases. From these plant species, more than 130 compounds, including fatty acids, flavonoids, terpenoids and steroids, phthalides, phenolic acids, procyanidins and coumarins were identified. Experimental evidences confirmed that the Hymenaea spp. could be used in treating inflammatory disorders, asthma, diarrhea, and some microbial infections. However, reports on the toxicity of Hymenaea species remain scarce. Conclusion Plants of this genus have offered bioactive samples, both from crude extracts and pure compounds, thus substantiating their effectiveness in traditional medicine. However, intensive investigations of all the species of Hymenaea spp. relating to phytochemical and pharmacological properties, especially their mechanism of action, safety and efficacy could be the future introspection.

Diterpenes: Advances in Neurobiological Drug Research

Article

Mar 2016
PHYTOTHER RES

A significant number of studies have been performed with diterpene effect on the brain. Our study aims to make a systematic revision on them. The initial purpose of this review was to screen diterpenes with neurological activity, in particular those that have already been studied and published in different journals (databases until August 2015). The second purpose was to make an action-wise discussion as results viewed on them by taking into drug discovery and development account. Diterpenes considered in this review were selected on the basis of updated information on them and having sufficient information on their screenings. We identified several examples of diterpenes having an interest in further study. We have included the possible sources of them as observed in evidence, their known molecular neurobiological mechanisms, and the active constituents responsible for such activities with the doses and test systems. Results suggest diterpenes to have neurobiological activities like neuro-protection, anti-epileptic, anxiolytic, anti-Alzheimer's disease, anti-Parkinson's disease, anti-cerebral ischemia, anti-neuropathic pain, anti-neuro-inflammatory, and many more. In conclusion, diterpenes may be the prominent candidates in neurobiological drug research. Copyright © 2016 John Wiley & Sons, Ltd.

Preliminary phytochemical screening of native Cerrado plants of medicinal popular use by the rural community of the Vale Verde settlement - Tocantins

Article

Full-text available

Dec 2012

This qualitative study aimed to characterize the groups of secondary metabolites and some constituents of 9 species of native medicinal plants of the Cerrado region used by the rural community of Vale Verde Settlement, identifying their biological and pharmacological potential. The information on medicinal plants were obtained through ethnobotanical and ethnopharmacological studies performed during the period 2010-2012. The botanical material collected was identified and deposited in the Herbarium of the Federal University of Tocantins, Porto Nacional (TO). The ethanolic and methanolic extracts were obtained from the oven dried material, filtered and concentrated in a rotary evaporator under reduced pressure, then weighed and placed again in an oven for 24h at 50 ° C, obtaining the yield (m / m), resulting from the ratio between the mass of concentrated extract and the mass after drying. Phytochemical analysis of selected plants was done using the methodology of Preliminary Prospecting, with tests for the detection of some important constituents and of the main groups of metabolites: saponins, phenols and tannins, catechins, steroids and triterpenoids, coumarins, anthraquinones and flavonoids. The tests were considered positive by the reactions of precipitates with colorations, the formation of foams and colored stains. Phytochemical tests performed on the extracts revealed the presence of constituents of secondary metabolism of plants, which can help to identify chemical markers of species. These markers are indispensable for testing quality and integrity of phytochemicals and a safer popular use of medicinal plants, enabling a better pharmacognostic control of these species and guidance for their use and applications in research by the preliminarily known bioactivity. In this case, it is especially due to the antimicrobial, antioxidant and anti insect activities, suggesting an association with the presence of phenolic compounds and flavonoids, positive in extracts of most species. These data are novel in Tocantins and strategic for the strengthening of conservation policies of Legal Reserve Areas within the Cerrado, priority biome for the conservation of biodiversity, improving the characterization of medicinal resources still available in the regional native flora, also foreseeing their biological and pharmacological applications.

