Cytotoxic Stilbenes and Canthinone Alkaloids from Brucea antidysenterica (Simaroubaceae).

A phytochemical study of the root and bark of Brucea antidysenterica J. F. Mill. (Simaroubaceae) afforded three new compounds, including a stilbene glycoside bruceanoside A (1), and two canthinone alkaloids bruceacanthinones A (3) and B (4), along with ten known secondary metabolites, rhaponticin (2), 1,11-dimethoxycanthin-6-one (5), canthin-6-one (6), 1-methoxycanthin-6-one (7), 2-methoxycanthin-6-one (8), 2-hydroxy-1,11-dimethoxycanthin-6-one (9), ß-carboline-1-propionic acid (10), cleomiscosin C (11), cleomiscosin A (12), and hydnocarpin (13). The structures of all the compounds were determined using spectrometric and spectroscopic methods including 1D and 2D NMR, and HRSEIMS. The identities of the known compounds were further confirmed by comparison of their data with those reported in the literature. The root and bark methanolic extracts, the dichloromethane and ethyl acetate soluble fractions, and the isolated compounds (3-13), were assessed for their cytotoxicity against the cancer cell lines A-549, MCF-7, and PC-3. The results suggested that compounds in the extracts might possess a synergic action in their cytotoxicity.

Ent-Clerodane Diterpenes from the Bark of Croton oligandrus Pierre ex Hutch. and Assessment of Their Cytotoxicity against Human Cancer Cell Lines.

New clerodane diterpenes, 12-epi-megalocarpodolide D (2) and an epimeric mixture of crotonolins A (3) and B (4), were isolated from the bark of Croton oligandrus following a bioassay-guided isolation protocol. Known compounds, megalocarpodolide D (1), 12-epi-crotocorylifuran (5), cluytyl-ferulate (6), hexacosanoyl- ferulate (7), vanillin (8), acetyl-aleuritolic acid (9) and lupeol (10), were also isolated. The structures of the isolated compounds (1-10) were elucidated by spectroscopic means. The cytotoxicity of compounds 1-10 was assessed against A549, MCF7, PC3 and PNT2 cell lines using the MTT assay. Compounds 1 and 2 showed moderate levels of activity against both A549 and MCF7 cells with 1 being the most active with IC50 values of 63.8 ± 13.8 and 136.2 ± 22.7 µM against A549 and MCF7 cells, respectively. The epimeric mixture of 3 and 4 was moderately active against A549 and PC3 cells (IC50 = 128.6 ± 31.0 and 111.2 ± 2.9 µM, respectively).

Cytotoxic Properties of the Stem Bark of Citrus reticulata Blanco (Rutaceae).

The bioassay-guided fractionation of the n-hexane extract of Citrus reticulata Blanco (Rutaceae) stem bark yielded scoparone (1), xanthyletin (2), lupeol (3), ß-amyrin (4), stigmasterol (5), ß-sitosterol (6) and palmitic acid. The structures of these compounds were determined by comprehensive spectroscopic analyses, i.e., 1D and 2D NMR and EI-MS, and by comparison with the reported data. Extracts, fractions and isolated compounds 1-6 were assessed for cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-dphenyltetrazolium bromide (MTT) assay against three human cancer cell lines, i.e., human lung adenocarcinoma cell line A549, human breast adenocarcinoma cell line MCF7 and human Caucasian prostate adenocarcinoma cell line PC3. Significant activity of the n-hexane and the dichloromethane extracts was observed against the breast cancer cell line MCF7 with IC50 s of 45.6 and 54.7 µg/mL, respectively. Moreover, the 70% ethyl acetate in n-hexane chromatographic fraction showed significant activity displaying IC50 values of 53.0, 52.4 and 49.1 µg/mL against the cancer cell lines A549, MCF7 and PC3, respectively. Encouragingly, an IC50 of 510.0 µg/mL against the human normal prostate cell line PNT2 indicated very low toxicity and hence favourable selectivity indices for the 70% ethyl acetate in n-hexane fraction in the range of 9.6-10.4 towards cell lines A549, MCF7 and PC3. Because compounds isolated from the above fraction only delivered IC50 values in the range of 18.2-96.3, 9.2-34.1 and 7.5-97.2 µg/mL against A549, MCF7 and PC3 cell lines, respectively, synergistic action between compounds is suggested. Bioassay results valorize the anticancer effectivity of the stem bark of this plant in Cameroonian pharmacopoeia. Copyright © 2017 John Wiley & Sons, Ltd.

GC-MS analysis and pharmacological evaluations of Phoenix sylvestris (Roxb.) seeds provide new insights into the management of oxidative stress and hyperglycemia.

Phoenix sylvestris Roxb. (Arecaceae) seeds are used in the treatment of diabetes in the traditional system of medicine. The present study evaluated antihyperglycemic and antioxidant activities as well as the total phenolic and flavonoid content of the methanol extract of P. sylvestris seeds (MEPS). The constituents of the extract were identified by GC-MS analysis. MEPS demonstrated strong antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 162.70 ± 14.99 µg) and nitric oxide (NO) (IC50 = 101.56 ± 9.46 µg/ml) free radicals. It also possesses a substantial amount of phenolics and flavonoids. It significantly (p < .05) reduced blood glucose levels in glucose-loaded and alloxan-induced diabetic mice at the doses of 150 and 300 mg/kg b.w., respectively. A total of 46 compounds were detected and identified by gas chromatography-mass spectroscopy (GC-MS) analysis, among which 8-methylisoquinoline N-oxide (32.82%) was predominant. The phytochemical study by GC-MS revealed that the MEPS possesses compounds which could be related to its antidiabetic and antioxidant activities. To recapitulate, P. sylvestris seeds can be a very good option for antidiabetic and antioxidant activity though further studies are still recommended to figure out the responsible phytochemicals and establish their exact mechanism of action.

Armenin and isoarmenin--two prenylated coumarins from the aerial parts of Artemisia armeniaca.

The reversed-phase (RP) preparative HPLC analyses of the MeOH extract of the aerial parts of Artemisia armeniaca yielded four prenylated coumarins, 7-hydroxy-8-(4-hydroxy-3-methylbutoxy)coumarin (named armenin), 8-hydroxy-7-(4-hydroxy-3-methylbutoxy)coumarin (named isoarmenin), lacarol, and deoxylacarol, together with five other compounds, including three flavonoid glycosides, quercetin 3-O-ß-D-glucopyranoside, rutin, and kaempferol 3-O-ß-D-glucopyranoside, and chlorogenic acid, and tryptophan. (10E,12Z)-9-Hydroxyoctadeca-10,12-dienoic acid (ß-dimorphecolic acid) was isolated from the CH(2)Cl(2) extract. Armenin and isoarmenin were new coumarins. Structures of all compounds were determined by spectroscopic means, including UV, MS, 1D- and 2D-NMR. The in vitro free-radical-scavenging property of the extracts and isolated compounds was evaluated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay.

Plukenetia huayllabambana Fruits: Analysis of Bioactive Compounds, Antibacterial Activity and Relative Action Mechanisms.

