Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
Nakashima
Souichi
S
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Matsuda
Hisashi
H
Oda
Yoshimi
Y
Nakamura
Seikou
S
Xu
Fengming
F
Yoshikawa
Masayuki
M
D000363:Agaricales / Q000201:enzymology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019607:Brassicaceae / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D010936:Plant Extracts; D012333:RNA, Messenger; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase