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1.
PLoS One ; 19(3): e0294999, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38483938

RESUMEN

Allium Cepa Linn. (Onions) has extensively been used in traditional medicine, is one of the important Allium species regularly used in our daily diet, and has been the source of robust phenolic compounds. The current study is intended to evaluate the fecundity-enhancing effect of A. Cepa on the reproductive performance of two successive generations of rats; F0 and F1. A. Cepa extract was initially tested for in vitro antioxidant assay via DPPH and ROS, followed by in vivo toxicity testing. In the fecundity assessment, eighteen pairs of male and female rats (n = 36, 1:1, F0 generation) were divided into three groups and dosed with 75mg/kg and 150 mg/kg daily of A. Cepa extract and saline respectively, up to pre-cohabitation, cohabitation, gestation and lactation period. The reproductive performance, including body weight, live birth index, fertility index, and litter size, was assessed. Various parameters like Hematological, Hormonal (FSH, LH, Testosterone, estradiol), antioxidant markers (SOD, Glutathione peroxidase) and lipid profile of F0 and F1 generations were assessed with evaluation of histopathology of male and female organs. Ethanolic extract of A. Cepa showed the greatest antioxidant potential in DPPH and ROS methods. The continued exposure of the F0 and F1 generations to A. Cepa extract did not affect body weight, fertility index, litter size, and survival index. However, semen pH, sperm motility, sperm count, sperm viability, and semen volume were significantly improved in both generations. We have found pronounced fecundity outcomes in both genders of F0 and F1 generations with A. Cepa 150mg/kg/day extract as compared to control. Results showed that A. Cepa significantly increased (P < 0.05) hemoglobin, follicular stimulating hormone (FSH), luteinizing hormone (LH), plasma testosterone and glutathione peroxidase activities, while total lipid, LDL, and cholesterol were significantly decreased (P < 0.05) in both generations. Histology of both generations of animals reveals enhanced spermatogenesis and enhanced folliculogenesis with improved architecture. Altogether, the present results suggest that A. Cepa extract improved fecundity in both male and female rats by improving hormonal activities and oxidative stress.


Asunto(s)
Antioxidantes , Cebollas , Ratas , Masculino , Femenino , Animales , Especies Reactivas de Oxígeno/farmacología , Antioxidantes/farmacología , Motilidad Espermática , Semillas , Reproducción , Fertilidad , Peso Corporal , Testosterona , Hormona Luteinizante/farmacología , Hormona Folículo Estimulante/farmacología , Glutatión Peroxidasa , Lípidos/farmacología
2.
Pak J Pharm Sci ; 36(2): 467-476, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37530154

RESUMEN

High levels of reactive oxygen species (ROS) in the body and diabetes are key factors for the development of hypercholesteremia and related neuropathic pains. Current study aimed to compare the antioxidant, antidiabetic and analgesic activities of aqueous methanolic extracts of C. viminalis L. and A. rosea L. leaves. HPLC method was used for phenolic content evaluation. Antioxidant capacity was determined by DPPH and analgesic activity was performed via acetic acid induced writhing reflex test. Whereas the antidiabetic activity was performed on Alloxan induced diabetes model. HPLC analysis indicated the presence of phenols in both extracts. Based on DPPH radical scavenging activity, C. viminalis and A.rosea L. both leaves extracts showed strong scavenging activity (IC50, 11.96±0.64lg/mL) and (IC50, 10.11±0.74lg/mL) respectively. Antidiabetic effect of C. viminalis L and A. rosea L. were also significant (p<0.05). Further biochemical analysis showed both leaves extracts significantly (P<0.05) reduces glucose, Low density lipid (LDL), triglycerides (TG), total cholesterol (TC) and urea while high density lipid (HDL) were improved. In writhing reflex test both extracts exhibited significant (P<0.01) analgesic activity which was comparable to Aspirin. In conclusion both C. viminalis L. and A. rosea L. leaves extracts displayed significant antioxidant, analgesic and antidiabetic activity.


