Therapeutic Applications of Limonene in Inflammatory Diseases

Limonene, a cyclic monoterpene abundant in citrus essential oils, has attracted growing interest for its anti-inflammatory properties across diverse disease models. Preclinical studies demonstrate that limonene modulates key inflammatory mediators, including nuclear factor-κB and activator protein-1, leading to reduced levels of pro-inflammatory cytokines such as tumour necrosis factor-α, interleukin-1β and interleukin-6. In gastrointestinal models, oral administration of limonene preserves mucosal integrity and attenuates lipopolysaccharide-induced jejunal injury by activating antioxidant pathways through Nrf2. In respiratory and dermal systems, limonene-enriched essential oils inhibit prostaglandin E₂ and nitric oxide release from activated macrophages, offering potential in atopic dermatitis and airway inflammation. Mechanistic insights also reveal modulation of toll-like receptor signalling and mitigation of oxidative stress. The compound’s low toxicity, oral bioavailability and its incorporation into nanoformulations or encapsulated matrices enhance targeted delivery and sustained release. Collectively, these findings underscore limonene’s versatility as a natural therapeutic agent and support its translation into nutraceuticals, topical formulations and adjuvant interventions in chronic inflammatory disorders.

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Therapeutic Applications of Limonene in Inflammatory Diseases publication trend

The graph below shows the total number of articles in therapeutic applications of limonene in inflammatory diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Monoterpene: A class of terpenes consisting of two isoprene units; limonene is a cyclic monoterpene with anti-inflammatory and antioxidant activities.

Nuclear factor-κB (NF-κB): A transcription factor that regulates genes involved in inflammation and immune responses.

Activator protein-1 (AP-1): A transcription factor complex that controls expression of inflammatory cytokines and enzymes.

Toll-like receptor 4 (TLR4): A membrane receptor recognising bacterial lipopolysaccharide and initiating downstream inflammatory signalling.

Pro-inflammatory cytokines: Signalling proteins such as TNF-α, IL-1β and IL-6 that promote inflammation and recruit immune cells.

Nrf2 pathway: A cellular defence mechanism activating antioxidant genes to neutralise oxidative stress.

References

1. Protective Effect of Citrus Medica limonum Essential Oil against Escherichia coli K99-Induced Intestinal Barrier Injury in Mice. Nutrients (2023).
2. Limonene Exerts Anti-Inflammatory Effect on LPS-Induced Jejunal Injury in Mice by Inhibiting NF-κB/AP-1 Pathway. Biomolecules (2024).
3. Therapeutic Applications of Terpenes on Inflammatory Diseases. Frontiers in Pharmacology (2021).