Adenostemmoic acid B suppresses NO production by downregulating the expression and inhibiting the enzymatic activity of iNOS
Adenostemmoic acid B suppresses NO production by downregulating the expression and inhibiting the enzymatic activity of iNOS
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DOI：
10.1016/j.phytol.2022.03.024
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发表时间：
2022-06
影响因子：
1.7
通讯作者：
Takahiro Kobayashi;Norika Tanaka;Mayu Suzuki;Miwa Maeda;Irmanida Batubara;D. Iswantini;M. Koketsu;Akie Hamamoto;H. Takemori
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文献类型：
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作者：
Takahiro Kobayashi;Norika Tanaka;Mayu Suzuki;Miwa Maeda;Irmanida Batubara;D. Iswantini;M. Koketsu;Akie Hamamoto;H. Takemori
腺梗霉酸B（AB）是腺梗霉中的一种主要化合物，具有抗黑素生成、抗炎和细胞毒活性。通过修饰AB的第19位（羧基：参与避免细胞毒性），我们成功地分离了这些活性。羧基的短链烷基化增强了抗黑素生成活性，而长链烷基化（疏水）导致一氧化氮（NO）的产生和诱导型NO合酶（iNOS）的表达抑制，而不具有抗黑素生成活性。这些长链衍生物的亲水性的重新修饰恢复了抗黑素生成活性，但没有抑制NO的产生。出乎意料的是，AB和衍生物与酸酐键连接的长链是新的iNOS抑制剂。这些结果表明，AB调节多种生理活动，通过调节不同的目标，包括iNOS。
Adenostemmoic acid B (AB) is a major compound found inAdenostemma lavenia; it shows anti-melanogenic, anti-inflammatory, and cytotoxic activities. By modifying the 19th position (carboxy: involved in the avoidance of cytotoxicity) of AB, we succeed to separate these activities. Short-chain alkylation of the carboxy group enhanced anti-melanogenic activity, while long-chain alkylation (hydrophobic) resulted in the suppression of nitric oxide (NO) production and inducible NO synthase (iNOS) expression without anti-melanogenic activity. Re-modification of hydrophilic properties in these long-chain derivatives restored anti-melanogenic activity but did not suppress NO production. Unexpectedly, AB and derivatives with long chains linked by an anhydride bond were new iNOS inhibitors. These results suggest that AB modulates multiple physiological activities by regulating different targets, including iNOS.