Asunto(s)
Antioxidantes , Malvaceae , Antioxidantes/química , Hipoglucemiantes/química , Extractos Vegetales/química , Analgésicos/farmacología , Lípidos/análisis , Hojas de la Planta/química
3.
Pak J Pharm Sci ; 34(2): 499-506, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34275822

RESUMEN

Natural oils are rich in polyunsaturated fatty acids (PUFs) like omega 3, omega 6 and other nutrients that boost physical and mental health. Traditionally these oils have been used to treat joint pain associated with several inflammatory conditions. In this study, we investigated the antioxidant and analgesic properties of the sesame oil (SO), fish oil (FO) and combination of these two oils (SO+FO). Different concentrations of the SO, FO and SO+FO combination 0.02-4mg/ml were used for assessing the free radical scavenging activity by DPPH method and the IC50 value was calculated. Acetic acid-induced abdominal writhing test, tail immersion and hot plate models were used to determined analgesic effect. Results showed that both oils were well tolerated as no signs of toxicity or death were noticed during the observational study period. SO+FO combination showed the best antioxidant properties as shown by DPPH assay. Similarly in analgesic models, SO and FO significantly reduced the number of abdominal contractions (p<0.05) however, SO+FO (1:1) exhibited highly significant results (p<0.001) in writhing reflex test. Furthermore, SO and FO both increased the reaction time on a hot plate as well as in tail flick test (p<0.05) whereas, SO+FO significantly increased reaction time (p<0.001) in hot plate and in tail flick test as compared to SO and FO single treatments. Conclusively, our results suggest that the combination of both oils (SO+FO) exhibited significant antioxidant and analgesic potential that it could be considered as one of the active combinations for relieving pain in adjunctive treatment for joint pain associated with rheumatoid arthritis.


Asunto(s)
Analgésicos/farmacología , Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Aceites de Pescado/farmacología , Nocicepción/efectos de los fármacos , Aceite de Sésamo/farmacología , Ácido Acético , Animales , Compuestos de Bifenilo , Calor , Indicadores y Reactivos , Inyecciones Intraperitoneales , Ratones , Estrés Oxidativo/efectos de los fármacos , Picratos , Tiempo de Reacción/efectos de los fármacos , Reflejo/efectos de los fármacos , Tiburones
4.
J Ethnopharmacol ; 279: 114402, 2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34245832

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Nepeta adenophyta Hedge (Lamiaceae) is an endemic therapeutic herb from Astore, Gilgit (Pakistan). This plant species has been reported among the local communities, especially for treating abdominal pain, kidney pain, menstrual pain, headache, and controlling bleeding disorders. Therefore, the scientific basis is provided for the relief of pain as it is used in various pain management among the natives, especially as ethnogynecological herbal remedy. AIM OF THE STUDY: The present study investigates the analgesic and anti-inflammatory effects of the ethanolic extract of N. adenophyta in animal models. Furthermore, the extract was also studied to determine their valuable phytoconstituents. MATERIAL AND METHODS: The biological effects were determined via tail-flick, hot plate, and acetic-acid-induced abdominal writhing methods. At the same time, anti-inflammatory activity was assesed via oxidative burst and antioxidant DPPH assay. Gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS) techniques were employed to understand the phytochemicals present in the crude ethanolic extract of Nepeta adenophyta. RESULTS: In the current study, Nepeta adenophyta extract exhibited potent analgesic and anti-inflammatory effects on different pain models and indicated that the analgesic effect of N. adenophyta extract is mediated both in central and peripheral ways. Dose-dependent and significant (P < 0.05) increases were shown in pain threshold, at 45 min post-treatment, with 20 and 40 mg/kg of the extract in the tail-flick model. The effects of the extract were similar to aspirin but lower to those by morphine (2.5 mg/kg) in the same tests. The extract (20-40 mg/kg) showed dose-dependent inhibition of writhing with a significant (P < 0.001) increase protection against thermal stimuli in hot plate test as compared to control and similar to aspirin and morphine. Further, the anti-inflammatory activity of the crude in oxidative burst and DPPH assays showed significant inhibitory activity. The chemical profile analysis showed major phytochemicals, including long chain derivatives of alkane and alcohol, phenolics, naphthalene, naphthopyran, androsten phenanthrenone, nepetalactones, flavonoids etc. CONCLUSIONS: Nepeta adenophyta Hedge is suggested as a natural alternative for mild pain relief. Our findings endorse the folklore use of N. adenophyta in different pain managements which can be attributed to the presence of polyphenolic compounds, naphthalene derivatives, flavanoids and nepetalactones etc.


