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Propolis is a natural resinous substance made by bees through mixing various plant sources. Propolis has been widely recognized as a functional food due to its diverse range of beneficial bioactivities. However, the therapeutic effects of consuming propolis against atopic dermatitis (AD) remain largely unknown. The current study aimed to investigate the potential efficacy of propolis against AD and explore the active compound as well as the direct molecular target. In HaCaT keratinocytes, propolis inhibited TNF-α-induced interleukin (IL)-6 and IL-8 secretion. It also led to a reduction in chemokines such as monocyte chemoattractant protein-1 (MCP-1) and macrophage-derived chemokine (MDC), while restoring the levels of barrier proteins, filaggrin and involucrin. Propolis exhibited similar effects in AD-like human skin, leading to the suppression of AD markers and the restoration of barrier proteins. In DNCB-induced mice, oral administration of propolis attenuated AD symptoms, improved barrier function, and reduced scratching frequency and transepidermal water loss (TEWL). In addition, propolis reversed the mRNA levels of AD-related markers in mouse dorsal skin. These effects were attributed to caffeic acid phenethyl ester (CAPE), the active compound identified by comparing major components of propolis. Mechanistic studies revealed that CAPE as well as propolis could directly and selectively target MKK4. Collectively, these findings demonstrate that propolis may be used as a functional food agent for the treatment of AD.

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Discovering new bioactivities and identifying active compounds of food materials are major fields of study in food science. However, the process commonly requires extensive experiments and can be technically challenging. In the current study, we employed network biology and cheminformatic approaches to predict new target diseases, active components, and related molecular mechanisms of propolis. Applying UHPLC-MS/MS analysis results of propolis to Context-Oriented Directed Associations (CODA) and Combination-Oriented Natural Product Database with Unified Terminology (COCONUT) systems indicated atopic dermatitis as a novel target disease. Experimental validation using cell- and human tissue-based models confirmed the therapeutic potential of propolis against atopic dermatitis. Moreover, we were able to find the major contributing compounds as well as their combinatorial effects responsible for the bioactivity of propolis. The CODA/COCONUT system also provided compound-associated genes explaining the underlying molecular mechanism of propolis. These results highlight the potential use of big data-driven network biological approaches to aid in analyzing the impact of food constituents at a systematic level.

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Propolis is a resinous substance generated by bees using materials from various plant sources. It has been known to exhibit diverse bioactivities including anti-oxidative, anti-microbial, anti-inflammatory, and anti-cancer effects. However, the direct molecular target of propolis and its therapeutic potential against skin aging in humans is not fully understood. Herein, we investigated the effect of propolis on ultraviolet (UV)-mediated skin aging and its underlying molecular mechanism. Propolis suppressed UV-induced matrix metalloproteinase (MMP)-1 production in human dermal fibroblasts. More importantly, propolis treatment reduced UV-induced MMP-1 expression and blocked collagen degradation in human skin tissues, suggesting that the anti-skin-aging activity of propolis can be recapitulated in clinically relevant conditions. While propolis treatment did not display any noticeable effects against extracellular signal-regulated kinase (ERK), p38, and c-jun N-terminal kinase (JNK) pathways, propolis exerted significant inhibitory activity specifically against phosphorylations of phosphoinositide-dependent protein kinase-1 (PDK1) and protein kinase B (Akt). Kinase assay results demonstrated that propolis can directly suppress phosphoinositide 3-kinase (PI3K) activity, with preferential selectivity towards PI3K with p110α and p110δ catalytic subunits over other kinases. The content of active compounds was quantified, and among the compounds identified from the propolis extract, caffeic acid phenethyl ester, quercetin, and apigenin were shown to attenuate PI3K activity. These results demonstrate that propolis shows anti-skin-aging effects through direct inhibition of PI3K activity.

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OBJECTIVE: Bee (Apis mellifera L.) venom (BV) has been used as a cosmetic ingredient owing to its anti-aging, anti-inflammatory, and antibacterial effects. The aim of this study was to assess the skin safety of BV. METHODS: For this purpose, skin phototoxicity and sensitization tests were conducted in healthy male Hartley guinea pigs. The animals were divided into three groups (n=5) for the phototoxicity test: G1 (negative control), G2 (BV gel treatment), and G3 (positive control). After specified treatments, the animals were irradiated with ultraviolet A (15 J/cm2 ). The photosensitivity test was also performed in three groups: G4 (negative control, n=5), G5 (BV gel treatment, n=10), and G6 (positive control, n=5). RESULTS: Erythema and edema were observed after 24, 48, and 72 hours in the positive control group, but not in the negative control and BV gel groups. Application of BV to the guinea pig skin had no toxic effects on any clinical signs, body weight, or mortality. In addition, it did not evoke a skin reaction in both either the skin phototoxicity and skin photosensitization tests. CONCLUSION: Therefore, it can be concluded that BV has the potential to be developed as a drug ingredient for topical uses.

