Metabolic Syndrome (MetS) is characterized by central obesity, hyperglycemia, dyslipidemia, and elevated blood pressure. Obesity contributes to low-grade inflammation, oxidative stress, metabolic endotoxemia, decreased adiponectin, and increased leptin, which play major roles in insulin resistance. Inflammation and insulin resistance enhance fatty acid release from adipose tissue, increasing hepatic uptake, VLDL production, and hypertriglyceridemia. Elevated VLDL further promotes triglyceride–HDL exchange via CETP, lowering HDL levels. Oxidative stress, increased angiotensin II production in adipose tissue, and upregulated receptor expression are also key factors in hypertension associated with MetS. Curcumin, a natural polyphenolic compound, has been shown to modulate many of these processes. Experimental evidence suggests that curcumin can reduce inflammation and oxidative stress, regulate adipokines, improve lipid metabolism, and support vascular health. Several clinical trials have also reported beneficial effects of curcumin supplementation on the components of MetS. In this review, we first summarize the main mechanisms underlying MetS and then discuss in detail the molecular and physiological effects of curcumin on these pathways. Finally, we provide an overview of clinical findings on curcumin and its potential as a supportive strategy in improving MetS.
Mucoadhesive drug delivery systems (MDDS) have emerged as an important strategy in modern pharmacology to enhance drug residence time, improve mucosal absorption, and optimize therapeutic performance across diverse administration routes. By enabling intimate and prolonged interactions with mucosal tissues, MDDS directly influence pharmacokinetic and pharmacodynamic outcomes while supporting patient-centric, non-invasive drug delivery. Recent advances in polymer engineering, surface functionalization, and formulation design have further expanded the capability of MDDS to overcome biological barriers and address key limitations associated with conventional dosage forms. This review provides a comprehensive and mechanistically driven analysis of MDDS, focusing on the fundamental principles of mucoadhesion and the physicochemical and biological factors governing adhesive strength, mucus penetration, and controlled drug release. A wide range of mucoadhesive delivery platforms, including films, gels, tablets, patches, hydrogels, and particulate systems, are discussed in relation to their structure–property–function relationships and pharmacological performance across oral, nasal, ocular, gastrointestinal, vaginal, rectal, and pulmonary routes. The role of natural, semi-synthetic, and synthetic polymers, together with advanced functionalization strategies such as thiolation, ligand incorporation, stimuli-responsive networks, and nanotechnology integration, is critically evaluated with respect to enhancing adhesion, permeability, and therapeutic efficacy. Beyond formulation design, the review emphasizes translational and drug discovery-relevant considerations, including Quality by Design (QbD), manufacturing scalability, regulatory and safety expectations, and clinically evaluated and Food and Drug Administration-approved mucoadhesive products. Selected clinical trials and case studies of successful and unsuccessful formulations are examined to highlight key challenges in clinical translation and to identify emerging opportunities. By bridging mechanistic understanding with applied pharmacology and translational development, this review positions MDDS as a versatile and clinically viable platform for advancing next-generation drug delivery strategies and accelerating their progression from discovery to patient care.
G-protein coupled receptor 40 (GPR40), also termed free fatty acid receptor 1 (FFAR1) is a promising molecular target for treating chronic metabolic and inflammatory diseases. Despite the antiasthmatic benefit of GPR40 agonists such as omega-3 polyunsaturated fatty acids, it remains unclear whether GPR40 activation improves allergic asthmatic outcomes. The present study investigated the ameliorative effect of GPR40 activation on IL-13-induced allergic inflammation in human bronchial epithelial 16HBE14o-cells and in the ovalbumin-induced asthmatic murine model. The increasing concentration of GPR40 agonists GW9508 and TAK875, markedly mitigated IL-13-induced STAT6 phosphorylation and MUC5AC hypersecretion, suggesting mitigated type 2 inflammation in 16HBE14o-cells. The selective GPR40 antagonists DC260126 and GW1100 both strikingly abolished the anti-inflammatory effect of GW9508. In the asthmatic mouse model, intraperitoneal administration of GW9508 (10 mg/kg) alleviated ovalbumin-induced mucus hypersecretion and airway inflammation, with a reduction in STAT6 phosphorylation in lung tissue. Our findings suggest that GPR40 activation represents a novel therapeutic strategy for STAT6-mediated or type-2-inflammation mediated diseases such as allergic asthma.
Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) in transplantation and major surgery, with limited effective pharmacological interventions. This study evaluated the prophylactic effect of desloratadine, a second-generation H1-receptor antagonist with anti-inflammatory and antioxidant properties, on renal IRI. Twenty-one male Sprague-Dawley rats were randomly assigned to three groups (n = 7 each): Sham, I/R (45 min ischemia followed by 24 h reperfusion), and I/R + desloratadine (5 mg/kg, orally, 1 h prior to ischemia). After 24 h of reperfusion, renal function, oxidative stress markers, histopathology, and antioxidant gene expression were assessed. I/R significantly impaired renal function (increased plasma creatinine and urea, decreased creatinine clearance; P < 0.001), reduced effective free-water reabsorption, and increased oxidative stress (elevated TOS, reduced TAC and GSH; P < 0.01-0.001). Desloratadine significantly improved renal function, restored tubular concentrating ability, reduced oxidative stress, and increased GSH levels (P < 0.05-0.001 vs. I/R). At the molecular level, I/R upregulated Nrf2 and HO-1 expression but downregulated Gclc and Gclm, while desloratadine further enhanced Nrf2/HO-1 expression and restored Gclc/Gclm levels. Histological analysis confirmed attenuation of tubular injury. In conclusion, desloratadine pretreatment is associated with protection against renal IRI, potentially through modulation of the Nrf2-GCL-GSH antioxidant pathway and preservation of tubular function. These findings support its potential repurposing as an adjuvant strategy in settings at risk of renal ischemic injury.
Actinomycetes are Gram-positive bacteria renowned for their capacity to produce chemically diverse secondary metabolites with significant pharmaceutical relevance. Widely distributed across marine and terrestrial environments, they exhibit remarkable metabolic adaptability that supports the synthesis of novel compounds under environmental stress. This review examines the biosynthetic diversity of actinomycetes, with a focus on non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), the principal enzymatic systems responsible for complex metabolite assembly. A clear distinction is made between synthetases (ATP-dependent enzymes such as NRPSs) and synthases (ATP-independent enzymes such as PKSs), addressing a key conceptual ambiguity. The modular architecture of NRPSs, including adenylation, thiolation, and condensation domains, is discussed in relation to peptide biosynthesis, while PKS systems are outlined based on their classification (Types I-III), domain organization, and chain elongation mechanisms. Hybrid PKS-NRPS pathways and inter-domain interactions are further highlighted for their role in expanding chemical diversity. Collectively, these biosynthetic systems highlight the potential of actinomycetes as a rich source of therapeutically relevant compounds, particularly in antimicrobial and anticancer drug discovery.