Asunto(s)
Analgésicos/farmacología , Antioxidantes/farmacología , Nepeta/química , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Analgésicos/química , Animales , Antioxidantes/química , Aspirina/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Ratones , Morfina/farmacología , Dolor/tratamiento farmacológico , Fitoquímicos/química , Fitoterapia , Extractos Vegetales/química , Ratas , Ratas Wistar , Pruebas de Toxicidad
5.
Pak J Biol Sci ; 23(11): 1357-1368, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33274862

RESUMEN

BACKGROUND AND OBJECTIVE: Hedera helix L. (Ivy) has been utilized as an alternative medicine for cough however, through extensive literature search; we found no reported activity of ivy on α-glucosidase inhibition, HbA1c levels and its protective effect on vital organs. Therefore, the present study aimed to evaluate the antidiabetic and protective effect of ivy in alloxan induced rat model. MATERIALS AND METHODS: The hypoglycemic activity of ivy was examined in normoglycemic, glucose overloaded and alloxan-induced rats. The antidiabetic potential was also confirmed by estimation of HbA1c and α-glucosidase inhibitory activity. RESULTS: Results of acute and chronic study revealed that ivy produced highly significant decline (p<0.01) in fasting and post-prandial blood sugar levels as compared to diabetic control and standard group respectively. Furthermore, highly significant decline (p<0.01) in HbA1c levels were seen after chronic administration of ivy indicating its therapeutic effect in lowering HbA1c levels during long term use. It was found that ivy produced stronger and highly significant (p<0.05) inhibition of α-glucosidase activity than the standard agent acarbose at 500 µg mL-1. CONCLUSION: The histopathological studies of vital organs revealed protective effect of ivy via maintaining the normal architecture as compared to alloxan model. Hence, our findings support the potential use of ivy for diabetes management.


Asunto(s)
Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Inhibidores de Glicósido Hidrolasas/farmacología , Hedera , Extractos Vegetales/farmacología , Hojas de la Planta , Aloxano , Animales , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/patología , Hemoglobina Glucada/metabolismo , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Hedera/química , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Ratas Sprague-Dawley , Factores de Tiempo
6.
Pak J Pharm Sci ; 33(3): 937-945, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-33191216

RESUMEN

The majority of the world population suffers from mental and behavioral disorder. It is the need of the time to find an alternate of presently available medicines in order to decrease the medical expense. Homeopathic remedies are available and prescribed by homeopaths for treatment of anxiety and depression. Unfortunately, no data are available that proves its potential to relieve mental illness. The current study is designed to assess neuro behavioral and antidepressant like effects of homeopathic remedies Staphysagria, Argentum nitricum and Ignatia amara in comparison with standard drug (escitalopram). Different neuro behavioral activities were analyzed. The animals were administered the doses of all homeopathic remedied (60 µl to the rats) and escitalopram (0.042 mg to rats) through the oral route. The activities were observed on day 30th and day 60th. Our result suggests that the swimming time in Staphysagria treated group were significantly improved (p<0.001) after day 60th and significance rise was observed (p<0.01) in Ignatia amara treated animals, whereas significant decline (p<0.05) in struggling time was observed in Argentum nitricum administered animals after the 60th day as compared to 30th day. The central square crossings were improved highly significantly (p<0.001) after the 30th day dosing, by all three remedies and peripheral squares crossing were found highly significantly increased (p<0.001) after chronic dosing in Staphysagria and Ignatia amara treated groups. It is concluded from the results that all three homeopathic remedies produce comparable effects like standard drug while among all three remedies Staphysagria possess a potent antidepressant activity. To the best of our knowledge the current study reports first time the anti-depressant potential of homeopathic remedies in rodents.


Asunto(s)
Antidepresivos/farmacología , Conducta Animal/efectos de los fármacos , Depresión/tratamiento farmacológico , Homeopatía , Locomoción/efectos de los fármacos , Extractos Vegetales/farmacología , Nitrato de Plata/farmacología , Animales , Delphinium , Depresión/fisiopatología , Modelos Animales de Enfermedad , Femenino , Masculino , Prueba de Campo Abierto , Ratas , Strychnos , Natación , Factores de Tiempo
7.
Curr Comput Aided Drug Des ; 16(4): 420-434, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32883197

