Piperlonguminine fromPiper longumwith 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.

Melanogenesis Stimulation in Murine B16 Melanoma Cells by Kava (Piper methysticum) Rhizome Extract and Kavalactones

“…This result may be in accordance with the report by Min et al 13) in which they described that an alkaloid amide, piperlonguminine isolated from roots and fruits of P. longum, showed an inhibitory effect on alphamelanocyte-stimulating hormone (a-MSH)-induced melanogenesis in B16 melanoma cells. Four extracts of several parts of P. kadsura showed no effect on both melanogenesis and cell proliferation at concentration of 10 mg/ml.…”

“…F from acetone afforded daucosterin [3-(b-D-glucopyranosyl)stigmasterol] 10) [6, mp 280-283°C (dec.), Rf 0.07, 66 mg]. Acetylation of 6 (10 mg) by the usual way gave a tetraacetyldaucosterin (mp 167-168°C, 11 mg) which was identified by direct comparison ( 1 H-, 13 C-NMR, and a mixed fusion) with an authentic sample.…”

Methylpiperate derivatives from Piper longum and their inhibition of monoamine oxidase

“…There have been many pharmacological reports of the activities of extracts or constituents from the fruits of P. longum such as hepatoprotective activity (Koul and Kapil, 1993), melanogenesis inhibitory effects (Min et al, 2004;Kim et al, 2006), acyl-CoA: cholesterol acyltransferase inhibitory effects , antiamoebic activity (Ghoshal and Lakshmi, 2002), antigiardial activity (Tripathi et al, 1999), mosquito larvicidal activity (Yang et al, 2002), immunomodulatory and antitumor activities (Sunila and Kuttan, 2004). A number of piperidine and pyrrolidine alkamide have been reported previously as constituents of P. longum (Chatterjee and Dutta, 1967;Das et al, 1996;Parmar et al, 1997;Wu et al, 2004).…”

Inhibitory effects of arbutin-β-glycosides synthesized from enzymatic transglycosylation for melanogenesis

“…One of the roles of melanin is to protect the skin and underlying tissues from UV-induced skin injury. However, excessive melanin production in the skin has negative hyper-pigmentation effects, inducing melasma, freckles, and senile lentigines (Ha et al 2005;Min et al 2004;Unver et al 2006). Epidermal and dermal hyper-pigmentation can be dependent on either an increased number of melanocytes or the actions of melanogenic enzymes (Griffiths et al 1993;Kanwar et al 1994).…”