General Pharmacology, Toxicology and Pharmaceutics, Veterinary, Biotechnology, Health, Toxicology and Mutagenesis
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Scopus Publications
Scopus Publications
Exploration of phytochemical compounds from Millets as NRF2 activators using molecular docking and molecular dynamics simulation approaches Nalban Nasiruddin, Manish Wanjari, Sudhir Matte, Anurag Kumar, Vaidehi Bagde, et al. Indian Journal of Biochemistry and Biophysics, 2025 Oxidative stress plays vital role in progression of several diseases like cardiovascular, neurological and gastrointestinal disorders. Millets, on regular consumption, are known to have beneficial effects. They are also rich in phytochemicals. In the current study, these phytochemicals are aimed against the complex of KEAP1-NRF2 and activating NRF-2 which is a potent inducer of anti-oxidant enzymes like heme-oxygenase and superoxide dismutase. Molecular docking was conducted to study compounds that can form an interaction similar to 1VX (co-crystalized ligand). CDOCKER interaction energies of isovitexin, vitexin, kaempferol, protocatechuic acid, and vanillic acid were better than 1VX. The best three molecules- isovitexin, vitexin and kaempferol, based ontheir CDOCKER interaction energy, were subjected to molecular dynamic simulation for 100 ns which revealed their stability at active site. Further MM-PBSA binding free energy of phytochemicals was calculated. Values of isovitexin, vitexin, kaempferol and 1VX are -32.04 Kcal/mol, -24.81Kcal/mol. -4.17 Kcal/mol, and -10.25 Kcal/mol, respectively, which indicate high degree of binding compared to co-crystallized ligand 1VX. Results indicated that selected compounds- isovitexin, vitexin, kaempferol can act as NRF2 activators which further can be confirmed through in vitro and in vivo studies.
A comprehensive computational study of Millets derived phytochemicals as potential inhibitors of NACHT domain of NLRP3 inflammasome: Molecular docking, molecular dynamics simulation, MM-PBSA free energy calculation and DFT analysis Nasiruddin Nalban, Manish wanjari, Sudhir Matte, Pallavi Jamadagni, Munaf Tamboli Indian Journal of Biochemistry and Biophysics, 2024 The NLRP3 inflammasome is a vital constituent in the innate immune response, which regulates the caspase-1 activation for the production of proinflammatory cytokines IL-1 and IL-18. NLRP3 inflammasome activation is the main cause of many inflammatory diseases and can contribute to onset of metabolic disorders. There is an urgent need to develop drugs that can inhibit activation of inflammasome. Now a days, millets are known to be rich in polyphenols, which have potential to become drug molecules. In the current study, we investigated the efficacy of phytochemicals of millets against NACHT domain of NLRP3inflammasomeby using various In silico techniques. The interaction affinities of polyphenolic compounds towards NLRP3 was evaluated via intramolecular by Quantum Mechanic, intermolecular by Molecular Docking, and spatial by Molecular dynamics simulations. Isovitexin, Kaempferol, Quercetin, Syringic acid Tricin showed highest (most negative) CDOCKER interaction energy among all phytochemicals and positive control MCC950. Two best compounds Isovitexin and Kaempferol along with MCC 950 were further studied through dynamic simulation, which showed their stability at active site. MM-PBSA binding free energy of phytochemicals Isovitexin, Kaempferol and MCC950 are -51.5813 kcal/mol, -26.6370 Kcal/mol and -12.7006 kcal/mol, respectively, which indicate high degree of binding compared to positive control further these compounds were studied through DFT to determine chemical stability.
Impact of Shodhana an Ayurvedic purification process on cytotoxicity and mutagenicity of Croton tiglium Linn. Pallavi Jamadagni, Anagha Ranade, Shraddha Bharsakale, Shridhar Chougule, Shrirang Jamadagni, Sharad Pawar, Goli Penchala Prasad, Sudesh Gaidhani, Arun Gurav Journal of Ayurveda and Integrative Medicine, 2023 BACKGROUND: Croton tiglium Linn. (CT) which is commonly called Jaypal is used in Ayurvedic preparations like Ichhabhedi Ras, Asvakancuki Rasa. Due to its toxic contents, seeds of Croton tiglium are purified before use, by the process mentioned in classical Ayurvedic texts called Shodhana meaning purification. OBJECTIVES: The objective of the present study is to study the impact of Ayurvedic Purification process on cytotoxicity and genotoxicity of Croton tiglium Linn. MATERIALS AND METHODS: Croton tiglium Linn. Seeds were processed for Shodhana by soaking in water, heating with milk (Snehan) and later grinding in Lemon Juice (Bhavana). Aqueous and Hydroalcoholic extracts were prepared before and after purification i.e. Shodhana. Cytotoxicity of the Croton tiglium was studied against Chinese Hamster Ovary cell line by MTT assay. Ames test was performed to study the mutagenicity of the extracts in Salmonella typhi TA 98, 100 and 102 strains. Phytoconstituents were studied by using LCMS analysis. RESULTS: ) of Croton tiglium seeds after purificationa from 3.03 mg/mL to 0.99 mg/mL in aqueous extract and 18.56 mg/mL to 5.45 mg/mL. Genotoxicity study by Ames test indicated Croton tiglium Linn. Croton tiglium Linn. Seeds are non-genotoxic in strains like S. typhi, TA 98, 100 and 102. There was change in Phytochemical profile before and after shodhana. CONCLUSION: Although both the concentrations are practically non-toxic, the decrease in cytotoxic concentration indicates Purification process as described in classical ayurvedic texts i.e. Shodhana has definitely increased the potency of the seeds of Croton tiglium Linn.