Phytochemical study guided by the myorelaxant activity of the crude extract, fractions and constituent from stem bark of Hymenaea courbaril L

Article

Jun 2013

Ethnopharmacological relevance: Hymenaea courbaril L. (Caesalpinoideae) is used in Brazilian folk medicine to treat anemia, kidney problems, sore throat and other dysfunctions of the respiratory system, such as bronchitis and asthma, although such properties are yet to be scientifically validated. Aim of the study: In order to give a scientific basis to support the traditional use of Hymenaea courbaril, this study was designed to evaluate antioxidant, myorelaxant and anti-inflammatory properties of the ethanol extract from stem bark and its fractions. The myorelaxant effect of astilbin, a flavonoid isolated from the bioactive ethyl acetate fraction (EAF), has also been evaluated. Material and methods: In the present study ethanol extract from stem bark (EEHC) and fractions were analyzed using bioassay-guided fractionation. The following activities were investigated: antioxidant by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, myorelaxant on rat tracheal smooth muscle, and anti-inflammatory using ovalbumin-induced leukocytosis and airway hyperresponsiveness in rats. Results: The results of the present investigation show that the whole extract of Hymenaea courbaril and some of its fractions strongly scavenged DPPH radical. The extract showed myorelaxant activity on rat trachea, being EAF its highest efficient fraction. Bio-guided study allowed the isolation of astilbin, a well-known flavonoid. The activity induced by this compound indicates that it may be partly responsible for the myorelaxant effect of EAF. EAF reduced contractions that depended on divalent cation inflow through voltage-operated Ca(2+) channels (VOCCs) or receptor-operated Ca(2+) channels (ROCCs), but it was more potent to inhibit VOCC- than ROCC-dependent contraction induced by Ca(2+) addition in ACh-enriched Ca(2+)-free medium. Oral pretreatment of antigen-challenged animals with EAF prevented airway hyperresponsiveness on KCl-induced contraction and reduced the number of total white cells, particularly eosinophils and neutrophils in bronchoalveolar lavage. Conclusions: This study provided scientific basis that Hymenaea courbaril presents potential antioxidant, myorelaxant and anti-inflammatory actions, which support its use in folk medicine to treat inflammatory airway diseases.

Predicting cyclooxygenase inhibition by three-dimensional pharmacophoric profiling. Part II: Identification of enzyme inhibitors from Prasaplai, a Thai traditional medicine

Article

Full-text available

Jan 2011

Prasaplai is a medicinal plant mixture that is used in Thailand to treat primary dysmenorrhea, which is characterized by painful uterine contractility caused by a significant increase of prostaglandin release. Cyclooxygenase (COX) represents a key enzyme in the formation of prostaglandins. Former studies revealed that extracts of Prasaplai inhibit COX-1 and COX-2. In this study, a comprehensive literature survey for known constituents of Prasaplai was performed. A multiconformational 3D database was created comprising 683 molecules. Virtual parallel screening using six validated pharmacophore models for COX inhibitors was performed resulting in a hit list of 166 compounds. 46 Prasaplai components with already determined COX activity were used for the external validation of this set of COX pharmacophore models. 57% of these components were classified correctly by the pharmacophore models. These findings confirm that the virtual approach provides a helpful tool (i) to unravel which molecular compounds might be responsible for the COX-inhibitory activity of Prasaplai and (ii) for the fast identification of novel COX inhibitors.

The Optical Rotation of Some C15-Oxygenated Labda-8(17),13-dienes

Article

Full-text available

Jul 1995

A range of C15-oxygenated labda-8(17),13-dienes has been synthesized optically pure to provide reference data for comparisons with naturally occurring compounds.

Prostaglandin synthetase-dependent cooxidation of (±)-benzo(a)pyrene-7,8-dihydrodiol by human lung and other mammalian tissues

