Satyndra Kumar Yadav

Mucuna pruriens seed extract reduces oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in paraquat-induced Parkinsonian mouse model

Parkinsons disease (PD) is a neurodegenerative disease which causes rigidity, resting tremor and postural instability. Treatment for this disease is still under investigation. Mucuna pruriens (L.), is a traditional herbal medicine, used in India since 1500 B.C., as a neuroprotective agent. In this present study, we evaluated the therapeutic effects of aqueous extract of M. pruriens (Mp) seed in Parkinsonian mouse model developed by chronic exposure to paraquat (PQ). Results of our study revealed that the nigrostriatal portion of Parkinsonian mouse brain showed significantly increased levels of nitrite, malondialdehyde (MDA) and reduced levels of catalase compared to the control. In the Parkinsonian mice hanging time was decreased, whereas narrow beam walk time and foot printing errors were increased. Treatment with aqueous seed extract of Mp significantly increased the catalase activity and decreased the MDA and nitrite level, compared to untreated Parkinsonian mouse brain. Mp treatment also improved the behavioral abnormalities. It increased hanging time, whereas it decreased narrow beam walk time and foot printing error compared to untreated Parkinsonian mouse brain. Furthermore, we observed a significant reduction in tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra (SN) and striatum region of the brain, after treatment with PQ which was considerably restored by the use of Mp seed extract. Our result suggested that Mp seed extract treatment significantly reduced the PQ induced neurotoxicity as evident by decrease in oxidative damage, physiological abnormalities and immunohistochemical changes in the Parkinsonian mouse.

Comparison of the neuroprotective potential of Mucuna pruriens seed extract with estrogen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model

Parkinsons disease (PD) is one of the most common neurodegenerative disease found in the aging population. Currently, many studies are being conducted to find a suitable and effective cure for PD, with an emphasis on the use of herbal plants. In Ayurveda, Mucuna pruriens (Mp), a leguminous plant, is used as an anti-inflammatory drug. In this study, the neuroprotective effect of an ethanolic extract of Mp seed is evaluated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD and compared to estrogen, a well reported neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were randomly divided into four groups: Control, MPTP, MPTP+Mp and MPTP+estrogen. The behavioural recovery in both Mp and estrogen treated mice was investigated using the rotarod, foot printing and hanging tests. The recovery of dopamine neurons in the substantia nigra (SN) region was estimated by tyrosine hydroxylase (TH), immunostaining. Additionally inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) immunoreactivity was evaluated to assess the level of oxidative damage and glial activation respectively. The levels of dopamine and its metabolite in the nigrostriatal region were measured by HPLC. Mp treatment restored all the deficits induced by MPTP more effectively than estrogen. Mp treatment recovered the number of TH-positive cells in both the SN region and the striatum while reducing the expression of iNOS and GFAP in the SN. Treatment with Mp significantly increased the levels of dopamine, DOPAC and homovanillic acid compared to MPTP intoxicated mice. Notably, the effect of Mp was greater than that elicited by estrogen. Mp down regulates NO production, neuroinflammation and microglial activation and all of these actions contribute to Mps neuroprotective activity. These results suggest that Mp can be an effective treatment for neurodegenerative diseases, especially PD by decreasing oxidative stress and possibly by implementing neuronal and glial cell crosstalk.

Increase in the expression of inducible nitric oxide synthase on exposure to bisphenol A: A possible cause for decline in steroidogenesis in male mice

Bisphenol A (BPA) is a well-known plasticizer and xenoestrogen that is responsible for many acquired reproductive difficulties, especially in men. Despite the prevalence of BPA in society, the mechanism behind reproductive deficits remains elusive. The present study investigates the mode of BPAs action by evaluating its effect on the expression of inducible nitric oxide synthase (iNOS) and steriodogenic acute regulatoryprotein (StAR) in male mice testis. Swiss albino mice were treated with a range BPA concentrations of 0.5, 50 and 100μg/kg body weight/day intraperitoneally for 60 days. Several markers of oxidative stress and male fertility were investigated. Nitrite levels, malondialdehyde levels and testicular injury scores were elevated whereas the sperm count, serum testosterone levels and catalase activity were reduced in the BPA groups. Mechanistically, an increase in iNOS expression was observed in the testis whereas the expression of the StAR was down regulated in the BPA treated mouse. These results suggest that BPA induces oxidative stress by altering the expression of iNOS, which consequently leads to the down regulation of StAR expression in the testis of male mouse.

