RESUMEN
Gout is an arthropathic and inflammatory disease. The prevalence and incidence of such disease has risen in last decades. It is associated with life style thus it could be recognize as life style diseases. In the present study, the flower extract of Alstonia scholaris Linn R.Br., Flower was initially subjected to extraction, isolation which leads to purification of pure eight compounds. All these compounds were identified using various spectroscopic techniques. In-vitro Xanthine oxidase inhibition activity was performed to determine the antigout potential of lead compounds. Compound 8 showed significant activity among all i.e. 14.7 ± 0.43 as compare to standard allopurinol 6.77 ± 0.26. Accordingly, in-silico studies using Autodock vina 4 showed the ligand-protein interaction of luteolin with 3AX7. The docking simulations showed significant binding pocket sites of respective proteins 3AX7 with the least binding energy -10.2 kcal/mol. Consequently, molecular docking simulations for 100ns indicated robust evidence with their conformational structural interaction which serve as active sites for Lead compound. Principal Component Analysis indicated first three PCs capture 23.8%, 39%, and 49% of structural variance in protein. Therefore compound 8 could be consider for potential drug design and development in gout therapy.
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Nano-sized silver has drawn a great deal of attention in the field of health sciences owing to its remarkable therapeutic applications. Interestingly, the method applied to synthesize nanoparticles and the choice of reagents considerably influence their therapeutic potential and toxicities. Current research has explored the toxicity, anti-inflammatory, antinociceptive, and antioxidant responses of the malonic acid-capped silver nanoparticles (MA-AgNPs (C) by using sodium borohydride as a reducing agent at low temperatures by employing both in vitro and in vivo approaches. Furthermore, it has highlighted the synergistic effect of these novel compounds with conventional anti-inflammatory therapeutic agents. Acute and sub-acute toxicity analysis performed following OECD guidelines showed that the studied MA-AgNPs (C) are safer, and prominent toxic signs have not been detected at the highest studied dose of 2,000 mg/kg. Cytotoxicity evaluation through brine shrimp lethality revealed 20% lethality at the highest concentration of 169.8 µg/mL. Significantly, positive anti-inflammatory and analgesic responses alone as well as synergism with the standard were identified through in vitro as well as in vivo methods which were more potent at a lower dose (200 mg/kg). Notably synergistic outcomes were more pronounced than individual ones, indicating their prominent effect as a feasible drug delivery system. IL-6 and TNF-α assessment in excised paw tissue through RTPCR technique further supported their anti-inflammatory potential. DPPH assay revealed eminent in vitro antioxidant activity which was further corroborated by in vivo antioxidant assessment through evaluation of SOD in excised paw tissue.
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A polyphenolic flavone Luteolin (3',4',5,7-tetrahydroxyflavone) is found in various plants and is traditionally used in Chinese medicine. It is obtained from Alstonia scholaris (L.) R.Br Flower belonging to the family Apocynaceae while investigation. Various studies have been demonstrated the antioxidant or antiulcer potential of luteolin from different plant sources. In the present investigation the antioxidant or antiulcer effect of the Luteolin has been carried out using molecular docking simulations. The objective of this study was to analyze the antioxidant and antiulcer potential of luteolin obtained during isolation. The in vitro biological evaluation has been supported by the in silico studies using Autodock vina 4 shows the ligand-protein interaction of lute olin with 1HD2, 4GY7 and 3O1Q. Luteolin showed significant DPPH scavenging and urease inhibition activity i.e., 23.4 ± 0.87, 6.21±0.45 IC50 (uM) respectively as compared to the standard BHA and thiourea 44.2±0.45, 22.4±0.29 IC50 (uM) respectively. The docking simulations showed significant binding pocket sites with the respective proteins1HD2, 4GY7 and 3O1Q with the least binding energy -6.8, -8.0 and -8.2 kcal/mol respectively. Thus, Strong evidence has been presented with their confirmation structural interaction via molecular docking with proteins that serve as binding sites for available Luteolin molecule. The findings justify the application of the compound as a novel antioxidant and antiulcer agent.
