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.

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.

To combat influenza A virus (IAV) infection, it is vital to develop effective therapeutic strategies, including immunomodulators. In this study, we examined the antiviral effects of Hovenia dulcis Thunb. honey (HDH) against IAV using RAW 264.7 cells. HDH treatment significantly reduced IAV infection and viral protein expression. Moreover, it enhanced the production of interferon (IFN)-β, activated the innate immune response through the cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway, and upregulated IFN signaling through signal transducer and activator of transcription (STAT)1/2 phosphorylation and interferon-stimulated gene (ISG) expression. In addition, HDH decreased IAV-induced intracellular and mitochondrial reactive oxygen species (ROS) production by upregulating the expression of antioxidant proteins, such as Sirt3 and SOD2. The results suggest that HDH is a potential therapeutic agent inhibiting viral replication and boosting host antiviral immunity.

Climate warming increasingly threatens honey bee health, yet diet-associated molecular patterns under thermal stress remain poorly understood. In this study, newly emerged honey bees were fed eight dietary treatments, including natural diets (honey and bee bread) and artificial diets (sugar syrup and pollen substitute diets), for 5 days before exposure to acute heat stress (45 °C for 4 h). Transcriptional responses were quantified by quantitative real-time PCR (qRT-PCR) using genes associated with nutrient sensing, metabolism, immunity, and stress responses, and the resulting expression profiles were analyzed using principal component analysis, hierarchical clustering, and univariate statistical analyses. Distinct diet-associated transcriptional patterns were observed under both baseline and heat-stress conditions. Under baseline conditions, transcriptional variation was primarily associated with nutrient-sensing and metabolic pathways, whereas under heat-stress conditions, metabolic and stress-response pathways contributed more strongly to transcriptional variation. Sugar syrup-fed honey bees exhibited elevated expression of several immune-related genes following heat stress, suggesting greater physiological disturbance. In contrast, honey- and bee bread-based diets exhibited more coordinated regulation of nutrient-sensing and metabolic pathways and comparatively lower expression of selected immune-related genes. These findings demonstrate that dietary quality is associated with distinct molecular profiles under thermal stress and provide mechanistic insights into the relationship between nutrition and gene expression under heat-stress conditions, supporting the development of nutrition-based strategies for promoting honey bee health under climate warming.

Heat events and nutritional stress threaten honey bee health, but how pollen substitute formulation shapes responses to acute heat remains unclear. Newly emerged Apis mellifera workers received three pollen substitute diets or two beebread-based reference diets for five days before exposure to 45 °C for 4 h. Expression of 12 genes related to nutrition, endocrine regulation, immunity, oxidative defense, and cellular stress was examined using mixed-effects and multivariate analyses. Immune-derived predicted biological age was estimated before and after heat exposure. Apparent consumption and survival were evaluated in an independent 18-day feeding assay without heat. Significant diet × heat interactions occurred for 10 genes, whereas tor and dome showed no significant interactions. At baseline, Diet2(M) exhibited a transcriptional profile similar to the control and a lower predicted biological age than Diet1(S) and Diet3(O). Diet2(M) also supported higher survival than Diet1(S), despite similar apparent consumption among substitute diets. These findings indicate that pollen substitute composition, rather than apparent consumption alone, can shape physiology and survival. Diet2(M) is therefore a priority candidate for colony-level evaluation, although improved heat tolerance was not demonstrated. These findings may guide the development of supplemental feeds supporting honey bee health under climate-related pollen scarcity and heat risk.