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Kasture S.,Pinnacle Biomedical Research Institute | Kasture V.,Pinnacle Biomedical Research Institute
Oriental Pharmacy and Experimental Medicine | Year: 2013

Medicinal plants have been a rich source of medicines. Mucuna pruriens is extensively used in Ayurveda to treat kampavat (Parkinson's disease in modern medicine), a disease characterized by excess of Vata. Clinical and preclinical studies have substantiated claims on its efficacy and safety in PD and there are indications that it is more effective than the levodopa in reducing dyskinesias. Several constituents of Mucuna seeds such as genistein, gallic acid, unsaturated acids, nicotine, bufotenin, harmin alkaloids, lecithin, etc. have been isolated which possess neuroprotective activity and support the antiPD activity of levodopa. The review describes various constituents of Mucuna pruriens seeds in context to therapeutic utility in treating Parkinson's disease. Since the conventional treatment of PD using levodopa with other add-on drugs is very expensive and Mucuna pruriens seeds are easily available and economic, the use of standardized extract of Mucuna seeds may drastically reduce the cost of treatment and also reduce the progression of disease. The review emphasizes the importance of holistic approach of Ayurveda in using the Mucuna pruriens in treatment of PD. Further studies may provide an approach to understand the mechanisms involved in treating PD with lesser adverse effects. © 2013 Institute of Korean Medicine, Kyung Hee University.


Karchuli M.S.,Pinnacle Biomedical Research Institute
Asian Journal of Pharmaceutical and Clinical Research | Year: 2014

Present study was performed to evaluate the effect of Mentha arvensis on cisplatin-induced nephrotoxicity in Sprague-Dawley rats. The M. arvensis hydroalcoholic extract (MAHE) was administered orally at two dose levels (200 mg/kg and 400 mg/kg). The kidney function test (estimation of serum creatinine, total protein, blood urea nitrogen [BUN], and urea), oxidative stress study (estimation of superoxide dismutase [SOD] activity, glutathione content, and lipid peroxides [LPO]), and histological studies were also conducted. MAHE was found effective at both doses, although high dose (400 mg/kg) was found more effective, which was evidenced by decrease in serum creatinine, total protein, BUN, urea, and LPO and increased in SOD activity. Histopathological studies were also confirmed the nephroprotective action of MAHE. Present investigation revealed that M. arvensis showed nephroprotective effect on cisplatin nephrotoxicity in Sprague-Dawley rats which may be due to the presence of flavonoids and related compounds. © 2014 Asian Journal of Pharmaceutical and Clinical Research. All rights reserved.


PubMed | University of Florence, University of Cagliari and Pinnacle Biomedical Research Institute
Type: | Journal: Parkinson's disease | Year: 2016

Parkinsons disease (PD) is one of the most common neurodegenerative diseases characterized by the clinical triad: tremor, akinesia, and rigidity. Several studies have suggested that PD patients show disturbances in olfaction as one of the earliest, nonspecific nonmotor symptoms of disease onset. We sought to use the fruit fly Drosophila melanogaster as a model organism to explore olfactory function in LRRK loss-of-function mutants, which was previously demonstrated to be a useful model for PD. Surprisingly, our results showed that the LRRK mutant, compared to the wild flies, presents a dramatic increase in the amplitude of the electroantennogram responses and this is coupled with a higher number of olfactory sensilla. In spite of the above reported results, the behavioural response to olfactory stimuli in mutant flies is impaired compared to that obtained in wild type flies. Thus, behaviour modifications and morphofunctional changes in the olfaction of LRRK loss-of-function mutants might be used as an index to explore the progression of parkinsonism in this specific model, also with the aim of studying and developing new treatments.


PubMed | CNR Institute of Neuroscience, Pinnacle Biomedical Research Institute, University of Cagliari and Italian Institute of Technology
Type: Journal Article | Journal: PloS one | Year: 2016

The common fruit fly Drosophila melanogaster (Dm) is a simple animal species that contributed significantly to the development of neurobiology whose leucine-rich repeat kinase 2 mutants (LRRK2) loss-of-function in the WD40 domain represent a very interesting tool to look into physiopathology of Parkinsons disease (PD). Accordingly, LRRK2 Dm have also the potential to contribute to reveal innovative therapeutic approaches to its treatment. Withania somnifera Dunal, a plant that grows spontaneously also in Mediterranean regions, is known in folk medicine for its anti-inflammatory and protective properties against neurodegeneration. The aim of this study was to evaluate the neuroprotective effects of its standardized root methanolic extract (Wse) on the LRRK2 loss-of-function Dm model of PD. To this end mutant and wild type (WT) flies were administered Wse, through diet, at different concentrations as larvae and adults (L+/A+) or as adults (L-/A+) only. LRRK2 mutants have a significantly reduced lifespan and compromised motor function and mitochondrial morphology compared to WT flies 1% Wse-enriched diet, administered to Dm LRRK2 as L-/A+and improved a) locomotor activity b) muscle electrophysiological response to stimuli and also c) protected against mitochondria degeneration. In contrast, the administration of Wse to Dm LRRK2 as L+/A+, no matter at which concentration, worsened lifespan and determined the appearance of increased endosomal activity in the thoracic ganglia. These results, while confirming that the LRRK2 loss-of-function in the WD40 domain represents a valid model of PD, reveal that under appropriate concentrations Wse can be usefully employed to counteract some deficits associated with the disease. However, a careful assessment of the risks, likely related to the impaired endosomal activity, is required.


