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Microbes & Immunity Broad-spectrum health benefits of honey
Pichichero et al. investigated the effect of Acacia honey and content of phenolic acids tend to vary depending on
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in melanoma cells. After implementing the Acacia honey the source of the plant and the geographic location. The
treatment, proteins responsible for the regulation of the analysis of Becerril-Sánchez et al. pointed out that phenolic
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cell cycle such as cyclin D1, CDK4, cyclin B1, and CDK1, compound concentration is also related to the color of
which are key proteins for advancing the cell cycle the honey, and that there were significant differences in
properly, were reduced, and the downregulation resulted the phenolic compound content and antioxidant capacity
in cell cycle blockage and inability to enter S phase. of honey originating in different regions. A comparison
revealed that compared with Polish honey, Manuka honey
Tulang honey has demonstrated a positive inhibitory possesses higher levels of phenolic acids and flavonoids,
effect on human breast and cervical cancers by activating which contribute to its superior antioxidant properties.
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the caspase-3 and caspase-9 pathways to induce apoptosis. These findings highlight that the antioxidant properties of
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It also alters mitochondrial membrane potential, leading different honeys are primarily influenced by their phenolic
to the release of cytochrome c, which further activates and flavonoid content, which can vary significantly between
the caspase pathway. Similar to Acacia honey, Tualang species. It was found that the phenolic acid content of honey
honey can regulate the cell cycle, preventing cancer cells was positively correlated with oxidative activity. 95-97
from progressing into the S phase. By investigating the
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effects of Tualang honey on oral squamous cell carcinoma Silva et al. found that flavonoids in honey effectively
and osteosarcoma, Ghashm et al. found that the honey- inhibited COX and LOX, reducing the production
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treated cells experienced increased levels of oxidative stress, of inflammatory mediators, modulating the NF-κB
marked by an accumulation of reactive oxygen species that signaling pathway, and reducing the expression of
led to mitochondrial damage and membrane potential anti-inflammatory genes. Their in vitro experiments
abnormalities, which accelerated apoptotic cell death. demonstrated that different types of honey possess
natural anti-inflammatory agents due to the presence
3.6. Antioxidant activity of flavonoids, which excel in reducing oxidative stress
The body produces a number of active free radicals during and inhibiting cytokine release, but caution should be
normal oxidative processes, usually found in respiration exercised with regard to their safety.
and enzymatic reactions. The external environment can 3.7. Anti-inflammatory activity
also contribute to the formation of free radicals, such as
ultraviolet light exposure and exposure to heavy metal The anti-inflammatory activity of honey is achieved
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chemicals and air pollutants in the environment. The through a variety of mechanisms and active ingredients,
antioxidant activity in honey comes mainly from phenolic such as regulating cytokine release, inhibiting enzyme
compounds, 64,89-91 including phenolic acids (p-coumaric activity to reduce prostaglandin synthesis, scavenging
acid, ferulic acid, caffeic acid, chlorogenic acid) and free radicals to inhibit and reduce oxidative damage,
flavonoids (quercetin, kaempferol, and populin). These enhancing cytoprotection, and regulating the immune
compounds neutralize free radicals, reducing cell and system to enhance anti-inflammatory capacity. The anti-
tissue damage, reducing the incidence of chronic diseases, inflammatory activity of honey is also partly responsible for
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and boosting immunity. The structure of phenolic acids promoting wound healing. Phenolic acids and flavonoids
generally includes one or more phenolic hydroxyl groups in honey inhibit COX-1 and COX-2 activity and block
the NF-κB pathway, thereby reducing inflammation.
and an aromatic ring. Phenolic hydroxyl groups can Topical application of honey reduces swelling and
provide hydrogen atoms or electrons to neutralize free oozing, promotes new tissue growth, and accelerates
radicals, and chlorogenic acid can also chelate copper healing. Some studies have found that honey can inhibit
and iron ions, preventing these ions from continuing to the release of tumor necrosis factor-alpha (TNF-α) and
catalyze the production of more free radicals. Oxidative IL-6, and that its wound-healing-promoting effects
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stress generated by free radicals activates the nuclear factor are also linked to antimicrobial activities. As a natural
kappa B (NF-κB) pathway, stimulating cytokine release anti-inflammatory agent, honey shows potential in the
and inducing inflammation. Phenolic acid can inhibit treatment of chronic diseases, making it a class of natural
cyclooxygenase (COX) and lipoxygenase (LOX) enzymatic medicines worth investigating.
activities and reduce prostaglandin and leukotriene
synthesis, thus slowing down inflammatory responses. 93 3.8. Wound healing effects
The content of phenolic acids in honey is affected by Due to its antibacterial and anti-inflammatory properties
source, region, and season, which dictate the variations in and its hypertonic, low pH environment, honey forms
antioxidant activity. Adgaba et al. claimed that the type a barrier on the surface of broken skin, promoting
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Volume 2 Issue 2 (2025) 8 doi: 10.36922/mi.6592

