Browsing by Author "Sunil Kumar Mishra"

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A Dual Therapeutic Approach to Diabetes Mellitus via Bioactive Phytochemicals Found in a Poly Herbal Extract by Restoration of Favorable Gut Flora and Related Short-Chain Fatty Acids
(Springer, 2024) Amit Kumar Singh; Pradeep Kumar; Sunil Kumar Mishra; Vishnu D. Rajput; Kavindra Nath Tiwari; Anand Kumar Singh; Tatiana Minkina; Ajay Kumar Pandey; Prabhat Upadhyay
Diabetes mellitus (DM), a metabolic and endocrine condition, poses a serious threat to human health and longevity. The emerging role of gut microbiome associated with bioactive compounds has recently created a new hope for DM treatment. UHPLC-HRMS methods were used to identify these compounds in a poly herbal ethanolic extract (PHE). The effects of PHE on body weight (BW), fasting blood glucose (FBG) level, gut microbiota, fecal short-chain fatty acids (SCFAs) production, and the correlation between DM-related indices and gut microbes, in rats were investigated. Chebulic acid (0.368%), gallic acid (0.469%), andrographolide (1.304%), berberine (6.442%), and numerous polysaccharides were the most representative constituents in PHE. A more significant BW gain and a reduction in FBG level towards normal of PHE 600 mg/kg treated rats group were resulted at the end of 28th days of the study. Moreover, the composition of the gut microbiota corroborated the study’s hypothesis, as evidenced by an increased ratio of Bacteroidetes to Firmicutes and some beneficial microbial species, including Prevotella copri and Lactobacillus hamster. The relative abundance of Bifidobacterium pseudolongum, Ruminococcus bromii, and Blautia producta was found to decline in PHE treatment groups as compared to diabetic group. The abundance of beneficial bacteria in PHE 600 mg/kg treatment group was concurrently associated with increased SCFAs concentrations of acetate and propionate (7.26 nmol/g and 4.13 nmol/g). The findings of this study suggest a promising approach to prevent DM by demonstrating that these naturally occurring compounds decreased FBG levels by increasing SCFAs content and SCFAs producing gut microbiota. Graphical Abstract: Flow chart summarizing research on the dual therapeutic approach to diabetes mellitus via bioactive chemicals found in a poly herbal extract and the management of gut microbiota in relation to DM. (SCFAs, short chain fatty acids; SMB53, a genus of bacterial microbiota of small intestine; LPS, lipopolysaccharide) (Figure presented.) © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
A network pharmacology approach with experimental validation to discover protective mechanism of poly herbal extract on diabetes mellitus
(Elsevier B.V., 2024) Amit Kumar Singh; Pradeep Kumar; Sunil Kumar Mishra; KavindraNath Tiwari; Anand Kumar Singh; Ajay Kumar Pandey; Ali A. Shati; Mohammad Y. Alfaifi; SeragEldin I. Elbehairi; R.Z. Sayyed
Objective: Polyherbal extracts (PHE) contain six traditional medicinal plants, and the efficacy of the medicinal plants used in the preparation of this PHE has been confirmed for the treatment of diseases like diabetes mellitus (DM). The aim of this study was to evaluate the efficacy and therapeutic mechanism of PHE through a network pharmacology approach to reveal the protective mechanism of Alpha-Tocospiro A (ATA) present in PHE on DM with experimental validation. Methods: In this study, Lipinski's rule (Swiss ADME) and drug-likeness score (MolSoft's) web pages were used to confirm the drug-likeness of identified constituents in PHE. Swiss Target Prediction (STP) genes were found for ATA-related genes. The DisGeNet database was used to screen genes associated with DM. String created a network diagram of the interactions between the ATA and DM genes. Top-scoring genes from the string network through CytoNCA plugged into Cytoscape 3.8.2 were selected as hub genes. In addition, the ShinyGO database is used to predict GO and KEGG pathway enrichment analyses. Results: A total of 675 and 105 therapeutic genes (STP) were associated with all bioactive compounds and ATA in the PHE screen, respectively. Additionally, a maximum of 2,803 DM-related genes (DisGeNet) were observed. Further, in the analysis, 331, 57 potential (intersecting) genes were identified in the correlation between the target genes of all compounds and ATA, respectively, of PHE and the target genes of DM. The identified hub gene “TNF” for both ATA and PHE was found to be precisely strengthened in 49 pathways, along with 14 signaling pathways out of more than 100 enriched KEGG pathways. This study predicted that ATA activates PI3K/Akt and MAPK pathways enriched with TNF by phosphorylating the insulin receptor (IR) β-subunit. The anti-diabetic activity of PHE was found to be good and primarily confirmed by in vitro α-glucosidase enzyme inhibition activity. Conclusion: The anti-diabetic activity of PHE was found to be effective and was confirmed by the enzyme inhibition activity in the primary study. This study predicted that ATA is a novel drug molecule in PHE that has a targeted mechanism of action and therapeutic effect on DM. © 2024 The Author(s)
Acute and sub-acute toxicity study of hydro-alcoholic leaves extract of Reinwardtia indica in rats
(Elsevier Masson SAS, 2019) Prabhat Upadhyay; Rashmi Shukla; Sunil Kumar Mishra