Article

Full-text available

Jun 1981

The prostaglandin synthetase-dependent cooxidation of (±)-trans-7,8-dihydroxy-7,8-dihydroxy-7,8-dihydrobenzo(a)-pyrene (BP-7,8-diol) was investigated using enzyme preparation derived from various mammalian tissues, including human lung. Incubation of this compound with arachidonic acid (AA) and ram seminal vesicle microsomes resulted in the formation of the benzo(a)pyrene (BP) tetrols 7,10/8,9 tetrol of BP and 7/8,9,10 tetrol of BP, which are formed upon solvolysis of (±)-trans-7β,8α-dihydroxy-9α,1α-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene . Microsomes derived from several target organs (rat lung and intestine, mouse skin, and guinea pig lung) and rabbit kidney also metabolized BP-7,8-diol to the 7,10/8,9 tetrol of BP and the 7/8,9,10 tetrol of BP in the presence of AA. Indomethacin inhibited AA-dependent oxidation in all tissues. The amounts of BP tetrols formed by the above tissues were comparable to that formed by ram seminal vesicles, even though these tissues possessed less than 1% of the prostaglandin synthetase activity of ram seminal vesicles. Using ram seminal vesicles as a model system, the optimal enzyme level was found to occur at very low levels of enzyme, actively suggesting that significant oxidation would occur in target organs which have a low level of prostaglandin synthetase. Also, all the tissues examined catalyzed the covalent binding of BP-7,8-diol to microsomal protein (6 to 13% of the total substrate metabolized), indicating the formation of reactive metabolite(s) during cooxidation. Cytochrome P-450 monooxygenase- and prostaglandin synthetase-dependent BP-7,8-diol oxidation were compared using enzyme preparations derived from pulmonary tissues. In the presence of reduced nicotinamide adenine dinucleotide phosphate, rat lung microsomes metabolized BP-7,8-diol to BP tetrols at a rate approximately 10 times faster than in the presence of AA. Using guinea pig lung microsomes, however, BP tetrol formation was about equal when either of these cofactors were utilized. Human lung microsomal prostaglandin synthetase-dependent oxidation of BP-7,8-diol was between 52 and 67% of the cytochrome P-450-dependent rates. Using these pulmonary tissues, BP-7,8-diol was converted to the 7,10/8,9 tetrol of BP and the 7/8,9,10 tetrol of BP in the presence of AA. In the presence of reduced nicotinamide adenine dinucleotide phosphate, two additional BP tetrols were formed, the 7,9,10/8 tetrol of BP and the 7,9/8,10 tetrol of BP. These results suggest that prostaglandin synthetase may serve as an alternative activating enzyme to cytochrome P-450 monooxygenases in the conversion of BP-7,8-diol to (±)-trans-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo(a)pyren e.

Clerodane-type diterpenes from the seed pods of Hymenaea courbaril var. stilbocarpa

Article

Full-text available

Jan 2002
PHYTOCHEMISTRY

Three known and two new diterpenes were isolated from the ethyl acetate extract of Hymenaea courbaril var. stilbocarpa seed pods. One of the compounds was elucidated as (5R*,8S*,9S*,10R*)-cleroda-3,13E-dien-15-oic acid and the other was elucidated, after treatment with diazomethane, as methyl (5S*,8S*,9S*,10R*)-cleroda-3,13E-dien-15-oate. The known diterpenes were identified as (-)-ozic acid, (-)-isoozic acid and (-)-kovalenic acid which were characterized as their methyl ester derivatives.

Common Trees of Puerto Rico and the Virgin Islands.

Article

Apr 1965

Medicinal plants of the world

Article

Jan 1981

Systematics of the genus Hymenaea L. (Leguminosae, Caesalpinioideae, Detarieae)

Article

Jan 1975

Arboles del Parque Deininger

Book

Jan 1982

Medicinal Plants of the Bible

Article

Nov 1984

Risk of Cardiovascular Events Associated With Selective COX-2 Inhibitors

Article

Aug 2001

Debabrata Mukherjee

Atherosclerosis is a process with inflammatory features and selective cyclooxygenase 2 (COX-2) inhibitors may potentially have antiatherogenic effects by virtue of inhibiting inflammation. However, by decreasing vasodilatory and antiaggregatory prostacyclin production, COX-2 antagonists may lead to increased prothrombotic activity. To define the cardiovascular effects of COX-2 inhibitors when used for arthritis and musculoskeletal pain in patients without coronary artery disease, we performed a MEDLINE search to identify all English-language articles on use of COX-2 inhibitors published between 1998 and February 2001. We also reviewed relevant submissions to the US Food and Drug Administration by pharmaceutical companies.Our search yielded 2 major randomized trials, the Vioxx Gastrointestinal Outcomes Research Study (VIGOR; 8076 patients) and the Celecoxib Long-term Arthritis Safety Study (CLASS; 8059 patients), as well as 2 smaller trials with approximately 1000 patients each. The results from VIGOR showed that the relative risk of developing a confirmed adjudicated thrombotic cardiovascular event (myocardial infarction, unstable angina, cardiac thrombus, resuscitated cardiac arrest, sudden or unexplained death, ischemic stroke, and transient ischemic attacks) with rofecoxib treatment compared with naproxen was 2.38 (95% confidence interval, 1.39-4.00; P = .002). There was no significant difference in cardiovascular event (myocardial infarction, stroke, and death) rates between celecoxib and nonsteroidal anti-inflammatory agents in CLASS. The annualized myocardial infarction rates for COX-2 inhibitors in both VIGOR and CLASS were significantly higher than that in the placebo group of a recent meta-analysis of 23 407 patients in primary prevention trials (0.52%): 0.74% with rofecoxib (P = .04 compared with the placebo group of the meta-analysis) and 0.80% with celecoxib (P = .02 compared with the placebo group of the meta-analysis).The available data raise a cautionary flag about the risk of cardiovascular events with COX-2 inhibitors. Further prospective trial evaluation may characterize and determine the magnitude of the risk.

