Novel isonahocol E-3 exhibits anti-inflammatory and anti-angiogenic effects in endothelin-1-stimulated human keratinocytes

作者：Sah Shyam Kishor; Kim Byung Hak; Park Geon Tae; Kim Sunghwan; Jang Kyoung Hwa; Jeon Ju Eun; Shin Jongheon; Kim Tae Yoon^*

来源：European Journal of Pharmacology, 2013, 720(1-3): 205-211.

DOI：10.1016/j.ejphar.2013.09.077

• Isonahocol E-3
• Inflammation
• Angiogenesis
• Endothelin-1 antagonist

Endothelin-1 (ET-1) is reported to be a potent mitogenic and pro-angiogenic factor that plays a vital role in both physiological and pathological processes. ET-1 is implicated in dermal cell proliferation and skin disorders, such as psoriasis and atopic dermatitis. ET 1, endothelin ETA receptor, and endothelin ETB receptor could be potential targets for developing specific therapeutics to treat such disorders. Here, we provide the first report that an isonahocol [2,-5-dihydroxy-3-(13-hydroxy 3, 7, 11, 15 tetramethyl-12-oxo hexadeca 2, 6, 14 trienyl)-phenyl]-acetic acid methyl ester (isonahocol E-3) from the brown algae Surgussum siliquastrum has functional antagonistic activities against ET-1 induced inflammatory and proangiogenic effects. Isonahocol E-3 significantly inhibited ET-1-induced cell proliferation, as well as inflammatory mediators, such as interleukin-6 (IL-6) and interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha), and pro-angiogenic factors including metalloproteinases in immortalized human keratinocytes. We also found that isonahocol E-3 reduced expression level of endothelin ETA receptor, and endothelin ETB receptor as well as suppressed ET-1-induced extracellular signal regulated kinase (ERK) phosphorylation. Taken together, our results suggest that isonahocol E-3 can exert anti-inflammatory and anti-angiogenic activities at least by regulating the expression of ET-1 receptors and ERK signaling pathway.

• 出版日期2013-11-15
• 单位河北医科大学