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Mucuna pruriens seed extract reduces oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in paraquat-induced Parkinsonian mouse model
(2013) Satyndra Kumar Yadav; Jay Prakash; Shikha Chouhan; Surya Pratap Singh
Parkinson's 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. © 2013 Elsevier Ltd. All rights reserved.
Neuroprotective effects of Withania somnifera in BPA induced-cognitive dysfunction and oxidative stress in mice
(BioMed Central Ltd., 2019) Hareram Birla; Chetan Keswani; Sachchida Nand Rai; Saumitra Sen Singh; Walia Zahra; Hagera Dilnashin; Aaina Singh Rathore; Surya Pratap Singh
Background: Bisphenol A (BPA), a major endocrine disruptor and a xenobiotic compound is used abundantly in the production of polycarbonate plastics and epoxy resins. Human exposure to this compound is primarily via its leaching from the protective internal epoxy resin coatings of containers into the food and beverages. In addition, the plastics used in dental prostheses and sealants also contain considerable amount of BPA and have a high risk of human exposure. Since it is a well-known endocrine disruptor and closely mimics the molecular structure of human estrogen thereby impairing learning and memory. Withania somnifera (Ws), commonly known as Ashwagandha is known for its varied therapeutic uses in Ayurvedic system of medicine. The present study was undertaken to demonstrate the impairment induced by BPA on the spatial learning, working memory and its alleviation by Ws in Swiss albino mice. The study was conducted on thirty Swiss albino mice, randomly distributed among three groups: control, BPA and BPA + Ws. The behavioral recovery after treatment with Ws was investigated using the Y-maize and Morris water maize test. Whereas, for the estimation of recovery of NMDA receptor which is related to learning and memory in hippocampus region by western blot and immunohistochemistry. Furthermore, the oxidative stress and antioxidant level was assessed by biochemical tests like MDA, SOD and catalase. Results: The study revealed that administration of Ws alleviated the behavioral deficits induced by BPA. Alongside, Ws treatment reinstated the number of NMDA receptors in hippocampus region and showed anti-oxidative property while ameliorating the endogenous anti-oxidant level in the brain. Conclusion: These findings suggest that Ws significantly ameliorates the level of BPA intoxicated oxidative stress thereby potentially treating cognitive dysfunction which acts as the primary symptom in a number of neurodegenerative diseases. © 2019 The Author(s).
Medicinal Plants and Natural Compounds as Antiparkinsonian Agents
(Bentham Science Publishers, 2022) Walia Zahra; Hareram Birla; Saumitra Sen Singh; Aaina Singh Rathore; Hagera Dilnashin; Richa Singh; Priyanka Kumari Keshri; Surya Pratap Singh
Medicinal plants have been used since ages for the treatment of human diseases in the Indian medicinal system of Ayurveda. Parkinson's diseases (PD) on the other hand is a kind of neurodegenerative disorder that shows debilitating symptoms; and the treatment of the disease rely on the symptomatic management. The drugs available for the treatment of the disease show severe side effects on prolonged usage. Thus, many medicinal plants and their derivative natural compounds have been tested for their anti-Parkinsonian activity with minimal side effects. Mucuna pruriens, Withania somnifera, Tinospora cordifolia are the example of medicinal plants that have shown anti-Parkinsonian activity while the natural compounds found in medicinal plants like Baicalein, curcumin, Ginseng, Resveratol have also maintained the nerve cell function and prevented the neuronal death. Thus, the polyphenols and other bioactive constituent of medicinal plants should be further studied for their therapeutic intervention against PD. © 2022, Bentham Books imprint. All Rights Reserved.
Neuroprotective role of withania somnifera root extract in maneb-paraquat induced mouse model of parkinsonism
(2013) Jay Prakash; Satyndra Kumar Yadav; Shikha Chouhan; Surya Pratap Singh
Parkinson's disease (PD) is a neurodegenerative disorder and these days a lot of emphasis is given on the treatment of this disease using herbal medicines. The present study evaluates the neuroprotective effect of Withania somnifera (Ws) root extract on Parkinsonian mice. The mice were divided into three groups; the first group served as control, the second group was given maneb (MB) and paraquat (PQ) and the last group was administered MB-PQ along with Ws root extract for 3, 6 and 9 weeks. The behavioral studies showed a significant improvement in the motor movement patterns and gripping ability of Ws root extract exposed Parkinsonian mice. Tyrosine hydroxylase (TH) immunostaining was reduced in the substantia nigra of MB-PQ exposed mice, while Ws co-exposure restored TH immunostaining significantly. Additionally, our results also demonstrate generation of oxidative stress in the nigrostriatal region of MB-PQ exposed mice. There was a marked decline in the level of catalase and a simultaneous increase in the level of nitrite and lipid peroxidation in Parkinsonian mice. Thus, the Ws root extract have shown to counteract the pro-oxidants and their associated oxidative stress in the PD model studied here. Our results clearly indicate the usefulness of Ws root extract in providing protection against MB-PQ induced nigrostriatal dopaminergic neurodegeneration and marked improvement in the behavioral, anatomical and the biochemical deformities. © 2013 Springer Science+Business Media New York.
