1.Suppression of adipocyte differentiation by 15-methoxypinusolidic acid through inhibition of PPARγ activity.
Lee YS1, Sung SH, Hong JH, Hwang ES. Arch Pharm Res. 2010 Jul;33(7):1035-41. doi: 10.1007/s12272-010-0709-0. Epub 2010 Jul 27.
Pinusolide and its derivative, 15-methoxypinusolidic acid (15-MPA) are diterpenoid compounds isolated from Biota orientalis, which has been used as a Korean folk medicine for treating inflammatory disorders. Pinusolide and 15-MPA suppress nitric oxide generation by suppressing inducible nitric oxide synthase and exerted anti-inflammatory functions, whereas other functions and regulatory mechanisms are largely unknown. In this study, we investigated whether pinusolide and 15-MPA modulate adipocyte differentiation from pre-adipocytes 3T3-L1 cells. We found that 15-MPA, not pinusolide, suppressed adipocyte differentiation in a dose-dependent manner, as revealed by lipid droplet formation and expression of adipogenic genes such as adiponectin and aP2. 15-MPA did not affect mRNA and protein levels of PPARgamma, a key adipogenic transcription factor, whereas transcriptional activity of PPARgamma was significantly attenuated by 15-MPA. While aP2 promoter activity was increased by ectopic overexpression of PPARgamma or by rosiglitazone-induced endogenous PPARgamma activation, PPARgamma-induced aP2 promoter activity was inhibited in the presence of 15-MPA.
2.A new neuroprotective pinusolide derivative from the leaves of Biota orientalis.
Koo KA1, Sung SH, Kim YC. Chem Pharm Bull (Tokyo). 2002 Jun;50(6):834-6.
A new pinusolide derivative, 15-methoxypinusolidic acid (1), and another new isopimarane diterpene, ent-isopimara-15-en-3 alpha,8 alpha-diol (2) with three known diterpenes, lambertianic acid (3), isopimara-8(9),15-dien-18-oic acid (4) and isopimara-7(8),15-dien-3 beta,18-diol (5) were isolated from the 90% MeOH fraction of Biota orientalis (L.) ENDL. (Cupressaceae) leaves. Chemical structures of 1-5 were elucidated by analyses of their spectral data, including the two-dimensional (2D) NMR technique. Compound 1 showed significant protective activity against glutamate-induced neurotoxicity in primary cultures of rat cortical cells.
3.Oligonucleotide microarray analysis of apoptosis induced by 15-methoxypinusolidic acid in microglial BV2 cells.
Choi Y1, Lim SY, Jeong HS, Koo KA, Sung SH, Kim YC. Br J Pharmacol. 2009 Jul;157(6):1053-64. doi: 10.1111/j.1476-5381.2009.00247.x. Epub 2009 May 19.
BACKGROUND AND PURPOSE: We conducted a genome wide gene expression analysis to explore the biological aspects of 15-methoxypinusolidic acid (15-MPA) isolated from Biota orientalis and tried to confirm the suitability of 15-MPA as a therapeutic candidate for CNS injuries focusing on microglia.
4.Pinusolide and 15-methoxypinusolidic acid attenuate the neurotoxic effect of staurosporine in primary cultures of rat cortical cells.
Koo KA1, Lee MK, Kim SH, Jeong EJ, Kim SY, Oh TH, Kim YC. Br J Pharmacol. 2007 Jan;150(1):65-71. Epub 2006 Dec 4.
BACKGROUND AND PURPOSE: Apoptosis is a fundamental process required for neuronal development but also occurs in most of the common neurodegenerative disorders. In an attempt to obtain an anti-apoptotic neuroprotective compound from natural products, we isolated the diterpenoids, pinusolide and 15-MPA, from B. orientalis and investigated their neuroprotective activity against staurosporine (STS) -induced neuronal apoptosis. In addition, we determined the anti-apoptotic mechanism of these compounds in rat cortical cells.