Asunto(s)
Alstonia/química , Luteolina/farmacología , Fitoquímicos/farmacología , Ureasa/antagonistas & inhibidores , Compuestos de Bifenilo , Depuradores de Radicales Libres , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Luteolina/química , Modelos Moleculares , Simulación del Acoplamiento Molecular , Estructura Molecular , Peroxirredoxinas/genética , Peroxirredoxinas/metabolismo , Fitoquímicos/química , PicratosRESUMEN
In the management of cardiovascular disorders, medicines from herbal sources have played a vital role through centuries. The following study was commenced in order to lay possible pharmacological foundation associated with medicinal uses of edible fruit of Grewia asiatica in hypertension through in-vitro method. In this study isolated atrial preparation of Guinea pig was used where crude ethanolic extract of Grewia asiatica fruit (Ga.Cr) decreased the force and rate of spontaneous atrial contractions (0.03-10mg/kg). In isolated rat aortic ring preparations previously vasoconstricted by phenylephrine and High K+, it also resulted in dose dependent vasodilation (0.01-10 mg/kg).In the presence of L-NAME, the relaxation curve of Ga.Cr was partially inhibited showing involvement of Nitric oxide (NO) mediated pathway. The speculative analysis contemplated that Ga.Cr has blood pressure reducing potentials through inhibition of Ca++ influx via Ca++ channels, its release from intracellular stores and through other means like NO mediated pathways.
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Antihipertensivos/farmacología , Frutas/química , Grewia/química , Extractos Vegetales/farmacología , Acetilcolina/farmacología , Animales , Antihipertensivos/aislamiento & purificación , Aorta/efectos de los fármacos , Aorta/fisiología , Cobayas , Atrios Cardíacos/efectos de los fármacos , Isoproterenol/farmacología , Contracción Muscular/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Extractos Vegetales/aislamiento & purificación , Ratas , Ratas Sprague-DawleyRESUMEN
Epilepsy, a neuronal disorder has affected 1% of the world's population. Almost 35-40% of these patients get resistant to available anti-epileptic drugs (AEDs). Recent studies have shown the role of inflammation in the pathophysiology of epilepsy and a combination of anti-inflammatory and antiepileptic drugs could prove beneficial against epileptic seizures. Therefore, we aimed to examine the effect of levetiracetam (LEV) and diclofenac sodium (DFS) combination on pilocarpine (PLC) induced epileptic seizures in mice. Mice were divided into control and treatment groups. LEV alone and in combination with DFS was given for 3 days. On 3rd day after administering the required drugs, pilocarpine challenge was given intraperitoneally. Then, behavioral changes were observed for 90 minutes, including latency to first seizure, continuous seizures, duration of continuous seizures, and survival rate. Results showed significant improvement in the latencies to first (P<0.001) and continuous seizures (P<0.05), duration of the continuous seizure (p=0.001), and survival rate (P<0.01) in the combination treatment group as compared to the control or individual drug treatment groups. DFS enhances the efficacy of LEV, however, further mechanistic studies will be required to conclude if DFS can be given in combination with LEV for epilepsy treatment.
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Antiinflamatorios no Esteroideos/farmacología , Anticonvulsivantes/farmacología , Convulsivantes , Diclofenaco/farmacología , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Levetiracetam/farmacología , Pilocarpina , Animales , Conducta Animal/efectos de los fármacos , Sinergismo Farmacológico , Epilepsia/mortalidad , Masculino , Ratones , Convulsiones/inducido químicamente , Convulsiones/mortalidad , Convulsiones/prevención & control , Análisis de SupervivenciaRESUMEN
Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used for the treatment and prevention of inflammation with the increase in number of side effects. Traditional plants have been used to treat inflammation owing to lesser adverse responses. Croton bonplandianus being an anti-inflammatory plant is extensively utilized all over the world. The methanolic and aqueous leaves extracts of Croton bonplandianus were exposed to anti-inflammatory activity in the carrageenan induced paw edema against standard diclofenac sodium, followed by the histopathlogical examination. The highest dose of methanolic extract were shown significant anti-inflammatory action having a significant P-value (P<0.05-0.001) compared with the diclofenac sodium (P<0.01-0.001) and aqueous extracts (P<0.5-0.01). The histopathological examination illustrated the vasodialation with reduction in the intensity of edema, neutrophils infiltration and other inflammatory cells. C. bonplandianus being a reactive oxygen species scavenger, responsible to exert an excellent anti-inflammatory activity. The present study confirmed the anti-inflammatory potential of drug extracts and authors recommended its utilization in the treatment of pain, inflammation and relevant diseases in future. However, phytochemical screening is to be required for the complete evaluation of active chemical constituent (s).
