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The Role of Natural Products in Inflammation
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The Role of Natural Products in Inflammation

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

Deadline for manuscript submissions: 23 October 2026 | Viewed by 5901

Special Issue Editor

Prof. Dr. Antonia Cianciulli

E-Mail Website
Guest Editor
Department of Biosciences, Biotechnologies and Environment, University of Bari, Bari, Italy
Interests: neuroinflammation; signaling; bioactive compounds; evolutionary computational study
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is widely known that inflammation, a complex biological response, plays a critical role in various diseases. While conventional anti-inflammatory drugs have shown efficacy, concerns regarding adverse effects have prompted interest in exploring natural alternatives. Natural products derived from plants, marine organisms, and microorganisms have been recognized for their potential to modulate inflammatory responses thus representing a starting point for the identification of new potential therapeutic compounds. This Special Issue aims to collect original research articles, reviews, and perspectives that explore the mechanisms of action of natural products in modulating inflammatory responses and their therapeutic applications, as well as the challenges and opportunities in this field. Papers that address the identification and characterization of novel natural products with anti-inflammatory activity, the mechanisms of action of natural products in regulating inflammatory pathways, and in vitro and in vivo studies evaluating the efficacy of natural products in inflammatory models are invited.

Prof. Dr. Antonia Cianciulli
Guest Editor

Manuscript Submission Information

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Keywords

  • inflammation
  • natural products
  • immunomodulation
  • bioactive compounds
  • drug discovery
  • drug target identification
  • anti-inflammatory activity
  • antioxidant activity
  • cellular signalling pathways

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Published Papers (3 papers)

