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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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    In silico and in vitro analysis of PPAR – α / γ dual agonists: Comparative evaluation of potential phytochemicals with anti-obesity drug orlistat
    (Elsevier, 2022) Deepa, P.R.; Sharma, Pankaj Kumar; Murugesan, Sankaranarayanan
    Obesity is an abnormal fat accumulation disorder in the metabolic syndrome constellation, and a risk factor for diabetes, cardiovascular disorders, non-alcoholic fatty liver disease (NAFLD), and cancer. Nuclear receptors (Peroxisome proliferator-activated receptor, PPAR) are implicated in metabolic syndrome and NAFLD, and have potential for therapeutic targeting. Nuclear receptors are ligand-dependent transcription factors that have diverse roles in metabolism, including regulating genes involved in lipid and glucose metabolism, modulating inflammatory genes, and are crucial for maintaining metabolic flexibility. PPAR activates adipose triglyceride lipase, which then releases fatty acids as ligands for PPAR, indicating the interdependency of nuclear receptors and lipases. Here, molecular docking was performed with selected phytochemical ligands that can bind with PPAR-α/γ (PDB ID: 2ZNN and 2ATH, respectively) using Glide module of Schrodinger software followed by molecular dynamics simulation study using Desmond module, and ADMET analysis. Interestingly, orlistat which is a well-known lipase and fatty acid synthase inhibitor also demonstrated favorable binding affinity with both PPAR-α/γ (−10.96 kcal/mol against PPARα and −10.26 kcal/mol against PPARγ). The highest docking scores were however shown by the flavonoids - rutin (−14.88 kcal/mol against PPARα and −13.64 kcal/mol against PPARγ), and its aglycone, quercetin (−10.08 kcal/mol in PPARα and −9.89 kcal/mol in PPARγ). The other phytochemicals (genistein, esculin, daidzin, naringenin, daidzein, dihydroxy coumarin, hydroquinone) showed lower binding affinity as dual agonists. The anti-obesity effects were experimentally validated in cultured adipocytes, which revealed better lipid inhibition by rutin and quercetin than orlistat (quercetin > rutin > orlistat) pointing to their strong potential in anti-obesity treatment.