Honey Phytochemicals: Bioactive Agents With Therapeutic Potential for Dermatological Disorders.

Honey has been reported to have a range of biological activities including antimicrobial, immunomodulatory, and wound healing effects. Indeed, medical-grade honey is currently used in hospitals for the clinical management of wound infections. Honey is also of scientific interest for its therapeutic effects on other dermatological disorders such as atopic dermatitis, rosacea, and skin cancer. Recent studies have uncovered that honey contains a range of phytochemicals including flavonoids, dicarboxylic acids, coumarins, and phenolic acids. In this review, PubMed was used to search the scientific literature on the biological properties of honey phytochemicals in relation to dermatological disorders and to evaluate their potential as bioactive agents, drugs, or cosmeceuticals for the treatment of skin disease. The review revealed that phytochemicals found in honey have antimicrobial, anti-inflammatory, antiaging, antioxidant, anticancer, depigmenting, photoprotective, wound healing, and skin barrier enhancing properties. Although further high-quality studies are required to establish clinical efficacy, these findings suggest that honey phytochemicals may have the potential to be used as bioactive agents for the management of a range of dermatological disorders including wounds, psoriasis, atopic dermatitis, vitiligo, rosacea, and skin cancer.

The effect of exposure to crude oil on the immune system. Health implications for people living near oil exploration activities.

People who reside near oil exploration activities may be exposed to toxins from gas flares or oil spills. The impact of such exposures on the human immune system has not been fully investigated. In this review, research investigating the effects of crude oil on the immune system is evaluated. The aim was to obtain a greater understanding of the possible immunological impact of living near oil exploration activities. In animals, the effect of exposure to crude oil on the immune system depends on the species, dose, exposure route, and type of oil. Important observations included; hematological changes resulting in anemia and alterations in white blood cell numbers, lymph node and splenic atrophy, genotoxicity in immune cells, modulation of cytokine gene expression and increased susceptibility to infectious diseases. In humans, there are reports that exposure to crude oil can increase the risk of developing certain types of cancer and cause immunomodulation.Abbreviations: A1AT: alpha-1 antitrypsin; ACH50: hemolytic activity of the alternative pathway; AHR: aryl hydrocarbon receptor; BALF: bronchoalveolar lavage fluid; COPD: chronic obstructive pulmonary disease; CYP: cytochrome P450; DNFB: 2, 4-dinitro-1-fluorobenzene; G-CSF: granulocyte-colony stimulating factor; IFN: interferon; IL: interleukin; 8-IP: 8-isoprostane; ISG15: interferon stimulated gene; LPO: lipid peroxidation; LTB4: leukotriene B4; M-CSF: macrophage-colony stimulating factor; MMC: melanomacrophage center; MPV: mean platelet volume; NK: natural killer; OSPM: oil sail particulate matter; PAH: polycyclic aromatic hydrocarbon; PBMC: peripheral blood mononuclear cell; PCV: packed cell volume; RBC: red blood cell; ROS: reactive oxygen species; RR: relative risk; TH: T helper; TNF: tumour necrosis factor; UV: ultraviolet; VNNV: Viral Nervous Necrosis Virus; WBC: white blood cell.

Knowledge, Attitudes, and Practices of Sun Exposure and Sun Protection among the Population of Kazakhstan: A Cross Sectional Study.

OBJECTIVE: The aims of this study were to assess knowledge, attitudes, and practices regarding sun exposure and sun protection among the population of Kazakhstan. METHOD: A cross sectional study was conducted by administering an online questionnaire via social networking sites to residents of Kazakhstan. The questionnaire was designed to determine demographic information as well as knowledge, attitudes and practices regarding sun exposure and sun protection. RESULT: The responses of 249 participants were analysed.  Descriptive tests, bivariate analyses, and multiple linear regression were used to statistically analyse the data. The mean age of the participants was 31.7 ± 11.5 (SD) years. Most participants were of Kazakh nationality (88.7%), female (71.0 %), urban residents (93.9 %), and possessed higher education degrees (88.0 %). The level of knowledge and attitudes were found to be moderate amongst the population whilst practices were determined to be low.  Knowledge (p=0.002), attitudes (p=0.002), female gender (p=0.002), and having children educated in school about sun safety (p=0.018) were significantly associated with improved sun-protective practices. CONCLUSION: This study has demonstrated low adoption of sun protective practices in the Kazakhstan population, despite the identification of certain characteristics associated with higher rates of practice.

