D-limonene exhibits anti-inflammatory and antioxidant properties in an ulcerative colitis rat model via regulation of iNOS, COX-2, PGE2 and ERK signaling pathways Original paper
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Dr. Umar
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Dr. Umar
Read MoreClinical Pharmacist and Clinical Pharmacy Master’s candidate focused on antibiotic stewardship, AI-driven pharmacy practice, and research that strengthens safe and effective medication use. Experience spans digital health research with Bloomsbury Health (London), pharmacovigilance in patient support programs, and behavioral approaches to mental health care. Published work includes studies on antibiotic use and awareness, AI applications in medicine, postpartum depression management, and patient safety reporting. Developer of an AI-based clinical decision support system designed to enhance antimicrobial stewardship and optimize therapeutic outcomes.
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Dr. Umar
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Researched by:
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Dr. Umar
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Dr. Umar
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Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Dr. Umar
What was studied?
This study tested whether D-limonene ulcerative colitis microbiome–relevant anti-inflammatory mechanisms could lessen disease severity in a dextran sulfate sodium (DSS)–induced ulcerative colitis (UC) rat model. Male Sprague–Dawley rats were assigned to control, DSS-UC (untreated), or DSS-UC treated with oral D-limonene at 50 or 100 mg/kg daily for 7 days. The investigators focused on clinical disease activity and colonic mucosal injury, then quantified inflammatory signaling (NF-κB p65, TNF-α, IL-1β, IL-6), oxidative stress defenses (SOD, GSH), tissue remodeling enzymes (MMP-2, MMP-9), and key inflammatory mediators/pathways (iNOS, COX-2, PGE2, TGF-β, and phosphorylated ERK1/2).
Who was studied?
Thirty-two healthy male Sprague–Dawley rats (8–10 weeks old, 220–300 g) were housed under controlled conditions and randomized into four groups (n=8/group): normal control, DSS-induced UC model, and two treatment groups receiving D-limonene (50 or 100 mg/kg). UC was induced with 2% DSS for 7 days, after which D-limonene was delivered by gastric gavage for 7 days (with controls receiving saline). Outcomes were assessed using daily disease activity measures and post-sacrifice colon scoring plus molecular assays from serum and colonic mucosa.
Most important findings
DSS-induced UC markedly worsened disease activity and colonic mucosal damage, and D-limonene significantly improved both indices at 50 and 100 mg/kg. Mechanistically, D-limonene reduced systemic inflammatory signaling—lowering NF-κB p65, TNF-α, IL-1β, and IL-6—while restoring antioxidant capacity (increased SOD and GSH). It also downregulated mucosal MMP-2 and MMP-9 mRNA, suggesting reduced extracellular matrix degradation and ulcer propagation. Crucially for inflammatory mediator biology, D-limonene decreased iNOS and COX-2 protein expression and reduced PGE2 production, while also lowering TGF-β mRNA and increasing phosphorylated ERK1/2. These effects collectively map onto pathways often influenced by microbial products (eg, LPS-driven NF-κB/COX-2/PGE2 signaling), making the findings directionally relevant to microbiome-host interaction models even though no microbiome sequencing or taxa-level associations were measured.
| Microbiome-signature-relevant feature | Direction with D-limonene in DSS-UC rats |
|---|---|
| Host inflammatory tone (NF-κB, TNF-α, IL-1β, IL-6) | Decreased |
| Oxidative stress defenses (SOD, GSH) | Increased |
| Barrier/tissue remodeling enzymes (MMP-2, MMP-9) | Decreased |
| Eicosanoid/inflammatory mediator axis (COX-2, PGE2; iNOS) | Decreased |
Key implications
Clinically, this work supports D-limonene as a candidate anti-inflammatory/antioxidant adjunct for colitis, with consistent improvement in macroscopic disease indices and broad suppression of canonical inflammatory mediators. For microbiome-focused clinicians and database builders, the key limitation is that host pathways were measured without microbial composition, metabolites, or functional readouts; therefore, no microbial signatures can be cataloged. However, the pattern—NF-κB/COX-2/PGE2/iNOS suppression plus improved redox balance—provides a mechanistic hypothesis: D-limonene may reduce inflammation commonly amplified by dysbiosis-associated microbial signals, and future translational studies should pair these endpoints with 16S/metagenomics and metabolomics to identify taxa and metabolite shifts linked to response.
Citation
Yu L, Yan J, Sun Z. D-limonene exhibits anti-inflammatory and antioxidant properties in an ulcerative colitis rat model via regulation of iNOS, COX-2, PGE2 and ERK signaling pathways.Molecular Medicine Reports. 2017;15:2339-2346. doi:10.3892/mmr.2017.6241