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BACKGROUND: Propolis (or bee glue), collected from botanical sources by honey bee, has been used as a popular natural remedies in folk medicine throughout the world. This study was conducted to assess growth inhibitory effects of ethanol extracts of propolis (EEPs) from 20 different regions in South Korea on human intestinal bacteria as well as their human ß-amyloid precursor cleavage enzyme (BACE-1), acetylcholinesterase (AChE) inhibitory, antioxidant, antiproliferative, and anti-human rhinovirus activities. METHODS: The Bonferroni multiple-comparison method was used to test for significant differences in total polyphenol and flavonoid contents among EEP samples using SAS 9.13 program. Correlation coefficient (r) analysis of the biological activities of EEP samples was determined using their 50 % inhibition concentration or minimal inhibitory concentration values and their polyphenol or flavonoid contents in 20 native Korean EEP samples. RESULTS: The amounts of total polyphenol and flavonoids in the Korean EEP samples ranged from 49 to 239 mg gallic acid equivalent (GAE)/g EEP (Brazilian, Chinese, and Australian samples, 127-142 mg GAE/g EEP) and from 21 to 50 mg quercetin equivalent (QE)/g EEP (Brazilian, Chinese, and Australian samples, 33-53 mg QE/g EEP), respectively. Correlation coefficient analysis showed that total polyphenol contents may be negatively correlated with 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity (r = -0.872) and total flavonoid content has no correlation with the activity (r = 0.071). No direct correlation between BACE-1 inhibition, AChE inhibition, or antiproliferative activity and total polyphenol or total flavonoid content in Korean EEP samples was found. Gram-positive and Gram-negative bacteria were observed to have different degrees of antimicrobial susceptibility to the EEP samples examined, although ciprofloxacin susceptibility among the bacterial groups did not differ greatly. CONCLUSIONS: Further studies will warrant possible applications of propolis as potential therapeutic BACE-1 blocker, antioxidant, antiproliferative agent, and antimicrobial agent.

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Methicillin-resistant Staphylococcus aureus (MRSA), along with other antibiotic resistant bacteria, has become a significant social and clinical problem. There is thus an urgent need to develop naturally bioactive compounds as alternatives to the few antibiotics that remain effective. Here we assessed the in vitro activities of bee venom (BV), alone or in combination with ampicillin, penicillin, gentamicin or vancomycin, on growth of MRSA strains. The antimicrobial activity of BV against MRSA strains was investigated using minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC) and a time-kill assay. Expression of atl which encodes murein hydrolase, a peptidoglycan-degrading enzyme involved in cell separation, was measured by reverse transcription-polymerase chain reaction. The MICs of BV were 0.085 µg/mL and 0.11 µg/mL against MRSA CCARM 3366 and MRSA CCARM 3708, respectively. The MBC of BV against MRSA 3366 was 0.106 µg/mL and that against MRSA 3708 was 0.14 µg/mL. The bactericidal activity of BV corresponded to a decrease of at least 3 log CFU/g cells. The combination of BV with ampicillin or penicillin yielded an inhibitory concentration index ranging from 0.631 to 1.002, indicating a partial and indifferent synergistic effect. Compared to ampicillin or penicillin, both MRSA strains were more susceptible to the combination of BV with gentamicin or vancomycin. The expression of atl gene was increased in MRSA 3366 treated with BV. These results suggest that BV exhibited antibacterial activity and antibiotic-enhancing effects against MRSA strains. The atl gene was increased in MRSA exposed to BV, suggesting that cell division was interrupted. BV warrants further investigation as a natural antimicrobial agent and synergist of antibiotic activity.

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Facial wrinkles are an undesirable outcome caused by extrinsic photodamage and intrinsic aging processes. Currently, no effective strategies are known to prevent facial wrinkles. We assessed the beneficial effects of bee-venom serum on the clinical signs of aging skin. Our results show that bee-venom serum treatment clinically improved facial wrinkles by decreasing total wrinkle area, total wrinkle count, and average wrinkle depth. Therefore, bee-venom serum may be effective for the improvement of skin wrinkles.

