Browsing by Author "Manish Singh"

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A therapeutic approach to target mitochondrial dysfunction using molecular docking studies: Screening of natural drugs for oral carcinoma
(Wolters Kluwer Medknow Publications, 2018) Manish Singh; Manish Tripathi; Alok Singh; Chandra Azad; Indrajeet Gambhir; Brijesh Kumar; Suresh Purohit
Background: Mitochondrial dysfunction is the major cause of various types of cancer, leading to death worldwide. The present study investigated the in silico binding potential of natural flavonoids and essential oils with human cyclophilin D (CyPD) protein. CyPD protein is a major molecular marker for apoptosis and has been reported to be elevated in oral carcinoma. Methods: PubChem database was used to check the efficacy of different active phytoconstituents (kaempferol, quercetin, eugenol, oxyresveratrol, tanshinone 2a, catechin, epicatechin, cinnamaldehyde, and emodin). These compounds were used as ligands to check their potential as anticancer agents against the inner mitochondrial membrane protein, CyPD. Docking studies were performed with the help of Discovery Studio 2.5 and Autodock. Emodin was used as a reference inhibitor to compare the results. Results: The binding energy (B.E.) of the reference inhibitor (known/established drug) emodin was observed-28.9 kcal/mol while novel inhibitors (catechin, cinnamaldehyde, epicatechin, eugenol, kaempferol, oxyresveratrol, quercetin, and tanshinone 2a) exhibited a range from-51.51 to-5.89 kcal/mol. Quercetin, kaempferol, and epicatechin (B.E.:-51.51,-34.79, and-30.62 kcal/mol, respectively) showed strong affinity as compared to reference inhibitor (B.E.:-28.9 kcal/mol). Conclusion: Quercetin, kaempferol, and epicatechin can be used as lead inhibitors against targeting CyPD. © 2018 Pharmacognosy Magazine. Published by Wolters Kluwer.
Acute and subacute toxicity study of ethanolic extract of Calotropis procera (Aiton) Dryand flower in Swiss albino mice
(Elsevier B.V., 2022) Ashutosh Kumar; Brijesh Kumar; Rajesh Kumar; Ajay Kumar; Manish Singh; Vinod Tiwari; Anshuman Trigunayat; Paramita Paul; Pratistha Singh
Background: Calotropis procera is a large shrub which consists many medicinal properties, used in treatment of snake bite, sinus fistula, rheumatism, mumps, burn injuries, inflammation and jaundice traditionally. All the parts of Calotropis procera were utilized in the treatment of diseases out of which leaves and roots were investigated for its toxicity profile that showed dose dependent toxicity. Toxicity profile of flowers of Calotropis procera was not investigated in the previous studies. The aim of this study was to explore the acute and subacute toxicity of ethanolic extract of Calotropis procera flowers for the safe use of traditional medicine. Method: In acute toxicity, a total of 20 female mice (Swiss albino), weighing between 23 and 32 g were randomly divided into four experimental groups: control, 300, 1000, and 2000 mg/kg groups with 5 mice each, and each received a single dose of extract at 300, 1000, or 2000 mg/kg, respectively. Animals were monitored for 14 days. In the subacute study, a total of 40 mice (23–32 g) were divided into 4 groups, each containing males and females. Group 1 (control group) received vehicle and groups 2, 3, and 4 received extract at doses of 300 mg/Kg, 1000 mg/Kg, 2000 mg/Kg of b.w., respectively, for 28 consecutive days. The study was conducted in compliance with the OECD guidelines 407 and 423. Results: Acute toxicity study showed no mortality at the dose of 2000 mg/Kg. In subacute toxicity study, statistical analysis of hematological and biochemical parameters showed no significant differences compared to control group except marked increase in segmented neutrophils. Histopathological studies revealed no significant structural differences among the treated groups and in comparison to control group. Conclusions: It was concluded that oral administration of doses of ethanolic extract of Calotropis procera flower, administered acutely, did not cause any mortality or notable changes at the dose of 2000 mg/Kg. Therefore, the approximate lethal dose (ALD) of in mice was higher than 2,000 mg/kg. In a 28-day subacute toxicity model, the extract did not cause any mortality, and no treatment-related changes were observed in body weight, organ weight, hematological and biochemical blood analysis, or histopathologic examinations at the extract dose of 2000 mg/Kg. These findings indicate that the no-observed-adverse-effect-level (NOAEL) of Calotropis procera flower ethanolic extract was greater than 2000 mg/kg/day. © 2022
Association of oxidative stress and endothelial dysfunction in hypertension
(Academic Press Inc., 2020) Pritee Chaudhary; Anand Pandey; Chandra Shekhar Azad; Neelam Tia; Manish Singh; Indrajeet Singh Gambhir
Background: Biomarkers of oxidative stress (OS) are involved in the pathophysiology of hypertension (HTN) and endothelial dysfunction is also related to HTN. Still, a significant association of OS, as well as endothelial function, remains unclear in HTN. Methods: Totalling 222 North Indian peoples aged 18–80 participated in the study. Of these participants, 74 were elderly hypertensive subjects (age ≥60 years), and 128 were normotensive subjects (age ≥60 years-control I; n = 74, and <60 years-control II; n = 74). OS was assessed by measurement of total oxidant status (TOS) and total antioxidant status (TAS) using a colorimetric and automated method developed by Erel O. Endothelial dysfunction was assessed by measurement of flow-mediated dilation (FMD) using doppler ultrasound system. Results: TOS and OSI were significantly increased and TAS and FMD significantly decreased in patients with HTN as compared to control I and control II. The increase in the level of TOS and a decrease in the level of TAS and FMD were also evident with advancing age. FMD was negatively correlated with TOS and positively correlated with TAS. Conclusion: Decreased TAS level, increased TOS level reflect OS that may be the reason for reduced FMD in elderly hypertensive patients. © 2019 Elsevier Inc.
