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Author: search.filters.author.Sharma, Pankaj Kumar

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    Targeting stearoyl-coa desaturase-1 (SCD1) by the drug–nutraceutical combination of montelukast and bixin in ameliorating steatotic NAFLD
    (ACS, 2025-10) Sharma, Pankaj Kumar; Murugesan, Sankaranarayanan; Deepa, P.R
    Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome, which progresses from simple fat accumulation (steatosis) to nonalcoholic steatohepatitis (NASH), fibrosis, and eventually liver cancer. Stearoyl-CoA desaturase 1 (SCD1), a key lipogenic enzyme, plays a significant role in the progression of NAFLD by promoting the accumulation of fat in the liver. This study investigated the drug-nutraceutical combination of Montelukast (a synthetic anti-inflammatory drug) and Bixin (an apo-carotenoid) as SCD1 inhibitors for treating fatty liver disease. Bixin was identified through virtual screening of a curated carotenoid database (carotenoid DB) targeting lipogenic enzyme SCD1. In the in vitro model of steatotic HepG2 cells, the combination treatment of Montelukast and Bixin showed a marked reduction (P < 0.05) in SCD1 gene expression (41%), protein expression (61%), and SCD1 enzyme activity (56.22%). The combination treatment showed a significant reduction of 21.64% (P < 0.05) in lipid accumulation relative to individual treatment with Bixin or Montelukast and was comparable with the reference drug Aramchol (21.83%). The markers of oxidative stress were also significantly reduced (P < 0.05), evidenced by decreased MDA (42.25%), RNS levels (32.59%), and ROS levels (30.72%) in the combination group. These findings suggest that Bixin and Montelukast in combination hold potential for managing the multiple aspects in the pathophysiology of NAFLD development and progression.
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    Promising trends in agricultural practices towards food security: expanding the desert landscape and flora into mainstream farming
    (Frontiers Media, 2025-11) Deepa, P.R.; Sharma, Pankaj Kumar
    Rapid climate change and degrading quality of once-fertile agricultural lands makes it imperative to turn attention towards marginal and desert lands for practice of farming. Additionally, wild xerophytes (desert plants) have been successfully thriving on such lands of extreme temperatures and water scarcity, and provide important clues for traits desired in food crops (such as stress tolerance). In past, the local human communities have derived nutrition from the underexplored (semi)arid plants during drought and famine. Latest technological innovations like application of clay nanoparticles and xerophyte-derived rhizobacteria, vertical farming, horticulture crop-based site management, and restoration of degraded agricultural lands using native and climate-resilient plant varieties offer a glimpse of hope. Therefore, (i) farming of popular food crops (like Solanum lycopersicum using techniques like drip irrigation) on desert lands, as well as, (ii) bringing desert plants (such as the superior varieties of tree legumes like Prosopis cineraria) into mainstream agriculture are two approaches that have shown promise. These actions would also align with the UN Sustainable Development Goals, viz.: SDG 2 (Zero hunger), SDG 12 (Responsible consumption and production) and SDG 13 (Climate action) in particular. Through the current article, we intend to highlight recent success stories on desert landscapes/plants and present the way forward for sustainable agriculture in future.
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    In silico and in vitro investigations reveal pan-PPAR agonist activity and anti-NAFLD efficacy of polydatin by modulating hepatic lipid-energy metabolism
    (Springer Nature, 2025) Sharma, Pankaj Kumar; Murugesan, Sankaranarayanan; Deepa, P.R.
