Browsing by Author "Ajay Kumar Pandey"

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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)
Literature Review of Vehicles Routing Problems Using Metaheuristics: Prospects and Trends
(Springer Science and Business Media Deutschland GmbH, 2024) Chitranshi Mishra; Manjari; Suneet Singh; Sunil K. Jauhar; Saurabh Pratap; Ajay Kumar Pandey
The field of GA and SA has made significant progress in solving complex optimization problems, and it continues to evolve with the emergence of new algorithms. This paper focuses on providing a comprehensive overview of the research conducted in GA and SA specifically related to vehicle routing and the application of genetic algorithms and simulated annealing. The study involves a bibliometric analysis of approximately 48 papers published from 2018 onwards. These papers are classified based on relevant keywords to examine the advancements and trends in the field. Additionally, this paper discusses recent developments, identifies research gaps, and outlines future directions specifically in the context of vehicle routing and the application of genetic algorithms and simulated annealing algorithms. © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2024.
Phytochemicals, Antioxidant, Anti-inflammatory Studies, and Identification of Bioactive Compounds Using GC–MS of Ethanolic Novel Polyherbal Extract
(Springer, 2023) Amit Kumar Singh; Pradeep Kumar; Vishnu D. Rajput; Sunil Kumar Mishra; Kavindra Nath Tiwari; Anand Kumar Singh; Tatiana Minkina; Ajay Kumar Pandey
Hyperglycemia is the hallmark of diabetes, which is a collection of related metabolic disorders. Over time, diabetes can cause a variety of problems, including cardiovascular disease, nephropathy, neuropathy, and retinopathy. Ethanolic novel polyherbal extract (PHE) was prepared by mixing equal amounts of the following ingredients: Terminalia chebula Retz. (TC), Terminalia bellerica Roxb. (TB), Berberis aristata DC. (BA), Nyctanthes arbostratis L. (NA), Premna integrifolia L. (PI), and Andrographis paniculata Nees. (AP). Analysis of PHE results revealed phytochemicals like glycosides, flavonoids, alkaloids, tannins, phytosterols, and saponins. The aim of the study was to prepare an ethanolic extract of PHE using the cold maceration technique, and identify bioactive molecules from gas chromatography–mass spectrometry (GC–MS) analysis, and evaluate biological responses by using in vitro studies like antioxidant and anti-inflammatory activity. PHE was found to contain a total of 35 phytochemicals in GC–MS of which 22 bioactive compounds were obtained in good proportion. There are a few new ones, including 2-buten-1-ol, 2-ethyl-4-(2, 2, 3-trimethyl-3-cyclopenten-1-yl (17.22%), 1, 2, 5, 6-tetrahydrobenzonitrile (4.26%), 4-piperidinamine, 2, 2, 6, 6-tetramethyl-(0.07%), undecanoic acid, 5-chloro-, chloromethyl ester (0.41%), are identified. Antioxidant activity was estimated using EC50 values of 392.143 µg/ml, which were comparable to the standard value of EC50 310.513 µg/ml obtained using DPPH. Antioxidant activity was estimated with EC50 392.143 µg/ml, comparable to standard EC50 310.513 µg/ml using DPPH. In vitro anti-inflammatory potential was found with IC50 of 91.449 µg/ml, comparable to standard IC50 89.451 µg/ml for membrane stabilization and IC50 of 36.940 µg/ml, comparable to standard IC50 35.723 µg/ml for protein denaturation assays. As a result, the findings of this study show an enrichment of bioactive phytochemicals that can be used to investigate biological activity. To better understand how diabetes receptors work, in silico studies like docking could be carried out. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.