Natural Products for Chronic Disease: Mechanisms and Applications

Dear Colleagues,

Chronic diseases, including fatty liver diseases, type 2 diabetes, cardiovascular disorders, neurodegenerative conditions, and certain cancers, represent a growing global health crisis, driven by aging populations, sedentary lifestyles, and environmental factors. Natural products, encompassing extracts and bioactive compounds derived from plants, animals, and microorganisms, have long been recognized as pivotal sources of therapeutic leads. At the molecular level, natural products modulate key pathways implicated in chronic disease pathogenesis. Mechanistic insights into the natural products require systems-level approaches that commonly transcend traditional single-target analysis. Recent advances in multi-omics, network pharmacology, and single-cell sequencing now provide a global snapshot of molecular perturbations induced by natural products, enabling unprecedented resolution of their pharmacological effects. Such multi-layered insights are critical for translating natural products into targeted therapies, and ensuring their efficacy is rooted in precise molecular and cellular mechanisms. Translational progress includes preclinical studies assessing efficacy in animal models and clinical trials validating disease remission. However, critical challenges hinder broader application, including poor bioavailability, off-target biological effects, and ill-defined structure–activity relationships. To address these barriers, innovative strategies are emerging: nanocarrier-mediated delivery systems enhance targeted accumulation at disease sites, prodrug designs improve pharmacokinetic profiles, and multi-omics-guided target deconvolution clarifies mechanistic specificity. Collectively, these approaches enable more precise therapeutic deployment, bridging preclinical promise with clinical utility.

This Special Issue focuses on unraveling the mechanistic underpinnings and exploring the translational potential of natural products in chronic disease management. We welcome original research papers, reviews, mini-reviews, systematic reviews, meta-analyses and short communications. Topics of interst include, but are not limited to, the following:

• Mechanistic studies investigating how natural products alleviate chronic diseases;
• Preclinical efficacy and safety evaluations of natural products in disease-specific animal models;
• Innovation in formulation and delivery technologies addressing pharmacokinetic limitations of natural products;
• Structure–activity relationship studies and rational molecular modification of natural products.

Dr. Zheng Li
Dr. Sokcheon Pak
Guest Editors

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