RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Nyctanthes arbor-tristis Linn. has been used by Ayruvedic physicians for the cure of different diseases including ulcers, gastric and inflammatory diseases. AIM OF THE STUDY: To isolate and identify compounds from this source and investigate their therapeutic potential for the treatment of gastric ulcer and related disorders. MATERIAL AND METHODS: The ethanol extract of fresh aerial parts of N. arbor-tristis was used in the present studies which was subjected to a bio-assay guided fractionation followed by chromatographic separations. The structures of pure compounds were elucidated using various spectroscopic techniques. The inhibition of urease enzyme was evaluated by weatherburn indophenol method. Molecular docking studies were determined by using Molecular Operating Environment (MOE) version 2020.0901 version. The intracellular ROS production from phagocytes was determined by chemiluminescence assay and NO generation was detected by Griess method. The proinflammatory cytokine TNF-α was quantified by ELISA. Cytotoxic activity was assessed by MTT assay. RESULTS: One previously undescribed iridoid glycoside arborside F (1) and four known iridoid glycosides arborside A (2), arborside C (3), loganin (4) and 7-O-trans-cinnamoyl-6ß-hydroxyloganin (5) were isolated and characterized in the present studies and their urease inhibitory activity was determined. Among these, 2 and 5 showed strong urease inhibition (IC50 = 12.1 ± 1.74 and 14.1 ± 0.59 µM respectively) (standard acetohydroxamic acid IC50 = 20.3 ± 0.42 µM), whereas rest of compounds showed moderate to low inhibition. Kinetic studies revealed that compounds 2 and 5 possess competitive type of inhibition. Molecular docking showed polar and non-polar interactions of compounds 2 and 5 with urease enzyme residues. Compounds 2 and 3 showed inhibition of ROS from whole blood (IC50 = 1.6 ± 0.3 and 2.5 ± 0.09 µg/mL respectively) and PMNs (IC50 = 1.5 ± 0.03 and 1.4 ± 0.0 µg/mL respectively). Compound 2 significantly inhibited nitric oxide and proinflammatory cytokine TNF-α (IC50 = 18.2 ± 3.0 and 73.8 ± 6.6 µg/mL respectively). Compounds 1, 4 and 5 were inactive on ROS. All isolated compounds were non-toxic on normal mouse fibroblasts (NIH-3T3) cells. CONCLUSIONS: The ethno pharmacological repute of N. arbor-tristis in treating gastric and anti-inflammatory ailments is supported by present studies which resulted in isolation of a potent urease inhibitory and anti-inflammatory agent arborside A (2) a potential anti-ulcer and anti-inflammatory drug lead.
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Extractos Vegetales , Ureasa , Ratones , Animales , Extractos Vegetales/uso terapéutico , Glicósidos Iridoides/farmacología , Cinética , Simulación del Acoplamiento Molecular , Especies Reactivas de Oxígeno , Factor de Necrosis Tumoral alfa , Antiinflamatorios/farmacologíaRESUMEN
A series of twenty alkyl derivatives (2-21) of 4-amino benzoic acid (1, PABA) have been prepared using potassium carbonate and opportune alkylating agents under simple and mild reaction conditions. Compounds (16-21) are reported for the first time. Electron impact mass spectrometry (EIMS), Fourier transform infrared (FTIR) and Proton nuclear magnetic resonance (1H-NMR) spectroscopic techniques were adopted for the characterization of these analogues. In the present study, the cytotoxic screening of sixteen compounds (3, 5-11, 13 and 15-21) was also achieved against lung (NCI-H460) and oral squamous carcinoma (CAL-27) cell lines. Compound 20 has shown magnificent inhibitory properties against NCI-H460 cell line (IC50 15.59 and 20.04 µM, respectively) at a lower dose than that of the control (cisplatin; IC50 21.00 µM). One-way analysis of variance (ANOVA), t-test and Pearson correlation coefficient (PCC) have been performed to determine the reliability of current data through statistical package for the social sciences (SPSS).