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39 pages, 1246 KB  
Review
Gaultherin, a Natural Alternative to Aspirin: A Comprehensive Review of Molecular Mechanisms, Pharmacokinetics, Biocompatibility, Isolation Techniques, and Plant Sources
by Piotr Michel
Int. J. Mol. Sci. 2025, 26(15), 7280; https://doi.org/10.3390/ijms26157280 - 28 Jul 2025
Cited by 3 | Viewed by 4557
Abstract
Gaultherin [methyl salicylate 2-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside] is a natural salicylate found in some plant species belonging primarily to the Ericaceae and Rosaceae families. Biological studies conducted since the beginning of the 21st century have suggested the potential use of gaultherin in treating various [...] Read more.
Gaultherin [methyl salicylate 2-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside] is a natural salicylate found in some plant species belonging primarily to the Ericaceae and Rosaceae families. Biological studies conducted since the beginning of the 21st century have suggested the potential use of gaultherin in treating various diseases related to inflammation and oxidative stress, including rheumatoid arthritis, sciatica, neuralgia, and muscular pain. The accumulated results indicated a targeted range of biological effects, particularly anti-inflammatory, antipyretic, and anti-rheumatic properties associated with reduced adverse outcomes. The molecular mechanisms involve the influence on several signalling pathways, including NF-κB, MAPK, and potentially AMPK, as well as the inhibition of critical pro-inflammatory enzymes, such as COX-2. This inhibition is achieved without affecting the COX-1 isoform, thereby preventing side effects such as bleeding ulcers or intracranial haemorrhage. This overview summarises the current knowledge about pharmacokinetics, molecular mechanisms, pharmacology, and biocompatibility of gaultherin. Additionally, four methods for isolating gaultherin from plant material and its distribution within the plant kingdom were the focal points of review and discussion. The paper also describes significant differences between synthetic aspirin and natural gaultherin in their biological potential and side effects, resulting from their different mechanisms of action. As a prodrug of salicylic acid, gaultherin releases salicylic acid gradually through enzymatic hydrolysis in the gastrointestinal tract. This controlled release minimises direct gastric irritation and accounts for its superior gastrointestinal safety profile compared to aspirin. Unlike aspirin, which irreversibly inhibits COX-1 and can lead to serious side effects with chronic use, gaultherin selectively inhibits COX-2 while sparing COX-1. These properties position gaultherin as a compelling natural alternative for patients requiring long-term anti-inflammatory therapy with reduced risk of gastrointestinal or bleeding complications. Full article
(This article belongs to the Special Issue The Role of Natural Products in Inflammation)
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25 pages, 6616 KB  
Article
Petasites japonicus Leaves Alleviate Depression in Dextran Sulfate Sodium-Induced Colitis Mice Through the BDNF/TrkB Pathway and Modulation of Inflammation
by Hwa Rang Na, Hyo Lim Lee, Hye Ji Choi, Yu Mi Heo, Yeong Hyeon Ju, Hyun-Jin Kim and Ho Jin Heo
Int. J. Mol. Sci. 2026, 27(7), 3274; https://doi.org/10.3390/ijms27073274 - 4 Apr 2026
Viewed by 449
Abstract
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder with a high incidence of anxiety and depression. However, the underlying mechanisms of these symptoms remain to be fully elucidated. This study investigated the effects and mechanisms of a 20% ethanolic extract of Petasites [...] Read more.
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder with a high incidence of anxiety and depression. However, the underlying mechanisms of these symptoms remain to be fully elucidated. This study investigated the effects and mechanisms of a 20% ethanolic extract of Petasites japonicus leaves (EPJ) on dextran sulfate sodium (DSS)-induced colitis and depression-like behaviors. The physiological compounds identified in the EPJ were citric acid, chlorogenic acid, caffeic acid, fukinolic acid, 3,5-dicaffeoylquinic acid, quercetin 3-O-β-D-glucose-6″-acetate, 4,5-dicaffeoylquinic acid, kaempferol-3-O-(6″-acetyl)-β-glucopyranoside, and pedunculoside. EPJ significantly alleviated DSS-induced colitis, as evidenced by improvements in body weight loss (87.41% vs. 76.02% in the DSS group), colon length (5.75 vs. 4.34 cm), intestinal permeability (52.80 vs. 163.01 μg/mL), and myeloperoxidase (MPO) activity (0.24 vs. 0.67 U/mg) (p < 0.05). Histological analysis further confirmed recovery of goblet cells and attenuation of muscle layer thickening. EPJ also reversed DSS-induced gut microbiota dysbiosis and contributed to the restoration of microbial homeostasis. Behavioral assessments showed that EPJ effectively ameliorated depression-like behaviors. EPJ improved antioxidant systems in colon and brain tissues by modulating malondialdehyde (MDA) levels and reduced glutathione (GSH) and superoxide dismutase (SOD) activity. EPJ further upregulated tight junction protein expression and suppressed TLR4/NF-κB inflammatory pathway activation in both colon and brain tissues. Moreover, EPJ modulated serum stress-related hormones, normalized hypothalamic–pituitary–adrenal (HPA) axis dysregulation, regulated the BDNF/TrkB signaling pathway, and modulated tryptophan–kynurenine metabolism. Collectively, these findings suggest that EPJ exerts protective effects against DSS-induced colitis and depression-like behaviors. Full article
(This article belongs to the Special Issue The Role of Natural Products in Inflammation)
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26 pages, 1500 KB  
Article
Curcumin Supplementation Reduces Inflammation, Neutrophil-to-Lymphocyte Ratio (NLR), and Antioxidant Status in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial
by Metha Yaikwawong, Khanittha Kamdee and Somlak Chuengsamarn
Int. J. Mol. Sci. 2026, 27(9), 3854; https://doi.org/10.3390/ijms27093854 - 27 Apr 2026
Viewed by 248
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion, and curcumin—a polyphenolic compound derived from Curcuma longa—has shown potential anti-inflammatory and antioxidant effects. This randomized, double-blind, placebo-controlled trial evaluated the effects of 1500 [...] Read more.
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion, and curcumin—a polyphenolic compound derived from Curcuma longa—has shown potential anti-inflammatory and antioxidant effects. This randomized, double-blind, placebo-controlled trial evaluated the effects of 1500 mg/day curcumin supplementation for 12 months in 114 adults with T2DM, with assessments including fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), insulin resistance (HOMA-IR), inflammatory cytokines (IL-6, IL-1β, TNF-α), high-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), antioxidant markers (SOD, GPx, TAS), and malondialdehyde (MDA). Curcumin supplementation was associated with significant reductions in pro-inflammatory cytokines (p < 0.001), hs-CRP and NLR (p < 0.05), and with improved antioxidant status as shown by increased TAS, SOD, and GPx together with reduced MDA levels (p < 0.001). Additionally, improvements in metabolic parameters were observed, including lower FPG (112.0 mg/dL vs. 134.5 mg/dL; p < 0.001), HbA1c (6.10% vs. 6.40%; p < 0.05), and HOMA-IR (4.88 vs. 6.71; p < 0.001). Overall, the findings suggest that long-term curcumin supplementation may contribute to improved inflammatory, antioxidant, and glycemic profiles in obese individuals with T2DM; however, further multi-center studies are needed to confirm these observations and clarify their clinical relevance. Full article
(This article belongs to the Special Issue The Role of Natural Products in Inflammation)
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