Antimicrobial Effect of Honey Phenolic Compounds against E. coli-An In Vitro Study.

Growing concern over antimicrobial resistance in chronic wound patients necessitates the exploration of alternative treatments from natural sources. This study suggests that honey's phenolic compounds may offer antimicrobial benefits, warranting further investigation for therapeutic development. The main aim of this study was to investigate the antimicrobial activity of phenolic compounds and to determine the effects of their sub-inhibitory concentrations against Escherichia coli (E. coli). 3-phenyllactic acid (PLA), p-coumaric acid (PCA), and phloretin were tested against the bacterial strain of E. coli ATCC 25922. Comparison of the antimicrobial activity of honey constituents in vitro was performed using a broth culture assay. Measurement of the inhibitory properties of constituents in vitro was conducted using disc and well diffusion assays. The effects of sub-inhibitory concentrations of PCA on the susceptibility of E. coli ATCC 25922 to penicillin-streptomycin were tested. The results demonstrated that PLA was the most efficient antimicrobial agent, followed by PCA, whereas phloretin, at lower (2 mg/mL) concentrations, led to an increase in the growth of E. coli. Various modifications of the agar diffusion assay did not reveal the antibacterial properties of the studied phytochemicals. The enhancing effect of a sub-inhibitory concentration of PCA in cooperation with penicillin-streptomycin was shown. These findings might be helpful for the further investigation and development of new antimicrobial agents for the treatment of skin infections and wounds.

Total serum IgA levels and HLA-DQB1*02:01 allelic status.

Immunoglobulin A Deficiency (IgAD) is the most common primary immunodeficiency and is significantly associated with Celiac Disease (CD), which recognizes a specific background of human leukocyte antigens (HLA) predisposition (including HLA-DQB1*02:01 allele). A number of studies investigated the role of HLA in IgAD etiopathogenesis: HLA-DQB1*02 alleles are included in the main haplotypes linked to this primary immunodeficiency. In this preliminary study, we investigated the potential impact of HLA-DQB1*02:01 allelic status on total serum IgA levels: 108 serum samples from the bone marrow donors' registry were analyzed for total IgA concentration with respect to the HLA-DQB1*02:01 status. Although total serum IgA levels between HLA-DQB1*02:01 carriers and HLA-DQB1*02:01 negative donors were not different, we observed a statistically significant difference (p=0.0118) in total serum IgA levels among donors with low IgA concentration (<80mg/dL) in the sub-analysis between HLA-DQB1*02:01 positive group (including both homozygous and heterozygous carriers) compared to HLA-DQB1*02:01 negative donors. Our results might suggest a role of HLA-DQB1*02:01 allelic variant in the determination of total serum IgA levels, at least in patients affected with IgA deficiency and/or otherwise predisposed to it; however, larger and more standardized studies are needed to confirm this speculation.

Qualitative phytochemical analysis and in vitro investigation of the immunomodulatory properties of honeys produced in Kazakhstan.

Honey is known to have antimicrobial, immunomodulatory and wound healing properties. The biological properties of honey have been attributed to phytochemicals derived from their source plants and research has focused on identifying the bioactive phytochemicals with therapeutic potential. In this study, we determined the ability of 5 honeys from Kazakhstan and manuka honey to stimulate TNF-α and TGF-ß production by human keratinocytes. TNF-α and TGF-ß levels increased over time in honey treated and untreated keratinocytes, whereas cells treated with sugar solutions that matched those of the honeys had reduced levels of both cytokines. This suggests that the non-sugar phytochemical components of the honeys may have prevented this decrease. Analysis by LC-MS confirmed that the honeys contained a diverse range of phytochemicals. Some phytochemicals e.g. pinobanksin and vanillin were present at different levels across the honey types, whereas other components, e.g. dicarboxylic acids and their glycosides, were abundant in all honeys.