RESUMEN
Phytochemical investigation of dried flower buds of Syzygium aromaticum (L.) Merr. & L.M.Perry. (clove) led to the isolation and identification of fourteen known compounds, oleanolic acid (1), betulinic acid (2), para methyl benzoic acid (3), sabrinic acid (4) eucalyptolic acid (5), nigricin (6), 3-O-trans-para-coumaroylmaslinic acid (7), methyl maslinate (8), maslinic acid (9), 3, 4, 5-trimethoxy-3',4'-O,O-methylideneflavellagic acid (10), lantanone (11) 3,4,3'-trimethoxyellagic acid (12), 11-oxo-oleanolic acid (13), and ß-sitosterol-3-O-ß-D-glucopyranoside (14). Their structures were identified by 1H NMR, 13C NMR, Mass spectroscopic techniques, and comparison with the literature data. Compounds 3, and 7-9 showed a strong mortality against root knot nematode, Meloidogyne incognita at 0.125% concentration after 72 hours (88-92% inhibition). Compound 4 showed a good anti-glycation activity with IC50 = 142.0 ± 1.8 µM when compared with standard, i.e. rutin (IC50 = 54.59 ± 2.20 µM). Compound 10 showed a comparable urease inhibitory activity (IC50 = 26.1 ± 0.19 µM) with the positive control thiourea (IC50 = 24.5 ± 0.34 µM).
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Ácido Oleanólico , Syzygium , Syzygium/química , Extractos Vegetales/farmacología , Espectroscopía de Resonancia MagnéticaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Nyctanthes arbor-tristis Linn. is native to Indo-Pak sub-continent and has high medicinal values in Ayureda. This plant has been used traditionally for the treatment of sciatica, rheumatism, chronic fever, diabetes, snakebite, dysentery, cachexia and cancer. Studies have shown many pharmacological properties such as anti-cancer efficacy against Dalton's ascetic lymphoma, cytotoxicity against T-cell leukemia, anti-inflammatory, anti-diabetic and anti-oxidant effects. AIM OF THE STUDY: Aim of the study was to explore the anti-inflammatory and anti-proliferative potential of N. arbor-tristis. MATERIAL AND METHODS: Ethanol extract of fresh and uncrushed aerial parts of N. arbor-tristis was used in the present study. A new compound nyctanthesin A was isolated following a bioactivity-guided fractionation and chromatographic separations. Its chemical structure was elucidated through spectral studies including 1D, 2D-NMR experiments and HREIMS. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) generation from phagocytes were detected by chemiluminescence technique and Griess method, respectively. TNF-α and TGF-ß production was quantified by ELISA. Anti-lymphoma and cytotoxic activities were assessed by alamar blue and MTT assays, respectively. The transcription and protein expression level of Bcl-2, COX-2, p38 MAPK, PDL-1, NF-κB, c-Myc and PNF-κB was performed by qRT-PCR and protein blot assays, respectively. RESULTS: Petroleum ether insoluble fraction of the ethanol extract of fresh and uncrushed aerial parts of N. arbor-tristis revealed anti-inflammatory potential by inhibiting ROS. A previously undescribed compound nyctanthesin A was isolated from this fraction and characterized by UV, IR, NMR and HREIMS. It showed significant anti-inflammatory property by inhibiting ROS, NO and TNF-α production. The strong anti-proliferative effects on B- cell lymphoma cells, DOHH2 and Raji, revealed its anti-lymphoma potential along with non-toxic profile against BJ and NIH-3T3 fibroblast cells of normal origin. The qRT-PCR results showed marked inhibition of Bcl-2, COX-2, p38 MAPK, PDL-1, c-Myc, NF-κB, and PNF-κB at transcription level in DOHH2 cells with comparatively lesser but significant effects in Raji cells, where the expression of Bcl-2 gene was not affected. The protein expression of PNF-κB in DOHH2 cells was inhibited by 66% (P < 0.05) and COX-2 in both cell lines was inhibited by 50% (P < 0.05) at 60 µg/mL. A moderate non-significant inhibition of TGF-ß (â¼20%) was observed in both cell lines at 100 µg/mL CONCLUSIONS: Scientific evidences reported here validate the anti-inflammatory and anti-cancer potential of the plant.
