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Natural Products in Immune Regulation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (20 August 2026) | Viewed by 1282

Editor


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Guest Editor
Department of Pathology, College of Korean Medicine, Gachon University, Seongnam-si 13120, Gyeonggi-do, Republic of Korea
Interests: inflammation; macrophage; cytokine; herbal medicine; nitric oxide; CHOP; ER stress; immunity; infection
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Special Issue Information

Dear Colleagues,

Natural products derived from plants, fungi, and marine organisms play an important role in modulating immune responses. These bioactive compounds affect both innate and adaptive immunity by modulating the activity of immune cells such as macrophages, T cells, dendritic cells, and natural killer cells. Key mechanisms include the suppression of proinflammatory cytokines (e.g., TNF-α, IL-6) and the enhancement of anti-inflammatory pathways, often mediated through the NF-Bκ, MAPK, JAK-STAT, and calcium-CHOP signaling cascades. 

Notable compounds such as baicalein, quercetin, wogonin, curcumin, resveratrol, and ginsenosides have demonstrated immunomodulatory effects in preclinical and clinical studies. These natural substances support immune balance not only in inflammatory control but also in autoimmune diseases, infections, and cancer immunotherapy. Some compounds act as immunostimulants, while others act as immunosuppressants, depending on the context and dose.

Recent advances in omics technologies, systems biology, molecular docking studies, and AI-based informatics have enabled the identification of immune-related targets from natural products, facilitating drug discovery and integrative medicine approaches. Overall, natural products are a valuable source for developing safe and effective immunomodulatory therapies, offering potential in both preventive and therapeutic strategies.

Prof. Dr. Wansu Park
Guest Editor

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Keywords

  • natural products
  • immune responses
  • immunomodulatory therapies

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Published Papers (2 papers)

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Research

24 pages, 110241 KB  
Article
Therapeutic Effects and Mechanisms of Sodium New Houttuyfonate in a Murine Model of Intra-Abdominal Candida albicans Infection
by Xiaoyu Peng, Yuxin Xie, Rong Wang, Wenjing Chen, Hong Yu and Zhangyong Song
Int. J. Mol. Sci. 2026, 27(14), 6437; https://doi.org/10.3390/ijms27146437 - 20 Jul 2026
Viewed by 335
Abstract
Excessive use of immunosuppressive agents compromises host immune defenses and broad-spectrum antimicrobial drugs disrupts the normal microbiota, thereby promoting the overgrowth and dissemination of Candida albicans. As an opportunistic pathogen that commonly resides in the intestinal microbiota, C. albicans can subsequently translocate [...] Read more.
Excessive use of immunosuppressive agents compromises host immune defenses and broad-spectrum antimicrobial drugs disrupts the normal microbiota, thereby promoting the overgrowth and dissemination of Candida albicans. As an opportunistic pathogen that commonly resides in the intestinal microbiota, C. albicans can subsequently translocate across the intestinal barrier and cause intra-abdominal infections. To investigate this process, a murine model of peritoneal C. albicans infection was established, in which sodium new houttuyfonate was administered for therapeutic evaluation. The therapeutic potential of sodium new houttuyfonate against abdominal C. albicans infection was evaluated through assessment of immune cell composition, peritoneal macrophage polarization, tissue fungal burden, and histopathological features. The molecular mechanisms of sodium new houttuyfonate therapy were also investigated with cellular experiments, including colony counting, real-time quantitative PCR, Western blotting, and the detection of reactive oxygen species (ROS) in RAW264.7 macrophages. Our results revealed that sodium new houttuyfonate exerts a dual anti-infective effect through its fungicidal activity and via the immunomodulation of immunoinflammatory states. Sodium new houttuyfonate also stimulates cytokine production (e.g., IL-1β, IL-6, IL-10, TNF-α, and MCP-1) via the TLR2/p38/NF-κB pathway and promotes the release of ROS and nitric oxide. Overall, these findings highlight the potential of exogenous sodium new houttuyfonate as a therapeutic option for abdominal C. albicans infection. Full article
(This article belongs to the Special Issue Natural Products in Immune Regulation)
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19 pages, 1869 KB  
Article
Anti-Inflammatory Effect of Palmatine Chloride on Lipopolysaccharide-Stimulated RAW 264.7 Mouse Macrophages via Calcium-CHOP Pathway
by Young-Jin Kim and Wansu Park
Int. J. Mol. Sci. 2026, 27(13), 5704; https://doi.org/10.3390/ijms27135704 - 24 Jun 2026
Viewed by 396
Abstract
Palmatine chloride (berbericinine, C21H22ClNO4) is a protoberberine alkaloid found in several plants, including Rhizoma Coptidis, Cortex Phellodendri, Rhizoma Corydalis, Guduchi (Tinospora cordifolia), and Tinospora sagittata roots. Palmatine chloride (PA) is known as an inhibitor of [...] Read more.
Palmatine chloride (berbericinine, C21H22ClNO4) is a protoberberine alkaloid found in several plants, including Rhizoma Coptidis, Cortex Phellodendri, Rhizoma Corydalis, Guduchi (Tinospora cordifolia), and Tinospora sagittata roots. Palmatine chloride (PA) is known as an inhibitor of dopamine generation. However, its effect on endoplasmic reticulum (ER) stress-related macrophage activation caused by endotoxin (lipopolysaccharide) is not yet well known. In this study, the effects of PA on pyroptotic responses of mouse macrophages (RAW 264.7) activated by endotoxin were investigated using Griess reagent assay for nitric oxide (NO) production, fluo-4 assay for cytosolic calcium release, dihydrorhodamine 123 assay for hydrogen peroxide production, multiple cytokine assay for cytokine production, real-time PCR for inflammatory gene transcriptions, and flow cytometry assay for p38 MAPK activation. Preliminary experiments using THP-1 human monocytic cells demonstrated that PA was not cytotoxic and significantly reduced basal NO production. Results revealed that PA significantly reduced excessive production levels of NO, hydrogen peroxide, pro-inflammatory cytokines (such as interleukin (IL)-6, CCL3 (MIP-1α), and CSF2 (GM-CSF)), and cytosolic calcium release in endotoxin-stimulated RAW 264.7, but significantly increased the production of anti-inflammatory cytokine IL-10. PA inhibited endotoxin-induced transcripts of Chop, Stat1, Fas, and c-Fos in activated RAW 264.7. It also decreased p38 MAPK phosphorylation and level of Fas in RAW 264.7 stimulated by endotoxin. To further interpret these findings, a network pharmacology-informed analysis based on large-scale literature mining was performed, supporting the multi-target regulatory role of PA in ER stress-related pathways. Briefly, PA exerts anti-inflammatory effects on endotoxin-stimulated RAW 264.7 via the calcium-CHOP pathway, consequently reducing endotoxin-induced production of pro-inflammatory mediators (NO, cytokines, etc.) and relieving ER stress-related pyroptotic cascade. Full article
(This article belongs to the Special Issue Natural Products in Immune Regulation)
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