Awanish Mishra | NIPER(National institute of pharmaceutical education & research (original) (raw)

Papers by Awanish Mishra

Phytotherapy Research

Flavonoids are natural polyphenolic compounds considered safe, pleiotropic, and readily available... more Flavonoids are natural polyphenolic compounds considered safe, pleiotropic, and readily available molecules. It is widely distributed in various food products such as fruits and vegetables and beverages such as green tea, wine, and coca‐based products. Many studies have reported the anticancer potential of flavonoids against different types of cancers, including solid tumors. The chemopreventive effect of flavonoids is attributed to various mechanisms, including modulation of autophagy, induction of cell cycle arrest, apoptosis, and antioxidant defense. Despite of significant anticancer activity of flavonoids, their clinical translation is limited due to their poor biopharmaceutical attributes (such as low aqueous solubility, limited permeability across the biological membranes (intestinal and blood‐brain barrier), and stability issue in biological systems). A nanoparticulate system is an approach that is widely utilized to improve the biopharmaceutical performance and therapeutic e...

Basic & Clinical Pharmacology & Toxicology, Jul 1, 2014

Epilepsy is one of the major neurological disorders still awaiting safer drugs with improved anti... more Epilepsy is one of the major neurological disorders still awaiting safer drugs with improved antiepileptic effect and lesser side effects. Apart from epilepsy itself, AEDs also have been shown to induce cognitive impairment in patients with epilepsy. There are limited data for the treatment of this menace. As cholinergic approach has widely been practiced for the restoration of memory in various neurodegenerative disorders, this study was envisaged to evaluate add on effect of acetylcholinesterase inhibitor (tacrine) with phenytoin in pentylenetetrazole-kindling-induced learning and memory deficit in mice. In this study, mice were kindled using subconvulsive dose of pentylenetetrazole (35 mg/kg, i.p.; at interval of 48 ± 2 hr) and successfully kindled animals were divided into different groups and treated with vehicle, phenytoin and phenytoinin in combination with tacrine (0.3 mg/kg), atropine (1 mg/kg) and tacrine + atropine. Effect of different interventions on learning and memory was evaluated using elevated plus maze and passive shock avoidance on days 5, 10, 15 and 20. Phenytoin-treated kindled animals were associated with learning and memory deficit, while tacrine supplementation improved memory deficit with increased seizure severity score. Atropine treatment significantly reversed the protective effect of tacrine. Neurochemical findings also support the behavioural finding of the study. Our results suggest the use of anticholinesterases, with better seizure tolerance, for the management of cognitive impairment of epilepsy, as adjunct therapy.

Metabolic Brain Disease, Aug 13, 2021

Neuroinflammation is one of the host defensive mechanisms through which the nervous system protec... more Neuroinflammation is one of the host defensive mechanisms through which the nervous system protects itself from pathogenic and or infectious insults. Moreover, neuroinflammation occurs as one of the most common pathological outcomes in various neurological disorders, makes it the promising target. The present review focuses on elaborating the recent advancement in understanding molecular mechanisms of neuroinflammation and its role in the etiopathogenesis of various neurological disorders, especially Alzheimer's disease (AD), Parkinson's disease (PD), and Epilepsy. Furthermore, the current status of anti-inflammatory agents in neurological diseases has been summarized in light of different preclinical and clinical studies. Finally, possible limitations and future directions for the effective use of anti-inflammatory agents in neurological disorders have been discussed.

