Statins, primarily prescribed for their lipid-lowering effects, have garnered significant attention for their potent anti-inflammatory effects. This review explores the underlying molecular pathways and clinical relevance of statins’ anti-inflammatory actions, extending beyond cardiovascular disease management to chronic inflammatory conditions and oncological applications. The lipid-lowering effect of statins stems from their ability to suppress HMG-CoA reductase, a crucial enzyme in cholesterol synthesis; however, their pleiotropic effects include modulation of critical inflammatory pathways such as the inhibition of NF-κB signalling, a reduction in pro-inflammatory cytokine production, and enhancement of endothelial function. We delve into the molecular pathways influenced by statins, including their effects on inflammatory mediators like C-reactive protein (CRP), interleukins (IL-6, IL-1β), and tumour necrosis factor-alpha (TNF-α). Clinical evidence supporting the efficacy of statins in managing chronic inflammatory diseases, such as rheumatoid arthritis, chronic obstructive pulmonary disease, diabetes, and osteoarthritis, is critically reviewed. Additionally, we investigate the emerging role of statins in oncology, examining their impact on inflammation-driven carcinogenesis, tumour microenvironment modulation, and cancer progression. Despite their broad therapeutic potential, the safety profile of statins, particularly concerning adverse effects such as myopathy, hepatotoxicity, and potential diabetes risk, is discussed. Controversies surrounding the extent of their anti-inflammatory benefits and the variability in patient responses are also addressed. This review consolidates the current literature, elucidating the biochemical mechanisms underlying the anti-inflammatory properties of statins and evaluating their clinical applications and associated controversies. Future research directions are identified, including the development of novel statin analogues with enhanced anti-inflammatory effects and the investigation of new therapeutic indications in inflammatory diseases and cancer. By providing an in-depth analysis, this review underscores the expanding therapeutic scope of statins and advocates for their integration into broader clinical strategies for the management of inflammation and cancer.

Background: Colorectal cancer (CRC) is a growing health concern globally and in regions such as the United Arab Emirates, where risk factors like obesity and hyperlipidaemia are prevalent. Chronic inflammation, driven by pathways involving protease-activated receptor 2 (PAR-2), plays a pivotal role in CRC progression, creating a tumour-promoting microenvironment. The overexpression of PAR-2 has been associated with increased tumour aggressiveness and drug resistance. While previous studies have focused on broad inflammatory modulation, this study explores the selective targeting of PAR-2 by atorvastatin (ATV) and rosuvastatin (RSV), highlighting their specificity by assessing minimal impact on PAR-1 expression, which serves as a control. Methods: HT-29 and Caco-2 CRC cell lines were employed to investigate the anti-inflammatory effects of ATV and RSV. Inflammation was induced with lipopolysaccharide (LPS), followed by treatment with varying concentrations of ATV and RSV. Western blotting and real-time polymerase chain reaction for quantification (qPCR) were performed to quantify PAR-2 and TNF-α at both the protein and mRNA levels. Enzyme linked immunosorbent assay (ELISA) was used to measure the secretion of TNF-α. Calcium signalling, which plays a crucial role in inflammation, was analysed using Fluo-4 AM dye, with fluorescence imaging capturing the effects of statin treatment on intracellular calcium influx. Results: LPS treatment significantly upregulated PAR-2 and TNF-α expression in both cell lines, validating the inflammatory model. Co-treatment with ATV or RSV reduced PAR-2 and TNF-α expression in a dose-dependent manner. The higher concentrations of ATV (50 µg/mL) and RSV (20 µg/mL) produced the most significant reduction in these inflammatory markers at both the protein and mRNA levels. Importantly, the treatment did not substantially alter PAR-1 expression, underlining the specificity of ATV and RSV in modulating PAR-2-mediated pathways. Additionally, statin treatment attenuated LPS-induced calcium influx, with fluorescence intensity decreasing markedly at higher concentrations of both statins. Conclusions: This study provides novel insights into the selective targeting of PAR-2 by ATV and RSV, distinguishing their effects from PAR-1. The reduction in PAR-2 expression and TNF-α secretion, along with the suppression of calcium signalling, underscores the potential of these statins as targeted anti-inflammatory agents in CRC. The findings highlight the therapeutic value of ATV and RSV in modulating inflammation through PAR-2-specific pathways, which may contribute to reduced cancer progression. These results pave the way for further preclinical and clinical evaluations to explore statins as adjunctive therapies in the management of CRC.

Male infertility has been viewed as a potential biomarker for systemic health and a predictor of future disease. With the global burden of neurodegenerative diseases (NDDs) on the rise, the current systematic review aims to synthesize the reported associations, risks, and shared molecular mechanisms between male infertility and NDDs. Following PRISMA 2020 guidelines, we systematically searched PubMed, Embase, Scopus, and Cochrane CENTRAL in January 2026. Studies examining the relationship between male infertility and NDDs were included. Screening and data extraction were performed by two independent reviewers with a third to resolve conflicts while quality appraisal (ROBINS-E and OHAT) was performed for all included studies. Studies used heterogeneous definitions of male infertility, including clinical diagnosis, semen parameters, and reproductive outcomes. Of the 1566 identified studies, 13 were included in this review including case-control studies, experimental investigations, in vitro studies, bioinformatic analyses, and pedigree studies. The available literature suggests possible mechanistic overlap between male infertility and neurodegenerative disease pathways, particularly in mitochondrial dysfunction, oxidative stress, and proteostasis. However, the evidence remains heterogeneous and preliminary, and large prospective studies are needed before male infertility assessment can be considered a marker of neurodegenerative risk. Registration: The study protocol was registered on PROSPERO (registration code: CRD420261301509).