    Polydatin (PD), a stilbenoid resveratrol-derivative in Vitaceae, Liliaceae, and Leguminosae, exhibits pharmacological protection in metabolic disorders. This study investigated Polydatin, as a potential pan-PPAR agonist for treating non-alcoholic fatty liver disease (NAFLD). High-throughput-virtual-screening (HTVS) was performed to identify potential pan-PPAR agonists, followed by in vitro testing of Polydatin in HepG2 steatosis model. Effects on lipid metabolism and oxidative stress, PPAR signaling gene expression analysis, and GC-MS profiling were compared with the hepatoprotectant Silymarin. Pan-PPAR targeted HTVS of PhytoHub natural products database, followed by molecular docking/dynamics simulations, revealed lead-candidate, Polydatin, which was tested in steatotic cells for gene and protein deregulations by qRT-PCR and western blot, followed by GC-MS analysis of biochemical metabolites. HTVS revealed 53 potential pan-PPAR agonists. Molecular docking and dynamics simulations suggested that PD, a stable ligand for PPARs (α,β/δ,γ), exhibited strong binding. Polydatin treatment decreased ALT, triglycerides, and oxidative stress, wherein ROS and malondialdehyde levels decreased by 60.94% and 28%, respectively. PD upregulated PPARs, AMPK, GLUT2, and CPT1α, while downregulating lipogenic enzymes (ACC1, FASN, SCD1). GC-MS analysis revealed Polydatin mediated impact on saturated FFAs-palmitic acid, stearic acid, and unsaturated fatty acid product of SCD1, oleic acid. HTVS identified PD as a promising pan-PPAR agonist, which favorably ameliorated changes in lipid, glucose, and overall energy metabolism in steatotic NAFLD, by modulating PPAR(α,β/δ,γ) expressions and associated downstream lipogenic and lipid-utilization mechanisms, supporting anti-steatotic efficacy of Polydatin.
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    Unraveling PPARβ/δ nuclear receptor agonists via a drug-repurposing approach: HTVS-based ligand identification, molecular dynamics, pharmacokinetics, and in vitro anti-steatotic validation
    (RSC, 2025-04) Sharma, Pankaj Kumar; Murugesan, Sankaranarayanan; Deepa, P.R.
    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors with a crucial regulatory role in carbohydrate and lipid metabolism and are emerging druggable targets in “metabolic syndrome” (MetS) and cancers. However, there is a need to identify ligands that can activate specific PPAR subtypes, particularly PPARβ/δ, which is less studied compared with other PPAR isoforms (α and γ). Herein, using the drug-repurposing approach, the ZINC database of clinically approved drugs was screened to target the PPARβ/δ receptor through high-throughput-virtual-screening, followed by molecular docking and molecular dynamics (MD) simulation. The top-scoring ligands were subjected to drug-likeness analysis. The hit molecule was tested in an in vitro model of NAFLD (non-alcoholic fatty liver disease). The top five ligands with strong binding affinity towards PPARβ/δ were canagliflozin > empagliflozin > lumacaftor > eprosartan > dapagliflozin. RMSD/RMSF analysis demonstrated stable protein–ligand complexation (PLC) by the top-scoring ligands with PPARβ/δ. In silico ADMET prediction analysis revealed favorable pharmacokinetic profiles of these top five ligands. Canagliflozin showed significant (P < 0.001) dose-dependent decrease in lipid accumulation and the associated oxidative stress-inflammatory response, suggesting its promising anti-steatotic potential. These outcomes pave the way for further validation and development of PPAR activity-modulating therapeutics
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    Bioactivity-guided purification and characterization of antioxidant, anti-gout and anti-diabetic polyphenols from Panchkuta: a traditional food combination of (semi) arid regions
    (Elsevier, 2024-12) Deepa, P.R.; Sharma, Pankaj Kumar
    Desert ecosystems have thrived in part because of the contribution of local traditions, along with conventional knowledge passed down through generations. Panchkuta, a combination of five plants, including Prosopis cineraria, Cordia dichotoma, Capparis decidua, Acacia senegal, and Mangifera indica, is a classic example of ethnic desert food and how communities utilize existing food resources to ensure nutritional security. In this study, we determined the total phenolic content, total flavonoid content, antioxidant, anti-gout, and anti-diabetic activities of crude and purified (using Amberlite XAD7HP and Sephadex LH-20) fractions of Panchkuta. Further, the phenolic compounds (quercetin, tiliroside, myricetin-3-O-galactoside, and others) responsible for these activities were identified by analytical techniques, including TLC, LC-MS, and HR-MS. The purified fraction showing maximum antioxidant activity in DPPH assay (Fraction 16, IC50–156.65 ± 12.6 μg/ml) was validated for its cytoprotective and anti-lipid peroxidative effects in the in vitro cell culture system (murine fibroblast cells). Fraction 9 showed the maximum anti-gout activity in xanthine oxidase assay (IC50- 80.59 ± 9.89 μg/ml) and fraction 11 showed the maximum anti-diabetic activity in α-amylase assay (IC50 of 101.54 ± 14.7 μg/ml). The study reinforces the understanding of traditional knowledge, relevance to One Health, and authenticates the potential medicinal value of Panchkuta through scientific validation.
