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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
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