Josamycin (EN-141) is a macrolide antibiotic exhibiting antimicrobial activity. The dissociation constant Kd from ribosome for Josamycin is 5.5 nM.

Ribosome:5.5 nM (Kd)

Josamycin 显著抑制了由 P. intermedia LPS 引发的 NO 产生以及 RAW264.7 细胞中 iNOS 蛋白和 mRNA 的诱导。同时，Josamycin 抑制了 LPS 刺激细胞释放 IL-1β，但未能减少 IL-1β mRNA 表达的程度。Josamycin 未能降低由 P. intermedia LPS 引发的 IL-1β mRNA 的稳定性，也未能抑制 LPS 引起的细胞内 IL-1β 表达。Josamycin 在 P. intermedia LPS 暴露的细胞中增强了 HO-1 的诱导，并且 HO-1 活性的抑制剂 SnPP 逆转了 Josamycin 对 LPS 引发的 NO 生成的抑制影响。Josamycin 减少了由 P. intermedia LPS 引起的 NF-κB 转录活性。此外，Josamycin 在 LPS 激活的细胞中提高了 SOCS1 mRNA 水平[1]。

Josamycin (0.1%) 通过局部给药的方式用于治疗通过2, 4, 6-三硝基氯苯（TNCB）诱导的具有AD样皮肤病变的NC/Nga小鼠。Josamycin的治疗效果通过测量皮肤严重程度得分、病变皮肤的组织学变化、血清中总IgE水平以及淋巴结和皮肤病变中的干扰素（IFN）-γ 和白细胞介素（IL）-4 的表达来评估[2]。

LPS was purified by employing phenol-water extraction protocol. Culture supernatants were analyzed for nitric oxide (NO) and interleukin (IL)-1β. Real-time PCR and immunoblotting were conducted to quantify mRNA and protein expression, respectively. The expression levels of IL-1β were analyzed by confocal laser scanning microscopy. NF-κB-dependent SEAP levels were estimated by reporter assay[1].

Topical treatment with josamycin significantly suppressed the increase in the skin severity score in NC/Nga mice. This suppressive effect was equal to that of betamethasone, and was associated with a decrease in the density of cellular infiltration into the dermis, the mast cell count in the dermis and the serum IgE level. Furthermore, topical application of josamycin reduced the expression of IFN-γ and IL-4 in auricular lymph node cells and the skin lesions[2].