Common Trees of Puerto Rico and the Virgin Islands.

Article

Nov 1974

Structure and stereochemistry of the diterpenes of Hymenaea courbaril (Caesalpinioideae) seed pod resin

Article

Dec 1973
TETRAHEDRON

The isolation and structure of four new bicarbocyclic diterpenes from seed pod resin of Guadeloupe-grown Hymenaea courbaril is described. The diterpene composition of this resin is more highly rearranged than those isolated from the trunk resin of the same tree. Cyclosativene, caryophyllene, α-himachalene, selina-4(14),7(11)-diene were identified as major sesquiterpene components while β-bourbonene, calarene, selina 4(14),7-diene, humulene, δ-cadinene, α-calacorene, α-muurolene were identified as minor components.

Studies toward the total synthesis of diterpenes in the labdane series. III. Synthesis of two epimeric 6, 7, 8-trihydroxylabdadienes

Article

Feb 1991
TETRAHEDRON

The syntheses of 6β,7β, 8α, and 6β, 7β, 8β-trihydroxy labdadienes, 2a and 2b respectively, were performed starting from the decalin 3, in order to determine the exact structure of compounds, isolated from plant sources, for which configuration at C-8 was not clearly demonstrated. As a result, the structure 2a was established with certainty for crotomachlin, a diterpine from Croton macrostachys.

Diterpenes in the bark of Hymenea coubaril

Article

Aug 1975

13C NMR spectral analysis of eperuane diterpenes

Article

Dec 1977

The 13C NMR spectra of some eperuane diterpenes have been recorded and the signals assigned. The substituent shielding effects in these compounds, in comparison with those observed in other series of diterpenes, are also presented.

Botany. (Book Reviews: Common Trees of Puerto Rico and the Virgin Islands)

Article

Jan 1965

Synthesis of Ambroxo (R) from labdanolic acid

Article

Jul 2002
TETRAHEDRON

A synthesis of the valuable amber-type odorant Ambrox® from labdanolic acid (main diterpenoid of the acid fraction of non-polar extracts of Cistus ladaniferus L.) is reported. The conversion is based on (a) the α,β-dehydrogenation of methyl labdanolate using an organoselenium reagent, (b) subsequent oxidative degradations of the side chain, and (c) final acid-promoted cyclization of the resulting tetranorlabdan-8α,12-diol. The influence of the temperature and solvent in the cyclization of the diol with p-toluenesulfonic acid is also described. Thus, Ambrox® has been obtained by a six-step procedure in 33% overall yield from methyl labdanolate.

Synthesis of (±)-Crotomachlin

Article

Feb 1996
SYNLETT

An efficient synthesis of (±)-crotomachlin (1) was accomplished starting from 4,4,10-trimethyl-9-methylene-Δ 6-8-octalone (4) in 7 steps.

Isolation of spatulenol and (−)‐caryophyllene oxide from Vernonia mollissima don and 1H and 13C reassignment by two‐dimensional NMR spectroscopy

Article

Feb 1990
MAGN RESON CHEM

Two sesquiterpenoids, spatulenol and (−)-caryophyllene oxide, were isolated from the hexane extract of the Brazilian plant Vernonia mollissima Don. The 1H and 13C NMR spectra of these compounds have been reassigned completely by COSY experiments and 13C/1H shift correlation diagrams.