RESUMEN

BACKGROUND: Parkinson's disease is characterized by decreased level of dopaminergic neurotransmitters and this decrease is due to the degradation of dopamine by protein Monoamine Oxidase B (MAO-B). In order to treat Parkinson's disease, MAO-B should be inhibited. OBJECTIVE: To find out the novel phytochemicals from plant Ocimum basilicum that can inhibit MAO-B by using the in silico methods. METHODS: The data of chemical constituents from plant Ocimum basilicum was collected and inhibitory activity of these phytochemicals was then predicted by using the Structure-Based (SB) and Ligand-Based Virtual Screening (LBVS) methods. Molecular docking, one of the common Structure-Based Virtual Screening method, has been used during this search. Traditionally, molecular docking is used to predict the orientation and binding affinity of the ligand within the active site of the protein. Molegro Virtual Docker (MVD) software has been used for this purpose. On the other hand, Random Forest Model, one of the LBVS method, has also been used to predict the activity of these chemical constituents of Ocimum basilicum against the MAO-B. RESULTS: During the docking studies, all the 108 compounds found in Ocimum basilicum were docked within the active site of MAO-B (PDB code: 4A79) out of which, 57 compounds successfully formed the hydrogen bond with tyr 435, a crucial amino acid for the biological activity of the enzyme. Rutin (-182.976 Kcal/mol), Luteolin (-163.171 Kcal/mol), Eriodictyol-7-O-glucoside (- 160.13 Kcal/mol), Rosmarinic acid (-133.484 Kcal/mol) and Isoquercitrin (-131.493 Kcal/mol) are among the top hits with the highest MolDock score along with hydrogen interaction with tyr 435. Using the RF model, ten compounds out of 108 chemical constituent of Ocimum basilicum were predicted to be active, Apigenin (1.0), Eriodictyol (1.0), Orientin (0.876), Kaempferol (0.8536), Luteolin (0.813953) and Rosmarinic-Acid (0.7738095) are predicted to be most active with the highest RF score. CONCLUSION: The comparison of the two screening methods show that the ten compounds that were predicted to be active by the RF model, are also found in top hits of docking studies with the highest score. The top hits obtained during this study are predicted to be the inhibitor of MAO-B, thus, could be used further for the development of drugs for the treatment of Parkinson's disease (PD).


Asunto(s)
Antiparkinsonianos/farmacología , Inhibidores de la Monoaminooxidasa/farmacología , Monoaminooxidasa/metabolismo , Ocimum basilicum/química , Fitoquímicos/farmacología , Antiparkinsonianos/química , Descubrimiento de Drogas , Humanos , Simulación del Acoplamiento Molecular , Inhibidores de la Monoaminooxidasa/química , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Fitoquímicos/química
8.
Pak J Pharm Sci ; 33(2): 511-521, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32276892

RESUMEN

Natural oils are enriched with polyunsaturated fatty acids (PUFAs) which are important for our health. Recent experimental data explained that PUFAs might have a beneficial effect on various brain functions such as anxiety, dementia, epileptic seizures, depression or bipolar and other neurobehavioral diseases. The objective of the current research work was to evaluate the effect of sesame oil, fish oil and mixture of both oils (1:1) on neurobehavioral changes and cognition. For this purpose shark fish oil and sesame oil were extracted out and there poly unsaturated and saturated fatty acids were analyzed by using GCFID that exposed the presence of different PUFs in shark fish oil, sesame oil and mixture of both oils. Neurobehavioral changes were seen after 5ml/kg/day sesame oil, 5ml/kg/day shark fish oil and 1:1 combination of both oil 5ml/kg/day administration on open field, cage crossing, light and dark, stationary rod, forced swimming induced depression test and water maze test. Our GCFID results showed sesame and fish oil enriched with higher amount of PUFs and showed significant anxiolytic and antidepressant like effect after 30 days of treatment (P<0.05) however combination of these both oils exhibited greater efficacy (P<0.01) in reducing anxiety and depression as imipramine standard drug. Results showed that combination of both oils (sesame oil and fish oil) could be a better option to treat neurobehavioral problems as compared to alone.


Asunto(s)
Suplementos Dietéticos , Aceites de Pescado/farmacología , Locomoción/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Aceite de Sésamo/farmacología , Natación/psicología , Animales , Aceites de Pescado/aislamiento & purificación , Locomoción/fisiología , Masculino , Aprendizaje por Laberinto/fisiología , Ratones , Aceite de Sésamo/aislamiento & purificación , Tiburones
9.
Pak J Pharm Sci ; 33(5): 1945-1953, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33824100