The present study was to assess the toxicity of hydro alcoholic leaves extract of Reinwardtia indica in Charles foster rats through an acute and sub-acute study. In the acute study, rats were treated orally with single dose and for sub-acute study different doses were given orally for 28 consecutive days. At the dose of 2000 mg/kg satellite group was also used for 6 weeks as per OECD guidelines-407. General behavioral parameters were assessed in acute toxicity and found no mortality or exterior signs of toxicity. While in the sub-acute study; biochemical, hematological and histopathology along with the body weight, food, and water consumptions parameters were screened in the animals after 14 & 28 days. The study reveals the insignificant (P < 0.05) change in treated group in comparison to the control. The hydroalcoholic leaves extract of Reinwardtia indica was found non-toxic up to 5000 mg/kg in acute study whereas up to 2000 mg/kg dose level in the sub-acute study. © 2018 Elsevier Masson SAS
Acute Febrile Illness in India: An Epidemiological Retrospective Study
(Bentham Science Publishers, 2025) Kaushalendra Kumar; Amit Kumar Tripathi; Vikas Kumar Sharma; Sunil Kumar Mishra; Ranjana Saksena Patnaik
Introduction: Acute febrile illness (AFI) is a frequent occurrence in India, often complicated by a multitude of pathogenic and etiological factors. In this context, it is important to analyze the biochemical, hematological, and epidemiological clinical parameters of AFI patients in the North Indian population. Methods: This study included 1,819 patients of various ages who presented with new-onset acute febrile illness (AFI) between 2017 and 2021. Among these patients, 211, with a median age of 40 years (ranging from 2 to 85 years), were selected for further analysis. At enrollment, clinical examination involved collecting respiratory tract specimens, blood, and urine samples for biochemical analysis, with subsequent data analysis conducted using statistical methods. Results and Discussion: The following biochemical parameters were analyzed: C-reactive protein (CRP), alkaline phosphatase (ALP), serum glutamate-pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transpeptidase (GGT), and total protein serum. The hematological parameters included total leukocyte count (TLC), lymphocyte count, monocyte count, eosinophil count, red blood cell count (RBCs), packed cell volume (PCV), erythrocyte sedimentation rate (ESR), hematocrit value, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Additionally, clinical parameters such as phosphorus, urea, calcium, sodium, uric acid, bilirubin, and potassium were measured. Specific values observed were: SGPT (~113 IU/L in 2018), SGOT (~81 U/L in 2019), GGT (~148 g/L in 2018), and total protein serum (~7 g/L in 2020). The hematological parameters (TLC, lymphocyte, monocyte, RBCs, PCV, ESR, MCV, and MCH). The regression analysis was conducted to explore the temperature recorded at the time of admission, the duration of hospital stays, and biochemical as well as hematological variables of patients suffering from AFI. Karl-Pearson's correlation coefficient and variance inflation factor for each variable mentioned above. Conclusion: Biochemical and hematological parameters were analyzed over different years of intake in patients with Acute Febrile Illness (AFI). Further investigation is required to explore the mechanistic pathways of infection, and preventive measures will be implemented using natural products and other therapeutic interventions. Our data will offer the first systematic assessment of the etiological factors, along with regression analysis and the Karl-Pearson correlation coefficient for each variable in AFI patients. © 2025 Bentham Science Publishers.
Ameliorative activity of ethanolic flower extract of Nyctanthes arbor-tristis (L.) against scopolamine-induced amnestic effect and profiling of active compounds using gas chromatography-Mass spectrometry and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry
(Wolters Kluwer Medknow Publications, 2018) Awadhesh Kumar Mishra; Prabhat Upadhyay; Jyoti Dixit; Pradeep Kumar; Kavindra Nath Tiwari; Sunil Kumar Mishra; Raghunath More; Jasmeet Singh
Background: Amnesia state damages the hippocampus and leads to the loss of short-term memory. Nyctanthes arbor-tristis (L.) is used in traditional medicines to treat various ailments. Objective: In the present investigation, we evaluated the efficacy of ethanolic extract of flowers of N. arbor-tristis against scopolamine-induced amnestic effect in male Wister rats and intended to identify the major compounds present in the extract. Materials and Methods: The anti-amnestic profile of flower extract was screened by elevated plus maze (EPM), passive avoidance (PA), and Morris water maze (MWM) tests. Results: EPM test confirmed the anxiolytic effect of the extract in rats and decreased the transfer latency in the protected arm of the EPM. During PA test, the extract resulted significant increase in step-down latencies during both the acquisition and retention sessions. In MWM task, the scopolamine injection significantly prolonged the escape latency time, whereas this time was shortened in flower extract-treated group. For the confirmation of anti-amnestic effect of extract, acetylcholine (Ach) content, acetylcholinesterase (AChE) activity, superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA) levels in hippocampus brain were evaluated. The extract significantly increased ACh content and decreased the activity of AChE in the hippocampus of the brain. Similarly, the extract declined the MDA and increased the GSH and SOD levels in brain tissues. The phytol (RT 19.69) and loliolide (RT 23.50) were identified in the extract through gas chromatography-mass spectrometry analysis. The four major compounds such as 4-coumaric acid, chlorogenic acid hemihydrate, chalcone, and melatonin were identified using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Conclusion: The anti-amnestic effect of ethanolic extract of the flower was confirmed. It contains several compounds which might be useful in the treatment and to control several neurodegenerative diseases. © 2019 Pharmacognosy Magazine Published by Wolters Kluwer - Medknow.
