Melanogenesis Inhibitory Activity of Diterpenoid and Triterpenoid Constituents from the Aerial Part of Isodon trichocarpus

A methanol extract from the aerial part of Isodon trichocarpus (Labiatae) demonstrated inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells (IC50 = 1.6 μg/mL). From the extract, nine diterpenoids (1–9) and four triterpenoids (10–13) were isolated. Among the isolates, enmein (1, IC50 = 0.22 μM), isodocarpin (2, 0.19 μM), nodosin (4, 0.46 μM), and oridonin (6, 0.90 μM) showed an inhibitory effect without notable cytotoxicity at the effective concentrations. These diterpenoids (1, 2, 4, and 6) inhibited the expression of tyrosinase, tyrosine-related protein (TRP)-1, and TRP-2 mRNA, which could be the mechanism of melanogenesis inhibitory activity.

[1]  T. Morikawa,et al.  Melanogenesis inhibitory activity of a 7-O-9'-linked neolignan from Alpinia galanga fruit. , 2016, Bioorganic & medicinal chemistry.

[2]  T. Morikawa,et al.  Quantitative Determination of Alkaloids in Lotus Flower (Flower Buds of Nelumbo nucifera) and Their Melanogenesis Inhibitory Activity , 2016, Molecules.

[3]  T. Hayakawa,et al.  Simultaneous quantitative analysis of 12 methoxyflavones with melanogenesis inhibitory activity from the rhizomes of Kaempferia parviflora , 2016, Journal of Natural Medicines.

[4]  Han-Dong Sun,et al.  Bioactive Enmein-Type ent-Kaurane Diterpenoids from Isodon phyllostachys. , 2016, Journal of natural products.

[5]  T. Morikawa,et al.  Total Synthesis of 4,5-Didehydroguadiscine: A Potent Melanogenesis Inhibitor from the Brazilian Medicinal Herb, Hornschuchia obliqua. , 2015, Journal of natural products.

[6]  T. Hayakawa,et al.  Dimeric pyrrolidinoindoline-type alkaloids with melanogenesis inhibitory activity in flower buds of Chimonanthus praecox , 2014, Journal of Natural Medicines.

[7]  Han-Dong Sun,et al.  Enmein-type 6,7-seco-ent-kauranoids from Isodon sculponeatus. , 2013, Journal of natural products.

[8]  Han-Dong Sun,et al.  Bioactive ent-kaurane diterpenoids from Isodon rosthornii. , 2013, Journal of natural products.

[9]  T. Maruyama,et al.  Authentication and chemical study of isodonis herba and isodonis extracts. , 2007, Chemical & pharmaceutical bulletin.

[10]  Han-Dong Sun,et al.  Diterpenoids from Isodon species and their biological activities. , 2006, Natural product reports.

[11]  W. Jia,et al.  Immunosuppressive ent-Kaurene Diterpenoids from Isodon serra , 2004 .

[12]  Yuan-jiang Pan,et al.  Stereochemistry Structure of Odonicin. , 2004 .

[13]  X. Tian,et al.  Enmein type diterpenoids from Isodon japonica. , 2001, Phytochemistry.

[14]  J. J. Lee,et al.  Kaurane diterpenes from Isodon japonicus inhibit nitric oxide and prostaglandin E2 production and NF-kappaB activation in LPS-stimulated macrophage RAW264.7 cells. , 2001, Planta medica.

[15]  Takashi Matsumoto,et al.  LONGIRABDOLIDE C, A NEW DITERPENOID FROM RABDOSIA LONGITUBA , 1994 .

[16]  H. Morita,et al.  An investigation of diterpenes from the leaves of Rabdosia trichocarpa and their antibacterial activity against oral microorganisms. , 1994, Chemical & pharmaceutical bulletin.

[17]  Han-Dong Sun,et al.  Revision of the structures of isodonal, rabdolasional and related diterpenoids. , 1990 .

[18]  Han-Dong Sun,et al.  Studies on the Diterpenoid Constituents of Rabdosia ternifolia: Structural Elucidation of New Diterpenoids, Rabdoternins A, B and C , 1990 .

[19]  E. Fujita,et al.  Terpenoids. IX. The Structure and Absolute Configuration of Isodocarpin, a New Diterpenoid from Isodon trichocarpus KUDO and I. japonicus HARA , 1968 .

[20]  E. Fujita,et al.  Terpenoids. VII. The Structure and Absolute Configuration of Nodosin, a New Diterpenoid from Isodon Species , 1968 .

[21]  T. Morikawa,et al.  Phenylethanoid and phenylpropanoid glycosides with melanogenesis inhibitory activity from the flowers of Narcissus tazetta var. chinensis , 2015, Journal of Natural Medicines.

[22]  Y. Takeda,et al.  Recent advances in the chemistry of diterpenoids from Rabdosia species , 1995 .

[23]  M. Node,et al.  Diterpenoids of Rabdosia species. , 1984, Fortschritte der Chemie organischer Naturstoffe = Progress in the chemistry of organic natural products. Progres dans la chimie des substances organiques naturelles.

[24]  D. Doddrell,et al.  The stereochemical dependence of 13C chemical shifts in olean-12-enes and urs-12-enes as an aid to structural assignment , 1974 .

[25]  Y. Nagao,et al.  Terpenoids. Part XXV. Structures and absolute configurations of isodoacetal, nodosinin, and odonicin, novel diterpenoids of Isodon japonicus , 1973 .

[26]  E. Fujita,et al.  Terpenoids. Part XV. Structure and Absolute Configuration of Oridonin isolated from Isodon japonicus and Isodon trichocarpus , 1970 .

[27]  K. Fuji,et al.  Terpenoids—II : The chemical conversion of enmein into (−)-Kaurane—the absolute configuration of enmein , 1966 .