Amelioration of Streptozotocin Induced Cytotoxicity by Mimosa pudica Root Extract - A Proteomic based in-vitro Study Pallavi Jamadagni, Sharad Pawar, Shrirang Jamadagni, Shridhar Chougule, Manish Wanjari, et al. Toxicology International, 2022 The in-vitrocytotoxicity was studied in a pancreatic cell line (RIN5F) using streptozotocin-induced cellular damage. The Cytotoxic dose of aqueous and hydro-alcoholic extracts of Mimosa pudica root powder before and after streptozotocin treatment was studied and protein expression was explored. Both the extracts were subjected to metabolite analysis by LCMS. Mimosa pudica root powder extracts prevented Streptozotocin-induced cellular damage. Proteomics studies indicated both aqueous and hydro-alcoholic extracts of Mimosa pudica regulate proteins related to insulin secretion, glucose uptake, and insulin resistance with marked changes in proteins involved in insulin secretion. The study first time reports cytotoxicity of Mimosa pudica in RIN5F cells and explores protein expression after Mimosa pudica treatment. It was also observed that the abundance of Mimosine is more in Hydro-alcoholic extracts as compared to aqueous extracts.
Tissue distribution of mercury and copper after Aarogyavardhini Vati treatment in rat model of CCl4 induced chronic hepatotoxicity Shrirang Jamadagni, Pallavi Jamadagni, Binita Angom, Dhirendranath Mondal, Sachchidanand Upadhyay, Sudesh Gaidhani, Jayram Hazra Journal of Ayurveda and Integrative Medicine, 2020 BACKGROUND: Aarogyavardhini Vati is a classical Ayurvedic herbomineral formulation. It contains mercury and copper compounds as principal minerals along with other minerals and herbal ingredients. Aarogyavardhini Vati is indicated in chronic liver ailments. However, safety concerns are often raised regarding the use of mercury containing ayurvedic drugs in disease conditions due to the risk of mercury and copper toxicity. OBJECTIVE: This study was performed to address the safety concerns regarding mercury and copper toxicity from Ayurvedic herbomineral formulations by investigating accumulation of these minerals in tissues and subsequent toxicity in chronic hepatotoxicity rat model. MATERIALS AND METHODS: for 8 weeks. Animals were treated with Aarogyavardhini Vati for various durations. Post treatment of 8 weeks, serum biochemical marker estimations was done. Estimation of mercury and copper from the liver, kidney and brain tissues was done after animal sacrifice. Histopathology evaluation of visceral organs was also performed. RESULTS: Treatment with Aarogyavardhini Vati exhibited significant accumulation of mercury in the kidney but not in the brain and liver. Similarly, no significant accumulation of copper was observed in liver, kidney, and brain due to the treatment of Aarogyavardhini Vati. Serum biochemical and histopathological changes were not affected by the treatment with Aarogyavardhini Vati. CONCLUSION: Aarogyavardhini Vati did not show any biologically significant potential to cause toxicity due to its mercury and copper content when administered for prolonged duration to rats with chronic hepatotoxicity.
Review of Holarrhena antidysenterica (L.) Wall. ex A. DC.: Pharmacognostic, pharmacological, and toxicological perspective PallaviShrirang Jamadagni, SharadD Pawar, ShrirangB Jamadagni, Shridhar Chougule, SudeshN Gaidhani, SN Murthy Pharmacognosy Reviews, 2017 Holarrhena antidysenterica (L.) Wall. ex A. DC. is a medicinal plant abundantly found in India. Its uses are mentioned in the classical Ayurvedic literature and by many folklore claims. The plant is also of extreme economic importance. Its seeds are mainly used as an antidiabetic remedy. All pharmacological and toxicological aspects of this plant are discussed in this review.