An introduction to nanopriming for sustainable agriculture
(IGI Global, 2023) Shreni Agrawal; Richa Das; Shivangee Solanki; Simran Choudhury; Indrani Bhattacharya; Pradeep Kumar; Amit Kumar Singh; Sunil Kumar Mishra; Kavindra Nath Tiwari
Plant seeds are of paramount importance in the agricultural sector as well as plant life cycle, and are being severely threatened by environmental changes such as biotic and abiotic stress, resource deficiency, climate fluctuation, etc. Cue, nano¬priming, a nascent yet innovative approach to seed technology, combining versatility of nanoparticles and engineered nanomaterials with 'seed-priming' to induce adaptive physiological changes, thus, improving seed quality and crop yield. This study reported mechanisms by which nano-priming synchronizes seed germination, breaks seed dormancy, boosts seed vigor, increases tolerance to periodic stress conditions, assists phyto-microbiota to thrive under environmental uncertainties, creates nanopores in shoots along with upregulation of aquaporin genes for better water uptake, and other reported changes at molecular, biochemical level. Withal, this study offers insight on the future of nano-priming when blended with cutting- edge technologies like cold plasma, artificial intelligence, and digital analysis to revolutionize the agrarian sector. © 2023, IGI Global. All rights reserved.
Application of Nano-Biochar to Improve Soil Quality and Sustainability
(Apple Academic Press, 2025) Shreni Agrawal; Pradeep Harish Kumar; Richa Das; Amit Kumar Singh; Praveen Kumar Shukla; Pooja Verma; Vishnu D. Rajput; Indrani Bhattacharya; Sunil Kumar Mishra; Kavindra Nath Tiwari
The Green Revolution has been beneficial in promoting the growth of human civilization, but it has also degraded the soil, destroyed biodiversity, and accelerated climate change. Advanced nanomaterials, including nano-biochar, have provided prolonged solutions for a wide range of current challenges. Nano-biochar is a specialized form of biochar with a structural size on the nanometer scale featuring better morphological and physiochemical properties. Nano-BC application improves soil qualities, making it better suited for plant growth and development. By enhancing soil porosity, resistivity, and water-holding capacities—all crucial for sustaining soil activity—Nano-BC offers an ideal soil habitat for bacteria. Biomass is pyrolyzed to produce the bulk parent biochar, which is then mechanically processed using various milling methods to generate nano-biochar. Different types of nano-biochar, such as biochar nanocomposites, magnetic nano-biochar, functional nanoparticles coated nano-biochar, and colloidal biochar, have greater environmental applications than normal biochar, such as improving plant growth, removing pesticides from soil, adding fertilizer, microbial growth, and managing disease. A large surface area, high degree of crystallinity, high nutritional quality, and good chemical group concentrations are a few of the distinctive characteristics of nano-biochar. The features of biochar basically depend on biomaterials that were utilized and the pyrolysis circumstances, with its distinctiveness resting on its large specific surface area and a constant source of carbon, which predispose to superior crop responses and soil health. These chapters discuss the production, types, and various applications of nano-biochar, as well as their significant contributions to agriculture, particularly in soil development. © 2025 by Apple Academic Press, Inc.
Appraisal on accumulation of nanoenabled agrochemicals in plants with subsequent morphophysiological implications
(Elsevier, 2024) Pradeep Kumar; Kajal Singh; Amit Kumar Singh; Nancy Singh; Sakshi Singh; Vishnu D. Rajput; Tatiana Minkina; Sunil Kumar Mishra; Kavindra Nath Tiwari
The use of agricultural goods that are nanoenabled with nanotechnology, including nanoemulsions, nanoherbicides, nanofertilizers, and nanopesticides, to enhance the efficacy of agrochemical distribution to crop plants has become a more practical option. Many experiments have shown that the use of nanoagrochemicals has the efficacy of lowering the negative effects of chemical-derived fertilizer on the natural environment, in addition to significantly boosting crop yield. Still, new evidence suggests that goods made using nanotechnology not only have the ability to boost agricultural productivity but also bring about changes to the condition of the crop. There have been reports of variations in the amount of carbohydrates, amino acids, and starch present, in addition to the necessary metals. The levels of verbi gratia, albumin, globulin, and prolamin have dramatically increased in rice that has been subjected to CeO2-engineered nanoparticles (ENPs), whereas the levels of calcium, magnesium, and phosphorus have risen in different crops that received treatments treated with CeO2, CuO, and ZnO ENPs. On the other hand, researchers found that Mo and Ni levels dropped in both cucumbers and kidney beans after they were treated with synthetic nanoparticles made of CeO2 and ZnO, respectively. However, brief studies on the particular effects of nanoenabled agrochemical in agricultural area have been disscussed. © 2024 Elsevier Inc. All rights reserved.