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Royal jelly has been widely used as a health supplement worldwide. However, royal jelly has been implicated in allergic reactions, and we developed a water-soluble royal jelly (WSRJ) without the allergy inducing protein. In this study, we aimed to identify the anti-melanogenic efficacy of WSRJ. B16F1 melanoma cells were first treated with 10 nM α-melanocyte stimulating hormone (α-MSH) and then with various doses of WSRJ. In addition, we investigated the mRNA and protein expression of melanogenesis-related genes such as tyrosinase, tyrosinase related protein-1 (TRP-1) and TRP-2 by reverse transcription-polymerase chain reaction and western blotting. WSRJ directly inhibited tyrosinase and cellular tyrosinase activity, which decreased melanin synthesis in α-MSH stimulated B16F1 melanoma cells a level comparable to that observed with arbutin. WSRJ decreased the mRNA and protein expressions of tyrosinase, TRP-1, and TRP-2, which was comparable to that observed with arbutin. WSRJ has strong anti-melanogenic activity, which invoice direct inhibition of tyrosinase enzyme activity and suppression of expression of melanogenesis related genes. Results from this study suggests that WSRJ is a potential candidate for the treatment of skin pigmentation.

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This study was conducted to confirm the possible use of female Yangwonjam as a host for synnemata production of Isaria tenuipes in eight local areas in Korea. Silkworm pupation rate, infection rate and synnemata characteristics of I. tenuipes were examined. Normal silkworms had a higher pupation rate than silkworms inoculated with I. tenuipes. The pupae survival percentage of normal silkworm in cocoons was 92.5~97.6%, whereas it ranged from 91.1~95.6% in silkworms sprayed with I. tenuipes. Female Yangwonjam showed the highest survival percentage at 97.6% among the silkworm varieties tested. I. tenuipes infection rate of larvae of 5th instar newly-exuviated silkworms was 89.2~90.7% in the spring rearing season and 98.2~99.3% in the autumn rearing season. Synnemata production of I. tenuipes was excellent in female Yangwonjam with an incidence rate of 98.0% followed by male Yangwonjam (94.1%) and Baegokjam (93.3%) in the spring rearing season. Synnemata living weight ranged from 1.44~0.94 g in the spring rearing season. The female Yangwonjam had the heaviest synnemata weight (1.44 g) in the spring rearing season. The synnemata of I. tenuipes produced on pupae were white or milky-white in color, and were similar in shape and color to wild synnemata collected in Korea.

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Honey production from approximately 1.6 million colonies owned by about 199,000 Korean beekeepers was almost 23,000 metric tons in 2009. Nosema causes significant losses in honey production and the virus decreases population size. We initiated a survey of honey bee colonies on the blooming period of Acacia to determine the prevalence of Nosema and virus in 2011. Most Korean beekeepers have moved from the south to north of Korea to get Acacia nectar for 2 mon. This provided a valuable opportunity to sample bees originating from diverse areas in one location. Twenty hives owned by 18 beekeepers were sampled in this year. Nosema spore counts ranged from zero to 1,710,000 spores per bee. The average number of nosema spores per bee was 580,000. Approximately 95% of the colonies were infected with Nosema, based on the presence of spores in the flowering period of Acacia. This indicates that Nosema is the predominant species affecting honeybee colonies. Also, the seven most important honeybee viruses were investigated by reverse transcription-PCR. Among them, four different viruses were detected in samples. Black queen cell virus was present in all samples. Chronic bee paralysis virus was detected in 10% of samples. Deformed wing virus was present in only 5% of the samples. Prevalence of Sacbrood virus was 15%. However, Cloudy wing virus, Israel acute paralysis virus and kashmir bee virus were not detected in any of samples.

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Effects of methyl alcohol on the morphology and conformational characteristics of silk sericin (SS) were studied. Scanning electron microscope showed that morphology of SS lyophilized was dramatically changed from sponge-like structure to spherical fine particle type. X-ray diffraction method, infrared spectroscopy, and differential scanning calorimetry showed that the conformation of SS was random coil structure regardless of the addition of methyl alcohol. On the other hand, circular dichroism showed that the molecular states of SS were more densely packed.

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