Development of extruded snack using Jatobá (Hymenaea stigonocarpa Mart) flour and cassava starch blends

Article

Mar 1999
J SCI FOOD AGR

The use of the jatobá trees (Hymenaea stigonocarpa Mart) by the timber industry poses an ecological problem in Brazil. The objective of this research was to investigate the use of jatobá flour for the production of snacks by the thermoplastic extrusion of a composite flour consisting of jatobá and cassava starch. Chemical analysis showed that the jatobá fruit provides high‐fibre flour (486 g kg−1) with 66 g kg−1 protein, and 398 and 88 g kg−1 of insoluble and soluble fibre, respectively. Such flour is of potential use for the production of high‐fibre snacks, allowing for the economical exploitation of the jatobá while preserving the tree. Composite flours with jatobá flour and cassava starch mixtures (150: 850, 300: 700, 450: 550), conditioned to moisture levels of 170, 200 and 230 g kg−1 were processed in a Brabender single‐screw extruder. The extrusion conditions were 150 rpm screw speed, 4 mm die diameter and 125, 150 and 175°C of barrel temperatures. The snacks produced were evaluated as to their sensory characteristics and response surface methodology was used to optimise the extrusion process. Response surface and contour diagrams revealed that all mixtures conditioned to 170 g kg−1 moisture and extruded at 150°C produced snacks of acceptable quality, higher levels of jatobá flour leading to significant quality losses with respect to sensory characteristics. © 1998 Society of Chemical Industry.

Potent lipid peroxidation inhibitors from Withania somnifera fruits

Article

Mar 2004
TETRAHEDRON

A bioassay-guided purification of the methanolic extract of Withania somnifera fruits yielded novel withanamides A–I (1–9) and withanolides (10–13). Among the withanolides, compound 10 is novel. The structures of these compounds were determined by using FABMS, HRFABMS, 1D and 2D NMR spectral and chemical methods. The withanamides possess novel chemical structures and consisted of serotonin, glucose and long-chain hydroxyl fatty acid moieties. The stereochemistry of the hydroxyl group in the long-chain fatty acid moiety in compound 1 was determined by the modified Mosher's ester method. Compounds 1–13 were tested for their ability to inhibit lipid peroxidation in a model system using large unilamellar vesicles. Withanamides 1–5 and 9 inhibited lipid peroxidation by 98, 93, 79, 94, 81 and 86%, respectively, at 1 μg/mL. However, compounds 6–8 inhibited the lipid peroxidation by 85, 82 and 90%, respectively, at 0.5 μg/mL. Withanolides 10–13 were also tested and only compound 12 inhibited the lipid peroxidation by 82% at 10 μg/mL. To evaluate the structure activity relationships of withanamides A–I, compounds 14–16 were purchased and their lipid peroxidation activity determined as in the case of compounds 1–9. Commercial antioxidants, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and tert-butylhydroquinone (TBHQ), were also tested in this assay at 1 μg/mL and showed 80, 81 and 85% of inhibition, respectively. Our results suggest that the potent antioxidant activity exhibited by novel withanamides is probably due to the hydroxylated long-chain acyl group. This is the first report of withanamides, unique serotonin conjugates, from W. somnifera fruits.

Biological relevance of terpenoids. Overview focusing on mono- di- and tetraterpenes

Article

Mar 2003

The role of fruit and vegetables in human nutrition and public health are taken into account in most nutritional recommendations. Fruit and vegetables contain an abundance of phenolic substances, terpenoids and other natural antioxidants that have been associated with protection from and treatment of chronic diseases such as heart disease or cancer. Terpenoids are a group of substances which occur in nearly every natural food. Their main subclasses discussed as beneficial to maintain and improve health are monoterpenes (like limonene, carvone or carveol), diterpenes (including the retinoids), and tetraterpenes (which include all different carotenoids like alpha- and beta-carotene, lutein, lycopene, zeaxanthine and cryptoxanthine). To be discussed as health promoting or biofunctional, the significant impact of a substance either on human metabolism or on well-defined and appropriate biomarkers must be shown. Based on the latter point, this paper reviews the literature on mono-, di- and tetraterpenes, with special focus on their impact on human health to answer the question of their biofunctionality. Special emphasis will be placed on their different mode of action, e.g. to affect oxidative stress, carcinogenesis and cardiovascular diseases.

Potentially Cancer Chemopreventive And Anti-Inflammatory Terpenoids From Natural Sources

Article

Dec 2003

Cancer chemoprevention by naturally occurring substances, especially by those occurring in vegetable foods and medicinal plants, seems to be a promis approach since various phytochemicals isolated from these sources have potent chemopreventive activity in animal experiments. Many phytochemicals have the adv of being non-toxic. A number of terpenoids, which occur as secondary metabolites in all major groups of organisms, from fungi to humans, have been shown to possess chemopreventive activities in animal models. In a recent publication we have discussed the antitumor-promoting and anti-inflammatory activities of nat occurring triterpenoids and sterols. In this review article we describe the potentially chemopreventive and anti-inflammatory activities of terpenoids of the sesqui-, di-, sester-, and meroterpenoid classes, and of retinoids. Terpenoids are minor but ubiquitous components of our diet, and are considered relatively non-toxic to humans. These compounds, therefore, have the potential of being used as cancer chemopreventive agents.