In vivo toxicity study of ethanolic extracts of evolvulus alsinoides & centella asiatica in swiss albino mice
(Open Access Macedonian Journal of Medical Sciences, 2019) Mukesh Kumar Yadav; Santosh Kumar Singh; Manish Singh; Shashank Shekhar Mishra; Anurag Kumar Singh; Jyoti Shankar Tripathi; Yamini Bhusan Tripathi
AIM: We aimed to investigate several parameters after the in vivo acute and sub-acute administration of ethanolic extracts from E. alsinoides & C. asiatica. METHODS: Malignant Ovarian Germ Cell Tumors for in vivo toxicity study guidelines 423 and 407 of Organization for Economic Co-operation and Development (OECD) were followed for acute and sub-acute toxicity assays respectively. For LD50 evaluation, a single dose of ethanolic extracts of Evolvulus alsinoides L. (EEA) and ethanolic extracts of Centella asiatica (ECA) was orally administered to mice at doses of 200, 400, 800, 1600 and 2000 mg/kg. Then the animals were observed for 72 hours. For acute toxicity evaluation, a single dose of both extracts was orally administered to mice at doses of 300, 600, 1200 and 2000 mg/kg and the animals were observed for 14 days. In the sub-acute study, the extracts were orally administered to mice for 28 days at doses of 300, 600, 1200 and 2000 mg/kg. To assess the toxicological effects, animals were closely observed on general behaviour, clinical signs of toxicity, body weight, food and water intake. At the end of the study, it was performed biochemical and hematological evaluations, as well as histopathological analysis from the following organs: brain, heart, liver, and kidney. RESULTS: The oral administration of E. alsinoides and C. asiatica ethanolic extracts, i.e. EEA 300, EEA 600, EEA 1200, EEA 2000, ECA 300, ECA 600, ECA 1200 & ECA 2000 mg/kg doses showed no moral toxicity effect in LD50, acute and sub-acute toxicity parameters. CONCLUSION: In this study, we had found that E. alsinoides & C. asiatica extract at different doses cause no mortality in acute and sub-acute toxicity study. Also, histopathology of kidney, liver, heart, and brain showed no alterations in tissues morphology. © 2019 Mukesh Kumar Yadav, Santosh Kumar Singh, Manish Singh, Shashank Shekhar Mishra, Anurag Kumar Singh, Jyoti Shankar Tripathi, Yamini Bhusan Tripathi.
Lipid-Based Nanocarriers for Brain Delivery of Drugs in Neurodegenerative Disorders
(CRC Press, 2024) Mukesh Kumar Yadav; Manish Singh; Pritee Chaudhary; Shardendu Kumar Mishra
The central nervous system (CNS) is vulnerable to neurodegenerative disorders like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis. These are chronic and progressive pathologies characterized by the loss of neurons and the formation of misfolded proteins, for example, α-synuclein, β- amyloid. A neurodegenerative disease is characterized by symptoms such as memory loss, moodiness, anxiety, depression, and agitation. Neurodegeneration involves structural and functional dysfunction of the blood-brain barrier (BBB) that acts as a shield to precent blood toxins from accessing the brain. With the focus on drug discovery and research for targeted drug therapy to the CNS, advancements in therapeutics and medicine have allowed for a better understanding of the many pathways involved in the emergence of neurodegenerative diseases. In this situation, nanotechnology methods have emerged as a viable tactic to enhance drug targeting to the brain and to boost bioavailability. Nanocarrier drug delivery for neurodegenerative diseases opens the door for promising approaches and advances in the diagnosis and treatment of various neurodegenerative diseases. Lipid-based nanocarriers, categorized as bilayered vesicular drug-delivery systems; unilayered lipid drug-delivery systems; and submicron emulsions have been developed to overcome shortcomings related to CNS delivery of therapeutic molecules. Over the years, various studies have used the application of lipid-based nanocarriers for the treatment of different neurological conditions. This chapter comprises knowledge about different neurodegenerative disorders, the role of the BBB, the development of lipid-based nanocarriers, and their application of drug-delivery systems in the treatment of neurodegenerative disorders. © 2024 selection and editorial matter, Anurag Kumar Singh, Vivek K. Chaturvedi, and Jay Singh; individual chapters, the contributors.
