title: Piperlonguminine from Piper longum with inhibitory effects on alpha-melanocyte-stimulating hormone-induced melanogenesis in melanoma B16 cells.
abstract: Skin hyperpigmentations such as melasma, freckles and senile lentigines can be subjectively treated by depigmenting agents. In our ongoing study to find melanogenesis inhibitors from natural sources, Piper longum L (fruits, Piperaceae) was discovered to have an inhibitory effect on alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanogenesis in melanoma B16 cells. Piperlonguminine has been identified as the melanogenesis inhibitor from P. longum by activity-guided extraction and isolation. The compound showed dose-dependent inhibitory effects with 85.1 +/- 4.9% inhibition at 25 microM, 62.1 +/- 6.1% at 12.5 microM, 36.4 +/- 4.6% at 6.3 microM and 18.4 +/- 5.1% at 3.1 microM on alpha-MSH-induced melanogenesis, showing an IC50 value of 9.6 microM. As a positive control, kojic acid exhibited an IC50 value of 44.6 microM on the melanogenesis. As to the mode of action, piperlonguminine showed an inhibitory effect on alpha-MSH-induced tyrosinase synthesis, documented by Western immunoblot analysis. However, piperlonguminine did not show an inhibitory effect on tyrosinase activity or a direct depigmenting effect of melanin.
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Chenogju, Korea.
authors.forename: Kyung Rak
authors.initials: KR
authors.lastname: Min
authors.forename: Kyeong-Soo
authors.initials: KS
authors.lastname: Kim
authors.forename: Jai Seup
authors.initials: JS
authors.lastname: Ro
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Jeong Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Jong Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects; D004148:Dioxolanes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005638:Fruit; D008543:Melanins / Q000096:biosynthesis; D051379:Mice; D014442:Monophenol Monooxygenase / Q000096:biosynthesis; D008517:Phytotherapy; D010859:Pigmentation Disorders / Q000188:drug therapy; D031701:Piper; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000521:alpha-MSH / Q000037:antagonists & inhibitors* / Q000187:drug effects*; D010881:Piperidones
chemical_list: D004148:Dioxolanes; D008543:Melanins; D014442:Monophenol Monooxygenase; D010936:Plant Extracts; D000521:alpha-MSH; C498077:piperlongumine; D010881:Piperidones