Plukenetia huayllabambana is an edible plant traditionally used to cure wounds and various infections. The present work assessed, for the first time, the antibacterial efficacy of solvent fractions from P. huayllabambana fruits. The crude methanol extract was obtained applying ultrasound-assisted extraction, followed by partitioning through successive depletion among solvents of increasing polarity to yield fractions (n-hexane, dichloromethane, ethyl acetate, and n-butanol). The minimal inhibitory concentration (MIC) was determined following antibacterial testing, using the broth microdilution technique against a panel of drug-resistant Gram-negative and Gram-positive bacteria. Possible modes of action of the most active fraction were also investigated. Gas chromatography-mass spectrometry (GC-MS) was used to identify phytocompounds that may account for the recorded activities. Methanol, n-hexane (PH-n-Hex), and ethyl acetate extracts inhibited 100% of studied bacteria, with the recorded MIC ranging from 0.125-1 mg/mL. PH-n-Hex appeared as the most active partition, exerting a bacteriostatic effect. PH-n-Hex probably acts by interfering with bacterial biofilm formation, proton pumps, and bacterial cell membrane integrity. The GC-MS analysis of PH-n-Hex led to the identification of 11 potentially bioactive components, including fatty acids, phytosterol, and diterpene alcohol as major ones. P. huayllabambana can be considered as a plant of pharmacological value-a source of potent anti-infective drug entities.

Antioxidant and Anti-Proliferative Properties of Hagenia abyssinica Roots and Their Potentially Active Components.

Hagenia abyssinica (Bruce) J. F. Gmel. is a multipurpose dioecious tree that has been used to treat various ailments, for example, the flowers of H. abyssinica have been widely used as a tea to treat intestinal parasites by local residents and the roots of H. abyssinica could also be used for anticancer purposes. Antioxidant activity could be one of the most important pathways to suppress cancer and there is hardly any information available on the specific chemical components corresponding to the bioactivities of H. abyssinica to date. The present study intended to screen and evaluate the antioxidant and anti-proliferative properties of five different fractions from H. abyssinica along with their corresponding total flavonoid and phenolic contents and then further identify those compounds with the most potent antioxidant and anti-proliferative activities using high performance liquid chromatography (HPLC) coupled to mass spectrometry (MS) and nuclear magnetic resonance (NMR). The total flavonoid and phenolic content assays showed that the ethyl acetate (EA) fraction of H. abyssinica had higher flavonoid and phenolic levels than the other four fractions. Furthermore, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) superoxide radical scavenging abilities, total antioxidant capacity (TAC) assay with 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS), and ferric-reducing antioxidant power (FRAP) were measured to evaluate the antioxidant activities of the five fractions and some pure compounds isolated from the EA fraction, which displayed higher antioxidant properties than that of the other fractions. Caffeic acid from the EA fraction showed even stronger DPPH scavenging ability (IC50 7.858 ± 0.31 µg/mL) than that of Vc (IC50 8.27 ± 0.11 µg/mL) as the positive control. The anti-proliferative properties of four fractions and the ethanol extract were evaluated by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay and the EA fraction exhibited higher anti-proliferative activities against three cancer cell lines than that of the other fractions. Additionally, the compounds with good antioxidant activity from the EA fraction of H. abyssinica were screened and identified using LC-MS and NMR and were also found to possess good anti-proliferative activity. In the MTT assay, the quercetin showed the strongest dose-dependent anti-proliferative activities to colon cancer cells (HT-29) and liver cancer cells (HepG2) among all of the compounds isolated. This study provided valuable information on the synergistic antioxidant and anti-proliferative properties of H. abyssinica.

Apocynin prevented inflammation and oxidative stress in carbon tetra chloride induced hepatic dysfunction in rats.

BACKGROUND: Liver fibrosis is a leading pathway to cirrhosis and a global clinical issue. Oxidative stress mediated tissue damage is one of the prime causes of hepatic dysfunction and fibrosis. Apocynin is one of many strong antioxidants. OBJECTIVE: To evaluate the effect of apocynin in the CCl4 administered hepatic dysfunction in rats. METHODS: Female Long Evans rats were administered with CCl4 orally (1mL/kg) twice a week for 2 weeks and were treated with apocynin (100mg/kg). Both plasma and liver tissues were analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase activities. Oxidative stress parameters were also measured by determining malondialdehyde (MDA), nitric oxide (NO), myeloperoxidase (MPO), advanced protein oxidation product (APOP). In addition, antioxidant enzyme activities such as superoxide dismutase (SOD) and catalase activities in plasma and liver tissues were analyzed. Moreover, inflammation and tissue fibrosis were confirmed by histological staining of liver tissue sections. RESULTS: Apocynin significantly reduced serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. It also exhibited a considerable reduction of the oxidative stress markers (MDA, MPO, NO, and APOP level) which was elevated due to CCl4 administration in rats. Apocynin treatment also restored the catalase and superoxide dismutase activity in CCl4 treated rats. Histological analysis of liver sections revealed that apocynin prevented inflammatory cells infiltration and fibrosis in CCl4 administered rats. CONCLUSION: These results suggest that apocynin protects liver damage induced by CCl4 by inhibiting lipid peroxidation and stimulating the cellular antioxidant system.

