2. Academic Validation
  3. Melanogenesis inhibitory activity of a 7-O-9'-linked neolignan from Alpinia galanga fruit

Melanogenesis inhibitory activity of a 7-O-9'-linked neolignan from Alpinia galanga fruit

  • Bioorg Med Chem. 2016 Dec 1;24(23):6215-6224. doi: 10.1016/j.bmc.2016.10.001.
Yoshiaki Manse 1,  Kiyofumi Ninomiya 2,  Ryosuke Nishi 1,  Iyori Kamei 1,  Yushi Katsuyama 1,  Takahito Imagawa 1,  Saowanee Chaipech 3,  Osamu Muraoka 2,  Toshio Morikawa 4
Affiliations

Affiliations

  • 1 Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
  • 2 Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan; Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
  • 3 Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan; Faculty of Agro-Industry, Rajamangala University of Technology Srivijaya, Thungsong, Nakhonsithammarat 80110, Thailand.
  • 4 Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan; Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. Electronic address: morikawa@kindai.ac.jp.
PMID: 27756508 DOI: 10.1016/j.bmc.2016.10.001
Abstract

An aqueous acetone extract from the fruit of Alpinia galanga (Zingiberaceae) demonstrated inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells (IC50=7.3μg/mL). Through bioassay-guided separation of the extract, a new 7-O-9'-linked neolignan, named galanganol D diacetate (1), was isolated along with 16 known compounds including 14 Phenylpropanoids (2-15). The structure of 1, including its absolute stereochemistry in the C-7 position, was elucidated by means of extensive NMR analysis and total synthesis. Among the isolates, 1 (IC50=2.5μM), 1'S-1'-acetoxychavicol acetate (2, 5.0μM), and 1'S-1'-acetoxyeugenol acetate (3, 5.6μM) exhibited a relatively potent inhibitory effect without notable cytotoxicity at effective concentrations. The following structural requirements were suggested to enhance the inhibitory activity of Phenylpropanoids on melanogenesis: (i) compounds with 4-acetoxy group exhibit higher activity than those with 4-hydroxy group; (ii) 3-methoxy group dose not affect the activity; (iii) acetylation of the 1'-hydroxy moiety enhances the activity; and (iv) phenylpropanoid dimers with the 7-O-9'-linked neolignan skeleton exhibited higher activity than those with the corresponding monomer. Their respective enantiomers [1' (IC50=1.9μM) and 2' (4.5μM)] and racemic mixtures [(±)-1 (2.2μM) and (±)-2 (4.4μM)] were found to exhibit melanogenesis inhibitory activities equivalent to those of the naturally occurring optical active compounds (1 and 2). Furthermore, the active compounds 1-3 inhibited Tyrosinase, tyrosine-related protein (TRP)-1, and TRP-2 mRNA expressions, which could be the mechanism of melanogenesis inhibitory activity.

Keywords

7-O-9′-Linked neolignan; Alpinia galanga; Galanganol D diacetate; Melanogenesis inhibitor; Phenylpropanoid.

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