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Antiinflamatorios/farmacología , Croton/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Animales , Croton/efectos adversos , Diclofenaco/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/tratamiento farmacológico , Edema/patología , Masculino , Hojas de la Planta/efectos adversos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Lumbar spine osteoarthritis with 40-85% prevalence, degeneration of spine with remarkable narrowing of disc space and osteophytes formation trigger pain in lower back. Pain in lower portion of back is now considered to be the second most commonly treated health issue in primary health care setups. This pain causes disability, functional loss and job absentees. Commonly pain is managed pharmacologically by NSAIDS but resulted in severe gastric side effects. The purpose of this trial was to appraise the properties of bromelain and papain, the vegetal proteolytic enzymes, in comparison with standard drug on LBP patients. Forty men and women with lumbar spine osteoarthritis were recruited and divided into group 1, received aceclofenac 100mg tablet b.i.d as standard treatment, group 2, patients treated with aceclofenac 100 mg tablet b.i.d and enzyme supplements 250 mg b.i.d for 6 weeks. All the participants were evaluated for their body mass index, vital signs and liver/kidney enzymes before and after treatment. Moreover intensity of pain were also measured through visual analogue scale (VAS) and oswestry low back pain questionnaire (ODI) before treatment (0 week), 3rd week and 6th week of treatment. The enzyme group patients showed significantly diminished pain scores VAS from 7.10±1.29 to 5.85±1.531*** (P=0.001), ODI score from 56.2±8.70 to 51.6±8.125*** (P=0.000), significantly diminished enzymes; ALP from 210.00±55.24 to 196.90±51.02 (P=0.054*) and serum creatinine from 0.97±0.153 to 0.87±0.139 (P=0.035*) and improved quality of life. Hence, this study suggested that the enzyme supplements for 6 weeks have prolonged beneficial carry-over effects in comparison to standard treatment without producing any change in BMI (P>0.05) and vital signs (P> 0.05).
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Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Dolor de la Región Lumbar/tratamiento farmacológico , Vértebras Lumbares , Osteoartritis de la Columna Vertebral/tratamiento farmacológico , Péptido Hidrolasas/uso terapéutico , Anciano , Femenino , Humanos , Riñón/enzimología , Hígado/enzimología , Dolor de la Región Lumbar/enzimología , Masculino , Persona de Mediana Edad , Osteoartritis de la Columna Vertebral/enzimología , Péptido Hidrolasas/farmacología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Glibenclamide (GBC) has been associated with hepatotoxicity in humans. This study conducted on rabbits to evaluate the hepatotoxicity of GBC alone and in combination therapy with propranolol (PPL). Liver enzymes like alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyltransferase (γ-GT) and bilirubin (BRB) are used to evaluate hepatotoxicity associated with GBC. Histological findings, micrometry and scanning electron microscopy (SEM) used to find hepatotoxicity by GBC and with PPL. GBC caused significant elevation of liver functions as compared to control (p<0.005). PPL reduced the level of serum ALT, ALP, γGT and BRB when administered with GBC (p<0.005). The results prevailed that there is a significant change in hepatic cells structure and significant change in its diameter of nucleus (p<0.05). The necrosis and granuloma with decreased in number of hepatic cells were observed in GBC treated rabbits. However, the combination of GBC with PPL has shown healthy and nearly similar structure as that of controlled group and confirmed by SEM microscopy. PPL reduced the blood flow to hepatic portal system and thus, avoid the noxious substances to liver. It is affirmed that the use of PPL offered beneficial effect on hepatotoxic drugs.