Ferulone A and ferulone B: two new coumarin esters from Ferula orientalis L. roots.

Ferula orientalis (Apiaceae) is a well-known perennial herb growing wild in Iran used in traditional medicine. To perform phytochemical studies, dried ground roots of F. orientalis were sequentially Soxhlet-extracted using n-hexane, dichloromethane and methanol. A combination of vacuum liquid chromatography and preparative thin-layer chromatographic analyses were performed to isolate coumarin esters. The structures of the isolated compounds were elucidated by spectroscopic means, and in vitro free-radical-scavenging property was determined by the DPPH assay. Two new coumarin esters, 7-O-(4,8,12,16-tetrahydroxy-4,8,12,16-tetramethyl-heptadecanoyl)-coumarinand 7-O-(4-hydroxy-4,8,12-trimethyl-trideca-7,11-dienoyl)-coumarin, named ferulone A and ferulone B, respectively, were isolated from the n-hexane extract of the roots of F. orientalis. Both compounds showed a low level of free-radical-scavenging property with the RC50 values of 0.252 and 0.556 mg/mL for compounds 1 and 2, respectively, as opposed to that of the positive control (quercetin) 0.004 mg/mL. This is the first report on the purification of coumarin esters from the genus Ferula.

Phytochemistry and pharmacology of the genus Drypetes: A review.

AIMS: Traditional medicinal use of species of the genus Drypetes is widespread in the tropical regions. The aim of this review is to systematically appraise the literature available to date on phytochemistry, ethnopharmacology, toxicology and bioactivity (in vitro and in vivo) of crude extracts and purified compounds. ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the genus Drypetes (Putranjivaceae) are used in the Subsaharan African and Asian traditional medicines to treat a multitude of disorders, like dysentery, gonorrhoea, malaria, rheumatism, sinusitis, tumours, as well as for the treatment of wounds, headache, urethral problems, fever in young children, typhoid and several other ailments. Some Drypetes species are used to protect food against pests, as an aphrodisiac, a stimulant/depressant, a rodenticide and a fish poison, against insect bites, to induce conception and for general healing. This review deals with updated information on the ethnobotany, phytochemistry, and biological activities of ethnomedicinally important Drypetes species, in order to provide an input for the future research opportunities. METHODS: An extensive review of the literature available in various recognized databases e.g., Google Scholar, PubMed, Science Direct, SciFinder, Web of Science, www.theplantlist.org and www.gbif.org, as well as the Herbier National du Cameroun (Yaoundé) and Botanic Gardens of Limbe databases on the uses and bioactivity of various species of the Drypetes was undertaken. RESULTS: The literature provided information on ethnopharmacological uses of the Subsaharan African and Asian species of the genus Drypetes, e.g., Drypetes aubrévillii, D. capillipes, D. chevalieri, D. gerrardii, D. gossweileri, D. ivorensis, D. klainei, D. natalensis, D. pellegrini (all endemic to Africa) and D. roxburghii (Asian species), for the treatment of multiple disorders. From a total of 19 species, more than 140 compounds including diterpenes, sesquiterpenes, triterpenes (friedelane, oleanane, lupane and hopane-type), flavonoids, lignans, phenylpropanoids and steroids, as well as some thiocyanates, were isolated. Several crude extracts of these plants, and isolated compounds displayed significant analgesic, anthelmintic, antidiabetic, anti-emetic anti-inflammatory, antioxidant, antiparasitic, central nervous system depressant, cytotoxic, and insecticidal activities both in vitro and in vivo. Some toxicities associated with the stem, bark, seed and leaf extracts of D. roxburghii, and the flavonoid, amentoflavone, isolated from the stem extract of D. littoralis as well as D. gerrardii, were confirmed in the animal models and in the rat skeletal myoblast cells assays. As a consequence, traditional medicine from this genus should in future be applied with care. CONCLUSIONS: Plants of this genus have offered bioactive samples, both from crude extracts and pure compounds, partly validating their effectivity in traditional medicine. However, most of the available scientific literatures lacks information on relevant doses, duration of the treatment, storage conditions and positive controls for examining bioefficacy of extract and its active compounds. Additional toxicological studies on the species used in local pharmacopeia are urgently needed to guarantee safe application due to high toxicity of some crude extracts. Interestingly, this review also reports 10 pimarane dinorditerpenoids structures with the aromatic ring C, isolated from the species collected in Asia Drypetes littoralis (Taiwan), D. perreticulata (China), and in Africa D. gerrardii (Kenya), D. gossweileri (Cameroon). These compounds might turn out to be good candidates for chemotaxonomic markers of the genus.

