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Cholestatic liver disease is characterized by the progressive destruction of biliary epithelial cells (BECs) followed by fibrosis, cirrhosis and liver failure. Activated hepatic stellate cells (HSCs) and portal fibroblasts are the major cellular effectors of enhanced collagen deposition in biliary fibrosis. Apamin, an 18 amino acid peptide neurotoxin found in apitoxin (bee venom), is known to block Ca2+-activated K+ channels and prevent carbon tetrachloride-induced liver fibrosis. In the present study, we aimed to ascertain whether apamin inhibits biliary fibrosis and the proliferation of HSCs. Cholestatic liver fibrosis was established in mouse models with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding. Cellular assays were performed on HSC-T6 cells (rat immortalized HSCs). DDC feeding led to increased hepatic damage and proinflammtory cytokine levels. Notably, apamin treatment resulted in decreased liver injury and proinflammatory cytokine levels. Moreover, apamin suppressed the deposition of collagen, proliferation of BECs and expression of fibrogenic genes in the DDC-fed mice. In HSCs, apamin suppressed activation of HSCs by inhibiting the Smad signaling pathway. These data suggest that apamin may be a potential therapeutic target in cholestatic liver disease.

Propionibacterium acnes (P. acnes) is a major contributing factor to the inflammatory component of acne. The many prescription medications for acne allow for a large number of potential combination treatments. However, several antibiotics, apart from their antibacterial effects, exert side‑effects, such as the suppression of host inflammatory responses. Purified bee venom (BV) is a natural toxin produced by honeybees (Apis mellifera L.). BV has been widely used as a traditional medicine for various diseases. In the present study, to investigate the therapeutic effects of BV against P. acnes-induced inflammatory skin disease, P. acnes was intradermally injected into the ears of mice. After the injection, BV was applied to the skin surface of the right ear. Histological observation revealed that P. acnes induced a considerable increase in the number of infiltrated inflammatory cells. However, treatment with BV markedly reduced these reactions compared with the P. acnes-injected mice not treated with BV. Moreover, the expression levels of tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were significantly reduced in the BV-treated mice compared with the untreated P. acnes-injected mice. In addition, treatment with BV significantly inhibited Toll-like receptor (TLR)2 and CD14 expression in P. acnes-injected tissue. The binding activity of nuclear factor-κB (NF-κB) and activator protein (AP)-1 was markedly suppressed following treatment with BV. The results from our study, using an animal model, indicate that BV exerts an inhibitory effect on inflammatory skin diseases. In conclusion, our data indicate that BV has potential for use as an anti-acne agent and may be useful in the pharmaceutical and cosmetics industries.

Propionibacterium acnes (P. acnes) cause inflammatory acne and play an important role in the pathogenesis of acne by inducing inflammatory mediators. P. acnes contributes to the inflammatory responses of acne by activating inflammatory cells, keratinocytes and sebocytes to secrete pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-8. Bee venom has traditionally been used in the treatment of certain immune-related diseases. However, there has not yet been a robust trial to prove the therapeutic effect of bee venom in skin inflammation. The aim of the present study was to investigate anti-inflammatory properties of bee venom in skin inflammation induced by P. acnes using keratinocytes (HaCaT) and monocytes (THP-1). P. acnes is known to stimulate the production of pro-inflammatory cytokines such as IL-1, IL-8, IL-12 and TNF-α. In the present study, the production of interferon-γ (IFN-γ), IL-1β, IL-8 and TNF-α was increased by P. acnes treatment in HaCaT and THP-1 cells. By contrast, bee venom effectively inhibited the secretion of IFN-γ, IL-1β, IL-8 and TNF-α. Furthermore, P. acnes treatment activated the expression of IL-8 and toll-like receptor 2 (TLR2) in HaCaT cells. However, bee venom inhibited the expression of IL-8 and TLR2 in heat-killed P. acnes. Based on these results, it is concluded that bee venom has an effective anti-inflammatory activity against P. acnes in HaCaT and THP-1 cells. Therefore, we suggest that bee venom is an alternative treatment to antibiotic therapy of acne.