Journal of Pharmaceutical Negative Results, 2011

Biochemical Pharmacology, 2022

Parkinson disease (PD) is a progressive neurodegenerative disorder prevalent mainly in geriatric ... more Parkinson disease (PD) is a progressive neurodegenerative disorder prevalent mainly in geriatric population. While, L-DOPA remains one of the major choices for the therapeutic management of PD, various motor and non-motor manifestations complicate the management of PD. In the last two decades, exhaustive research has been carried out to explore novel therapeutic approaches for mitigating motor and non-motor symptoms of PD. These approaches majorly include receptor-based, anti-inflammatory, stem-cell and nucleic acid based. The major limitations of existing therapeutic interventions (of commonly oral route) are low efficacy due to low brain bioavailability and associated side effects. Nanotechnology has been exploited and has gained wide attention in the recent years as an approach for enhancement of bioavailability of various small molecule drugs in the brain. To address the challenges associated with PD therapy, nose-to-brain delivery utilizing nanomedicine-based approaches has been found to be encouraging in published evidence. Therefore, the present work summarises the major challenges and limitations with antiparkinsonian drugs, novel therapeutic interventions, and scope of nanomedicine-based nose-to-brain delivery in addressing the current challenges of antiparkinsonian therapy. The manuscript tries to sensitize the researchers for designing brain-targeted nanomedicine loaded with natural/synthetic scaffolds, biosimilars, and nucleic acids that can bypass the first-pass effect for the effective management of PD.

Current nanomedicine, Aug 13, 2020

Cancer chemotherapeutic administration by oral route has the potential to create "hospitalization... more Cancer chemotherapeutic administration by oral route has the potential to create "hospitalization free chemotherapy". Such a therapeutic approach will improve patient compliance and significantly reduce the cost of treatment. In current clinical practice, chemotherapy is primarily carried out by intravenous injection or infusion and leads to various unwanted effects. Despite the presence of oral delivery challenges like poor aqueous solubility, low permeability, drug stability and substrate for multidrug efflux transporter, cancer chemotherapy delivery through oral administration has gained much attention recently due to having more patient compliance compared to the intravenous mode of administration. In order to address the multifaceted oral drug delivery challenges, a hybrid delivery system is conceptualized to merge the benefits of both polymeric and lipid-based drug carriers. Polymer-lipid hybrid systems have presented various significant benefits as an efficient carrier to facilitate oral drug delivery by surmounting the different associated obstacles. This carrier system has been found suitable to overcome the numerous oral absorption hindrances and facilitate the intravenous-to-oral switch in cancer chemotherapy. In this review, we aimed to discuss the different biopharmaceutic challenges in oral delivery of cancer chemotherapy and how this hybrid system may provide solutions to such challenges.

Metabolic Brain Disease, Jan 23, 2015

Our previous work demonstrated, chronic epilepsy affects learning and memory of rodents along wit... more Our previous work demonstrated, chronic epilepsy affects learning and memory of rodents along with peculiar neurochemical changes in discrete brain parts. Most commonly used antiepileptic drugs (phenytoin and sodium valproate) also worsen learning and memory in the patients with epilepsy. Therefore this study was designed to carry out comparison of behavioral and neurochemical changes with phenytoin and sodium valproate treatment in pentylenetetrazole-kindling induced learning and memory deficit to devise add on therapy for this menace. For the experimental epilepsy, animals were kindled using PTZ (35 mg/kg; i.p., at 48±2 h intervals) and successful kindled animals were involved in the study. These kindled animals were treated with saline, phenytoin (30 mg/kg/day, i.p.) and sodium valproate (300 mg/kg/day, i.p.) for 20 days. These animals were challenged with PTZ challenging dose (35 mg/kg) on day 5, 10, 15 and 20 to evaluate the effect on seizure severity score on different days. Effect on learning and memory was evaluated using elevated plus maze and passive shock avoidance paradigm. On day 20, after behavioral evaluations, animals were sacrificed to analyze glutamate, GABA, norepinephrine, dopamine, serotonin, total nitrite level and acetylcholinesterase level in cortex and hippocampus. Behavioral evaluations suggested that phenytoin and sodium valproate treatment significantly reduced seizure severity in the kindled animals, while sodium valproate treatment controls seizures with least memory deficit in comparison to phenytoin. Neurochemical findings revealed that elevated cortical acetylcholinesterase level could be one of the responsible factors leading to memory deficit in phenytoin treated animals. However sodium valproate treatment reduced cortical acetylcholinesterase level and had least debilitating consequences on memory deficit. Therefore, attenuation of elevated AChE activity can be one of add-on approach for management of memory deficit associated with conventional AEDs.