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Linfoma no Hodgkin , Oleaceae , Antiinflamatorios/farmacología , Ciclooxigenasa 2/genética , Etanol , Humanos , Lipopolisacáridos , Linfoma no Hodgkin/tratamiento farmacológico , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Oleaceae/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Proteínas Proto-Oncogénicas c-bcl-2 , Especies Reactivas de Oxígeno , Factor de Crecimiento Transformador beta , Factor de Necrosis Tumoral alfa , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
Six natural products (1-6) were isolated from the fresh leaves of Carissa carandas including ursolic acid (1), ursolic acid-γ-lactone (2), 27-O-Z-p-coumaroyl ursolic acid (3), 23-hydroxy ursolic acid (4), uvaol (5) and ursolic aldehyde (6). Their structure elucidation was done by modern spectroscopic techniques including 1H-NMR, 13C-NMR and comparison with reported data. All compounds were known, while 2-4 were isolated for the first time from the genus Carissa. Isolated compounds were screened for their cytotoxic via MTT assay and anti-inflammatory potential via luminol-enhanced chem-iluminescence assay. Compounds 3 and 4 showed potent activity against lung cancer cell line (NCI-H460), and 4 showed potent anti-inflammatory activity against reactive oxygen species production from human whole blood phagocytes. Compound 5 displayed good selective cytotoxicity against NCI-H460 and did not provoke cytotoxicity against normal cell line upto 250 µM. Compounds 3-5 were identified as potential anti-cancer drug leads.
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Antineoplásicos , Apocynaceae , Antiinflamatorios/farmacología , Apocynaceae/química , Fitoquímicos/farmacología , Extractos Vegetales/químicaRESUMEN
BACKGROUND: Studies on the interaction between bioactive molecules and HIV-1 virus have been the focus of recent research in the scope of medicinal chemistry and pharmacology. OBJECTIVE: Investigating the structural parameters and physico-chemical properties of elucidating and identifying the antiviral pharmacophore sites. METHODS: A mixed computational Petra/Osiris/Molinspiration/DFT (POM/DFT) based model has been developed for the identification of physico-chemical parameters governing the bioactivity of 22 3-hydroxy-indolin-2-one derivatives of diacetyl-L-tartaric acid and aromatic amines containing combined antiviral/antitumor/antibacterial pharmacophore sites. Molecular docking study was carried out with HIV-1 integrase (pdb ID: 5KGX) in order to provide information about interactions in the binding site of the enzyme. RESULTS: The POM analyses of physico-chemical properties and geometrical parameters of compounds 3a-5j, show that they are bearing a two combined (O,O)-pockets leading to a special platform which is able to coordinate two transition metals. The increased activity of series 3a-5j, as compared to standard drugs, contains (Osp2,O sp3,O sp2)-pharmacophore site. The increase in bioactivity from 4b (R1, R2 = H, H) to 3d (R1, R2 = 4-Br, 2-OCH3) could be attributed to the existence of π-charge transfer from para-bromo-phenyl to its amid group (COδ---NHδ+). Similar to the indole-based reference ligand (pdb: 7SK), compound 3d forms hydrogen bonding interactions between the residues Glu170, Thr174 and His171 of HIV-1 integrase in the catalytic core domain of the enzyme. CONCLUSION: Study confirmed the importance of oxygen atoms, especially from the methoxy group of the phenyl ring, and electrophilic amide nitrogen atom for the formation of interactions.
