Polyphenol-Based Pharmacological Strategies for Fibrosis and Oxidative Tissue Injury: Mechanisms, Delivery, and Therapeutic Potential

Inflammation and oxidative stress are closely interconnected biological processes involved in physiological defense mechanisms and in the development of chronic tissue injury and disease. When these responses become persistent or dysregulated, they may contribute to cellular injury, mitochondrial dysfunction, altered redox balance, extracellular matrix remodeling, fibrosis, impaired tissue function and disease progression. This Research Topic focuses on these processes in fibrosis-associated and toxicant- or metabolic injury, with particular emphasis on the liver, heart, kidney and retina, as well as defined cellular and tissue models of oxidative or inflammatory damage.Bioactive phytochemicals, particularly polyphenols such as flavonoids, flavonolignans, curcuminoids, phenolic acids and standardized polyphenol-rich plant extracts, have attracted considerable interest because of their antioxidant, anti-inflammatory, antifibrotic, immunomodulatory and cytoprotective properties. Examples include chrysin, quercetin, silymarin, curcuminoids, rosmarinic acid, ascorbic acid and extracts of medicinal plants. These compounds may regulate key molecular pathways involved in inflammation and oxidative stress, including TGF-β/Smad signalling, NF-κB signalling, Nrf2-mediated antioxidant responses, cytokine production, galectin-mediated fibrogenesis, mitochondrial function, apoptosis, autophagy, inflammasome-related mechanisms and regulatory miRNAs.This Research Topic aims to explore the pharmacological potential of these compounds in modulating inflammatory, oxidative and fibrotic pathways, while linking molecular mechanisms to measurable pharmacological outcomes. Attention will be given to cellular targets, redox-sensitive signalling pathways, extracellular matrix remodelling, inflammasome activation, mitochondrial responses and cytoprotective effects in relevant experimental models. Studies of liver, cardiac, renal, pulmonary and retinal fibrosis; diabetes-associated tissue injury; drug-induced toxicity; and xenobiotic- or heavy-metal-induced oxidative injury are particularly encouraged.Although many phytochemicals exhibit promising biological effects, their translation into therapeutic applications remains challenging. Issues such as low aqueous solubility, variable chemical stability, rapid metabolism, low and variable bioavailability, dose-dependent responses, limited molecular specificity and complex pharmacokinetic profiles require further investigation. In this context, advanced delivery systems, nanoformulations, encapsulation approaches and supramolecular carriers may improve the stability, bioavailability, tissue distribution, targeting and therapeutic efficacy of phytochemical-based interventions. Relevant approaches include cyclodextrin inclusion complexes, calixarene–cyclodextrin systems, polymeric and inorganic nanoparticles, nanofibres, hydrogels, liposomes and related delivery platforms.The Research Topic also welcomes studies that assess the safety, biocompatibility and physicochemical properties of phytochemical delivery systems. Formulation studies should, where possible, compare the formulated compound with the free compound at matched or clearly justified doses. Biological studies should define the molecular and functional endpoints used to support the proposed mechanism, rather than relying only on descriptive antioxidant assays or histological observations. Negative, dose-limiting and formulation-associated toxicity findings are also welcome when supported by appropriate experimental controls.We welcome research investigating how bioactive phytochemicals, antioxidants and phytochemical-based formulations modulate inflammatory, oxidative and fibrotic processes. The scope includes, but is not limited to, the following themes:• Molecular mechanisms of polyphenols in inflammation, oxidative stress and fibrosis;• Regulation of TGF-β/Smad, NF-κB, Nrf2, galectin, cytokine, inflammasome and miRNA pathways;• Antioxidant, antifibrotic and cytoprotective effects in cellular, tissue and animal models;• Effects on mitochondrial function, apoptosis, autophagy and cellular stress;• Pharmacological interventions in liver, cardiac, renal, pulmonary and retinal fibrosis;• Protection against diabetes-, drug-, xenobiotic- and heavy-metal-induced tissue injury;• Molecular, redox, mitochondrial, inflammatory and extracellular-matrix biomarkers;• Delivery systems improving phytochemical stability, solubility, bioavailability, targeting and efficacy;• Physicochemical properties, release, biocompatibility, biodistribution and safety of formulations;• Antioxidant protection in defined cell and tissue culture models, including in vitro maturation;• Dose–response, pharmacokinetic and pharmacodynamic comparisons of free and formulated compounds;• Translational potential and limitations of phytochemical-based therapies.Please note, all submissions to any section of the journal Frontiers in Pharmacology using plant extracts or preparations must adhere to THE FOUR PILLARS OF ETHNOPHARMACOLOGY here, as a baseline standard for sample characterization. Topic editors: Cornel Balta, Oana-Maria Boldura, Miruna Stan Source: https://www.frontiersin.org/research-topics/83310/polyphenol-based-pharmacological-strategies-for-fibrosis-and-oxidative-tissue-injury-mechanisms-delivery-and-therapeutic-potential