Screening seeds of Scottish plants for antibacterial activity.

Based on ethnopharmacological and taxonomic information, seeds of 21 Scottish plant species from 14 different families were obtained from authentic seed suppliers. Their n-hexane, dichloromethane and methanol extracts were assessed for antibacterial activity against 11 pathogenic bacterial species. Methanol extracts of 11 plant species showed significant antibacterial activity. Malva moschata and Prunus padus were active against five bacterial species, Reseda lutea against four, Centaurium erythraea and Crithmum maritimum against three, Calluna vulgaris against two, and Armeria maritima, Centaurea scabiosa, Daucus carota, Rosa canina and Stellaria holostea against one bacterial species. C. erythraea and P. padus were also active against methicillin resistant Staphylococcus aureus.

Synthesis of 5,6-dichloroindan-1-acids and their tetrazolyl derivatives as analgesic and anti-inflammatory agents.

Indan derivatives, namely, 5-(5',6'-dichloroindan-1'-yl)-tetrazole (12a) and 5-(5',6'-dichloroindan-1'-yl)- methyltetrazole (12b), were synthesized conveniently from 5,6-dichloroindan-1-carboxylic acid (9a) and 5,6- dichloroindan-1-acetic acid (9b), respectively, as potential analgesic and anti-inflammatory agents. The analgesic and anti-inflammatory properties of 9a, 9b, 12a and 12b were evaluated by the acetic acid induced writhing in Swiss albino mice and the carrageenan-induced rat paw edema models, respectively. Compounds 9a and 12a exhibited significant analgesic activity with the doses of 50 and 100 mg/kg body weight, comparable to that of the positive controls, phenylbutazone, indomethacin and aminopyrine. The anti-inflammatory potencies of 9a and 12a were also comparable to that of the positive control, phenylbutazone. Compounds 9b and 12b showed analgesic and anti-inflammatory activities, but were weaker than that of compounds 9a and 12a.

Free radical scavengers from the aerial parts of Euphorbia petiolata.