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Fármacos Anti-VIH/farmacología , Integrasa de VIH/efectos de los fármacos , Indoles/farmacología , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/química , Sitios de Unión , Teoría Funcional de la Densidad , Inhibidores de Integrasa VIH/síntesis química , Inhibidores de Integrasa VIH/química , Inhibidores de Integrasa VIH/farmacología , VIH-1/efectos de los fármacos , VIH-1/enzimología , Indoles/síntesis química , Indoles/química , Ligandos , Simulación del Acoplamiento Molecular , Relación Estructura-ActividadRESUMEN
Phytochemical investigation of clove resulted in the isolation of two new natural compounds, a ferulic acid derivative, sabrinic acid (1) and a benzophenone derivative (2) together with two known compounds kaempferol-3,5-dimethyl ether (3) and 4-methyl benzoic acid (4). Compounds 3 and 4 were isolated for the first time from the genus Syzygium. The structures of compounds were elucidated through modern spectroscopic techniques including 1D and 2D NMR spectroscopy.
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Benzofenonas/química , Ácidos Cumáricos/química , Syzygium , Benzofenonas/aislamiento & purificación , Ácidos Cumáricos/aislamiento & purificación , Flores/química , Estructura Molecular , Syzygium/químicaRESUMEN
One novel ursolic acid derivative sabiracin 1 (11,25-epoxy-3ß-hydroxy-urs-12-en-28-oic acid) was isolated from the leaves of Carissa carandas, together with five known compounds para hydroxy benzaldehyde (2), ursolic acid (3), carissin (4), 22α-hydroxyursolic acid (5) and ß-sitosterol-3-O-ß-D-glucopyranoside (6). Compounds 2 and 5 were isolated for the first time from this genus. Structure elucidation was done by the help of spectroscopic techniques. Compounds 1-3, 5 and 6 were examined against oral cancer (CAL-27) and lung cancer (NCI-H460) cell lines. 6 showed good activity against oral cancer (IC50 18.69 µM), moderate activity against lung cancer (IC50 63.34 µM) and no cytotoxicity against normal cell lines.
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Apocynaceae , Triterpenos , Estructura Molecular , Hojas de la Planta , Triterpenos/farmacologíaRESUMEN
In this study, oleanolic acid and its derivatives were studied for their invivo nematicidal activity against root-knot nematode (RKN) Meloidogyne incognita. A series of C-28-oleanolates including five new (5, 7-10) and seven known (1-4, 6, 11, 12) compounds were synthesised and their nematicidal activity was determined and compared with the standard nematicide furadan for the first time. The structures of the compounds were elucidated through 1H NMR, 13C NMR and EIMS. Compounds 4, 5, 7, 8 and 10 showed â¼ 90% inhibition of RKN at 0.125% concentration after 72 h showing their potential use in nematicidal control.
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Carbofurano , Ácido Oleanólico , Tylenchoidea , Animales , Antinematodos/farmacología , Ácido Oleanólico/farmacologíaRESUMEN
The methanolic extract (SA-EXT) of Syzygium aromaticum flower buds and its fractions tested against three human cancer cell lines viz uterine cervix (HeLa), breast (MCF-7) and lung NCI (H-460) using sulforhodamine-B assay. The ethyl acetate soluble sub fraction (SA-EAS) was active only against HeLa cells with GI50value of 36± 3.4µg/mL. The most active sub-fraction (SA-PES-Fr-2) showed growth inhibition (GI50: 36, 50 and 68µg/ml against MCF-7, HeLa and NCI-H-460 cancer cell lines, respectively) with cytotoxic effect LC50= 88 ± 3.4 µg/mL against HeLa and LC50=86 ± 2.8 µg/mL against MCF-7. The most active sub-fraction (SA-PES-Fr-2) analyzed by GC and GC-MS techniques revealed that eugenol was most abundant (85.34%) along with minor constituents. Thus it can be concluded that growth inhibitory and cytotoxic effect residing in Syzygium aromaticum flower buds (clove) is more likely due to eugenol.