Neuroprotective activity of evolvulus alsinoides & centella asiatica ethanolic extracts in scopolamine-induced amnesia in swiss albino mice
(Open Access Macedonian Journal of Medical Sciences, 2019) Mukesh Kumar Yadav; Santosh Kumar Singh; Manish Singh; Shashank Shekhar Mishra; Anurag Kumar Singh; Jyoti Shankar Tripathi; Yamini Bhusan Tripathi
AIM: To carry out the comparative nootropic, neuroprotective potentials of two medicinal plant species. MATERIAL AND METHODS: For neuroprotective activity; behavior models (elevated plus maze & morris water maze), in vivo antioxidant (superoxide dismutase, catalase, lipid peroxidation & reduced glutathione), inflammatory markers (IL-1β, IL-6 & TNF-α) and acetylcholine esterase (AChE) assessment procedures followed at different dosages i.e. 250 & 500 mg/kg of Evolvulus alsinoides and Centella asiatica ethanolic extracts. At the end of the study, it was performed histopathological analysis of the following organs: brain, heart, liver, and kidney. RESULTS: In oral administration of different doses of ethanolic extracts of both medicinal plants i.e. Sco + EEA 250 = 2.49 ± 0.29, Sco + EEA 500 = 2.67 ± 0.36, Sco + ECA 250 = 2.33 ± 0.17, Sco + ECA 500 = 2.77 ± 0.21, Sco + EEA + ECA 250 = 2.61 ± 0.32 and Sco + EEA + ECA 500 = 2.79 ± 0.16 U/mg of protein respectively against the scopolamine induced group Sco (control) = 5.51 ± 0.35 U/mg of protein extracts shows neuroprotective and nootropic activity with reducing AChE level in the brain homogenate of swiss albino mice. CONCLUSION: Since the E. alsinoides & C. asiatica are already used in traditional Indian medicine as the neuroprotective agent and also found promising effects over inflammatory diseases, wound healing, and immunomodulatory activity. The neuroprotective effect of both plants extracts attributed to inhibition of AChE activity and improve the spatial memory formation. © 2019 Mukesh Kumar Yadav, Santosh Kumar Singh, Manish Singh, Shashank Shekhar Mishra, Anurag Kumar Singh, Jyoti Shankar Tripathi, Yamini Bhusan Tripathi.
NLPRL@INLI-2018: Hybrid gated LSTM-CNN model for Indian native language identification
(CEUR-WS, 2018) Rajesh Kumar Mundotiya; Manish Singh; Anil Kumar Singh
Native language identification (NLI) focuses on determining the native language of the author based on the writing style in English. Indian native language identification is a challenging task based on users comments and posts on social media. To solve this problem, we present a hybrid gated LSTM-CNN model to solve this problem. The final vector of a sentence is generated at hybrid gate by joining the two distinct vector of a sentence. Gate seeks the optimum mixture of the LSTM and CNN level outputs. The input word for LSTM and CNN are projected into high-dimensional space by embedding technique. We obtained 88.50% accuracy during training on the provided social media dataset, and 17.10% is reported in the final testing done by Indian native language identification (INLI) workshop organizers. © 2018 CEUR-WS. All Rights Reserved.
Pharmacokinetic screening to estimate the drug likeliness characteristics of selected herbal anticancer drugs
(Research Journal of Pharmacy and Technology, 2023) Manish Singh; Brijesh Kumar; Alok K Singh; Chandra Shekhar Azad; Mukesh K Yadav; Ashutosh Kumar; Rajesh Kumar; Ajay Kumar; Pritee Chaudhary
The pharmacokinetic parameters of a drug plays a very essential role in determining the therapeutic success of an experimental compound, so it is one of the aspects of drug discovery which are essential to be determined in the early phases. The pharmacokinetic studies further help the drug discovery team to optimize their in vivo pharmacokinetic and drug safety bioassays.Low solubility, low absorbency, and chemical instability can seriously affect bioassay results. Today a lot of computational software are available which use their algorithms to calculate the pharmacokinetic parameters of the selected compounds and hence may help the drug discovery team to move in a direction where the chances of getting a good clinical candidate are higher. This paper presents the screening of nine selected herbal anticancer agents (Catechin, Cinnamaldehyde, Epicatechin, Eugenol, Oxyresveratrol, Quercetin, Crocin, Kaempferol, and Emodin) based upon their pharmacokinetic properties with the help of Discovery Studio 2.5. The main parameters which are estimated under this pharmacokinetic ADMET (absorption, distribution, metabolism, excretion and toxicity) study are aqueous solubility, human intestinal absorption, plasma protein binding (PPB), blood-brain-barrier (BBB) penetration, cytochrome P4502D6 inhibition and hepatotoxicity levels. Four compounds (Cinnamaldehyde, Eugenol, Crocin and Oxyresveratrol) were found to possess the required pharmacokinetic properties and are suitable for further anticancer in vivo and in vitro analysis. © RJPT All right reserved.