PubMed | CNR Institute of Neuroscience, Pinnacle Biomedical Research Institute, University of Cagliari and Italian Institute of Technology
Type: | Journal: Scientific reports | Year: 2017

The present study was aimed at characterizing the effects of Withania somnifera (Wse) and Mucuna pruriens (Mpe) on a Drosophila melanogaster model for Amyotrophic Lateral Sclerosis (ALS). In particular, the effects of Wse and Mpe were assessed following feeding the flies selectively overexpressing the wild human copper, zinc-superoxide dismutase (hSOD1-gain-of-function) in Drosophila motoneurons. Although ALS-hSOD1 mutants showed no impairment in life span, with respect to GAL4 controls, the results revealed impairment of climbing behaviour, muscle electrophysiological parameters (latency and amplitude of ePSPs) as well as thoracic ganglia mitochondrial functions. Interestingly, Wse treatment significantly increased lifespan of hSDO1 while Mpe had not effect. Conversely, both Wse and Mpe significantly rescued climbing impairment, and also latency and amplitude of ePSPs as well as failure responses to high frequency DLM stimulation. Finally, mitochondrial alterations were any more present in Wse- but not in Mpe-treated hSOD1 mutants. Hence, given the role of inflammation in the development of ALS, the high translational impact of the model, the known anti-inflammatory properties of these extracts, and the viability of their clinical use, these results suggest that the application of Wse and Mpe might represent a valuable pharmacological strategy to counteract the progression of ALS and related symptoms.


Patil R.A.,MGVs Pharmacy College | Kasture S.B.,Pinnacle Biomedical Research Institute
Natural Product Research | Year: 2012

In this study, the neuroprotective potential and in vivo antioxidant status of extract of roots and rhizomes of Rubia cordifolia L (MERC) in reserpine-induced orofacial dyskinesia was studied. Reserpine (1 mg/kg, s.c.) on day 1, 3 and 5 was used to induce orofacial dyskinesia. At the end of treatment schedule, MERC significantly inhibited reserpine-induced vacuous chewing movements, tongue protrusions, orofacial bursts, catalepsy. MERC significantly increased locomotion and rearing in open field test. MERC exhibited significant elevation in the levels of superoxide dismutase, catalase, glutathione reductase and inhibition of lipid peroxidation in forebrain region, compared with the reserpine treated group. It significantly elevated dopamine levels in the forebrain region. GCMS revealed the presence of anthraquinones, having strong antioxidant activity. It is concluded that oxidative stress might play an important role in reserpine-induced abnormal oral movements and MERC significantly protected animals against reserpine-induced orofacial dyskinesia and has great potential in treatment of neuroleptic induced orofacial dyskinesia. © 2012 Taylor & Francis Group, LLC.


Patil R.A.,MGVs Pharmacy College | Hiray Y.A.,MGVs Pharmacy College | Kasture S.B.,Pinnacle Biomedical Research Institute
Indian Journal of Pharmacology | Year: 2012

Context: Reserpine-induced orofacial dyskinesia is an animal model of tardive dyskinesia which may be associated with neurodegeneration and free radical damage. Aim: The aim was to assess the neuroprotective potential and in vivo antioxidant status of alcoholic extract of roots and rhizomes of Nardostachys jatamansi (ANJ) and its triterpenes (TNJ) in reserpine-induced orofacial dyskinesia. Materials and Methods: In the present study, repeated treatment with reserpine (1.0 mg/kg) on each other day for a period of 5 days (days 1, 3, and 5) significantly induced vacuous chewing movements (VCMs) and tongue protrusions (TPs) in rats. The effect on reserpine-induced catalepsy was also studied. The effect of ANJ and TNJ on levels of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH) and inhibition of lipid peroxidation (LPO) in the forebrain region was assessed. Statistical Analysis: All observations were expressed as mean ± SEM. Statistical analysis was performed by the one-way ANOVA followed by Dunnett′s test. P<0.05 was regarded as statistically significant. Results: At the end of the treatment schedule, ANJ and TNJ significantly inhibited reserpine-induced VCM, TP, and catalepsy, and significantly increased the locomotion and rearing in the open-field test. Treatment with ANJ and TNJ exhibited significant elevation in the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH) and inhibition of lipid peroxidation (LPO) in forebrain region compared to the reserpine treated group. Conclusions: The study concludes that ANJ and TNJ significantly protected animals against reserpine-induced orofacial dyskinesia as well as catalepsy suggesting its potential value in the treatment of neuroleptic-induced orofacial dyskinesia and Parkinson′s disease.