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Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Syzygium/química , Compuestos Orgánicos Volátiles/farmacología , Acetatos/química , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Eugenol/análisis , Eugenol/farmacología , Flores/química , Cromatografía de Gases y Espectrometría de Masas , Células HeLa , Humanos , Células MCF-7 , Metanol/química , Compuestos Orgánicos Volátiles/químicaRESUMEN
BACKGROUND: Endophytic fungi are receiving attention as sources of structurally novel bioactive secondary metabolites towards drug discovery from natural products. This study reports the isolation and characterization of secondary metabolites from an endophytic fungus Aspergillus nidulans, associated with Nyctanthes arbor-tristis Linn., a plant which has a traditional use to cure many ailments including cancer. OBJECTIVE: The objective of this study was to evaluate the antiproliferative activity of the metabolites of A. nidulans from N. arbor-tristis on three human cancer cell lines, lung (NCI-H460), breast (MCF-7) and uterine cervix (HeLa), and carry out their characterization. METHODS: The extracts of the endophytic fungus cultured on potato dextrose agar were subjected to various chromatographic techniques. Structures of pure compounds were determined using spectroscopic techniques. The non-polar constituents were analyzed by GC-MS. Antiproliferative activity was determined by sulforhodamine B (SRB) assay. RESULTS: The extracts and fractions showed moderate to good growth inhibition of the aforementioned human cancer cell lines. The broth extract was most potent (IC50 = 10 ± 3.1 µg/mL and LC50= 95 ± 3.9) against HeLa whereas petroleum ether insoluble fraction of mycelium was most active against NCI-H460 and MCF-7 (IC50 = 10 ± 2.1 µg/mL and 18 ± 3.1 µg/mL respectively). GC-MS led to identify 12 compounds in mycelium and 19 compounds in broth. Four pure compounds were isolated and characterized one compound 5, 10-dihydrophenazine-1-carboxylic acid (1) from broth and three 1-hydroxy-3-methylxanthone (2), ergosterol (3) and sterigmatocystin (4) from mycelium. 1 has not been reported earlier as a plant/fungal metabolite while 2-4 are new from this source. Sterigmatocystin exhibited growth inhibitory effect (IC50 = 50 ± 2.5 µM/mL) against only MCF-7 cell line whereas other compounds had IC50 > 100. CONCLUSIONS: In this paper, the cytotoxicity of mycelium and broth constituents of endophytic fungus Aspergillus nidulans from Nyctanthes arbor-tristis is reported for the first time. The study shows that fungus Aspergillus nidulans from Nyctanthes arbor-tristis is capable of producing biologically active natural compounds and provides a scientific rationale for further chemical investigations of endophyte-producing natural products.
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Antineoplásicos/farmacología , Aspergillus nidulans/metabolismo , Productos Biológicos/farmacología , Endófitos/metabolismo , Oleaceae/microbiología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/metabolismo , Aspergillus nidulans/fisiología , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Productos Biológicos/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Endófitos/fisiología , HumanosRESUMEN
The aim of the current work was to explore the muscle relaxant effect of pistagremic acid (PA) isolated from Pistacia integerrima in various animal paradigms. In a rotarod test, PA caused a significant (p<0.05) muscle relaxant potential in a dose-dependent manner. When studied in the inclined plane test, pretreatment with PA (5 and 10 mg/kg) caused promising activity (p<0.05) after treatment for 30, 60 and 90 min. The muscle relaxant potential of PA was strongly complimented by the traction and chimney tests, showing a dominant effect after 60 min of treatment. In conclusion, PA possesses strong muscle relaxant activity in various animal-based models.