Journal of epilepsy research, Mar 27, 2020

Recent studies have recognised the memory deficit as one of the most common psychiatric issues in... more Recent studies have recognised the memory deficit as one of the most common psychiatric issues in the patients with epilepsy, which severely affects the quality of life. Our previous studies have demonstrated the possible involvement of serotonergic system in the pathogenesis of epilepsy and associated memory deficit. The possible involvement of 5-HT1A and 5-HT2A/2C receptor has not been explored yet. Therefore, this study has been envisaged to explore the effect of 5-HT1A and 5-HT2A/2C receptor modulation on epilepsy and memory deficit in pentylenetetrazole-kindled mice. Methods: In the present experimental approach, we examined the efficacy of modulation of 5-HT1A and 5-HT2A/2C receptor in pentylenetetrazole-induced kindling in male Swiss mice (n=75). Mice were kindled by sub-convulsive dose of pentylenetetrazole (35 mg/kg, intraperitoneal injection), at the interval of 48±2 hours). Successfully kindled animals were treated with 5-HT1A and 5-HT2A/2C receptor modulators. The effect of different treatments on seizure severity score and memory impairment was analysed. Results: 5-HT1A receptor agonist improved the memory functions while seizure severity was not improved, and the opposite effect was observed with 5-HT1A receptor antagonist. On the other hand, 5-HT2A/2C receptor agonist significantly improved memory deficit as well as seizure severity in the kindled animals. Conclusions: The outcome of the study indicates the possible involvement of 5-HT2A/2C receptor in the pathogenesis of epilepsy and associated memory deficit, which can be further explored for its management.

Neurochemical Research, Oct 8, 2013

Pentylenetetrazole-kindling induced memory deficit has been validated in our previous study. The ... more Pentylenetetrazole-kindling induced memory deficit has been validated in our previous study. The present study attempts a neurochemical investigation to reveal possible targets for treatment of memory deficit associated with pentylenetetrazole-kindling. Kindling was induced by administering subconvulsive dose of pentylenetetrazole (35 mg/kg; i.p.) at an interval of 48 ± 2 h. Successfully kindled animals were divided into two groups (interictal and postictal group), while non-kindled (naive) animals served as naïve group. In postictal group, animals were challenged with pentylenetetrazole (35 mg/kg) on days 5, 10, 15 and 20. Learning and memory were evaluated in all experimental groups using elevated plus maze and passive shock avoidance paradigm on days 5, 10, 15 and 20. After behavioral evaluations on day 20, all animals were sacrificed to remove their brains. Neurochemical (glutamate, GABA, norepinephrine, dopamine and serotonin) changes and acetylcholinesterase activity and total nitrite level were estimated using HPLC-FD methods and microplate reader method respectively, in discrete brain parts. The results of the neurochemical estimation demonstrated the imbalance in excitatory/inhibitory tone, reduction in monoamine level, elevated nitrosative and acetylcholinesterase activity in the cortex and hippocampus, as responsible factors for the pathobiology of learning and memory deficit in epilepsy. Restoration of these changes may be targeted for the management of memory deficit in epileptic patients.

Electronics, Feb 15, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Electronics

Cancer is one of the leading causes of death worldwide. In the last few decades, cancer treatment... more Cancer is one of the leading causes of death worldwide. In the last few decades, cancer treatment has come a long way, but multidrug resistance (MDR) in cancer still has low survival rates. It means that much research is required for an accurate diagnosis and effective therapy. The new era of cancer research could include theranostic approaches and targeted delivery of chemotherapeutic agents utilizing the nanoparticulate system. Recently, there has been much interest gained among researchers for carbon-based and graphene-based quantum dots due to their higher biocompatibility and ease of biofunctionalization compared to conventional heavy metal quantum dots. Moreover, these quantum dots have various interesting utilities, including bioimaging, biosensing, quantum dots-mediated drug delivery, and their role in photodynamic therapy (PDT) and photothermal therapy (PTT). The current review highlighted the utility of hybrid quantum dots as a theranostic system in different cancers and d...

