The Anti‑Inflammatory Effects of Honey

Inflammation is a defensive response of the body to injury or infection, but persistent chronic inflammation is closely associated with the development of several major diseases. In recent years, honey, as a natural food product, has attracted widespread attention for its anti-inflammatory activity. Based on existing literature, this article systematically reviews the evidence for the anti-inflammatory effects of honey from three perspectives: cellular studies, animal experiments, and clinical research. It also explores the potential active components and mechanisms of action.

1. Cellular studies: regulation of immune cell inflammatory responses by honey

1.1 Inhibition of macrophage activation and release of inflammatory mediators

Macrophages play a central role in the inflammatory response, and their over-activation can lead to excessive release of pro-inflammatory cytokines. Chen et al. (2022) showed that honey extracts exhibit good anti-inflammatory activity in vitro. At a concentration of 90 μg/L, honey extract effectively alleviated lipopolysaccharide (LPS)-induced inflammatory responses in macrophages, as demonstrated by:

• Inhibition of pro-inflammatory cytokine release;
• Activation of anti-inflammatory factor secretion;
• Reduced activation of inflammatory signalling pathways.

1.2 Protection of intestinal epithelial cells against inflammation and barrier dysfunction

Intestinal epithelial cells are the first line of defence against intestinal inflammation. Wang (2022) established an LPS-induced Caco-2 cell model to explore the anti-inflammatory activity of honey and its characteristic markers, as well as its protective effects on intestinal epithelial cells. The results showed that honey and three characteristic components -kynurenic acid, methyl indole-3-acetate, and 3-amino-2-naphthoic acid – exerted intestinal anti-inflammatory effects through the following mechanisms:

• downregulation of pro-inflammatory gene expression;
• upregulation of tight junction protein-related gene expression, thereby enhancing intestinal barrier function;
• upregulation of antioxidant-related gene expression.

2. Animal studies: effects of honey in various models of inflammation

2.1 Digestive system inflammation

AL MASAUDI et al. (2017) and SAAD et al. (2017) evaluated the anti-inflammatory effects of honey using an acetic acid-induced chronic gastric ulcer model. The results showed that honey (0.625–2.5 g/kg) significantly reduced gastric mucosal myeloperoxidase (MPO) activity and inflammatory cytokine concentrations.

2.2 Systemic chronic inflammation

In a rat model of LPS-induced chronic subclinical systemic inflammation, YAZAN et al. (2019) found that honey treatment reduced the expression of nuclear factor-κB (NF-κB) – a key transcription factor in the inflammatory response – in liver, kidney, heart, and lung tissues. Honey also improved the histological structure and functional parameters of these organs.

2.3 Metabolic inflammation and non-alcoholic steatohepatitis

Studies by XIAO J et al. (2016) and KALANTARI N et al. (2016) showed that oral administration of honey in rats ameliorated high-fat diet-induced non-alcoholic steatohepatitis by inhibiting the TXNIP-NLRP3 inflammasome pathway. MONICA et al. (2019) reported that continuous honey intake for four months maintained insulin sensitivity in rats, increased adiponectin and peroxisome proliferator-activated receptor-γ (PPARγ) levels, and reduced Toll-like receptor 4 (TLR4)-mediated inflammatory status, suggesting a protective effect of honey on adipocyte function.

2.4 Nephrotoxic injury

RANIA et al. (2015) demonstrated that oral administration of honey in mice effectively prevented cisplatin-induced nephrotoxicity (cisplatin is an anti-cancer chemotherapeutic agent) through inhibition of inflammatory responses.

3. Clinical studies: effects of honey intervention in patients with inflammatory diseases

3.1 Chemo-/radiotherapy-induced oral mucositis

Oral mucositis is a common toxicity following chemotherapy and radiotherapy, severely affecting patients' quality of life and treatment adherence. Yang C. et al. (2018) systematically evaluated the efficacy of honey in cancer patients with chemo-/radiotherapy-induced oral mucositis and concluded that adjuvant application of pure natural topical honey is effective and safe, and can be used as a first-line adjuvant therapy to alleviate oral mucositis.

3.2 Chronic gastric ulcer

ZHAO H et al. (2019) found that phenolic components in honey increased levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), nitric oxide (NO), and MPO in patients, while reducing concentrations of inflammatory cytokines in colon tissue, including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). BATTINO et al. (2021) also confirmed that honey exerts systemic anti-inflammatory effects by modulating pro-inflammatory factors, C-reactive protein (CRP), and anti-inflammatory factors.

4. Active components: phenolic compounds in honey with anti-inflammatory potential

Honey is rich in flavonoids and polyphenols, which are considered important material bases for its anti-inflammatory activity. Several individual components have been tested for anti-inflammatory activity, as summarised below:

In addition, VANDAMME et al. (2013) and YAZAN et al. (2019) systematically evaluated the overall anti-inflammatory properties of honey using carrageenan-induced and LPS-induced inflammation models, respectively, both with positive results.

It should be noted that despite these advances, the specific active components responsible for honey's anti-inflammatory effects and their complete molecular mechanisms have not yet been fully elucidated. Honey is a complex system containing hundreds of components, and its anti-inflammatory effect likely results from the synergistic action of multiple constituents. Factors such as floral source, geographical origin, and processing method may all influence the activity profile of honey.

5. Antimicrobial and tissue repair effects: synergistic mechanisms underlying honey's anti-inflammatory action

Inflammation is often closely associated with infection by pathogenic microorganisms. Honey exhibits broad-spectrum antimicrobial activity and can reduce inflammation at its source by inhibiting the overgrowth and proliferation of pathogenic bacteria. Based on this property, honey has important applications in wound treatment:

• Burn wounds: Topical application of honey effectively reduces wound inflammation, and its moisture-retentive properties help create a moist healing microenvironment, promote granulation tissue formation, and accelerate wound healing (Zhang et al., 2021).
• Oral and sinus inflammation: Honey also shows adjunctive therapeutic effects in oral inflammation and chronic sinusitis.
• Digestive tract inflammation and gut microbiota: Honey alleviates digestive tract inflammation while improving gut microbiota composition. Studies have shown that honey improves intestinal absorption and gut microbiota composition in premature infants (Zhu et al., 2025).

Conclusion

Synthesising the available research evidence, the value of honey in the field of anti-inflammation is supported at multiple levels – from cellular studies and animal experiments to clinical practice. The core mechanisms underlying honey's anti-inflammatory effect can be summarised as follows: (1) inhibition of pro-inflammatory cytokine (e.g., IL-6, TNF-α) release, together with activation of anti-inflammatory factor expression; (2) interference with the activation of key inflammatory signalling pathways such as NF-κB and NLRP3; (3) enhancement of antioxidant enzyme activity and strengthening of the intestinal epithelial barrier; and (4) reduction of infection-induced inflammation at the source through synergistic antimicrobial action.

It is worth noting that although the anti-inflammatory efficacy of honey has been demonstrated in many studies, the specific active components and the precise molecular mechanisms involved have not yet been fully resolved. As a natural complex system containing hundreds of chemical constituents, the anti-inflammatory effect of honey is likely attributable to the synergistic action of multiple flavonoids, phenolic acids, and other minor substances, rather than to a single component. Furthermore, factors such as floral origin, geographical source, processing method, and storage conditions may all influence the final biological activity of honey.

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