Novel isonahocol E(3) exhibits anti-inflammatory and anti-angiogenic effects in endothelin-1-stimulated human keratinocytes.
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 ET(A) receptor, and endothelin ET(B) receptor could be potential targets for developing specific therapeutics to treat such disorders. Here, we provide the first report that an isonahocol [2,-5-hihydroxy-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 Sargassum 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-α (TNF-α), and pro-angiogenic factors including metalloproteinases in immortalized human keratinocytes. We also found that isonahocol E(3) reduced expression level of endothelin ET(A) receptor, and endothelin ET(B) receptor as well as suppressed ET-1 induced extracellular signal-regulated kinase (ERK) phosporylation. 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.
Shyam Kishor
SK
Sah
Byung-Hak
BH
Kim
Geon-Tae
GT
Park
Sunghwam
S
Kim
Kyoung Hwa
KH
Jang
Ju Eun
JE
Jeon
Jongheon
J
Shin
Tae-Yoon
TY
Kim
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010648:Phenylacetates / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D019332:Endothelin-1; D010648:Phenylacetates; C000590652:isonahocol E(3); D048049:Extracellular Signal-Regulated MAP Kinases; D020782:Matrix Metalloproteinases