Phool Chandra

Microbial Metabolites as Systemic Signaling Molecules: Integrating Metabolism, Immunity, and Organ Crosstalk in Health and Disease.

The gut microbiota produces a wide variety of metabolites that are essential for host-microbe communication and play a critical role in regulating host physiology, metabolism, and immunity. Among the most important of these metabolites are Short-Chain Fatty Acids (SCFAs), bile acid derivatives, tryptophan metabolites, polyamines, vitamins, and polyphenol-derived compounds. These bioactive metabolites regulate energy homeostasis, glucose and lipid metabolism, intestinal barrier integrity, immune signaling, and gene expression. Moreover, they influence systemic physiological processes, including cardiovascular and neuroendocrine functions, while playing a pivotal role in regulating hepatic and adipose tissue metabolism and maintaining intestinal homeostasis. Dysbiosis-induced alterations in microbial metabolic activity have been associated with the development of several chronic diseases, including obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, cardiovascular diseases, cancer, autoimmune disorders, and neurological conditions. Consequently, therapeutic strategies aimed at modulating microbial metabolism, such as probiotics, prebiotics, postbiotics, dietary interventions, faecal microbiota transplantation, and synthetic biology-based approaches, are being extensively investigated, with microbial metabolites emerging as promising pharmacological targets. Despite these advances, significant challenges remain regarding their mechanistic understanding, standardisation, safety, and successful translation into clinical practice. The integration of multi-omics technologies, artificial intelligence, and precision microbiome-based interventions is expected to accelerate the development of personalized therapeutic strategies and enhance the clinical applicability of microbial metabolite research.

Integrative In Vitro and In Silico Evaluation of Flavonoid-enriched Carica papaya Linn. Extract Targeting Oncogenic Pathways in A549 Lung Cancer Cells

Non-Small Cell Lung Carcinoma (NSCLC) specifically is still one of the top causes of cancer-related death globally. The multi-targeted mechanisms and lower toxicity of natural products make them intriguing pharmacological candidates. Using a combination of in vitro and in silico methods, the current study assessed the anticancer potential of the Ethanol Extract of Carica papaya Linn. roots (EECP). Phytochemical profiling and High-Performance Thin-Layer Chromatography (HPTLC) analysis confirmed the presence of flavonoids, including rutin. The 2,2-diphenyl-1- picrylhydrazyl (DPPH) assay was used to assess antioxidant activity. Cytotoxicity against Human lung adenocarcinoma cell line (A549) and normal human lung fibroblast cell line (WI-38) cells was evaluated, along with apoptosis via nuclear condensation, Deoxyribonucleic Acid (DNA) fragmentation, and Reactive Oxygen Species (ROS) accumulation. Molecular docking (SwissDock) and Absorption, Distribution, Metabolism, and Excretion (ADME) predictions were performed to assess protein interactions, drug-likeness, and oral bioavailability. EECP exhibited strong antioxidant activity (IC₅₀ = 4.07 μg/mL) and selective cytotoxicity toward A549 cells (IC₅₀ = 89.96 ± 0.24 μg/mL) with lower toxicity in WI-38 fibroblasts. Treatment induced significant ROS generation (213% at 300 μg/mL) and apoptotic changes. Docking studies revealed strong interactions of quercetin (–9.758 kcal/mol) and kaempferol (–9.353 kcal/mol) with oncogenic proteins, comparable to staurosporine (–10.439 kcal/mol). ADME predictions supported favorable bioavailability and drug-likeness. Ethanolic extract demonstrated potent antioxidant activity (IC50 = 4.07 μg/mL) and selective cytotoxicity against A549 cells (IC50 = 89.96±0.24 μg/mL), with comparatively lower toxicity in WI-38 cells (IC50 = 75.83±0.34 μg/mL). Apoptosis was associated with nuclear condensation, DNA fragmentation, and a 213% increase in ROS at 300 μg/mL. Docking studies indicated strong binding of quercetin (-9.758 kcal/mol) and kaempferol (-9.353 kcal/mol) to oncogenic proteins, comparable to that of staurosporine (-10.439 kcal/mol), mediated by hydrogen bonds and hydrophobic interactions. Phenolic acids showed moderate interactions, and carpaine/ ergosta derivatives showed weaker interactions. ADME analyses revealed favourable oral bioavailability and high gastrointestinal absorption for key flavonoids. Ethanolic extract induces oxidative stress-mediated apoptosis and regulates key signalling proteins, including Protein Kinase B (Akt) and tumor suppressor p53 (p53). Overall, the EECP exhibits strong anticancer potential by inducing ROS-mediated apoptosis and regulating Akt and p53, supporting further preclinical evaluation of C. papaya Linn. root flavonoids for lung cancer.

In-silico molecular design approach of some phytoconstituents from Nardostachys jatamansi as HIV/AIDS agents

Physicochemical Science of Electrospun Nanofibers as Drug Delivery Systems for Improved Clinical Outcomes

The interactive combination of physics‐based structural engineering and chemistry‐based functional modification offers an efficient framework for developing the next‐generation nanofiber‐based drug delivery systems.