| In vitro: |
| Arch Pharm Res. 2010 Jul;33(7):1035-41. | | Suppression of adipocyte differentiation by 15-methoxypinusolidic acid through inhibition of PPARĪ³ activity.[Pubmed: 20661713] | 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-Methoxypinusolidic acid suppress nitric oxide generation by suppressing inducible nitric oxide synthase and exerted anti-inflammatory functions, whereas other functions and regulatory mechanisms are largely unknown.
METHODS AND RESULTS:
In this study, we investigated whether pinusolide and 15-Methoxypinusolidic acid modulate adipocyte differentiation from pre-adipocytes 3T3-L1 cells. We found that 15-Methoxypinusolidic acid, 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-Methoxypinusolidic acid did not affect mRNA and protein levels of PPARgamma, a key adipogenic transcription factor, whereas transcriptional activity of PPARgamma was significantly attenuated by 15-Methoxypinusolidic acid. 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-Methoxypinusolidic acid.
CONCLUSIONS:
These results suggest that 15-Methoxypinusolidic acid suppresses adipocyte differentiation through the inhibition of PPARgamma-dependent adipogenic gene expression. | | Toxicol In Vitro. 2006 Sep;20(6):936-41. | | 15-Methoxypinusolidic acid from Biota orientalis attenuates glutamate-induced neurotoxicity in primary cultured rat cortical cells.[Pubmed: 16564156] |
METHODS AND RESULTS:
15-Methoxypinusolidic acid (15-MPA), a pinusolide derivative isolated from Biota orientalis (Cupressaceae) leaves prevented glutamate-induced excitotoxicity in primary cultured rat cortical cells in vitro.
15-Methoxypinusolidic acid had more selectivity in protecting neurons against N-methyl-D-aspartate (NMDA)-induced neurotoxicity than that induced by kainic acid (KA). The glutamate-induced increase of intracellular calcium ([Ca2+]i) in cortical cells was effectively reduced by 15-Methoxypinusolidic acid . Moreover, 15-Methoxypinusolidic acid could successfully reduce the subsequent overproduction of nitric oxide (NO) and the level of cellular peroxide, and inhibit glutathione (GSH) depletion and lipid peroxidation induced by glutamate in our cultures.
CONCLUSIONS:
Collectively, these results suggested that 15-Methoxypinusolidic acid attenuated glutamate-induced excitotoxicity via stabilization of [Ca2+]i homeostasis and suppression of oxidative stress possibly through the actions on the NMDA receptors. |
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