Tumor Cell Proliferation and Cyclooxygenase Enzyme Inhibitory Compounds in Amaranthus tricolor

Article

Nov 2004

Ames BN, Shigenaga MK, Hagen TMOxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 90:7915-7922

Article

Oct 1993

Metabolism, like other aspects of life, involves tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids. Dietary fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day, the opportunity for improving health by improving diet is great.

Antioxidant Activities of Isoflavones and Their Biological Metabolites in a Liposomal System

Article

Sep 1998

Genistein and daidzein, the two major soy isoflavones, principally occur in nature as their glycosylated or methoxylated derivatives, which are cleaved in the large intestine to yield the free aglycones and further metabolites. The objective of this study was to compare the antioxidant activities of genistein and daidzein with their glycosylated and methoxylated derivatives and also those of their human metabolites. The abilities of these compounds to inhibit lipid peroxidation in a liposomal system were evaluated using fluorescence spectroscopy, and structural criteria that enhance antioxidant activity were established. The peroxidation initiators employed in the study were Fe(II) and Fe(III) metal ions and aqueous-phase, azo-derived peroxyl radicals. Both the parent isoflavonoids and their metabolites were more effective at suppressing metal-ion-induced peroxidations than the peroxyl-radical-induced peroxidation. Antioxidant activities for the isoflavone metabolites were comparable to or superior to those for the parent compounds. Equol and its 4-hydroxy and 5-hydroxy derivatives were the most potent antioxidants in the study, suggesting that absence of the 2, 3-double bond and the 4-oxo group on the isoflavone nucleus enhances antioxidant activity. Additionally, the number and position of hydroxyl groups were determining factors for isoflavonoid antioxidant activity, with hydroxyl substitution being of utmost importance at the C-4' position, of moderate importance at the C-5 position, and of little significance at the C-7 position.

Cyclo-oxygenase-2: pharmacology, physiology, biochemistry and relevance to NSAID therapy

Article

Dec 1999

Cyclo-oxygenase is expressed in cells in two distinct isoforms. Cyclo-oxygenase-1 is present constitutively whilst cyclo-oxygenase-2 is expressed primarily after inflammatory insult. The activity of cyclo-oxygenase-1 and -2 results in the production of a variety of potent biological mediators (the prostaglandins) that regulate homeostatic and disease processes. Inhibitors of cyclo-oxygenase include the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin, ibuprofen and diclofenac. NSAIDs inhibit cyclo-oxygenase-2 at the site of inflammation, to produce their therapeutic benefits, as well as cyclo-oxygenase-1 in the gastric mucosa, which produces gastric damage. Most recently selective inhibitors of cyclo-oxygenase-2 have been developed and introduced to man for the treatment of arthritis. Moreover, recent epidemiological evidence suggests that cyclo-oxygenase inhibitors may have important therapeutic relevance in the prevention of some cancers or even Alzheimer's disease. This review will discuss how the new advancements in NSAIDs research has led to the development of a new class of NSAIDs that has far reaching implications for the treatment of disease. British Journal of Pharmacology (1999) 128, 1121–1132; doi:10.1038/sj.bjp.0702897

Screening Brazilian plant species for in vitro inhibition of 5-lipoxygenase

Article

Feb 2000
PHYTOMEDICINE

Plants from the Brazilian flora were evaluated for the inhibition of 5-lipoxygenase. The species were selected based on their traditional use and on a chemosystematic approach. In total, 19 species belonging to 13 families have been investigated. Hedychium coronarium J. Koenig (Zingiberaceae), Xylopia frutescens Aubl. (Annonaceae) and Hymenaea courbaril L. (Leguminosae) presented a high 5-lipoxygenase inhibitory activity. Some hypothesis about the nature of the active compounds are discussed, based on reports of the chemical constitution of these species or other species from the same botanical family.