Identification of components in Kazakhstan honeys that correlate with antimicrobial activity against wound and skin infecting microorganisms.

BACKGROUND: Antimicrobial drug resistance is a major public health threat that can render infections including wound and skin infections untreatable. The discovery of new antimicrobials is critical. Approaches to discover novel antimicrobial therapies have included investigating the antimicrobial activity of natural sources such as honey. In this study, the anti-microbial activity and chemical composition of 12 honeys from Kazakhstan and medical grade manuka honey were investigated. METHODS: Agar well diffusion and broth culture assays were used to determine anti-microbial activity against a range of skin and wound infecting micro-organisms. Folin-Ciocalteu method was used to determine the total phenol content of the honeys and non-targeted liquid chromatography analysis was performed to identify components that correlated with antimicrobial activity. RESULTS: In the well diffusion assay, the most susceptible micro-organisms were a clinical isolate of Methicillin resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis (ATCC 19433). Buckwheat & multi-floral honey from Kazakhstan demonstrated the highest antimicrobial activity against these two micro-organisms. Kazakhstan honeys with a buckwheat floral source, and manuka honey had the highest total phenol content. Non-targeted liquid chromatography analysis identified components that correlated with anti-microbial activity as hydroxyphenyl acetic acid, p-coumaric acid, (1H)-quinolinone, and abscisic acid. CONCLUSIONS: The Kazakhstan honeys selected in this study demonstrated antimicrobial activity against wound and skin infecting micro-organisms. Compounds identified as correlating with antimicrobial activity could be considered as potential bioactive agents for the treatment of wound and skin infections.

Honey Combination Therapies for Skin and Wound Infections: A Systematic Review of the Literature.

Topical application of medical grade honey is recommended for the clinical management of wound infections. The suitability of honey as a wound healing agent is largely due to its antibacterial activity, immune modulatory properties, and biocompatibility. Despite the usefulness of honey in wound healing, chronic wound infections continue to be a global problem requiring new and improved therapeutic interventions. Several recent studies have investigated the effects of combining honey with other therapies or agents with the aim of finding more efficacious treatments. In this systematic review, the database PubMed was used to carry out a search of the scientific literature on the combined effects of honey and other therapies on antimicrobial activity and wound and skin healing. The search revealed that synergistic or additive antimicrobial effects were observed in vitro when honey was combined with antibiotics, bacteriophages, antimicrobial peptides, natural agents, eg, ginger or propolis and other treatment approaches such as the use of chitosan hydrogel. Outcomes depended on the type of honey, the combining agent or treatment and the microbial species or strain. Improved wound healing was also observed in vivo in mice when honey was combined with laser therapy or bacteriophage therapy. More clinical studies in humans are required to fully understand the effectiveness of honey combination therapies for the treatment of skin and wound infections.

The effect of chronic ultraviolet radiation on the human immune system.

A single or a limited number of UVR exposures is recognized to suppress cell-mediated immunity in human subjects. The complex pathway leading from the absorption of photons by chromophores in the skin to the generation of T regulatory cells has been, at least partially, elucidated. However, the effect of repeated UV exposures on immune responses and associated mediators is not well studied, particularly to assess whether they lead, first, to the development of photoprotection so that these immune changes are reduced or no longer occur, and, secondly, to the development of photoprotection against the normal downregulation of immunity induced by a high UV dose. For almost all the parameters evaluated in this review--epidermal DNA damage/erythema, urocanic acid, Langerhans and dendritic cells, natural killer cells, macrophages, mast cells, contact and delayed hypersensitivity responses--none, aside from epidermal DNA damage/erythema and macrophage phagocytic activity, show convincing evidence of photoadaptation or, where appropriate, photoprotection. It is concluded that repeatedly irradiating individuals with UVR is likely to continue to result in downregulation of immunity.

Non-Melanoma Skin Cancers at Sites of Previous Frostbite: Case Report and Review.