Assessment of antioxidant potential in seed extracts of Nyctanthes arbor-tristis L. and phytochemical profiling by Gas Chromatography-Mass Spectrometry system
(Faculdade de Ciencias Farmaceuticas (Biblioteca), 2022) Awadhesh Kumar Mishra; Kavindra Nath Tiwari; Rajesh Saini; Jitendra Kumar Chaurasia; Sunil Kumar Mishra
The present study has been carried out with the seed extracts of Nyctanthes arbor-tristis L. (Parijat) and evaluates its antioxidant potential and profiling the phytochemical constituents by Gas Chromatography-Mass Spectrometry (GC-MS) analysis. The antioxidant potential of the seed extracts was measured by four different in vitro assay like 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, superoxide anion free radical scavenging activity, ferric reducing antioxidant power (FRAP) and lipid peroxidation inhibition potential (LPIP) assay. The total phenol content (TPC) and total flavonoid content (TFC) were estimated. The ethyl acetate extract (EAE) of seeds showed potential DPPH free radical scavenging activity (EC50 129.49±3.55µg/ml), superoxide anion radical (EC50 969.94±8.03µg/ml) and LPIP (EC50 452.43±5.07 µg/ml) activities. The total phenol content was maximum in aqueous extract (AQE) which was 201.00±0.20 µg/mg gallic acid equivalent. The EAE was rich with total flavonoid and it was found to be 34.50±0.40 µg/mg rutin equivalent. The EAE was subjected for phytochemical-profiling using GC-MS system. The presence of different phytoconstituents supports the medicinal value of the seeds. The results suggest that EAE constitutes a promising new source of novel compounds. Further, it can be used for isolation and purification of specific compounds which have good antioxidant activities and possess useful biological activities. © 2022, Faculdade de Ciencias Farmaceuticas (Biblioteca). All rights reserved.
Berberine's antihyperglycemic effects via modulation of pancreatic ferroptosis and the CDC42-AR/PTGS2/ESR1 signaling pathway: A genomic and network pharmacology approach
(Elsevier B.V., 2025) Amit Kumar Singh; Pradeep Harish Kumar; Manjeet Kumar Sah Gond; Sunil Kumar Mishra; Kavindra Nath Tiwari; Anand Kumar Singh
Diabetes mellitus (DM) is a prevalent metabolic disorder. The increase in lethality associated with ferroptosis, a novel form of programmed cell death in pancreatic tissues at the molecular level, arises from the accumulation of reactive molecules, such as oxygen species, generated through lipid metabolism, which is linked to the cells' reduced capacity to manage oxidative stress. Recent studies have highlighted that ferroptosis plays a crucial role in the onset, progression, and development of DM and its various complications. A thorough understanding of the molecular mechanisms governing iron metabolism and its contribution to ferroptosis in DM could enhance disease management strategies. To address this, a bioinformatics approach was employed to investigate the antidiabetic potential of key target genes, including CDC42, AR, PTGS2, and ESR1, using a polyherbal extract (PHE) enriched with berberine (BBR), offering a novel perspective in DM treatment. Findings revealed that BBR (constituting 6.442 % in PHE and 0.399 % in Berberis aristata) was identified at retention times of 7.14 in PHE and 6.80 in BA, respectively, as the most significant compound in the positive mode of HR-MS analysis. The antihyperglycemic effect of PHE resulted in a notable decrease in fasting blood glucose (FBG) levels within 30 min of glucose loading in different experimental rat groups. The outcomes suggest that the target genes CDC42 and AR/PTGS2/ESR1 could be downregulated by BBR-enriched PHE, potentially modulating pancreatic ferroptosis in DM. © 2024 Elsevier B.V.