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Fármacos Neuromusculares/farmacología , Pistacia/química , Triterpenos/farmacología , Animales , Ratones , Ratones Endogámicos BALB C , Actividad Motora/efectos de los fármacos , Prueba de Desempeño de Rotación con Aceleración ConstanteRESUMEN
Recent efforts to develop cure for chronic diabetic complications have led to the discovery of potent inhibitors against aldose reductase (AKR1B1, EC 1.1.1.21) whose role in diabetes is well-evident. In the present work, two new natural products were isolated from the ariel part of Ocimum basilicum; 7-(3-hydroxypropyl)-3-methyl-8-ß-O-d-glucoside-2H-chromen-2-one (1) and E-4-(6'-hydroxyhex-3'-en-1-yl)phenyl propionate (2) and confirmed their structures with different spectroscopic techniques including NMR spectroscopy etc. The isolated compounds (1, 2) were evaluated for in vitro inhibitory activity against aldose reductase (AKR1B1) and aldehyde reductase (AKR1A1). The natural product (1) showed better inhibitory activity for AKR1B1 with IC50 value of 2.095±0.77µM compare to standard sorbinil (IC50=3.14±0.02µM). Moreover, the compound (1) also showed multifolds higher activity (IC50=0.783±0.07µM) against AKR1A1 as compared to standard valproic acid (IC50=57.4±0.89µM). However, the natural product (2) showed slightly lower activity for AKR1B1 (IC50=4.324±1.25µM). Moreover, the molecular docking studies of the potent inhibitors were also performed to identify the putative binding modes within the active site of aldose/aldehyde reductases.
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Aldehído Reductasa/antagonistas & inhibidores , Benzopiranos/química , Inhibidores Enzimáticos/química , Glucósidos/química , Ocimum basilicum/química , Fenilpropionatos/química , Aldehído Reductasa/metabolismo , Benzopiranos/aislamiento & purificación , Benzopiranos/metabolismo , Benzopiranos/farmacología , Sitios de Unión , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Glucósidos/aislamiento & purificación , Glucósidos/metabolismo , Glucósidos/farmacología , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Conformación Molecular , Simulación del Acoplamiento Molecular , Ocimum basilicum/metabolismo , Fenilpropionatos/aislamiento & purificación , Fenilpropionatos/metabolismo , Fenilpropionatos/farmacología , Componentes Aéreos de las Plantas/química , Componentes Aéreos de las Plantas/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Estructura Terciaria de ProteínaRESUMEN
To treat Alzheimer's disease (AD), the available candidates are effective only against mild AD or have side effects. So, a study was planned to synthesis new candidates that may have good potential to treat AD. A series of new anthrarobin acyl derivatives (2-8) were synthesized by the reaction of anthrarobin (1) and acetic anhydride/acyl chlorides. The product were characterized by 1H NMR and EI-MS, and evaluated for butyrylcholinesterase (BuChE) inhibition activity. Compounds 5 and 4 showed notable BuChE inhibitory potential with IC50 5.3 ± 1.23 and 17.2 ± 0.47 µM, respectively when compared with the standard eserine (IC50 7.8 ± 0.27 µM), compound 5 showed potent BuChE inhibition potential than the standard eserine. The active compounds 5 and 4 have acyl groups at 2-OH and 10-OH positions which may be responsible for inhibitory potential as this orientation is absent in other products. In silico studies of 5 and 4 products revealed the high inhibitory potential due to stable binding of ligand with the BuChE active sites with docking energy score -18.8779 kcal/mol and -23.1159 kcal/mol, respectively. Subsequently, compound 5 that have potent BuChE inhibitory activity could be the potential candidate for drug development for Alzheimer's disease.