Cyclooxygenases: Structural, Cellular, and Molecular Biology

Article

Feb 2000

The prostaglandin endoperoxide H synthases-1 and 2 (PGHS-1 and PGHS-2; also cyclooxygenases-1 and 2, COX-1 and COX-2) catalyze the committed step in prostaglandin synthesis. PGHS-1 and 2 are of particular interest because they are the major targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2 inhibitors. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of these enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and how differences in the structure of PGHS-2 confer on this isozyme differential sensitivity to COX-2 inhibitors. We further examine the evidence for independent signaling by PGHS-1 and PGHS-2, and the complex mechanisms for regulation of PGHS-2 gene expression.

Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: Down-regulation of COX-2 and iNOS through suppression of NF-??B activation

Article

Oct 2001
MUTAT RES-FUND MOL M

A wide array of phenolic substances, particularly those present in edible and medicinal plants, have been reported to possess substantial anticarcinogenic and antimutagenic activities. The majority of naturally occurring phenolics retain antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activity. Cyclooxygenase-2 (COX-2) inducible and nitric oxide synthase (iNOS) are important enzymes that mediate inflammatory processes. Improper up-regulation of COX-2 and/or iNOS has been associated with pathophysiology of certain types of human cancers as well as inflammatory disorders. Since inflammation is closely linked to tumor promotion, substances with potent anti-inflammatory activities are anticipated to exert chemopreventive effects on carcinogenesis, particularly in the promotion stage. Examples are curcumin, a yellow pigment of turmeric (Curcuma longa L., Zingiberaceae), the green tea polyphenol epigallocatechin gallate (EGCG), and resveratrol from grapes (Vitis vinifera, Vitaceae) that strongly suppress tumor promotion. Recent studies have demonstrated that eukaryotic transcription factor nuclear factor-kappa B (NF-kappa B) is involved in regulation of COX-2 and iNOS expression. Several chemopreventive phytochemicals have been shown to inhibit COX-2 and iNOS expression by blocking improper NF-kappa B activation. Multiple lines of compelling evidence indicate that extracellular-regulated protein kinase and p38 mitogen-activated protein kinase are key elements of the intracellular signaling cascades responsible for NF-kappa B activation in response to a wide array of external stimuli. Curcumin, EGCG and resveratrol have been shown to suppress activation of NF-kappa B. One of the plausible mechanisms underlying inhibition of NF-kappa B activation by aforementioned phytochemicals involves repression of degradation of the inhibitory unit I kappa B alpha, which hampers subsequent nuclear translocation of the functionally active subunit of NF-kappa B.

Mukherjee D, Nissen SE, Topol EJRisk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 286: 954-959

Article

Feb 2002

Atherosclerosis is a process with inflammatory features and selective cyclooxygenase 2 (COX-2) inhibitors may potentially have antiatherogenic effects by virtue of inhibiting inflammation. However, by decreasing vasodilatory and antiaggregatory prostacyclin production, COX-2 antagonists may lead to increased prothrombotic activity. To define the cardiovascular effects of COX-2 inhibitors when used for arthritis and musculoskeletal pain in patients without coronary artery disease, we performed a MEDLINE search to identify all English-language articles on use of COX-2 inhibitors published between 1998 and February 2001. We also reviewed relevant submissions to the US Food and Drug Administration by pharmaceutical companies. Our search yielded 2 major randomized trials, the Vioxx Gastrointestinal Outcomes Research Study (VIGOR; 8076 patients) and the Celecoxib Long-term Arthritis Safety Study (CLASS; 8059 patients), as well as 2 smaller trials with approximately 1000 patients each. The results from VIGOR showed that the relative risk of developing a confirmed adjudicated thrombotic cardiovascular event (myocardial infarction, unstable angina, cardiac thrombus, resuscitated cardiac arrest, sudden or unexplained death, ischemic stroke, and transient ischemic attacks) with rofecoxib treatment compared with naproxen was 2.38 (95% confidence interval, 1.39-4.00; P =.002). There was no significant difference in cardiovascular event (myocardial infarction, stroke, and death) rates between celecoxib and nonsteroidal anti-inflammatory agents in CLASS. The annualized myocardial infarction rates for COX-2 inhibitors in both VIGOR and CLASS were significantly higher than that in the placebo group of a recent meta-analysis of 23 407 patients in primary prevention trials (0.52%): 0.74% with rofecoxib (P =.04 compared with the placebo group of the meta-analysis) and 0.80% with celecoxib (P =.02 compared with the placebo group of the meta-analysis). The available data raise a cautionary flag about the risk of cardiovascular events with COX-2 inhibitors. Further prospective trial evaluation may characterize and determine the magnitude of the risk.