RESUMEN

We determined anti-Parkinson's activity of M. chamomilla L. tea in chlorpromazine (CPZ) developed investigational animal model. In this research, effects of M. chamomilla L. tea 2.14ml/ kg P.O were studied on cataleptic behavior and its effect on brain histopathological changes and immunohistochemistry (IHC) in rats. The experimental design was developed by administering CPZ (3mg/kg, I/P) for twenty-one days to produce Parkinson's disease-like symptoms to 4 animal groups. We observed that chlorpromazine significantly produced motor dysfunctions (catalepsy) in a time period of twenty-one days. The M. chamomilla L. significantly (P<0.005) minimized/shorten/taper down catalepsy in rats just like standard group (Levodopa/carbidopa treated group). The maximum reduction was observed from both treated and standard groups on the 21st day. M. chamomilla L. treated rats mid brain sections showed presence of proliferative blood vessels, increase cellularity with reactive glial cells as compared to CPZ group. Furthermore, immunostaining CD68 & CD21 of M. chamomilla L. treated rats mid brain region showed few CD68 cells & no polymorphs neutrophils after CD21 staining. Thus, this research work disclosed the neuroprotective effect of M. chamomilla L. tea against Parkinson's disease-like symptoms or anti-Parkinson's activity induced by CPZ.


Asunto(s)
Antiparkinsonianos/farmacología , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Catalepsia/prevención & control , Matricaria , Actividad Motora/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Trastornos Parkinsonianos/prevención & control , Extractos Vegetales/farmacología , Animales , Antiparkinsonianos/aislamiento & purificación , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Catalepsia/inducido químicamente , Catalepsia/patología , Catalepsia/fisiopatología , Clorpromazina , Modelos Animales de Enfermedad , Masculino , Matricaria/química , Fármacos Neuroprotectores/aislamiento & purificación , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/patología , Trastornos Parkinsonianos/fisiopatología , Extractos Vegetales/aislamiento & purificación , Ratas Wistar
10.
Pak J Pharm Sci ; 33(4): 1747-1753, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33583812

RESUMEN

The novel coronavirus (nCOVID-19) has spread to endless nations and turn out to be a pandemic around the globe. Because of the developing number of affirmed cases and open public hazard owing to its high risk of infection rate, it has expected a lot of consideration from world health organizations and national health regulatory and monitoring agencies. The world is in surge to explore or discover novel treatment options and vaccine that can lead to cure. There is no proven effective treatment for nCOVID-19 however along with available antiviral therapy Chinese researchers recommended herbal treatments as effective and alternative treatments options to treat this pandemic. Herbal products are wealthy in dynamic phytochemicals, such as the terpenoids, various collection of flavonoids, sulfides, lignans constiuents, coumarins concentrates, saponins moities, polyphenolics composite, numerous alkaloids, polyines, furyl mixtures, proteins and related compounds, thiophenes and peptides groups. In this review we discussed pathogeneis, immunity and current herbal treatment strategies of nCOVID-19 to cure this world wide pandemic.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Fitoterapia , Preparaciones de Plantas/uso terapéutico , COVID-19/inmunología , COVID-19/prevención & control , Citrus , Curcuma , Medicamentos Herbarios Chinos/uso terapéutico , Zingiber officinale , Glycyrrhiza , Humanos , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Inmunidad Innata/inmunología , Nigella sativa , SARS-CoV-2
11.
Pak J Pharm Sci ; 32(4(Supplementary)): 1829-1834, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31680079

RESUMEN

Monoamine oxidase A (MAO-A), an enzyme found on outer mitochondrial membrane, catalyzes the oxidative deamination of biogenic amines. Recently, it has been studied that MAO-A have a role in the cancer progression by elevating the generation of Reactive oxygen species (ROS) and by promoting epithelial to mesenchymal transition (EMT) through activation of Vascular endothelial growth factor (VEGF) and its co-receptor neuropilin-1. In this study, an attempt has been made to identify new lead candidates for inhibiting the MAO-A induced initiation and progression of cancer by using molecular docking method. For this purpose, 967 phyto-chemicals from African medicinal plants (AfroDb) were docked gainst the MAO-A (PDB ID: 2Z5X) using Molegro Virtual Docker (MVD) software. MVD calculates the binding energies of target enzyme and ligands at lowest energy conformations by using the piecewise linear potential (PLP) scoring functions. Evaluation of docking studies suggests that compounds Quercetin (ZINC03869685), Apigenin (ZINC03871576), Luteolin (ZINC18185774), [(2R,3S,4R,5S) 3,4,5 trihydroxytetrahydropyran-2-yl]methyl (ZINC14422042) and Scutellarein (ZINC05842416) are docked with highest MVD score -104.412 kcal/mol, -100.189 kcal/mol, -98.5797 kcal/mol, -98.1878 kcal/mol, -97.5296 kcal/mol respectively, therefore, can effectively inhibit MAO-A enzyme and can serve a role as potential lead compounds for developing new drugs for the suppression of cancer.