Unraveling the AKT/ERK cascade and its role in Parkinson disease
(Springer Science and Business Media Deutschland GmbH, 2024) Priyanka Kumari Keshri; Surya Pratap Singh
Parkinson disease represents a significant and growing burden on global healthcare systems, necessitating a deeper understanding of their underlying molecular mechanisms for the development of effective treatments. The AKT and ERK pathways play crucial roles in the disease, influencing multiple cellular pathways that support neuronal survival. Researchers have made notable progress in uncovering how these pathways are controlled by upstream kinases and how their downstream effects contribute to cell signalling. However, as we delve deeper into their intricacies, we encounter increasing complexity, compounded by the convergence of multiple signalling pathways. Many of their targets overlap with those of other kinases, and they not only affect specific substrates but also influence entire signalling networks. This review explores the intricate interplay of the AKT/ERK pathways with several other signalling cascades, including oxidative stress, endoplasmic reticulum stress, calcium homeostasis, inflammation, and autophagy, in the context of Parkinson disease. We discuss how dysregulation of these pathways contributes to disease progression and neuronal dysfunction, highlighting potential therapeutic targets for intervention. By elucidating the complex network of interactions between the AKT/ERK pathways and other signalling cascades, this review aims to provide insights into the pathogenesis of Parkinson disease and describe the development of novel therapeutic strategies. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.
Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis
(Birkhauser Verlag AG, 2017) Susan Westfall; Nikita Lomis; Imen Kahouli; Si Yuan Dia; Surya Pratap Singh; Satya Prakash
The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health. In particular, the gastrointestinal tract communicates with the central nervous system through the gut–brain axis to support neuronal development and maintenance while gut dysbiosis manifests in neurological disease. There are three basic mechanisms that mediate the communication between the gut and the brain: direct neuronal communication, endocrine signaling mediators and the immune system. Together, these systems create a highly integrated molecular communication network that link systemic imbalances with the development of neurodegeneration including insulin regulation, fat metabolism, oxidative markers and immune signaling. Age is a common factor in the development of neurodegenerative disease and probiotics prevent many harmful effects of aging such as decreased neurotransmitter levels, chronic inflammation, oxidative stress and apoptosis—all factors that are proven aggravators of neurodegenerative disease. Indeed patients with Parkinson’s and Alzheimer’s diseases have a high rate of gastrointestinal comorbidities and it has be proposed by some the management of the gut microbiota may prevent or alleviate the symptoms of these chronic diseases. © 2017, Springer International Publishing.
Increase in the expression of inducible nitric oxide synthase on exposure to bisphenol A: A possible cause for decline in steroidogenesis in male mice
(Elsevier, 2015) Shikha Chouhan; Satyndra Kumar Yadav; Jay Prakash; Susan Westfall; Amrita Ghosh; Neeraj Kumar Agarwal; Surya Pratap Singh
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 BPA's 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 100. μg/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. © 2014 Elsevier B.V.