Isolation and Absolute Configuration of ent -Halimane Diterpenoids from Hymenaea courbaril from the Suriname Rain Forest 1

Article

Feb 2002

Bioactivity-directed fractionation of a methanol extract of Hymenaea courbaril afforded the three new diterpenoids (13R)-13-hydroxy-1(10),14-ent-halimadien-18-oic acid (1), (2S,13R)-2,13-dihydroxy-1(10),14-ent-halimadien-18-oic acid (2), and (13R)-2-oxo-13-hydroxy-1(10),14-ent-halimadien-18-oic acid (3). The configurations of these compounds were determined from X-ray crystallography of 1, circular dichroism of 2 and 3, and spectral studies of prepared derivatives. Compound 1 exhibited weak cytotoxicity toward the 1138 mutant yeast strain and the A2780 human ovarian cancer cell line.

Antioxidant and Cyclooxygenase Activities of Fatty Acids Found in Food

Article

May 2002

Several commercially available C-8 to C-24 saturated and unsaturated fatty acids (1-29) were assayed for cyclooxygenase-I (COX-I) and cyclooxygenase-II (COX-II) inhibitory and antioxidant activities. Among the saturated fatty acids tested at 60 microg mL(-1), there was an increase in antioxidant activity with increasing chain length from octanoic acid to myristic acid (C-8-C-14) and a decrease thereafter. All unsaturated fatty acids tested at 60 microg mL(-1) showed good antioxidant activity except for undecylenic acid (12), cis-5-dodecenoic acid (13), and nervonic acid (29). The highest inhibitory activities among the saturated fatty acids tested on cyclooxygenase enzymes COX-I and COX-II were observed for decanoic acid to lauric acid (3-5) at 100 microg mL(-1). Similarly, among the unsaturated fatty acids tested, the highest activities were observed for cis-8,11,14-eicosatrienoic acid (25) and cis-13,16-docosadienoic acid (27) at 100 microg mL(-1).

Cyclooxygenase-2 enzyme inhibitory triterpenoids from Picrorhiza kurroa seeds

Article

Dec 2005
LIFE SCI

A bioassay guided phytochemical study of the ethyl acetate extract of the seeds of Picrorhiza kurroa afforded a new triterpenoid, 2alpha, 3beta, 19beta, 23-tetrahydroxyolean-12-en-28-O-beta-D-glucoside (1), along with five known triterpenoids, 2alpha, 3beta, 19beta, 23-tetrahydroxyolean-12-en-28-oic acid (2), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-O-beta-d-glucoside (3), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-oic acid (4), 2alpha, 3beta, 19beta, trihydroxyolean-12-en-28-oic acid (5), and 2alpha, 3beta, 6beta, 23-tetrahydroxyolean-12-en-28-oic acid (6). Their structures were established by extensive NMR spectral studies. The acetyl derivatives, compounds 7 and 8, were prepared from compounds 1 and 2, respectively, to aid in their structure elucidation. The inhibition of cyclooxygenase-2 (COX-2) enzyme by compounds 1--6 at 100 microg/mL was 38.3%, 39%, 37%, 49.6%, 25%, and 45.0%, respectively. However, compounds 1--6, at 100 microg/mL, did not inhibit cyclooxygenase-1 (COX-1) enzyme. Compound 1 is a novel triterpenoid and compounds 1--6 are isolated for the first time from the seeds of P. kurroa.

Some leguminous trees providing useful fruits in the north of Brazil

Jan 1984
231-234

D B Arckcoll

Arckcoll, D. B. (1984). Some leguminous trees providing useful fruits in the north of Brazil. Pesquisa Agropecuaria Brasilia, 19, 231-234.

Oxidants, antioxidants and degenerative disorders diseases of aging

Jan 1993
7915-7922

B N Ames
M K Shigenaga
T M Hagen

Ames, B. N., Shigenaga, M. K., & Hagen, T. M. (1993). Oxidants, antioxidants and degenerative disorders diseases of aging. Proceedings of National Academy of Sciences, 90, 7915-7922.

Terpenoids from Stinking toe (Hymneae courbaril) fruits with cyclooxygenase and lipid peroxidation inhibitory activities

Abstract

No full-text available

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