Toxicity study of swarna bhasma, an ayurvedic medicine containing gold, in wistar rats Pallavi Shrirang Jamadagni, Shrirang B. Jamadagni, Arjun Singh, Rajendra Kumar Singh, Sachchidanand N. Upadhyay, Sudesh N. Gaidhani, Jayram Hazra Toxicology International, 2015 Objectives : This study was conducted to estimate No Observed Effect Level (NOEL) or no observed adverse effect level of Swarna Bhasma an Ayurvedic classical preparation of gold in Wistar rats. Materials and Methods : Swarna Bhasma was prepared as per classical Ayurvedic text and analyzed for physicochemical properties. A total of 40 Wistar rats of either sex with an average body weight of 150-200 g were divided into four groups with 10 animals of both sexes in each group. Group I served as control and was given vehicle (Honey:Water in 2:3 ratio) Group II, III, IV were orally administered Swarna Bhasma @ 13.5, 6.75, 1.35 mg/kg body weight for 90 consecutive days. The effect of the drug was observed on ponderal changes, hematological, and biochemical parameters. At the end of the study, all animals were sacrificed and examined for gross pathological changes. Histopathological evaluation was performed only for control and high-dose group and of animals that were moribund sacrificed. Results : Swarna Bhasma was found to be safe at all levels tested. No significant treatment-related clinical signs were noted in all groups studied. The food and water consumption was not affected at highest given dose, i.e., 13.5 mg/kg body weight. No major alterations were observed during histopathological evaluation. Conclusion : This study indicates 13.5 mg/kg body weight as NOEL for Swarna Bhasma in Wistar rats.
Punarnava mandur: Toxicity study of classical ayurvedic formulation in wistar rats P S Jamadagni, S B Jamadagni, M Neogy, R K Singh, S N Upadhyay, J Hazra International Journal of Research in Ayurveda and Pharmacy, 2013 Punarnava Mandur is an iron containing classical Ayurvedic formulation which was studied for repeated dose oral toxicity study in Wistar rats for 90 days. Total 48 Wistar rats (24 male and 24 female) were selected based on the body weight and were randomly distributed into four groups followed by administration of Punarnava Mandur at the dose of 0, 90, 450, 900 mg/kg body weight for 90 consecutive days. Body weight, Weekly Feed and Water consumption, Clinical Chemistry, Hematology, Differential leukocyte Count, Reticulocyte count and Organ weights were recorded and analyzed statistically. At termination, rats were sacrificed, examined for gross pathological changes, organs were collected, weighed and processed for histopathological evaluation. There was no effect on body weights and feed consumption, no abnormal findings in the histopathological evaluation of high dose group animals but there was significant increase in weight of liver in females of high dose group as compared to control. Hence, the dose level 450 mg/kg of Punarnava Mandur was found as NOAEL (No Observable Adverse Effect Level). However, the NOEL (No Observed Effect Level) could not be established. It was suggested to carry out a toxicity study at possible higher doses so as to establish target organ of toxicity.
Spontaneous Nonmetastatic Choriocarcinoma, Yolk Sac Carcinoma, Embryonal Carcinoma, and Teratoma in the Testes of a Swiss Albino Mouse Shrirang B. Jamadagni, Pallavi S. Jamadagni, Shannon H. Lacy, Bruce Williams, Sachchida N. Upadhyay, Sudesh N. Gaidhani, J. Hazra Toxicologic Pathology, 2013 A 12-week-old Swiss Albino mouse was presented with unilateral (left) testicular enlargement of approximately 1.5 cm in diameter and the right testicle mildly reduced in size and weight. Histopathology evaluation revealed three distinct neoplasms in the left testicle: choriocarcinoma, yolk sac carcinoma, and embryonal carcinoma. Teratoma was diagnosed in the right testicle. The histomorphological and immunohistochemical characteristics of the tumor are presented here. To the best of the authors’ knowledge, this is the first report of spontaneous nonmetastasizing choriocarcinoma, yolk sac carcinoma, embryonal carcinoma, and teratoma in testes of a Swiss albino mouse.
A Spontaneous Teratocarcinoma in the Testis of a Swiss Albino Mouse S. B. Jamadagni, P. S. Jamadagni, S. N. Upadhyay, S. N. Gaidhani, J. Hazra Toxicologic Pathology, 2011 A unilateral non-metastatic embryonal carcinoma and teratoma of the testis was observed in a 12-week-old Swiss Albino mouse at the end of a 28-day repeated dose toxicity study. The teratocarcinoma almost completely replaced the parenchyma of the left testis. The tumor was composed of sheets and rosettes of primitive embryonal cells, anaplastic cells, skeletal muscle tissue, sebaceous gland tissue, keratinized stratified squamous epithelium, and ciliated cuboidal epithelium. The histomorphological characteristics of the tumor were reviewed and presented in this report. To the best of the authors' knowledge, this is the first report of spontaneous teratocarcinoma of testis in the Swiss Albino strain of mice.