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BACKGROUND: Fungi performing a wide range of function in soil by secreting low molecular weight compound known as secondary metabolites. S. rolfsii is a soil borne phytopathogenic fungi was used for the production of bioactive compounds. OBJECTIVE: The present study belongs to evaluate the anticancer potentials of a secondary metabolites isolated from S. rolfsii, their multidrug resistance (MDR), and molecular docking study. METHOD: (1S,3R,4R,5R,E)-3-(3-(3,4-Dihydroxyphenyl)acryloyloxy)-1,4,5 trihydroxycyclohexanecarboxylic acid (1), or best known as chlorogenic acid, was isolated from the ethyl acetate fraction of crude secondary metabolites produced by the soil borne Fungus Screlotium rolfsii. Structure of chlorogenic acid (1) was confirmed by means of FT-IR, 1H NMR, 13C NMR, and mass spectrometry as well as by melting point. RESULTS: Effect of compound 1 on the reversion of multidrug resistant (MDR) mediated by Pglycoprotein (P-gp) against cancer cells was evaluated with a rhodamine-123 exclusion screening test on human mdr1 gene transfected mouse gene transfected L5178 and L5178Y mouse T-cell lymphoma. Compound 1 was also evaluated for Anti-proliferative effect on the L5178 mouse Tcell lymphoma cell line. CONCLUSION: Results from the present investigation revealed that compound 1 exhibits excellent MDR reversing effect in a dose-dependent manner against mouse T-lymphoma cell line. Compound 1 also showed anti-proliferative effect on L5178Y mouse T-lymphoma cell line.
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Antineoplásicos Fitogénicos/farmacología , Ácido Clorogénico/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Hongos/química , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ácido Clorogénico/química , Ácido Clorogénico/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Ratones , Estructura Molecular , Microbiología del Suelo , Relación Estructura-ActividadRESUMEN
Diospyros lotus L. possesses different therapeutic activities such as antioxidant, anti-proliferative, anti-microbial and sedative. However, no studies on the sedative-hypnotic activity of 7-methyljuglone are reported. In the present study, we have evaluated in vivo the anxiolytic-hypnotic like effects of 7-methyljuglone in mice with open field and phenobarbitone-induced sleeping time tests. We have also assessed in silico the involvement of GABAA, GABAB and 5HT1 neurotransmission in its mechanism of action. The intraperitoneal administration of 7-methyljuglone (2.5-10mg/kg) reduce significantly the number of crossed lines in mice open field test and concomitantly it shown a significant activity in term of onset of sleeping time and also in its duration. Moreover, 7-methyljuglone demonstrated in silico an interesting interaction with GABAA but not GABAB and 5HT1binding sites. All of these results, taken together, 7-methyljuglone may be an innovative candidate for designing new pharmaceutical and therapeutic applications.
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Diospyros/química , Hipnóticos y Sedantes/farmacología , Naftoquinonas/farmacología , Extractos Vegetales/farmacología , Animales , Antioxidantes/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
Pistacia genus belong to family Anacardiaceae and it is versatile in that its member species have food (P. vera), medicinal (P. lentiscus) and ornamental (P. chinensis) values. Various species of this genus have folkloric uses with credible mention in diverse pharmacopeia. As a trove of phenolic compounds, terpenoids, monoterpenes, flavonoids, alkaloids, saponins, fatty acids, and sterols, this genus has garnered pharmaceutical attention in recent times. With adequate clinical studies, this genus might be exploited for therapy of a multitude of inflammatory diseases, as promised by preliminary studies. In this regard, the ethnomedicinal, phytochemistry, biological potencies, risks, and scopes of Pistacia genus have been reviewed here.
