The Regulatory Mechanisms of Natural Bioactive Molecules on Metabolism and Immunity

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological Factors".

Deadline for manuscript submissions: 10 October 2026 | Viewed by 438

Special Issue Editor


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Guest Editor
Department of Biology Education, Daegu University, 201, Daegudae-ro, Gyeongsan-si 38453, Republic of Korea
Interests: natural product; metabolic reprogramming; anti-inflammatory; immune pathways

Special Issue Information

Dear Colleagues,

Natural bioactive molecules play pivotal roles in the regulation of metabolic homeostasis and immune function. Dietary phytochemicals, microbial metabolites, and endogenous natural compounds have been shown to modulate key signaling pathways involved in glucose and lipid metabolism, energy balance, inflammation, and immune surveillance. Dysregulation of metabolism–immunity crosstalk is increasingly recognized as a central feature of metabolic disorders, chronic inflammation, cancer, and autoimmune diseases. This Special Issue aims to highlight recent advances in elucidating the molecular and cellular mechanisms by which natural bioactive molecules regulate metabolic and immune pathways. We welcome original research and reviews addressing signaling networks, target identification, and therapeutic potential in metabolic and immune-related diseases.

Dr. Dong-Oh Moon
Guest Editor

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Keywords

  • natural bioactive molecules
  • metabolic regulation
  • immune modulation
  • inflammation and immunity
  • immunometabolism

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Published Papers (1 paper)

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Review

31 pages, 8507 KB  
Review
Natural Products Targeting PAD4 in NETosis: Structural and Mechanistic Insights into Direct and Indirect Inhibition
by Dong Oh Moon
Biomolecules 2026, 16(3), 420; https://doi.org/10.3390/biom16030420 - 12 Mar 2026
Viewed by 305
Abstract
Peptidyl arginine deiminase 4 (PAD4) is a Ca2+-dependent enzyme that catalyzes histone citrullination and plays a central role in chromatin decondensation during neutrophil extracellular trap (NET) formation. Dysregulated PAD4-mediated NETosis contributes to the pathogenesis of diverse inflammatory and immune-related diseases, including [...] Read more.
Peptidyl arginine deiminase 4 (PAD4) is a Ca2+-dependent enzyme that catalyzes histone citrullination and plays a central role in chromatin decondensation during neutrophil extracellular trap (NET) formation. Dysregulated PAD4-mediated NETosis contributes to the pathogenesis of diverse inflammatory and immune-related diseases, including autoimmune disorders, cancer, and thrombosis. Although several synthetic PAD4 inhibitors have been developed, their therapeutic application has been limited by issues related to selectivity, irreversible covalent reactivity, and suboptimal pharmacokinetic properties, prompting growing interest in natural products as alternative modulators of PAD4 activity and NETosis. This article presents a structural and mechanistic overview of natural products that target PAD4 and regulate NETosis. Based on enzyme kinetics, structural analyses, and functional validation, natural PAD4 modulators are classified into four categories: (i) active-site-directed inhibitors that bind within the U-shaped substrate tunnel, (ii) mixed and active-site-adjacent inhibitors that engage surface pockets flanking the catalytic site, (iii) allosteric and hybrid modulators that bind to regulatory regions distinct from the active site, and (iv) functionally validated PAD4 binders supported by biophysical and cellular evidence. Integration of structural, biochemical, and cellular data highlights that indirect or noncanonical modes of PAD4 regulation represent biologically coherent strategies for controlling pathological NETosis. Full article
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