Bio-based synthesis of silver nanoparticles using leaf extract of Uraria picta (Jacq.) Desv. ex DC.: Characterization and evaluation of its activity against Leishmania donovani
(Springer Science and Business Media Deutschland GmbH, 2024) Jyoti Dixit; Pradeep Kumar; Rajan Singh; Pooja Verma; Kavindra Nath Tiwari; Rakesh Kumar Singh; Sunil Kumar Mishra; Jasmeet Singh
Uraria picta is used as a folk medicine to cure various ailments. Regardless of ethnobotanical application, a therapeutic study of the plant parts has yet to be reported. Aqueous leaf extract was enriched with secondary metabolites like phenols, alkaloids, and terpenoids. Total phenol (60.97 mgG−1 GAE), total flavonoid (52.36 mgG−1 RE), and antioxidant activity (IC50 2666.95 µgmL−1) of the extract were measured. Bio-based silver nanoparticles (LEUP-AgNPs) were fabricated using a secondary metabolite-enriched leaf extract of U. picta (LEUP), and characterization of LEUP-AgNPs was done. The LEUP-AgNPs were crystalline, circular (13.04 ± 5.97 nm), monodisperse (pdi 0.205), and stable (-17.8 mV). The LEUP-AgNPs surface was composed of carbon, nitrogen, oxygen, and silver. A comparative study was performed to evaluate the potential of LEUP and LEUP-AgNPs against promastigotes and intra-RAW264.7 macrophage amastigotes of Leishmania donovani. A high dose of LEUP and LEUP-AgNPs significantly inhibited the growth of promastigotes up to 53% and 68%, with an IC50 value of 47.90 µgmL−1 and 6.79 µgmL−1, respectively. LEUP and LEUP-AgNPs higher doses also inhibited intracellular amastigotes up to 53% and 80% with an IC50 value of 6.72 µgmL−1 and 1.16 µgmL−1, respectively. The microscopic examination revealed that LEUP-AgNPs lead to size reduction and aggregations of promastigotes. The LEUP-AgNPs efficiently declined the number of amastigotes per RAW 264.7 macrophages compared to LEUP. LEUP-AgNPs had no cytotoxic effects on RAW 264.7 macrophages based on the CC50 value. Findings showed LEUP-AgNPs were more efficient than LEUP in controlling L. donovani, which induces visceral leishmaniasis. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.
Characteristic, dynamic, and near-saturation regions of out-of-time-order correlation in Floquet Ising models
(American Physical Society, 2022) Rohit Kumar Shukla; Sunil Kumar Mishra
We study characteristic, dynamic, and saturation regimes of the out-of-time-order correlation (OTOC) in the constant-field Floquet system with and without longitudinal field. In the calculation of OTOC, we take local spins in longitudinal and transverse directions as observables which are local and nonlocal in terms of Jordan-Wigner fermions, respectively. We use the exact analytical solution of OTOC for the integrable model (without the longitudinal field term) with transverse direction spins as observables and numerical solutions for other integrable and nonintegrable cases. OTOCs in both cases depart from unity at a kick equal to the separation between the observables when the local spins are in the transverse direction, and one additional kick is required when the local spins are in the longitudinal direction. The number of kicks required to depart from unity depends on the separation between the observables and is independent of the Floquet period and system size. In the dynamic region, OTOCs show power-law growth in both models, the integrable one (without longitudinal field) and the nonintegrable one (with longitudinal field). The exponent of the power-law increases with increasing separation between the observables. Near the saturation region, OTOCs grow linearly at a very low rate. © 2022 American Physical Society.
Clinical efficacy of Gojihvadi Kwath, Shirishadi Kwath, Sanjeevani Vati, Panchagavya Ghrita Granules & Shunthi Churna for COVID-19 management, a randomized controlled trial
(National Institute of Science Communication and Policy Research, 2024) Parameswarappa S. Byadgi; Meena Kumari; Vishwambhar Singh; Arun Kumar Dwivedi; Sunil Kumar Mishra; Sushil Kumar Dubey; Ashvanee Kumar Chaudhary; R.N. Chaurasia; Namrata Joshi; Hitesh Jani; Rajeev Kumar Mishra; T.B. Singh; P.S. Arunima; Remya Jayakumar
The obscure disease pattern of COVID-19 have to be evaluated with Ayurvedic interventions and the present clinical trial was a randomized open label parallel three-arm control trial on the major and minor symptomatic patients with the recent pandemic. The patients were recruited from the Super specialty building of Sir Sunderlal hospital, COVID-19 ward and home isolated ones. The Ayurvedic intervention includes the 15 days oral administration (Group A) –Gojihvadi Kwath, Sanjeevani Vati; Panchagavya Ghrit Granules; Shunthi (Dry ginger powder) plus conventional treatment, in (Group B) – Shirishadi Kwath, Sanjeevani Vati; Panchagavya Ghrit Granules; Shunthi (Dry ginger powder) plus conventional treatment and in Group C (control group) only the conventional medicines. Assessment was done based on the RT-PCR reports, signs and symptoms. The results point out the efficacy of trial medicine (that is group A and B) to discharge the patients earlier than those from the control group. The early reduction in the signs and symptoms noted were also observed. Group B showed a faster recovery from dry cough and shortness of breath and improvement in appetite. Home-isolation patients showed faster recovery of clinical symptoms than the hospitalized patients. Ayurvedic interventions can accelerate viral load clearance associated with quicker recovery and concurrently decrease the risk of viral dissemination. Additionally, there were no adverse reactions observed with these trial medicines. © 2024, National Institute of Science Communication and Policy Research. All rights reserved.