The association between ultraviolet radiation exposure and skin cancer is well established. Limited studies have reported an association between frostbite and the development of non-melanoma skin cancer but evidence for a proven link is insufficient and possible carcinogenic mechanisms have not been fully explored. In this report, 3 cases of non-melanoma skin cancer (1 case of basal cell carcinoma and 2 cases of squamous cell carcinoma of the skin) which developed at a site of previous frostbite caused by exposure to extremely cold temperatures in Astana, the capital city of Kazakhstan, are described.

The incidence and body site of skin cancers in the population groups of Astana, Kazakhstan.

BACKGROUND AND AIMS: Data on cutaneous malignant melanoma (CMM), squamous cell carcinoma of the skin (SCC), and basal cell carcinoma (BCC) in populations consisting of multi-racial groups in the Commonwealth of Independent States are limited. Here, the main aim was to analyse the incidence and body site of these cancers in the population groups of Astana, Kazakhstan (2007-2016). METHODS: Annual age standardised incidences and body sites of BCC, SCC, and CMM in Astana's population, divided into "Kazakhs and other Turkic/Asian" and "Russian and other European/Caucasian" groups, were calculated from histologically confirmed cases reported to Astana Oncology Centre. RESULTS: During the period January 2007 to October 2016, 647 skin cancers were diagnosed. The age and sex standardised incidence of BCC, SCC, and CMM increased significantly between 2007 to 2011 and 2012 to 2016. Higher incidences occurred in the Russian and other European/Caucasian group compared with the Kazakh and other Turkic/Asian group for the 3 skin cancers. BCC was the most common type of skin tumour, followed by SCC, and then CMM, in both population groups and sexes. The head/neck was the commonest site for BCC and SCC in all groups. For CMM, the most frequent site was the trunk in the Russian group and the head/neck in the Kazakh group. CONCLUSION: The incidence of skin tumours in Astana rose over the past 10 years. Differences in skin phototypes and sun exposure/ protection behaviours may account for the more frequent occurrence of skin tumours in the Russian population group compared with the Kazakh population group.

Honey: A realistic antimicrobial for disorders of the skin.

Resistance of pathogenic microorganisms to antibiotics is a serious global health concern. In this review, research investigating the antimicrobial properties of honeys from around the world against skin relevant microbes is evaluated. A plethora of in vitro studies have revealed that honeys from all over the world have potent microbicidal activity against dermatologically important microbes. Moreover, in vitro studies have shown that honey can reduce microbial pathogenicity as well as reverse antimicrobial resistance. Studies investigating the antimicrobial properties of honey in vivo have been more controversial. It is evident that innovative research is required to exploit the antimicrobial properties of honey for clinical use and to determine the efficacy of honey in the treatment of a range of skin disorders with a microbiological etiology.

Honey: A Therapeutic Agent for Disorders of the Skin.

Problems with conventional treatments for a range of dermatological disorders have led scientists to search for new compounds of therapeutic value. Efforts have included the evaluation of natural products such as honey. Manuka honey, for example, has been scientifically recognised for its anti-microbial and wound healing properties and is now used clinically as a topical treatment for wound infections. In this review, scientific evidence for the effectiveness of honey in the treatment of wounds and other skin conditions is evaluated. A plethora of in vitro studies have revealed that honeys from all over the world have potent antimicrobial activity against skin relevant microbes. Moreover, a number of in vitro studies suggest that honey is able to modulate the skin immune system. Clinical research has shown honey to be efficacious in promoting the healing of partial thickness burn wounds while its effectiveness in the treatment of non-burn acute wounds and chronic wounds is conflicted. Published research investigating the efficacy of honey in the treatment of other types of skin disorders is limited. Nevertheless, positive effects have been reported, for example, kanuka honey from New Zealand was shown to have therapeutic value in the treatment of rosacea. Anti-carcinogenic effects of honey have also been observed in vitro and in a murine model of melanoma. It can be concluded that honey is a biologically active and clinically interesting substance but more research is necessary for a comprehensive understanding of its medicinal value in dermatology.

An action spectrum for the production of cis-urocanic acid in human skin in vivo.

