Natural Products and Their Derivatives in Cancer, Cardiovascular disease, and COVID-19: Mechanistic Insights, Formulation Strategies, and Therapeutic Potential

Natural compounds and their derivatives have traditionally made a significant contribution to pharmacotherapy, especially in cancer, cardiovascular, infectious, and COVID-19-related diseases. They offer significant advantages over traditional small molecules, including high structural diversity, rigid scaffold architecture and rich stereochemistry, and the ability to modulate multiple biological pathways and targets. Moreover, their use in traditional medicine provides valuable information for drug discovery; however, traditional uses alone do not establish their safety and efficacy. The development of natural products into clinically useful drugs remains challenging due to technical barriers in screening, isolation, characterization, and optimization, poor bioavailability, and patent and regulatory challenges. The current development of analytical technology and nanocarrier-based delivery systems, including polymeric nanoparticles, solid lipid nanoparticles, micelles, and liposomes, is addressing such challenges and limitations by improving drug stability, solubility, bioavailability, and targeted delivery. This has sparked interest in natural products as potential drugs for treating diseases like cancer, cardiovascular diseases, and COVID-19-related diseases. Therefore, this review comprehensively discusses the mechanisms by which natural products exert their therapeutic effect and highlights recent advances in formulation and drug delivery strategies. It also summarizes current applications of formulation approaches and discusses their potential to improve the therapeutic efficacy and clinical translation of natural-based therapies. The review bridges mechanistic insights with innovative formulation strategies to provide a focused perspective on the potential of natural products for disease management.