Reversed-phase preparative high-performance liquid chromatography (HPLC) of the methanol extract of the aerial parts of Euphorbia petiolata Banks & Soland, an endemic Iranian medicinal plant, yielded ten free radical scavengers including eight flavonoid glycosides myricetin 3-O-glucoside (1), kaempferol 3-O-(2-O-galloyl)-glucoside (2), myricetin 3-O-rhamnoside (3), quercetin 3-O-glucoside (4), kaempferol 3-O-glucoside (5), quercetin 3-O-rhamnoside (6), kaempferol 3-O-rhamnoside (7), and quercetin 3-O-rutinoside (10), a coumarin esculetin (8) and a phenylpropanoid 2-hydroxydihydrocinnamic acid (9). The structures of these compounds were elucidated conclusively by spectroscopic means and also by direct comparison of their spectroscopic data with respective published data. The free radical scavenging properties of these compounds were assessed by the 2,2-diphenyl-1-picrylhydrazyl assay.

Free-radical-scavenging principles from Phlomis caucasica.

Seven free-radical-scavenging phenolic compounds including five flavonoids, rutin (1), chrysoeriol 7-O-rutinoside (2), kaempferol 3-O-glucoside (3), chrysoeriol 7-O-glucoside (4) and naringenin (5), and two phenylethanoid glycosides, forsythoside B (6) and acteoside (7) were isolated from the methanol extract of the aerial parts of the Iranian medicinal plant Phlomis caucasica by reversed-phase preparative high-performance liquid chromatography (HPLC), and the structures of these compounds were elucidated by spectroscopic means. The free-radical-scavenging properties of 1-7 were assessed by 2,2-diphenyl-1-picryl hydrazyl (DPPH) assay. Among these compounds, forsythoside B (6) and acteoside (7) were found to be the most potent antioxidants with the RC(50) values of 4.97 and 4.27 microg/ml, respectively.

Further sesquiterpenes from Polygonum viscosum (Polygonaceae).

Two new sesquiterpenes, 4-methoxycarbonyl-7-(1-methylethyl)-6-oxo-3,3a,7,8,8a-pentahydroazulene-1-carboxylic acid (viscoazusone) and 1,4-dimethoxy-carbonyl-7-(1-methylethyl)-6-oxo-3,3a,7,8,8a-pentahydroazulene (viscoazulone), were isolated from the whole plant of Polygonum viscosum. The structures of these compounds were determined by spectroscopic means.

Bioactivity of Excoecaria agallocha / Bioatividade de Excoecaria agallocha

The results of neuropharmacological, microbiological and toxicological studies on the ethanol extract of the bark of Excoecaria agallocha are reported. The extract (100 and 200 mg/kg dosages) was found to produce a profound decrease in exploratory activity in a dose-dependent manner. It also showed a marked sedative effect as evidenced by a significant reduction in gross behaviour and potentiation of sodium thiopental-induced sleeping time. The totality of these effects showed that the extract possesses depressant action on the central nervous system (CNS). The extract of E. agallocha exhibited significant in vitro antibacterial activity against Staphylococcus aureus, Shigella dysenteriae, Shigella sonnei and Enterococci with the zones of inhibition ranging from 11 to 15 mm. While the extract showed considerable brine shrimp toxicity (LD50 = 20 mg/mL), it displayed only low level of toxicity in mice.

Os resultados dos estudos neurofarmacológicos, microbiológicos e toxicológicos do extrato etanólico da casca de Excoecaria agallocha são reportados. O extrato (dosagens de 100 e 200 mg/kg) produziu uma diminuição profunda na atividade exploratória de maneira dose-dependente. Ele também mostrou um efeito sedativo marcante conforme evidenciado por uma redução significativa no comportamento total e potencialização do tempo de sono induzido por tiopental sódico. A totalidade destes efeitos mostrou que o extrato possui ação depressora sobre o sistema nervoso central (SNC). O extrato de E. agallocha exibiu significante atividade antibacteriana in vitro contra Staphylococcus aureus, Shigella dysenteriae, Shigella sonnei e Enterococci com as zonas de inibição medindo entre 11 a 15 mm. Enquanto o extrato mostrou considerável toxicidade em Artemia salina (DL50 = 20 mg/mL), ele exibiu apenas baixo nível de toxicidade em camundongos.