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A new synthetic protectin D1 analog 3-oxa-PD1n-3 DPA reduces neuropathic pain and chronic itch in mice
Organic & Biomolecular Chemistry ( IF 2.9 ) Pub Date : 2021-3-2 , DOI: 10.1039/d0ob02136a Jannicke Irina Nesman 1 , Ouyang Chen , Xin Luo , Ru-Rong Ji , Charles N Serhan , Trond Vidar Hansen
Organic & Biomolecular Chemistry ( IF 2.9 ) Pub Date : 2021-3-2 , DOI: 10.1039/d0ob02136a Jannicke Irina Nesman 1 , Ouyang Chen , Xin Luo , Ru-Rong Ji , Charles N Serhan , Trond Vidar Hansen
Affiliation
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The resolution of inflammation is a biosynthetically active process controlled by the interplay between oxygenated polyunsaturated mediators and G-protein coupled receptor-signaling pathways. These enzymatically oxygenated polyunsaturated fatty acids belong to distinct families of specialized pro-resolving autacoids. The protectin family of mediators has attracted an interest because of their potent pro-resolving and anti-inflammatory actions verified in several in vivo disease models. Herein, we present the stereoselective synthesis and biological evaluations of 3-oxa-PD1n-3 DPA, a protectin D1 analog. Results from mouse models indicate that the mediators protectin D1, PD1n-3 DPA and the new analog 3-oxa-PD1n-3 DPA all relieved streptozotocin-induced diabetic neuropathic pain at doses of 90 and 300 pmol, equivalent to 30 and 100 ng, respectively, following intrathecal (I.T.) injection. Of interest, at a low dose of only 30 pmol (10 ng; I.T.) only 3-oxa PD1n-3 DPA was able to alleviate neuropathic pain, directly compared to vehicle controls. Moreover, using a chronic itch model of cutaneous T-cell lymphoma (CTCL), all three compounds at 300 pmol (100 ng) showed a significant reduction in itching for several hours. The biomolecular information on the structure-functions of the protectins and the new synthetic analog 3-oxa-PD1n-3 DPA is of interest towards developing new immunoresolvents.
中文翻译：
一种新的合成保护素 D1 类似物 3-oxa-PD1n-3 DPA 可减轻小鼠的神经性疼痛和慢性瘙痒
炎症的消退是一个生物合成活性过程，由含氧多不饱和介质和 G 蛋白偶联受体信号通路之间的相互作用控制。这些酶氧化多不饱和脂肪酸属于特殊的促分解自体酸的不同家族。保护素介质家族因其在多种体内疾病模型中得到验证的有效促消退和抗炎作用而引起了人们的兴趣。在此，我们介绍了保护素 D1 类似物3-oxa-PD1 n-3 DPA的立体选择性合成和生物学评价。小鼠模型的结果表明，保护素 D1、PD1 n-3 DPA和新类似物 3-oxa-PD1 n-3 DPA 介质在 90 和 300 pmol（相当于 30 和 100 pmol）剂量下均能缓解链脲佐菌素诱导的糖尿病神经性疼痛。鞘内（IT）注射后分别为ng。有趣的是，与载体对照直接相比，在仅 30 pmol（10 ng；IT）的低剂量下，仅 3-oxa PD1 n-3 DPA能够减轻神经性疼痛。此外，使用皮肤 T 细胞淋巴瘤 (CTCL) 的慢性瘙痒模型，所有三种化合物在 300 pmol (100 ng) 浓度下均显示出在数小时内显着减少瘙痒。有关保护素和新合成类似物 3-oxa-PD1 n-3 DPA结构功能的生物分子信息对于开发新的免疫溶剂很有意义。
更新日期：2021-03-09
中文翻译：
一种新的合成保护素 D1 类似物 3-oxa-PD1n-3 DPA 可减轻小鼠的神经性疼痛和慢性瘙痒
炎症的消退是一个生物合成活性过程，由含氧多不饱和介质和 G 蛋白偶联受体信号通路之间的相互作用控制。这些酶氧化多不饱和脂肪酸属于特殊的促分解自体酸的不同家族。保护素介质家族因其在多种体内疾病模型中得到验证的有效促消退和抗炎作用而引起了人们的兴趣。在此，我们介绍了保护素 D1 类似物3-oxa-PD1 n-3 DPA的立体选择性合成和生物学评价。小鼠模型的结果表明，保护素 D1、PD1 n-3 DPA和新类似物 3-oxa-PD1 n-3 DPA 介质在 90 和 300 pmol（相当于 30 和 100 pmol）剂量下均能缓解链脲佐菌素诱导的糖尿病神经性疼痛。鞘内（IT）注射后分别为ng。有趣的是，与载体对照直接相比，在仅 30 pmol（10 ng；IT）的低剂量下，仅 3-oxa PD1 n-3 DPA能够减轻神经性疼痛。此外，使用皮肤 T 细胞淋巴瘤 (CTCL) 的慢性瘙痒模型，所有三种化合物在 300 pmol (100 ng) 浓度下均显示出在数小时内显着减少瘙痒。有关保护素和新合成类似物 3-oxa-PD1 n-3 DPA结构功能的生物分子信息对于开发新的免疫溶剂很有意义。
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