TCE-mediated neuroprotection against rotenone-induced dopaminergic neuronal death in PD mice: insights into the Nrf-2/PINK1/Parkin-mitophagy pathway
(Springer, 2025) Hagera Dilnashin; Shekhar Singh; Poonam Rawat; Aaina Singh Singh Rathore; Richa S. Singh; Priyanka Kumari Keshri; Nitesh Kumar Gupta; Singh Ankit Satyaprakash; Surya Pratap Singh
Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of Parkinson’s disease (PD). In a previous study, we reported that an extract of T. cordifolia (TCE) possessed antioxidant and anti-apoptotic properties that improved mitochondrial function against rotenone-induced neurotoxicity. However, the underlying molecular mechanism remains unclear. In this study, we found that rotenone (ROT)-induced PD mice exhibited mitochondrial abnormalities, including defective mitophagy, mitochondrial reactive oxygen species (ROS) overexpression, and mitochondrial fragmentation, accompanied by reduced expression of Pink1 and Parkin and increased apoptosis. These changes were partially reversed following oral administration of TCE. Moreover, TCE restored the activity and translocation of NF-E2-related factor 2 (Nrf2) and upregulated the expression of antioxidant enzymes (SOD1, SOD2, GSH, and GSSH). Interestingly, ROT also activates mitophagy. Our results suggest that ROT toxicity can cause neuronal cell death through mitophagy-mediated signaling in PD mice. However, TCE reversed this activity by inhibiting autophagic protein (LC3B-II/LC3B-I) activation and increasing specific mitochondrial proteins (TOM20, Pink1, and Parkin). Our findings indicated that TCE provides neuroprotection against rotenone-induced toxicity in PD mice by stimulating endogenous antioxidant enzymes and inhibiting ROT-induced oxidative stress by potentiating the Nrf-2/Pink1/Parkin-mediated survival mechanism. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
NF-κB-Mediated Neuroinflammation in Parkinson’s Disease and Potential Therapeutic Effect of Polyphenols
(Springer, 2020) Saumitra Sen Singh; Sachchida Nand Rai; Hareram Birla; Walia Zahra; Aaina Singh Rathore; Surya Pratap Singh
Different animal and human studies from last two decades in the case of Parkinson’s disease (PD) have concentrated on oxidative stress due to increased inflammation and cytokine-dependent neurotoxicity leading to induction of dopaminergic (DA) degeneration pathway in the nigrostriatal region. Chronic inflammation, the principle hallmark of PD, forms the basis of neurodegeneration. Aging in association with activation of glia due to neuronal injury, perhaps because of immune alterations and genetic predispositions, leads to deregulation of inflammatory pathways premising the onset of PD. A family of inducible transcription factors, nuclear factor-κB (NF-κB), is found to show expression in various cells and tissues, such as microglia, neurons, and astrocytes which play an important role in activation and regulation of inflammatory intermediates during inflammation. Both canonical and non-canonical NF-κB pathways are involved in the regulation of the stimulated cells. During the prodromal/asymptomatic stage of age-associated neurodegenerative diseases (i.e., PD and AD), chronic neuroinflammation may act silently as the driver of neuronal dysfunction. Though research has provided an insight over age-related neurodegeneration in PD, elaborative role of NF-κB in neuroinflammation is yet to be completely understood and thus requires more investigation. Polyphenols, a group of naturally occurring compound in medicinal plants, have gained attention because of their anti-oxidative and anti-neuroinflammatory properties in neurodegenerative diseases. In this aspect, this review highlights the role of NF-κB and the possible therapeutic roles of polyphenols in NF-κB-mediated neuroinflammation in PD. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Neuroprotection of rotenone-induced parkinsonism by ursolic acid in pd mouse model
(Bentham Science Publishers, 2020) Walia Zahra; Sachchida Nand Rai; Hareram Birla; Saumitra Sen Singh; Aaina Singh Rathore; Hagera Dilnashin; Richa Singh; Chetan Keswani; Rakesh K. Singh; Surya Pratap Singh
Background: Parkinson’s Disease (PD) is characterized by both motor and non-motor symptoms. The presynaptic neuronal protein, α-Synuclein, plays a pivotal role in PD pathogenesis and is associated with both genetic and sporadic origin of the disease. Ursolic Acid (UA) is a well-known bioactive compound found in various medicinal plants, widely studied for its anti-inflammatory and antioxidant activities. Objective: In this research article, the neuroprotective potential of UA has been further explored in the Rotenone-induced mouse model of PD. Methods: To investigate our hypothesis, we have divided mice into 4 different groups, control, drug only control, Rotenone-intoxicated group, and Rotenone-intoxicated mice treated with UA. After the completion of dosing, behavioral parameters were estimated. Then mice from each group were sacri-ficed and the brains were isolated. Further, the biochemical tests were assayed to check the balance between the oxidative stress and endogenous anti-oxidants; and TH (Tyrosine Hydroxylase), α-Synuclein, Akt (Serine-threonine protein kinase), ERK (Extracellular signal-regulated kinase) and inflammatory parameters like Nuclear factor-κB (NF-κB) and Tumor Necrosis Factor-α (TNF-α) were assessed using Immunohistochemistry (IHC). Western blotting was also done to check the expressions of TH and α-Synuclein. Moreover, the expression levels of PD related genes like α-Synuclein, β-Synuclein, Interleukin-1β (IL-1β), and Interleukin-10 (IL-10) were assessed by using Real-time PCR. Results: The results obtained in our study suggested that UA significantly reduced the overexpression of α-Synuclein and regulated the phosphorylation of survival-related kinases (Akt and ERK) apart from alleviating the behavioral abnormalities and protecting the dopaminergic neurons from oxidative stress and neuroinflammation. Conclusion: Thus, our study shows the neuroprotective potential of UA, which can further be explored for possible clinical intervention. © 2020 Bentham Science Publishers.

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