Computational exploration of the dual role of the phytochemical fortunellin: Antiviral activities against SARS-CoV-2 and immunomodulatory abilities against the host
(Elsevier Ltd, 2022) Shivangi Agrawal; Ekta Pathak; Rajeev Mishra; Vibha Mishra; Afifa Parveen; Sunil Kumar Mishra; Parameswarappa S. Byadgi; Sushil Kumar Dubey; Ashvanee Kumar Chaudhary; Vishwambhar Singh; Rameshwar Nath Chaurasia; Neelam Atri
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections generate approximately one million virions per day, and the majority of available antivirals are ineffective against it due to the virus's inherent genetic mutability. This necessitates the investigation of concurrent inhibition of multiple SARS-CoV-2 targets. We show that fortunellin (acacetin 7-O-neohesperidoside), a phytochemical, is a promising candidate for preventing and treating coronavirus disease (COVID-19) by targeting multiple key viral target proteins. Fortunellin supports protective immunity while inhibiting pro-inflammatory cytokines and apoptosis pathways and protecting against tissue damage. Fortunellin is a phytochemical found in Gojihwadi kwath, an Indian traditional Ayurvedic formulation with an antiviral activity that is effective in COVID-19 patients. The mechanistic action of its antiviral activity, however, is unknown. The current study comprehensively evaluates the potential therapeutic mechanisms of fortunellin in preventing and treating COVID-19. We have used molecular docking, molecular dynamics simulations, free-energy calculations, host target mining of fortunellin, gene ontology enrichment, pathway analyses, and protein-protein interaction analysis. We discovered that fortunellin reliably binds to key targets that are necessary for viral replication, growth, invasion, and infectivity including Nucleocapsid (N-CTD) (−54.62 kcal/mol), Replicase-monomer at NSP-8 binding site (−34.48 kcal/mol), Replicase-dimer interface (−31.29 kcal/mol), Helicase (−30.02 kcal/mol), Papain-like-protease (−28.12 kcal/mol), 2′-O-methyltransferase (−23.17 kcal/mol), Main-protease (−21.63 kcal/mol), Replicase-monomer at dimer interface (−22.04 kcal/mol), RNA-dependent-RNA-polymerase (−19.98 kcal/mol), Nucleocapsid-NTD (−16.92 kcal/mol), and Endoribonuclease (−16.81 kcal/mol). Furthermore, we identify and evaluate the potential human targets of fortunellin and its effect on the SARS-CoV-2 infected tissues, including normal-human-bronchial-epithelium (NHBE) and lung cells and organoids such as pancreatic, colon, liver, and cornea using a network pharmacology approach. Thus, our findings indicate that fortunellin has a dual role; multi-target antiviral activities against SARS-CoV-2 and immunomodulatory capabilities against the host. © 2022 Elsevier Ltd
CRISPR Plants against Fungal Diseases: Methods and Applications
(CRC Press, 2025) Lara Jadhav; Richa Das; Shreni Agrawal; Indrani Bhattacharya; Pradeep Harish Kumar; Amit Kumar Singh; Vishnu D. Rajput; Tatiana Mikhailovna Minkina; Kavindra Nath Tiwari; Sunil Kumar Mishra
There is a long list of fungal pathogens that severely affect the vegetation globally. Worldwide, 10–23% of crops are lost to fungal infections every year, and an additional 10–20% is lost post-harvest. Fungi have become a global threat to food security because of their capacity to grow exponentially. Conventional methods of disease control such as breeding for resistance and the use of chemical fungicides have shortcomings in terms of sustainability and effectiveness. However, clustered regularly interspaced palindromic repeat (CRISPR) plants have come to light as a significant tool in combating fungal diseases. CRISPR/CRISPR-associated (Cas) protein 9 (CRISPR/Cas9) is a revolutionary technology for gene editing based on an adaptive immune strategy observed in bacteria and archaea. The emergence of CRISPR technology has tremendously helped in the improvement of economically important crops because of its simplicity, cost-effectiveness, specificity, and user-friendliness. Researchers can improve the defense response of plants or stop the virulence factor expression in fungi. This chapter provides a brief summation of different methods of CRISPR technology in developing fungal disease-resistant plants. These methods involve using CRISPR technology to edit host plant genomes or by targeting fungal pathogens. We have also focused on CRISPR-mediated gene regulation methods such as CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa), which can help us to regulate the expression of specific genes involved in plant–fungal interaction. Another method involves a combination of RNA interference with CRISPR technology. Each method mentioned in this chapter is supported by examples of research studies conducted by different researchers and scientists. © 2025 Taylor & Francis Group, LLC.