Effect of Bisphenol A on human health and its degradation by microorganisms: a review

Bisphenol A (BPA), is an industrially important compound and is widely used for the production of polycarbonates and other plastics. Over the past few years, there have been many issues raised all over the world on the use of BPA. BPA is known to possess estrogenic activities; hence, it mimics the role of estrogen once it enters living systems. Thus, it has been placed in the category of compounds called endocrine disruptors. It can cause damage to reproductive organs, thyroid gland, and brain tissues at developmental stages, and most recently it has also been linked to cancer development in humans. Here, in this review, we aim to summarize the various effects of BPA on humans and animals, and at the same time we wish to throw some light on the emerging field of biodegradation of BPA in the natural environment. A few studies conducted recently have tried to isolate BPA-degrading microorganisms from various sites, like water bodies receiving wastes from industries, landfills, etc. In the present scenario, with huge controversies on the use of BPA, we emphasize on bridging the gap between studies, aiming at finding the damage caused by BPA, and the studies which aim at the safe removal of BPA from the environment, with the help of naturally occurring microbes. Once this gap is filled, we will be able to find a way which will allow the use of BPA in manufacturing plastics, without its accumulation in the environment.

Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced Parkinsonian mouse model.

Parkinsons disease (PD) is characterized by a slow and progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc) region of brain. Oxidative stress and inflammation plays important role in the neurodegeneration and development of PD. Ursolic Acid (UA: 3β-hydroxy-urs-12-en-28-oic acid) is a natural pentacyclic triterpenoid found in various medicinal plants. Its anti-inflammatory and antioxidant activity is a well-established fact. In this paper, the neuroprotective efficiency of UA in MPTP induced PD mouse model has been explored. For this purpose, we divided 30 mice into 5 different groups; first was control, second was MPTP-treated, third, fourth and fifth were different doses of UA viz., 5 mg/kg, 25 mg/kg, and 50 mg/kg body weight (wt) respectively, along with MPTP. After 21 days of treatment, different behavioral parameters and biochemical assays were conducted. Tyrosine hydroxylase (TH) immunostaining of SN dopaminergic neurons as well as HPLC quantification of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) were also performed. Our results proved that, UA improves behavioral deficits, restored altered dopamine level and protect dopaminergic neurons in the MPTP intoxicated mouse. Among three different doses, 25 mg/kg body wt was the most effective dose for the PD. This work reveals the potential of UA as a promising drug candidate for PD treatment.

Mucuna pruriens reduces inducible nitric oxide synthase expression in Parkinsonian mice model

Parkinsons disease is one of the most common neurodegenerative disease found in aged peoples. Plentiful studies are being conducted to find a suitable and effective cure for this disease giving special impetus on use of herbal plants. The study aimed at investigating the effect of ethanolic extract of Mucuna pruriens (Mp) on level of nitric oxide (NO) in paraquat (PQ) induced Parkinsons disease (PD) mouse model and its subsequent contribution to lipid peroxidation. Twenty four Swiss albino mice were divided into three groups; Control, PQ and PQ+Mp. PQ doses were given intraperitoneally, twice in a week and oral dose of ethanolic extract of Mp seed was given for 9 weeks. Nitrite content and lipid peroxidation was measured in all treated groups along with respective controls. RNA was isolated from the nigrostriatal tissue of control and the treated mice and was reverse transcribed into cDNA. PCR was performed to amplify iNOS mRNA and western blot analysis was performed to check its protein level. We had also perfused the mice in all treated group and performed Tyrosine hydroxylase (TH) and iNOS immunoreactivity in substantia nigra region of mice brain. PQ-treatment increased nitrite content, expression of iNOS and lipid peroxidation compared to respective controls. Mp treatment resulted in a significant attenuation of iNOS expression, nitrite content and lipid peroxidation demonstrating that it reduces nitric oxide in PQ-induced Parkinsons disease. Interestingly; we also observed that mRNA, protein expression and immunoreactivity of iNOS was significantly decreased after Mp treatment and TH immunoreactivity was significantly improved after the treatment of Mp. Our results demonstrated that Mp protects the dopaminergic neurons from the NO injury in substantia nigra.