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    Anti-obesity and anti-steatotic effects of bixin (apocarotenoid from bixa orellana l. Seeds): dose-dependent correlations with bioactivity
    (MDPI, 2024-12) Sharma, Pankaj Kumar; Deepa, P.R.
    Annatto, a tropical shrub from Central and South America and parts of India, contains Bixin, an apocarotenoid pigment. Bixin is conventionally used as a natural food colorant and is now receiving attention for its health-promoting nutraceutical properties, particularly in chronic diseases (metabolic syndrome—MetS—and cancers). This study investigates the dose-dependent anti-obesity and anti-steatotic effects of Bixin in in vitro cell culture models. The anti-adipogenic and anti-steatotic effects of Bixin were examined in well-established in vitro models of obesity and non-alcoholic fatty liver disease (NAFLD/steatosis) using 3T3-L1 preadipocytes (by a differentiation protocol) and HepG2cells (steatosis-induced with oleic acid), respectively. Bixin was administered in the following concentration range: 1 μg mL−1–20 μg mL−1 (obesity model) and 2.5 μg mL−1–10 μg mL−1 (NAFLD/steatosis model). The neutral lipid content was estimated by Oil Red O staining; ROS/RNS were quantified by 2′,7′-dichlorofluorescein diacetate (DCFDA) and nitrite assays; and malondialdehyde (MDA), the biochemical marker of lipid peroxidation, was assessed by TBARS assay. At lower concentrations, 5 μg mL−1 in steatotic cells and 10 μg mL−1 in matured adipocytes, Bixin significantly reduced lipid accumulation in both hepatocytes and adipocytes (p < 0.05), demonstrating its potential as an anti-steatotic and anti-obesity agent. This beneficial effect was correlated with a reduction in oxidative stress levels (decreased MDA and ROS/RNS levels). Strikingly, at higher concentrations (>10 μg mL−1), Bixin showed increased lipid accumulation and oxidative stress. Bixin exhibits anti-obesity and anti-steatotic effects at lower doses, which correlates with its antioxidant properties. However, its bioactivity is dose-dependent, meaning that at higher concentrations, it ceases to inhibit adipogenesis. This opposing response is accompanied by elevated oxidative stress levels, indicating a pro-oxidant effect at higher doses, which suggests its anti-cancer potential. The present study highlights the significance of dosage optimization of nutraceuticals and dietary ingredients with respect to their intended biological applications, such as MetS and cancer treatment.
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    Chromatographic analysis of bioactive metabolites from a traditional food combination of (semi) arid regions—panchkuta: insights for sustainable functional foods development
    (MDPI, 2024-10) Sharma, Pankaj Kumar; Deepa, P.R.
    Conventional agriculture may not meet the needs of the growing human population and sustainable development. These issues necessitate a shift towards traditional foods and underutilized desert plants, offering promising sustainable agricultural and food security alternatives. ‘Panchkuta’, a blend of five plants (Prosopis cineraria, Acacia senegal, Capparis decidua, Cordia dichotoma, and Mangifera indica), is a traditional food combination from (semi) arid regions. In this study, the bioactive metabolites were identified through analytical techniques, including TLC and GC-MS analysis. Tapping these underexplored plants can help design and develop healthy functional foods and nutraceutical products.
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    Anti-adipogenic and anti-steatotic potential of edible pigment bixin and annatto seed extracts: LC-MS based bioactive profiling and in vitro biochemical validation
    (Elsevier, 2025-02) Sharma, Pankaj Kumar; Deepa, P.R.
