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稳定的环腺苷酸单核苷酸类似物,二丁酰环腺苷酸单核苷酸(丁酰环腺苷酸),在急性皮肤炎症模型中具有活性。

The stable cyclic adenosine monophosphate analogue, dibutyryl cyclo-adenosine monophosphate (bucladesine), is active in a model of acute skin inflammation.

出版信息

Arch Dermatol Res. 2012 May;304(4):313-7. doi: 10.1007/s00403-012-1216-6.

Abstract

Anti-inflammatory therapeutic options for the topical treatment of skin diseases with inflammatory or allergic contribution are mostly limited to topical glucocorticoids and calcineurin inhibitors. Both compound classes induce adverse effects. Elevation of intracellular cyclic adenosine monophosphate (cAMP) by inhibition of phosphodiesterase 4 was shown to induce potent anti-inflammatory effects, but the safety profile of currently available compounds is not sufficient. A different approach to increase intracellular cAMP is the substitution of chemically stabilized cAMP analogues. Bucladesine is a stabilized cAMP analogue with an excellent safety profile which had been marketed as topical treatment of impaired wound healing. In the current study, a novel water free emulsion containing bucladesine was evaluated for anti-inflammatory effects. In the arachidonic acid induced ear oedema model in mice, single or multiple administration of an emulsion containing 1.5% was capable of significantly reducing the inflammatory oedema. The data indicate that bucladesine represents an interesting treatment option for skin diseases where an anti-inflammatory activity is indicated. Due to the established clinical safety, this agent may bridge the gap between potent agents such as glucocorticoids or calcineurin inhibitors and emollients without active compounds.

摘要

用于治疗具有炎症或过敏贡献的皮肤病的局部抗炎治疗选择大多限于局部糖皮质激素和钙调磷酸酶抑制剂。这两类化合物都有不良反应。通过抑制磷酸二酯酶 4 升高细胞内环腺苷单磷酸 (cAMP) 已显示出强大的抗炎作用,但目前可用化合物的安全性特征还不够。增加细胞内 cAMP 的另一种方法是用化学稳定的 cAMP 类似物替代。Bucladesine 是一种具有良好安全性的稳定 cAMP 类似物,曾被用作治疗受损伤口愈合的局部治疗药物。在本研究中,评估了一种含有 Bucladesine 的新型无水乳剂的抗炎作用。在小鼠的花生四烯酸诱导的耳部水肿模型中,单次或多次给予含有 1.5%Bucladesine 的乳剂能够显著减轻炎症性水肿。这些数据表明,Bucladesine 为具有抗炎活性的皮肤病提供了一种有趣的治疗选择。由于已确立的临床安全性,该药物可能在具有活性化合物的强效药物(如糖皮质激素或钙调磷酸酶抑制剂)和保湿剂之间架起桥梁。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f6d/3332354/aedb21070aca/403_2012_1216_Fig1_HTML.jpg

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