Design, synthesis and biological evaluation of novel piperic acid and benzylpiperazine hybrid molecules for improvement of memory impairment via cholinesterase inhibitory activity
(Springer Science and Business Media Deutschland GmbH, 2025) Jitendra Kumar; Gauri Shankar; S. Dasaratha Kumar; Gourav Singh; T. A. Gajendra; Sanskriti Rai; Upesh Mandloi; Saripella Srikrishna; Saroj Kumar; Amit Kumar Singh; Pradeep Harish Kumar; Kavindra Nath Tiwari; Sairam Krishnamurthy; Gyan Prakash Modi; Sunil Kumar Mishra
In this paper, we have developed a series of piperic acid (PA) derivatives to overcome the inherent constraints linked to PA for Alzheimer's disease (AD) management. We have carried out a comprehensive study to investigate the structure–activity relationship (SAR) of PAanalogs to enhance their inhibitory properties towards cholinesterase enzymes. Compound 3m exhibited notable inhibition against butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) among all developed analogs (BChE (µM), 1.03 ± 0.011; AChE (µM), 4.26 ± 0.13 respectively) over PA (AChE% inhibition at 20 µM, 7.14 ± 0.98; BChE% inhibition at 20 µM, 5.87 ± 0.76). Compound 3m was chosen for further biological investigations based on these encouraging outcomes. 3 m demonstrated a binding affinity for AChE’s peripheral anionic site, indicating its interaction with this specific enzyme region. Additionally, it also possesses favorable permeability across the blood–brain barrier, with a Pe (permeability coefficient) value of 5.79 ± 1.12. The molecular docking investigations unveiled the ability of 3mto intricately engage with AChE and BChE.In cell-based cytotoxicity tests, compound 3m displayed cell-friendly characteristics across different tested concentrations. Notably, 3m exhibited the ability to counteract scopolamine-induced memory impairmentin mice, enhancing both spatial and cognitive memories. These results strongly suggest that 3m can behave as a potential compound for AD management. © The Author(s), under exclusive licence to the Institute of Chemistry, Slovak Academy of Sciences 2024.
Design, synthesis and biological evaluation of novel piperic acid and benzylpiperazine hybrid molecules for improvement of memory impairment via cholinesterase inhibitory activity
(Springer Science and Business Media Deutschland GmbH, 2024) Jitendra Kumar; Gauri Shankar; Sunil Kumar; Gourav Singh; T.A. Gajendra; Sanskriti Rai; Upesh Mandloi; Saripella Srikrishna; Saroj Kumar; Amit Kumar Singh; Pradeep Kumar; Kavindra Nath Tiwari; Sairam Krishnamurthy; Gyan Modi; Sunil Kumar Mishra
In this paper, we have developed a series of piperic acid (PA) derivatives to overcome the inherent constraints linked to PA for Alzheimer's disease (AD) management. We have carried out a comprehensive study to investigate the structure–activity relationship (SAR) of PAanalogs to enhance their inhibitory properties towards cholinesterase enzymes. Compound 3m exhibited notable inhibition against butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) among all developed analogs (BChE (µM), 1.03 ± 0.011; AChE (µM), 4.26 ± 0.13 respectively) over PA (AChE% inhibition at 20 µM, 7.14 ± 0.98; BChE% inhibition at 20 µM, 5.87 ± 0.76). Compound 3m was chosen for further biological investigations based on these encouraging outcomes. 3 m demonstrated a binding affinity for AChE’s peripheral anionic site, indicating its interaction with this specific enzyme region. Additionally, it also possesses favorable permeability across the blood–brain barrier, with a Pe (permeability coefficient) value of 5.79 ± 1.12. The molecular docking investigations unveiled the ability of 3mto intricately engage with AChE and BChE.In cell-based cytotoxicity tests, compound 3m displayed cell-friendly characteristics across different tested concentrations. Notably, 3m exhibited the ability to counteract scopolamine-induced memory impairmentin mice, enhancing both spatial and cognitive memories. These results strongly suggest that 3m can behave as a potential compound for AD management. Graphical abstract: (Figure presented.) © The Author(s), under exclusive licence to the Institute of Chemistry, Slovak Academy of Sciences 2024.
Development of Epigallocatechin and Ascorbic Acid Dual Delivery Transferosomes for Managing Alzheimer’s Disease: In Vitro and in Vivo Studies
(American Chemical Society, 2024) Gaurav Mishra; Rajendra Awasthi; Sunil Kumar Mishra; Anurag Kumar Singh; Anurag Kumar Tiwari; Santosh Kumar Singh; Manmath K. Nandi
Epigallocatechin-3-gallate (EGCG) and ascorbic acid (AA)-loaded transferosomes (TRANS) were developed for brain delivery. The investigation covered EGCG-TRANS, AA-TRANS, and EGCG-AA-TRANS formulations using the film hydration technique. We analyzed the formed transferosomes to confirm the presence of vesicles loaded with the respective drugs and their performance within a living organism. The sizes of the particles for EGCG-TRANS, AA-TRANS, and EGCG-AA-TRANS were measured correspondingly at 174.2 ± 1.80, 132.7 ± 12.22, and 184.31 ± 9.5 nm. The appearance of diffused rings in the scanning electron microscopic image suggests that the payload has a crystalline structure. The atomic force microscope image displayed minimal surface irregularities, potentially indicating the presence of a lipid layer on the surface. Hemolysis results indicated the safety of the vesicles. The results showed 10.23, 7.21, and 8.20% of hemolysis for EGCG-TRANS, AA-TRANS, and EGCG-AA-TRANS, respectively. In the case of EGCG-AA-TRANS, the release of EGCG was determined to be 61.65% ± 4.61 after 72 h when exposed to phosphate buffer saline (pH 7.4). In vivo studies show a good response against Alzheimer’s disease (AD). EGCG-AA-TRANS (82.166%) exhibited a higher percentage of AChE inhibition in comparison to EGCG-TRANS (66.550%) and AA-TRANS (53.466%). Intranasal delivery of EGCG-AA-TRANS resulted in approximately a 5-fold enhancement in memory. Formulation allowed EGCG and AA to accumulate in various organs, including the brain. The results suggest that EGCG-AA-TRANS could be safe and effective for treating AD. © 2024 The Authors. Published by American Chemical Society.