    The rising prevalence of metabolic syndrome (MetS), such as obesity and its hepatic complication, and non-alcoholic fatty liver disease (NAFLD), necessitates safe, effective, and protective interventions. Natural products, such as carotenoids, including bixin derived from annatto seeds, have emerged as promising candidates due to their multifaceted pharmacological properties. This study aimed to characterize the edible food pigment bixin and other co-existing bioactives in acetone- and ethyl lactate-extracts of Bixa Orellana L. seeds, followed by their anti-adipogenic and anti-steatotic assessments using in-vitro models of obesity and NAFLD. LC-MS analysis revealed the presence of various phytochemicals in the bixin rich solvent extracts. In vitro studies demonstrated differential and significant anti-adipogenic and anti-steatotic effects of bixin (pure pigment) and solvent extracts of annatto seeds (P < 0.05). The LC-MS profiling of annatto seed extracts revealed the presence of bixin and several bixinoids. Other key phytochemicals that were identified were eicosatrienoic acid, geranylgeraniol, hypolatein, δ-tocotrienol, caffeoyl acid derivative, and zeaxanthin, which were differentially abundant in each solvent extract. Bixin and coexisting bioactives in the annatto seed extracts demonstrated significant anti-oxidant, anti-inflammatory, and anti-lipidemic effects (P < 0.05) in the present in vitro MetS models. Further studies may be directed toward evaluating the nutraceutical potential of bixin in combination with the implicated phytochemicals in the extracts for treating metabolic disorders.
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    Matters of the desert: A perspective on achieving food and nutrition security through plants of the (semi) arid regions
    (Elsevier, 2023-12) Deepa, P.R.; Sharma, Pankaj Kumar; Joshi, Mukul
    The semi- and arid agro-climatic zones of India harbor numerous plants, many occurring as wild and neglected inhabitants of the desert landscape, that bear edible fruits. They are capable of growing in extreme temperatures, on marginal lands and water-scarce conditions. These also represent sustainable food sources for the future. The benefits that they confer to the ecosystems and communities can be manifold: (a) as influencers of agricultural productivity for other crops (like cereals) in agroforestry systems; (b) as balanced functional foods by way of providing high quality protein, macro- and micronutrients to target protein-calorie malnutrition; (c) as sources of antioxidants, nutraceuticals and bioactive leads to target the ever-increasing burden of non-communicable diseases like obesity, diabetes and cardiovascular disorders. A few representative examples of the promising desert plants include: Prosopis cineraria, Acacia senegal, Cyamopsis tetragonoloba (cluster bean), Capparis decidua, Ziziphus mauritiana (Indian jujube), Cordia dichotoma, Leptadenia pyrotechnica, Calligonum polygonoides, and millets. Even though the potential of such plants has been recognized by food and agricultural scientists, research gaps like low yield, disease vulnerability, presence of anti-nutrients, unavailable genomic sequence information, exclusion from the formal food value chain, and poor marketing strategies, prevent the realization of their full potential. The current perspective looks at the promise afforded by underutilized plants of the Indian desert regions in ensuring food and nutrition security as well as the possibility of developing value-added agri-food products from them. The complementary role that food processing technologies can play in achieving the desired goals would also be highlighted so as to transform the desert plants from traditional to ‘climate-smart’ future foods.
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    Arid/semi-arid flora as a treasure trove of bioactives and bioenergy: the case for underutilized desert legumes towards environmental sustainability
    (Springer, 2024) Deepa, P.R.; Sharma, Pankaj Kumar
    As the spectre of climate change gains in strength with each passing moment, many of our mundane food crops like rice face the heat, leading to uncertain yields and unforeseen disease outbreaks. Subsequently, mankind is forced to look for alternative food choices that should primarily come from indigenous plants that are less demanding in terms of usage of water and application of chemical-based fertilizers/pesticides. There are plants growing in the wild in the arid and semi-arid zones of Rajasthan, India, that can come to the rescue, with an added potential for development into valuable functional foods—i.e., not only as source of carbohydrates, proteins, and micro-nutrients but also that of health benefiting nutraceuticals (like antioxidant flavonoids) and relevant enzymes. The other parts (non-edible) of these plants have often also been traditionally validated via diverse ethnomedicinal practices; these could also be useful bioenergy sources. Keeping in mind the broader aim of looking at future functional foods that are also required to be environmentally sustainable, the current report: (a) reviews the extant literature on underutilized legumes from arid/semi-arid zones, (b) discusses current status with respect to biological activities present therein, and (c) suggests pertinent research questions and solution paths in the domains of bioactives, bioenergy, and sustainable environment.