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Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Gliburida/farmacología , Hígado/efectos de los fármacos , Propranolol/farmacología , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Antioxidantes , Aspartato Aminotransferasas/metabolismo , Bilirrubina/metabolismo , Tetracloruro de Carbono/farmacología , Catalasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Humanos , Hígado/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Conejos , Superóxido Dismutasa/metabolismo , gamma-Glutamiltransferasa/metabolismoRESUMEN
Histopathological studies are an essential element to ascertain comprehensive safety profile of a drug. Unfortunately limited data are available about the toxicity of herbal remedies. Since a popular medicinal plant Holoptelea integrifolia (Roxb) Planch. contains various bioactive molecules, the present study is aimed to assess the histopathological alterations induced by aqueous extract of Holoptelea integrifolia on liver and kidney of wistar albino rat. In this study 60 rats divided in two groups; control and treated with aqueous extract of Holoptelea integrifolia (250mg/kg body weight) for 5 days. Histopathlogical studies by hematoxylin and eosin (H&E) staining were done on the liver and kidney tissues at the end of dosing by using standard procedure. Microscopic examination was then carried out to observe any pathological changes in the animals. The result showed that there is no significant variation in the basic architecture of liver and kidney as compared to control male wistar albino rats. In conclusion, aqueous extract of leaves of H. integrifolia may be safe and nontoxic. Further work on pharmacological aspects is required to evaluate the clinical potential of this plant for different ailments.
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Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Hojas de la Planta/química , Ulmaceae/química , Animales , Riñón/patología , Hígado/patología , Masculino , Extractos Vegetales/química , Plantas Medicinales/química , Ratas Wistar , Agua/químicaRESUMEN
The aim of present study is to evaluate the antidiabetic and hepatoprotective effect of Guaiacum officinale in streptozotocin induced male albino rats. The methanolic bark extract of Guaiacum officinale was administered at a dose of 500 mg/kg and Glibenclamide was used as a standard drug at a dose of 0.5mg/kg for 28 days. The animals were divided in to four groups. Control group n=12, received distilled water. Positive control group (STZ group) n=12 received streptozotocin at 30 mg/kg dose through I/P route. Standard group (STZ+ GLB group): n=12 received Glibenclamide. Treated group (STZ+ extracted group): n=12 received bark extract of Guaiacum officinale. Blood glucose level was significantly reduced after oral adminstration of bark extract in streptozotocin induced diabetic rats. The SGOT level significantly reduced in Guaiacum officinale treated group as compare to control, pronounced reduction of ALT level as compared to GLB and the ALP levels was highly significantly reduced in Guaiacum officinale treated group while GLB is unable to improve ALP levels in GLB treated diabetic albino rats. The level of direct bilirubin in Guaiacum officinale treated group was found to be insignificant as compared to control and STZ treated group while the level of indirect bilirubin was significantly reduced in STZ treated group as compare to control. Histopathological studies showed that Guaiacum officianle have hepatoprotective effect in experimental induced male albino rats.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Guaiacum , Hipoglucemiantes/farmacología , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Glucemia/análisis , Diabetes Mellitus Experimental/fisiopatología , Hígado/patología , Hígado/fisiopatología , Masculino , Corteza de la Planta , Ratas , Ratas Wistar , EstreptozocinaRESUMEN
Among the neurodegenerative disorders, Parkinson disease (PD) is ranked as second most common. The pathological hallmark is selective degeneration of the dopaminergic neurons in the nigro-striatal regions of brain with appearance of the Lewy bodies. Present study explores the neuro-protective potential of polydatin in terms of amelioration of degeneration of dopaminergic neurons in nigro-striatal regions of brain and distorted neuromotor behavior in the rotenone model of Parkinson's disease. Thirty-six male Sprague Dawley rats were divided into three groups. Group A (control), Group B (rotenone treated) and Group C (rotenone+polydatin treated). Rotenone was administrated intraperitoneally (i.p) at a dose of 3 mg/kg/body weight while polydatin was given i.p. at a dose of 50 mg/ kg/body weight for four weeks. Then, animals were sacrificed; substantia nigra (SN) & striatum isolated from brain and five micron thick sections were prepared. Cresyl violet (CV), H&E and Immuno-histochemical staining using anti-TH antibody was done. Motor behavior was assessed weekly throughout the experiment using five different methods. Rotenone treated parkinsonian animals showed deterioration of motor behavior, weight loss, loss of dopaminergic neurons and diminished immune-reactivity in the sections from the nigrostriatal regions of these animals Polydatin+rotenone treatment showed contradicting effects to parkinsonism, with amelioration in weight loss, neuro-motor behavior, dopaminergic loss and immune-reactivity against dopaminergic neurons. Present study revealed a neuro-protective potential of polydatin in animal model of PD by ameliorating the neuro-motor abnormalities and degeneration of dopaminergic neurons in nigrostriatal regions.
