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Molecular Mechanisms of Natural Product-Induced Immune Modulation: From Signaling Pathways to Therapeutic Targets

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: 20 September 2026 | Viewed by 3289

Special Issue Editor

Prof. Dr. Suyun Lyu

E-Mail Website
Guest Editor
Department of Pharmacy, Sunchon National University, Suncheon 57922, Jeollanam-do, Republic of Korea
Interests: natural products; anticancer; immunomodulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products represent an invaluable source of bioactive compounds with diverse immunomodulatory properties. Despite their long history in traditional medicine, the molecular mechanisms underlying their immune-regulating effects remain incompletely understood. This Special Issue aims to explore how natural products modulate immune responses at the molecular level, bridging traditional knowledge with modern molecular biology. We welcome original research articles, reviews, and communications that investigate the molecular basis of natural-product-induced immunomodulation.

Topics of interest include, but are not limited to, the following: mechanisms of immune cell activation or suppression; inflammatory and anti-inflammatory pathways; innate and adaptive immune responses; molecular targets in autoimmune diseases, chronic inflammation, and cancer immunity; host–pathogen interactions and antimicrobial immunity; structure–activity relationships and target identification; biomarker discovery and mechanism-based therapeutic applications; synergistic effects and molecular interactions of natural product combinations; and novel methodologies for studying natural product immunology.

This Special Issue provides a platform for researchers from diverse fields—including natural product chemistry, immunology, molecular biology, and pharmacology—to share discoveries that advance our understanding of how natural molecules influence immune function and disease.

Prof. Dr. Suyun Lyu
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Issues in Molecular Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • natural products
  • immunomodulation
  • immune responses
  • molecular mechanisms
  • immune cell activation
  • inflammation pathways
  • autoimmune diseases

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Published Papers (4 papers)

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Research

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14 pages, 2032 KB  
Article
N-(p-Coumaroyl) Serotonin Ameliorates LPS-Induced Inflammation in BV2 Microglia via MAPK/NF-κB Inactivation and HO-1/NQO1 Upregulation
by Chang Hyeon Jeon, Soo-Jin Park, Seok Han Yun, Hyun-Jae Jang, Mun-Ock Kim and Jae-Won Lee
Curr. Issues Mol. Biol. 2026, 48(2), 232; https://doi.org/10.3390/cimb48020232 - 21 Feb 2026
Viewed by 737
Abstract
Uncontrolled inflammation contributes to the development of neurodegenerative diseases (NDs) like Alzheimer’s disease (AD). N-(p-Coumaroyl) serotonin (CS) has demonstrated a significant capacity to modulate hyper-inflammation. We explored whether CS could mitigate inflammatory responses in endotoxin-challenged microglial cells and sought to [...] Read more.
Uncontrolled inflammation contributes to the development of neurodegenerative diseases (NDs) like Alzheimer’s disease (AD). N-(p-Coumaroyl) serotonin (CS) has demonstrated a significant capacity to modulate hyper-inflammation. We explored whether CS could mitigate inflammatory responses in endotoxin-challenged microglial cells and sought to elucidate the specific molecular mechanisms governing these effects. ELISA, nitric oxide (NO) assays, Western blotting and immunocytochemistry were performed to study inflammatory responses and related signal transduction mechanisms. CS pretreatment effectively attenuated the inflammatory output in endotoxin-primed microglial models. This was evidenced by a significant reduction in key cytokines (such as IL-6, TNF-α, and MCP-1) and a concomitant decrease in the protein levels of iNOS and COX-2. These effects were mediated through the disruption of MAPK/NF-κB signaling cascades and the sequestration of NF-κB within the cytoplasm. Beyond its anti-inflammatory role, CS promoted the HO-1/NQO1 signaling pathway and interfered with the LPS-mediated TLR4/MyD88 cascade. Our collective evidence indicates that the modulation of microglia-mediated inflammation by CS is underpinned by the suppression of MAPK/NF-κB and the induction of antioxidant systems, suggesting that CS may have the potential to improve NDs. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Natural Product-Induced Immune Modulation: From Signaling Pathways to Therapeutic Targets)
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15 pages, 3408 KB  
Article
Therapeutic Effects of Cephalotaxus harringtonia Leaf Extract on Hepatocellular Carcinoma via Regulation of the Intrinsic Apoptosis Pathway and Cell Cycle
by Dae-Han Park, Sonny C. Ramos, Hyun Bo Sim, Ju-Bin Lee, Ho-Yeol Jang, Beom-Gyun Jeong, Kyung-Wuk Park, Kyung-Yun Kang and Jong-Jin Kim
Curr. Issues Mol. Biol. 2025, 47(12), 994; https://doi.org/10.3390/cimb47120994 - 27 Nov 2025
Cited by 1 | Viewed by 812
Abstract
Apoptosis induction in tumor cells is a fundamental therapeutic approach in cancer treatment, with growing interest in plant-derived compounds that offer potent efficacy and reduced toxicity. Cephalotaxus harringtonia, traditionally used in East Asian medicine, contains several bioactive constituents, including homoharringtonine (HHT) and [...] Read more.
Apoptosis induction in tumor cells is a fundamental therapeutic approach in cancer treatment, with growing interest in plant-derived compounds that offer potent efficacy and reduced toxicity. Cephalotaxus harringtonia, traditionally used in East Asian medicine, contains several bioactive constituents, including homoharringtonine (HHT) and quercetin 3-β-D-glucoside (Q3G), which are known for their anticancer properties. This study investigated the anticancer effects of C. harringtonia leaf extract (CHLE) and its two major compounds, quercetin 3-β-D-glucoside (Q3G) and HHT, against human liver cancer cell lines (HepG2). CHLE exhibited selective cytotoxicity and apoptosis specifically in HepG2 cells while showing minimal toxicity toward normal kidney cells (HK-2). Mechanistic analyses revealed that CHLE induced apoptosis through a mitochondria-mediated intrinsic pathway, characterized by increased reactive oxygen species production, mitochondrial membrane depolarization, and BAX upregulation. These findings demonstrate that C. harringtonia leaf extract possesses potent, selective anticancer activity and may serve as a promising natural candidate for the prevention and therapeutic management of liver cancer. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Natural Product-Induced Immune Modulation: From Signaling Pathways to Therapeutic Targets)
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Review

