Table 3.
In vitro studies on the therapeutic application of bee venom for skin disease.
| Disease | Model | Venom/Compound/(Bee Species) | Dose | Results | Mechanism/Molecular Response | Reference |
|---|---|---|---|---|---|---|
| Acne | THP-1 cell dealt with heat-killed P. acnes | BV (Apis melifera) | Three CONC: 0.1 µg/mL, 1 µg/mL, 5 µg/mL for 48 h |
Significant reduction of TNF-α, IL-8 in a concentration-dependent manner (p < 0.05). Lowest TNF-α at 5 µg/mL Lowest IL-8 at 1 µg/mL |
Not reported | [32] |
| Acne | THP-1 cell dealt with heat-killed P. acnes | BV (Apis melifera) | Three CONC: 1 ng/mL, 10 ng/mL, 100 ng/mL for 8 h |
Significant reduction of TNF-α, IL-8, IFN-γ at all doses compared to control (p < 0.05). Reduced in dose dependent manner. |
TLR2 expression significantly suppressed | [107] |
| Acne | THP-1 cell treated with heat-killed P. acnes | Melittin (Apis melifera) | Three CONC: 0.1 ng/mL, 0.5 ng/mL, 1 ng/mL. for 8 h |
Significant reduction of TNF-α, IL-8 at all doses compared to control (p < 0.05). Reduced in dose-dependent manner. |
Melittin significantly reduced the phosphorylation of IKK, IκB and NF- κB. Inhibiting the NF- κB signaling pathways. |
[107] |
| Acne | HaCat cell treated with heat-killed P. acnes | BV (Apis melifera) | Three CONC: 1 ng/mL, 10 ng/mL, 100 ng/mL for 8 h |
Significant reduction of TNF-α, IL-8, IFN-γ at 10, 100 ng/mL in comparison to control (p < 0.05). Reduced in dose-dependent manner. |
TLR2 expression significantly suppressed | [107] |
| Acne | HaCat cell dealt with heat-killed P. acnes | Melittin (Apis melifera) | 1 µg/mL | Significant reduction of TNF-α, IL-1β, IL-8, IFN-γ compared with control (p < 0.05). | TLR2 and 4 expression significantly decreased. Melittin significantly reduced the phosphorylation of IKK, IκB, NF- κB and p-38. Inhibiting the NF-κB and MAPK signaling pathways. |
[31] |
| Alopecia | hDPC treated with 0.1% dexamethasone | BV (Apis melifera) | Three CONC: 100 ng/mL, 200 ng/mL, 500 ng/mL for 24 h |
Significant increase of FGF-2, FGF-7, IGF-1R and VEGF compared with DEX only. (p < 0.001–p < 0.05). Protein-level of VEGF is increased 1.95-, 2.95-, 2.08 and 1.47-fold with 100, 200, 500 ng/mL BV and 2% minoxidil respectively. |
Not reported | [35] |
| Atopic dermatitis | Hacat cell treated with TNF-α and IFN-γ | Melittin (Apis melifera) | Three CONC: 0.1 µg/mL, 0.5 µg/mL, 1 µg/mL. |
IL-1β, IL-6 and IFN-γ were decreased in a dose-dependent manner. mRNA of CCL17 and CCL22 were significantly decreased in a dose-dependent manner in melitin 0.5 and 1 in comparison to control (p < 0.05). pJAK2, pSTAT1 and pSTAT3 expression was decreased in melittin 1 µg/mL |
NF- κB DNA-binding activity was markedly reduced. | [54] |
| Atopic dermatitis | Hacat cell treated by 50 ng/mL of IL-4 and IL-13 | Melittin (Apis melifera) | Three CONC: 0.1 µg/mL, 0.5 µg/mL, 1 µg/mL. for 24 h |
Filaggrin expression was remarkably elevated in a dose-dependent manner in all doses compared to control (p < 0.05) pSTAT3 expression was significantly decreased in melittin 1 µg/mL |
Not reported | [55] |
| Melanoma | Human melanoma A2058 cells | BV (Apis melifera) | 4 µg/mL | Application of 4 mg/mL BV for 2 h resulted in the death of approximately 80% of A2058 cells. | BV generated reactive oxygen species (ROS) and altered mitochondrial membrane potential transition. BV causes apoptosis in AIF/EndoG-dependent but caspase-independent manner. BV interfered with AKT and MAPK family kinase activation. BV treatment significantly reduced phosphorylated AKT and p38 BV made ER and extracellular Ca2+ drift to the cytosol. |
[60] |
| Photoaging | HDF cell irradiated by UVB (312 nm) | PLA2-free BV(PBV) and BV (Apis melifera) | PBV: 1.5 µg/mL, 3.0 µg/mL, BV 1.5 µg/mL, 3.0 µg/mL |
Both PBV and BV significantly restored Type 1 procollagen synthesis in UVB-irradiated HDF cells except for BV 3 μg/mL (p < 0.05). Type 1 collagen significantly increased in both BV, PBV compared with control (p < 0.05). (Degree: 3.0 BV > 1.5 BV > 3.0 PBV > 1.5 PBV) |
PBV and BV treatments significantly attenuated the MMP-1, 2 and 3 expressions (p < 0.05). Both PBV and BV significantly inhibited the UVB-stimulated phosphorylations of ERK1/2 and p38 (p < 0.05). |
[68] |
| Photoaging | Hacat cell irradiated by UVB (312 nm) | PLA2-free BV(PBV) and BV (Apis melifera) | PBV: 1.5 µg/mL, 3.0 µg/mL, BV: 1.5 µg/mL, 3.0 µg/mL. |
PBV and BV treatments significantly attenuated the MMP-1, 13 expressions (p < 0.05). Both PBV and BV significantly inhibited the UVB-stimulated phosphorylations of ERK1/2 and p38 (p < 0.05). |
[68] | |
| Photoaging | HDF cell irradiated by UVB (280–350 nm) | BV (Apis melifera) | Three CONC: 0.01 µg/mL, 0.1 µg/mL, 1 µg/mL for 24 h |
BV significantly decreased MMP-1 expressions by 50–80% while MMP-3 expression by 50–85% compared to controls (p < 0.05). The biggest MMP-1 and MMP-3 inhibitions were observed at a 0.1 µg/mL. |
Not reported | [67] |
| Vitiligo | Human epidermal melanocyte | BV (Apis melifera) | 10 µg/mL | Melanocyte proliferation and melanin content were remarkably increased compared to control (p < 0.05), similar to melanocyte treated with 10 µM forskolin but no more than. | Forskolin increased the cAMP level 40-fold, but BV only tripled. Based on this, the cAMP level does not appear to be the deciding factor | [89] |
Abbreviations: AIF: apoptosis-inducing factor, AKT: protein kinase B, cAMP: cyclic adenosine monophosphate, CONC: concentration, DEX: dexamethasone, EndoG: endonuclease G, ER: endoplasmic reticulum, ERK1/2: extracellular signal-regulated kinase 1 and 2, FGF: fibroblast growth factor, HaCat: human keratocyte, HDF: human dermal fibroblasts, hDPC: human dermal papilla cell, HEK: human epidermal keratinocyte, IGF-1R: insulin-like growth factor 1 receptor, MAPK: mitogen-activated protein kinase, P. acnes: Propionibacterium acnes, pJAK: phosphorylated janus kinases, pSTAT3: phosphorylated signal transducer and activator of transcription, TLR2: Toll-like receptor 2, UVB: ultraviolet, VEGF: vascular endothelial growth factor.