Development of plant tissue culture system for Nyctanthes arbor-tristis L. in a controlled environmental system from shoot-tip culture and genetic homogeneity evaluation utilizing inter simple sequence repeat (ISSR) and start codon targeted (SCoT) markers
(Springer Nature, 2025) Awadhesh Kumar Mishra; Kavindra Nath Tiwari; Pallavi Mishra; Rajesh Saini; Shailesh Kumar Tiwari; Sunil Kumar Mishra
An efficient in vitro shoot development profile is developed from the shoot-tip culture of N. arbor-tristis L. To evaluate cytokinin efficacy for manifold shoot regeneration from the shoot-tip, it was cultured on tissue culture Murashige and Skoog medium augmented with various strengths of cytokinin. The results emphasized that medium augmented with 5 mg l−1 BA was found most appropriate for the in vitro shoot development from the cultured explant. This media supported induction of the maximum shoot regeneration efficiency (75.33 ± 1.76), maximum number of shoots/explant (28.23 ± 0.52) and shoot length (4.53 ± 0.12 cm) without callus formation. The effect of variation in nitrogen content (KNO3 and NH4NO3) in medium on shoot regeneration potential was studied. The optimum regeneration from selected explant was achieved on medium compositions M3 (1900 mg l−1 KNO3 + 1650.00 mg l−1 NH4NO3) and M9 (1650.00 mg l−1 NH4NO3 + 1900 mg l−1 KNO3) respectively. The best in vitro root induction (69.50 ± 0.76%), the maximum roots/shoot (10.31 ± 0.82), and its optimum length (2.96 ± 0.14 cm) were achieved once microshoots were sub-inoculated on full-strength Murashige and Skoog medium after being pulse treated with 300 mg l−1 IBA for up to 30 min. The molecular authentication of regenerated shoots to the mother plant was confirmed using the inter simple sequence repeat (ISSR) and start codon targeted (SCoT) primers. Thus, this protocol may aid the consistent production of quality planting stocks, which can be used for transformation study and in other ethnomedicinal purposes. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.
Direct shoot regeneration from cotyledonary node of Uraria picta (Jacq.) Desv. ex DC., an important plant of dashmula drugs, and assessment of genetic fidelity, metabolic profiling, and anti-diabetic activity
(Elsevier B.V., 2024) Jyoti Dixit; Pooja Verma; Pallavi Mishra; Kavindra Nath Tiwari; Shailesh Kumar Tiwari; Sunil Kumar Mishra; Jasmeet Singh
Uraria picta root is used in the polyherbal product ‘Dashmula’. Its exploitation for formulation preparation has depleted its availability, leading to medicine adulteration. Direct shoot regeneration from the cotyledonary node holds promise as a source of raw material. This study aimed to develop a regeneration protocol for U. picta and validate its genetic and metabolic fidelity. The seeds of U. picta showed low germination rates, prolonged dormancy, and poor viability. Root exploitation in the wild poses a threat to its availability in nature. Seedling's derived cotyledonary nodes cultured on B5 medium supplemented with BAP (0.5–3 mg L−1), Kinetin (0.5–3 mg L−1), Thidiazuron (0.01–1 mg L−1), and meta-Topolin (0.1–4 mg L1). To address hyperhydricity in regenerated shoots, cotyledonary nodes were cultured on high-agar concentration media. Microshoots were exposed to IBA solution (50–800 mg L−1) pulse treatment for rooting. Tissue-cultured plants genetic fidelity was assessed using ISSR and SCoT markers, while metabolic fidelity was studied with HRMS. The chlorophyll content, antioxidant, and antidiabetic activity of micropropagated plants were evaluated. The highest shoot regeneration frequency, with a maximum of 6.57±0.278 shoots per explant, was achieved using 2 mg L−1 meta-Topolin. The shoots were elongated, had expanded leaves, and were hyperhydrated. BAP (2 mg L−1) induced a maximum of 9.83±0.333 shoot buds per explant. BAP caused explant browning, profuse callus formation, dwarfing, and hyperhydric shoots. Hyperhydricity was alleviated with a higher agar concentration (1 %). IBA (400 mg L−1) induced a maximum of 2.18±0.090 roots per shoot and a root length of 9.23±0.033 cm. Tissue-cultured and mother plants exhibited clonal fidelity, similar metabolite and chlorophyll content, strong antioxidant activity, and equal efficacy for inhibiting α-amylase and α-glucosidase. This method can propagate elite clones of U. picta and offer its improvement via genetic transformation. © 2024 Elsevier B.V.