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19 pages, 894 KB  
Review
Natural Products Targeting Immune Mechanisms in Ocular Inflammation: Uveitis and Dry Eye
by Wenjia Lu, Mingming Yang, Yaru Zou, Jing Zhang, Kyoko Ohno-Matsui and Koju Kamoi
Curr. Issues Mol. Biol. 2026, 48(4), 367; https://doi.org/10.3390/cimb48040367 - 1 Apr 2026
Viewed by 704
Abstract
At present, the clinical management of ocular inflammatory diseases predominantly relies on chemically synthesized therapeutic agents. Although these therapies demonstrate established efficacy, their long-term use is associated with substantial economic burden. In addition, they may cause ocular side effects and systemic adverse reactions [...] Read more.
At present, the clinical management of ocular inflammatory diseases predominantly relies on chemically synthesized therapeutic agents. Although these therapies demonstrate established efficacy, their long-term use is associated with substantial economic burden. In addition, they may cause ocular side effects and systemic adverse reactions involving the cardiovascular, hepatic, and renal systems. In contrast, natural products have attracted increasing attention in recent years because many are accessible, relatively cost-effective, and potentially well tolerated. Studies indicate that various natural products exert anti-inflammatory and immunomodulatory effects by inhibiting inflammatory signaling pathways such as NF-κB and MAPK, regulating immune cell function and alleviating oxidative stress responses. These multifunctional properties support their potential therapeutic value in various inflammatory diseases. Notably, several natural products have shown potential benefits in clinical trials; however, their investigation and application in ocular diseases remain relatively limited. In this review, we focus on uveitis and dry eye disease (DED) as representative ocular disease models and systematically summarize the current research progress on four natural products—Paeonia lactiflora extracts, resveratrol and its derivatives, curcumin, and boswellic acids in experimental studies of ocular diseases. We particularly focus on their effects in alleviating ocular surface inflammation and intraocular inflammatory responses through their immunomodulatory mechanisms. This review aims to provide a mechanistic framework for understanding the potential role of natural products as complementary or alternative strategies to current therapeutic approaches, while informing the development of novel therapeutics and future research directions in ocular diseases. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Natural Product-Induced Immune Modulation: From Signaling Pathways to Therapeutic Targets)
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24 pages, 780 KB  
Review
Icariin Modulates the Reproductive-Immune Axis: Molecular Insights and Therapeutic Potential
by Rongyu Wang, Yan Chen, Qinwen Xiao, Lirong Tang and Nannan Zhang
Curr. Issues Mol. Biol. 2026, 48(4), 366; https://doi.org/10.3390/cimb48040366 - 1 Apr 2026
Viewed by 555
Abstract
The immune system is a pivotal regulator of reproductive physiology, maintaining tissue homeostasis essential for successful pregnancy while contributing to infertility and reproductive disorders when dysregulated. Natural products represent a valuable source of novel immunomodulatory agents. Icariin (ICA), a prenylated flavonoid glycoside isolated [...] Read more.
The immune system is a pivotal regulator of reproductive physiology, maintaining tissue homeostasis essential for successful pregnancy while contributing to infertility and reproductive disorders when dysregulated. Natural products represent a valuable source of novel immunomodulatory agents. Icariin (ICA), a prenylated flavonoid glycoside isolated from Epimedium species (Horny Goat Weed), has a long-standing traditional use for “invigorating yang,” which modern research attributes to its reproductive function-enhancing properties. This review synthesizes emerging evidence that the beneficial effects of ICA on female and male reproductive health are primarily mediated through its sophisticated immunomodulatory actions on the reproductive–immune axis. We systematically dissect the molecular mechanisms by which ICA reprograms the reproductive immune microenvironment, focusing on its regulation of macrophage polarization, T-helper cell (Th1/Th2/Th17) and regulatory T-cell (Treg) balance, and suppression of key pro-inflammatory signaling pathways (NF-κB, NLRP3 inflammasome, JAK-STAT) in ovarian, uterine, and testicular tissues. This review provides a detailed account of how ICA modulates reproductive disorders via regulating immune responses, with the aim of offering innovative strategies for the design of novel immunomodulatory therapies targeting reproductive diseases. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Natural Product-Induced Immune Modulation: From Signaling Pathways to Therapeutic Targets)
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