Mohan M.,Mgvs Pharmacy College | Kamble S.,Mgvs Pharmacy College | Gadhi P.,Computerised Laboratory | Kasture S.,Pinnacle Biomedical Research Institute
Food and Chemical Toxicology | Year: 2010

Nephrotoxicity is one of the important side effects of anthracycline antibiotics. The aim of the study was to determine the protective effect of Solanum torvum on doxorubicin-induced nephrotoxicity in rats using biochemical and histopathological approaches. Oxidative stress is the main factor in doxorubicin (DOX) induced nephrotoxicity. Wistar rats received either DOX (67.75 mg/kg, i.v, 2 days before sacrifice) or S. torvum (100 mg/kg and 300 mg/kg, p.o.) prior to DOX treatment or S. torvum (100 mg/kg and 300 mg/kg, p.o.) extract alone for 4 weeks. Nephrotoxicity was assessed by measuring the abnormal levels of serum creatinine and blood urea nitrogen (BUN). The anti-oxidant defence enzymes superoxide dismutase (SOD) and catalase (CAT) of kidney tissue were also measured at the end of the treatment schedule. Treatment with S. torvum (100 mg/kg and 300 mg/kg) significantly (p < 0.05) decreased the levels of creatinine and BUN and significantly (p < 0.05) increased the anti-oxidant defence enzyme levels of SOD and CAT. Histopathological changes showed that DOX caused significant structural damages to kidneys like tubular necrosis, renal lesions and glomerular congestion which was reversed with S. torvum. The results suggest that S. torvum has the potential in preventing the nephrotoxicity induced by doxorubicin. © 2009 Elsevier Ltd. All rights reserved.


Mohan M.,JKK Nataraja Dental College and Hospital | Waghulde H.,JKK Nataraja Dental College and Hospital | Kasture S.,Pinnacle Biomedical Research Institute
Phytotherapy Research | Year: 2010

Acute subcutaneous administration of Angiotensin II (Ang II) causes a rise in blood pressure in diabetic Wistar rats. Diabetes was induced using streptozotocin (70 mg/kg, i.v.). Chronic administration of pomegranate juice (PJ) extract (100 mg/kg and 300 mg/kg; p.o. for 4 weeks) obtained from Punica granatum (punicaceae) fruits reduced the mean arterial blood pressure and vascular reactivity changes to various catecholamines and also reversed the biochemical changes induced by diabetes and Ang II. PJ treatment also caused a significant decrease in levels of thiobarbituric acid reactive substances (TBARS) in kidney and pancreas while activities of enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH) showed significant elevation. The cumulative concentration response curve (CCRC) of Ang II was shifted towards right in rats treated with PJ using isolated strip of ascending colon. In histopathological examination, PJ treatment prevented the tubular degenerative changes induced by diabetes. The results suggest that the PJ extract could prevent the development of high blood pressure induced by Ang II in diabetic rats probably by combating the oxidative stress induced by diabetes and Ang II and by inhibiting ACE activity. In conclusion, PJ has antihypertensive action in Ang II diabetic model. Copyright © 2009 John Wiley & Sons, Ltd. 10.1002/ptr.3090.


Mohan M.,JKK Nataraja Dental College and Hospital | Patankar P.,JKK Nataraja Dental College and Hospital | Ghadi P.,Computerised Laboratory | Kasture S.,Pinnacle Biomedical Research Institute
Journal of Pharmacology and Pharmacotherapeutics | Year: 2010

Objective: To determine the protective role of Punica granatum L. (Punicaceae) seed juice extract and its butanolic fraction on heart rate, electrocardiographic patterns, vascular reactivity to catecholamines, cardiac marker enzymes, antioxidant enzymes together with morphologic and histopathological changes in isoproterenol-induced myocardial infarction in male Wistar rats. Materials and Methods: The effects of Punica granatum seed juice extract (100 mg/kg, p.o. and 300 mg/kg, p.o.) and butanolic fraction of Punica granatum seed juice extract (100 mg/kg., p.o.) on cardiac parameters were studied. Isoproterenol hydrochloride was used to induce myocardial infarction in Wistar rats. At the end of the experiment, heart rate, ECG, pressure rate index and cardiac marker enzyme levels were assessed. Results: Rats treated with isoproterenol (85 mg/kg, administered subcutaneously twice at an interval of 24 h) showed a significant increase in heart rate, ST elevation in ECG, pressure rate index and a significant increase in the levels of cardiac marker enzymes-lactate dehydrogenase, and creatine kinase in serum. Isoproterenol significantly reduced superoxide dismutase and catalase activity and increased vascular reactivity to various catecholamines. Pretreatment with PJ (100 mg/kg, p.o. and 300 mg/kg, p.o.) and B-PJ (100 mg/kg., p.o.) for a period of 21 days significantly inhibited the effects of ISO on heart rate, PRI, ECG patterns, levels of LDH, CK, SOD, CAT, and vascular reactivity changes. Treatment with PJ (100 mg/kg and 300 mg/kg) and B-PJ (100 mg/kg., p.o.) alone did not alter any of the parameters as compared to vehicle-treated Wistar rats. Punica granatum-treated animals showed a lesser degree of cellular infiltration in histopathological studies. Conclusion: Punica granatum ameliorates cardiotoxic effects of isoproterenol and may be of value in the treatment of MI.

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