Fitoterapia. 2026 Sep 4:107451. doi: 10.1016/j.fitote.2026.107451. Online ahead of print.
ABSTRACT
Hypercholesterolemia is increasingly recognized as a multifactorial metabolic disorder characterized by dysregulated cholesterol homeostasis and chronic inflammation, both of which accelerate atherosclerosis and cardiovascular disease. MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators linking sterol regulatory element-binding proteins (SREBPs) and nuclear factor-kappa B (NF-κB), thereby integrating lipid metabolism with inflammatory signaling. Herbal phytochemicals possess promising hypolipidemic and anti-inflammatory activities; however, their clinical application is limited by poor bioavailability, rapid metabolism, and inadequate tissue targeting. Nanoparticle-based delivery systems have been developed to overcome these limitations by enhancing stability, cellular uptake, and targeted intracellular delivery. This review summarizes current evidence regarding the regulatory effects of herbal nanoparticles on miRNA-mediated modulation of the SREBP-NF-κB signaling pathway in hypercholesterolemia. A systematic literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar for studies published between 2010 and May 2026. Available evidence demonstrates that nanoformulated phytochemicals improve bioavailability and effectively regulate key miRNAs, including miR-33a/b, miR-122, miR-155, miR-21, and miR-146a. These molecular changes suppress SREBP-mediated cholesterol synthesis, enhance cholesterol efflux, attenuate NF-κB-driven inflammatory responses, and restore lipid homeostasis. Collectively, herbal nanoparticles act as both efficient drug delivery platforms and molecular modulators of the miRNA-SREBP-NF-κB regulatory axis. Despite encouraging preclinical findings, clinical translation remains constrained by challenges related to formulation standardization, scalable manufacturing, long-term safety, and regulatory approval. Future studies should prioritize mechanistic investigations, standardized nanoparticle formulations, and well-designed clinical trials to validate miRNA-targeted herbal nanomedicine as a precision therapeutic strategy for hypercholesterolemia and associated cardiovascular disorders.
PMID:42697381 | DOI:10.1016/j.fitote.2026.107451