Entre los trastornos neurodegenerativos, la enfermedad de Parkinson (EP) se clasifica como la segunda más común. El sello patológico es la degeneración selectiva de las neuronas dopaminérgicas en las regiones nigro-estriatales del cerebro, con la aparición de los cuerpos de Lewy. El presente estudio explora el potencial de protección neuronal de la polidatina en términos de la mejora de la degeneración de las neuronas dopaminérgicas en las regiones nigro-estriatales del cerebro y el comportamiento neuromotor distorsionado en el modelo de rotenona de la enfermedad de Parkinson. Treinta y seis ratas macho Sprague Dawley se dividieron en tres grupos: Grupo A (control), Grupo B (tratado con rotenona) y Grupo C (tratamiento con rotenona + polidatina). La rotenona se administró por vía intraperitoneal (i.p.) a una dosis de 3 mg/kg/peso corporal, mientras que la polidatina se administró i.p. a una dosis de 50 mg/kg/ peso corporal durante cuatro semanas. Posteriormente, los animales fueron sacrificados. Se aislaron la substantia nigra (SN) y cuerpo estriado de los cerebros y se realizaron secciones de cinco micras de espesor. Se realizó una tinción de violeta de cresilo (CV), H&E y tinción inmunohistoquímica usando anticuerpo anti-TH. El comportamiento motriz se evaluó semanalmente durante todo el experimento utilizando cinco métodos diferentes. Los animales parkinsonianos tratados con rotenona mostraron deterioro del comportamiento motriz, pérdida de peso, pérdida de neuronas dopaminérgicas y disminución de la reactividad inmune en las secciones de las regiones nigroestriadas. El tratamiento con polidatina + rotenona mostró efectos contrarios al parkinsonismo, con mejoría en la pérdida de peso, en el comportamiento motor, en la pérdida dopaminérgica y en la reactividad inmune contra las neuronas dopaminérgicas. El presente estudio reveló un potencial de protección neuronal de la polidatina en el modelo animal de la EP al mejorar las anomalías neuro-motoras y la degeneración de las neuronas dopaminérgicas en las regiones nigroestriatales.
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Animales , Masculino , Ratas , Enfermedad de Parkinson/tratamiento farmacológico , Estilbenos/administración & dosificación , Glucósidos/administración & dosificación , Enfermedad de Parkinson/patología , Rotenona/toxicidad , Inmunohistoquímica , Dopamina , Ratas Sprague-Dawley , Fármacos Neuroprotectores , Modelos Animales de Enfermedad , Trastornos del Movimiento/prevención & control , Degeneración Nerviosa/prevención & controlRESUMEN
Unpredictable outcomes of life saving drugs have been seen in patients who receive different cardioselective drugs for longer periods. Many studies have been conducted to explore these responses. This study shows the down regulation of adrenergic receptors due to chronic use of lisinopril, an ACE inhibitor as a cause of poor response of adrenaline. Langendroff's technique was used. The data obtained from ten rabbits shows that effective dose of lisinopril (10mg/kg daily orally) reduces the inotropic and chronotropic effects of adrenaline significantly (P<0.05).Therefore it is suggested to use higher doses of adrenaline in cardiac units in patients who have used therapeutic doses of lisinopril for longer periods provided it is supported by clinical studies.