Asunto(s)
Inhibidores de la Monoaminooxidasa/farmacología , Monoaminooxidasa/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Fitoquímicos/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Cinética , Modelos Moleculares , Conformación Molecular , Simulación del Acoplamiento Molecular , Unión Proteica , Quercetina/farmacología , Factor A de Crecimiento Endotelial Vascular
12.
Pak J Pharm Sci ; 32(3 (Supplementary)): 1207-1213, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31303592

RESUMEN

Ligand based virtual screening (LBVS) is based on the hypothesis that similar structures have similar biological functions. In this research paper, ligand based virtual screening has been performed in order to predict the inhibitors for monoamine oxidase (MAO-B), an enzyme specifically involved in the metabolism of non-hydroxylated amines such as benzylamine and beta-phenylethylamine (PEA), thus, could be the target to treat various neurodegenerative disorders like Parkinson's disease. For this purpose, Afro Database, a subset of ZINC natural compound database has been screened using Random Forest Modeling (RF). For the training of RF model, 36 reference molecules, the known inhibitors of MAO have been collected from Duke's phyto-chemical and ethno-botanical database. As an outcome of this screening, 31 compounds out of 968 compounds from Afro Database (compounds from African medicinal plants) are predicted to be active as MAO-B inhibitor, Out of the 31 predicted active compounds, Norlichexanthone (ZINC05765089) is predicted to be most active against MAO-B with highest RF score 0.795181, along with the other top hits, could be the putative drug candidates for the prevention/ treatment of Parkinson's disease.


Asunto(s)
Inhibidores de la Monoaminooxidasa/farmacología , Fitoquímicos/farmacología , Plantas Medicinales/química , África , Evaluación Preclínica de Medicamentos/métodos , Ligandos , Modelos Teóricos , Inhibidores de la Monoaminooxidasa/química , Fitoquímicos/química , Xantonas/química , Xantonas/farmacología
13.
Bioorg Med Chem ; 20(3): 1251-8, 2012 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-22261024

RESUMEN

Data on phytochemical constituents of plants commonly used in traditional Indonesian medicine have been compiled as a computer database. This database (the Indonesian Herbal constituents database, IHD) currently contains details on ∼1,000 compounds found in 33 different plants. For each entry, the IHD gives details of chemical structure, trivial and systematic name, CAS registry number, pharmacology (where known), toxicology (LD(50)), botanical species, the part(s) of the plant(s) where the compounds are found, typical dosage(s) and reference(s). A second database has been also been compiled for plant-derived compounds with known activity against the enzyme, aldose reductase (AR). This database (the aldose reductase inhibitors database, ARID) contains the same details as the IHD, and currently comprises information on 120 different AR inhibitors. Virtual screening of all compounds in the IHD has been performed using Random Forest (RF) modelling, in a search for novel leads active against AR-to provide for new forms of symptomatic relief in diabetic patients. For the RF modelling, a set of simple 2D chemical descriptors were employed to classify all compounds in the combined ARID and IHD databases as either active or inactive as AR inhibitors. The resulting RF models (which gave misclassification rates of 21%) were used to identify putative new AR inhibitors in the IHD, with such compounds being identified as those giving RF scores >0.5 (in each of the three different RF models developed). In vitro assays were subsequently performed for four of the compounds obtained as hits in this in silico screening, to determine their inhibitory activity against human recombinant AR. The two compounds having the highest RF scores (prunetin and ononin) were shown to have the highest activities experimentally (giving ∼58% and ∼52% inhibition at a concentration of 15µM, respectively), while the compounds with lowest RF scores (vanillic acid and cinnamic acid) showed the lowest activities experimentally (giving ∼29% and ∼44% inhibition at a concentration of 15µM, respectively). These simple virtual screening studies were thus helpful in identifying novel inhibitors of AR, but yielded compounds with only very modest (micromolar) potency.


Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Diseño de Fármacos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Plantas Medicinales/química , Aldehído Reductasa/metabolismo , Inteligencia Artificial , Simulación por Computador , Bases de Datos Factuales , Humanos , Indonesia , Modelos Biológicos , Programas Informáticos
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