Journal of Functional Biomaterials

Psoriasis is a typical dermal condition that has been anticipated since prehistoric times when it... more Psoriasis is a typical dermal condition that has been anticipated since prehistoric times when it was mistakenly implicit in being a variant of leprosy. It is an atypical organ-specific autoimmune disorder, which is triggered by the activation of T-cells and/or B-cells. Until now, the pathophysiology of this disease is not completely explicated and still, many research investigations are ongoing. Different approaches have been investigated to treat this dreadful skin disease using various anti-psoriatic drugs of different modes of action through smart drug-delivery systems. Nevertheless, there is no ideal therapy for a complete cure of psoriasis owing to the dearth of an ideal drug-delivery system for anti-psoriatic drugs. The conventional pharmacotherapy approaches for the treatment of psoriasis demand various classes of anti-psoriatic drugs with optimum benefit/risk ratio and insignificant untoward effects. The advancement in nanoscale drug delivery had a great impact on the estab...

European Journal of Neurology

The gut–brain axis augments the bidirectional communication between the gut and brain and modulat... more The gut–brain axis augments the bidirectional communication between the gut and brain and modulates gut homeostasis and the central nervous system through the hypothalamic–pituitary–adrenal axis, enteroendocrine system, neuroendocrine system, inflammatory and immune pathways. Preclinical and clinical reports showed that gut dysbiosis might play a major regulatory role in neurological diseases such as epilepsy, Parkinson's, multiple sclerosis, and Alzheimer's disease. Epilepsy is a chronic neurological disease that causes recurrent and unprovoked seizures, and numerous risk factors are implicated in developing epilepsy. Advanced consideration of the gut–microbiota–brain axis can reduce ambiguity about epilepsy pathology, antiepileptic drugs, and effective therapeutic targets. Gut microbiota sequencing analysis reported that the level of Proteobacteria, Verrucomicrobia, Fusobacteria, and Firmicutes was increased and the level of Actinobacteria and Bacteroidetes was decreased i...

CRC Press eBooks, Oct 13, 2022

Bioengineering

Osteoporosis, a chronic bone disorder, is one of the leading causes of fracture and morbidity ris... more Osteoporosis, a chronic bone disorder, is one of the leading causes of fracture and morbidity risk. Numerous medicinally important herbs have been evaluated for their efficacy in improving bone mass density in exhaustive preclinical and limited clinical studies. Nigella sativa L. has been used as local folk medicine, and traditional healers have used it to manage various ailments. Its reported beneficial effects include controlling bone and joint diseases. The present manuscript aimed to provide a sound discussion on the pharmacological evidence of N. sativa and its active constituent, thymoquinone, for its utility in the effective management of osteoporosis. N. sativa is reported to possess anti-IL-1 and anti-TNF-α-mediated anti-inflammatory effects, leading to positive effects on bone turnover markers, such as alkaline phosphatase and tartrate-resistant acid phosphatase. It is reported to stimulate bone regeneration by prompting osteoblast proliferation, ossification, and decreasi...

PLANT CELL BIOTECHNOLOGY AND MOLECULAR BIOLOGY, Dec 31, 2020

Frontiers in Pharmacology, Apr 7, 2022

Parkinson's disease (PD) is the second leading neurodegenerative disease that is characterized by... more Parkinson's disease (PD) is the second leading neurodegenerative disease that is characterized by severe locomotor abnormalities. Levodopa (L-DOPA) treatment has been considered a mainstay for the management of PD; however, its prolonged treatment is often associated with abnormal involuntary movements and results in L-DOPA-induced dyskinesia (LID). Although LID is encountered after chronic administration of L-DOPA, the appearance of dyskinesia after weeks or months of the L-DOPA treatment has complicated our understanding of its pathogenesis. Pathophysiology of LID is mainly associated with alteration of direct and indirect pathways of the cortico-basal gangliathalamic loop, which regulates normal fine motor movements. Hypersensitivity of dopamine receptors has been involved in the development of LID; moreover, these symptoms are worsened by concurrent non-dopaminergic innervations including glutamatergic, serotonergic, and peptidergic neurotransmission. The present study is focused on discussing the recent updates in molecular mechanisms and therapeutic approaches for the effective management of LID in PD patients.

Environmental Toxicology and Pharmacology

Nanotheranostics for Treatment and Diagnosis of Infectious Diseases