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Fitoquímicos/química , Fitoquímicos/farmacología , Pistacia/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Alcaloides/química , Alcaloides/farmacología , Flavonoides/química , Flavonoides/farmacología , Fenoles/química , Fenoles/farmacología , Fitoterapia/métodos , Saponinas/química , Saponinas/farmacología , Terpenos/química , Terpenos/farmacologíaRESUMEN
Two new dimeric naphthoquinones, 5',8'-dihydroxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (1; Di-naphthodiospyrol D) and 5',8'-dihydroxy-5,8-dimethoxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (2; Di-naphthodiospyrol E), along with known naphthoquinones diospyrin (3) and 8-hydroxy diospyrin (4) were isolated from the chloroform fraction of extract of Diospyros lotus roots. Their structures were elucidated by advanced spectroscopic analyses, including HSQC, HMBC, NOESY, and J-resolved NMR experiments. The fractions and compounds 1-4 were evaluated for urease activity and phosphodiesterase-I, carbonic anhydrase-II and α-chymotrypsin enzyme inhibitory activities. Compounds 1 and 2 and their corresponding fractions showed significant and selective inhibitory effects on urease activities. The IC50 values of 1 and 2 were 260.4 ± 6.37 and 381.4 ± 4.80 µmol·L-1, respectively, using thiourea (IC50 = 21 ± 0.11 µmol·L-1) as the standard inhibitor. This was the first report demonstrating that the naphthoquinones class showed urease inhibition.
Asunto(s)
Diospyros/química , Inhibidores Enzimáticos/farmacología , Naftoquinonas/farmacología , Extractos Vegetales/farmacología , Ureasa/antagonistas & inhibidores , Bioensayo , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Estructura Molecular , Naftoquinonas/química , Naftoquinonas/aislamiento & purificación , Extractos Vegetales/química , Raíces de PlantasRESUMEN
The present study deals with the anti-hyperalgesic and anti-inflammtory effects of flavonoids (1-4) isolated from the chloroform fraction of Pistacia integerrima galls. The structure of isolated compounds was elucidated by using advance spectroscopy analysis and comparing their physical spectral data with reported one. The pretreatment of compounds (1-4) caused significant anti-hyperalgesic effects in acetic acid induced writhing test in a dose dependent manner. The compounds strongly complimented the effects in both phases of formalin test. However, the administration of naloxone did not abolish the induced antinociceptive effects and therefore suggested the absence of opioid receptor involvement. The pretreatment of flavonoids (1-4) elicited marked anti-inflammtory effects in carrageenan induced paw edema test in mice during various assessment times (1-5 h). The effects were dose dependent and maximum results were observed after 3rd h of treatments which remained significant up to 5th hour. It is concluded that the isolated flavonoids (1-4) possessed strong anti-hyperalgesic and anti-inflammtory activity and thus are strong candidates for further detail studies.
Asunto(s)
Analgésicos/farmacología , Antiinflamatorios/farmacología , Conducta Animal/efectos de los fármacos , Flavonoides/farmacología , Pistacia/química , Extractos Vegetales/farmacología , Analgésicos/uso terapéutico , Animales , Antiinflamatorios/uso terapéutico , Edema/tratamiento farmacológico , Edema/fisiopatología , Flavonoides/uso terapéutico , Masculino , Ratones , Ratones Endogámicos BALB C , Manejo del Dolor/métodos , Dimensión del Dolor , Extractos Vegetales/uso terapéuticoRESUMEN
This study deals with the isolation of the active constituent(s) from a methanolic extract of Pistacia integerrima J. L. Stewart barks and it was also oriented to evaluate the in vivo and in silico anti-inflammatory activity. By NMR and crystallography techniques, we have isolated a triterpenoid identified as daturaolone (compound 1). This compound showed in vivo a significant and dose dependent (1-30 mg/kg) anti-inflammatory activity on carrageenan-induced mouse paw oedema (ED50 = 10.1 mg/kg) and on acetic acid-induced writhing responses in mice (ED50 = 13.8 mg/kg). In the in vivo experiments, the effect of tested compound was also evaluated in presence of the reference drug diclofenac (1-30 mg/kg). Moreover, in silico analysis of receptor ligand complex shows that compound 1 interacts with cyclooxygenases (COXs) binding sites displaying an interesting interaction with COX-1. These findings suggest that compound 1 isolated from P. integerrima possesses in vivo anti-inflammatory and antinociceptive potentials, which are supported in silico by an interaction with COXs receptors.