Urocanic acid (UCA) is present at millimolar concentrations in mammalian epidermis and undergoes photoisomerization from the naturally occurring trans-isomer to the cis-isomer on exposure to ultraviolet radiation (UVR). Cis-UCA causes downregulation of various immune responses in mouse and human experimental models and has been proposed as both a chromophore and a mediator of UV-induced immune suppression. In this study, the wavelength dependence from 260-340 nm for trans to cis-UCA photoisomerization in human skin was analyzed in five healthy volunteers. The resulting action spectrum demonstrated maximal cis-UCA production in the UVB spectral region of 280-310 nm. This spectral peak is red-shifted to longer wavelengths compared with the erythemal action spectrum. The cis-UCA action spectrum can be used to predict the ability of sunscreens to protect against UVR-induced cis-UCA formation and may assist in explaining discrepancies between sunscreens' abilities to protect against erythema and photoimmunosuppression.

Decrease in langerhans cells and increase in lymph node dendritic cells following chronic exposure of mice to suberythemal doses of solar simulated radiation.

Exposure of certain strains of mice to ultraviolet radiation (UVR) causes suppression of some innate and adaptive immune responses. One such consequence of acute UVB exposure is a reduction in the number of Langerhans cells (LC) in the epidermis and an increase in dendritic cells (DC) in lymph nodes draining the irradiated skin sites. Exposure to chronic UVB irradiation also has effects on the immune system, but it is unknown what effects are caused by repeated doses of solar simulated radiation (SSR). Consequently, the main aims of the present study were to determine whether repeated exposure to low doses of SSR would lead to similar changes in these cell populations and whether chronic doses of SSR activate a protective photoadaptation mechanism. Groups of C3H/HeN mice were irradiated daily with 3.7 J/cm(2) SSR from Cleo Natural lamps for 2, 10, 20, 30 or 60 days. Further groups of mice received an additional dose of 7.4 J/cm(2) SSR on days 2, 10, 30 or 60 to test for photoadaptation. The numbers of LC in the epidermis and DC in the lymph nodes draining irradiated skin sites were counted 24 h after the final irradiation. With the exception of mice irradiated for only 2 days, LC were significantly reduced throughout the chronic irradiation protocol, and no recovery occurred. DC numbers were significantly increased in the draining lymph nodes of mice irradiated for 20 days and 60 days.

Adaptation to the UV-induced suppression of phagocytic activity in murine peritoneal macrophages following chronic exposure to solar simulated radiation.

Exposure of certain strains of mice to ultraviolet radiation (UVR) is known to suppress both local and systemic immune responses, including a reduction in the phagocytic activity of peritoneal macrophages. However, in many instances, the immunological effects have been observed following a single or a limited number of doses of UVR from sources containing a higher proportion of UVB than that emitted by the sun. The first aim of the present study was to establish whether a single exposure of C3H/HeN mice to solar simulated radiation (SSR) suppressed the ability of the peritoneal macrophages to phagocytose opsonised sheep red blood cells. The mice were irradiated with SSR from Cleo Natural lamps and a single dose of 31.9 J cm(-2) was found to be the minimal dose for significant suppression of macrophage phagocytic activity. Such a dose did not modulate the surface expression of I-A(k), CD11b, CD86 or FcgammaRII/III (CD32/16) on the macrophages. The second aim was to assess whether repeated SSR exposures with a dose below the minimal immunosuppressive dose affected macrophage activity and, if so, to test for photoadaptation by repeated exposures followed by a single, normally immunosuppressive dose of SSR, and then assaying the macrophage activity. Groups of mice were irradiated on each of 2, 10 and 30 days with 14.9 J cm(-2) SSR, followed in some instances by a single additional exposure of 31.9 J cm(-2) on the same day as the last irradiation. The phagocytic activity of the peritoneal macrophages was tested 24 h later. It was reduced by 32%, 18% and 4% respectively after 2, 10 and 30 repeated exposures to SSR, and by 39%, 21% and 7% respectively after 2, 10 and 30 repeated exposures plus the additional higher dose at the end. Thus, although the macrophage activity was initially suppressed by the SSR, photoadaptation of this immune parameter occurred following repeated exposures.