Role of estrogen and levodopa in 1-methyl-4-pheny-l-1, 2, 3, 6-tetrahydropyridine (mptp)-induced cognitive deficit in Parkinsonian ovariectomized mice model: A comparative study

Parkinsons disease (PD) is one of the most common neurodegenerative disease found in the aging population. Currently, many studies are being conducted to find a suitable and effective cure for PD, with an emphasis on the use of herbal plants. In this study, the neuroprotective effects of estrogen was evaluated in the 1-methyl-4-phe-nyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD with cognitive deficit and compared to Levodopa (LD), a well reported neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were randomly divided into four groups: Control, MPTP, MPTP+LD and MPTP+estrogen. The behavioral recovery in both LD and estrogen treated mice were investigated using the rotarod, foot printing, narrow beam walking test and hanging tests. Non-motor behavioral recovery in both LD and estrogen treated were investigated using the Y-maze and Morris water maze. Furthermore, we performed the biochemical test i.e. catalase, lipid and nitrite in prefrontal cortex as well as nigrostriatal region of mouse brain. We also performed the acetylcholine esterase activity in prefrontal cortex and nigrostriatal region of mice brain. The recovery of dopamine neurons in the substantia nigra (SN) region was estimated by immunostaining of tyrosine hydroxylase (TH). Estrogen treatment restored all the deficits induced by MPTP more effectively than levodopa. Estrogen treatment recovered the number of TH-positive cells in both the SN region. Treatment with Estrogen significantly increased the levels of catalase, decreased the level of lipid and nitite in both region SN as well as prefrontal cortex region. Notably, the effect of estrogen was greater than that elicited by levodopa. Acetylcholine esterase activity was significantly increased in MPTP and it was found to be decreased by the treatment of estrogen as well as levodopa, although decrease in the activity was highly significant in estrogen treated group. Our result suggested that estrogen treatment significantly reduced the MPTP induced neurotoxicity as evident by decrease in oxidative damage, physiological abnormalities and immunohistochemical changes in the Parkinsonian mouse with cognitive deficit as compared to levodopa treatment.

Role of ethanolic extract of Bacopa monnieri against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mice model via inhibition of apoptotic pathways of dopaminergic neurons

Parkinsons disease (PD) is a neurodegenerative disease which causes rigidity, resting tremor and postural instability. The neuroprotective effects of an ethanolic extract of Bacopa monnieri (BM) were evaluated in a Parkinsonian mice model induced by the MPTP. The present study investigates the mechanisms of neuroprotection elicited by BM, an herb traditionally recognized by the Indian system of medicine, Ayurveda. An ethanolic extract of BM was co-treated with the MPTP induced mouse model of PD and was shown to significantly rescue the motor behaviour (Rotarod, Grip Strength and Foot Printing test). Furthermore, on biochemical parameters too BM significantly showed protective effect as Catalase, LPO, Nitrite, SOD, GR, GPx parameters showed marked improvement and levels of Dopamine, DOPAC and HVA were enhanced significantly. There was a significant reduction in tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra (SN) in MPTP treated group, which was considerably restored by the use of BM extract. BM also facilitated neuroprotection by creating an anti-apoptotic environment indicated by reduced apoptotic (Bax and caspase-3) and increased levels of anti-apoptotic (Bcl2) protein expression, respectively. Altogether, the present study suggests that BM treatment provides nigrostriatal dopaminergic neuroprotection against MPTP induced Parkinsonism by the modulation of oxidative stress and apoptotic machinery possibly accounting for the behavioural effects.