Modulation of Glial Responses by Furanocembranolides: Leptolide Diminishes Microglial Inflammation in Vitro and Ameliorates Gliosis In Vivo in a Mouse Model of Obesity and Insulin Resistance
Corraliza-Gomez, Miriam
Consejo Superior de Investigaciones Cientificas (CSIC)
Diaz-Marrero, Ana R.
Consejo Superior de Investigaciones Cientificas (CSIC)
de la Rosa, Jose M.
Consejo Superior de Investigaciones Cientificas (CSIC)
D'Croz, Luis
Universidad de Panama
Darias, Jose
Consejo Superior de Investigaciones Cientificas (CSIC)
Arranz, Eduardo
Consejo Superior de Investigaciones Cientificas (CSIC)
Cozar-Castellano, Irene
Consejo Superior de Investigaciones Cientificas (CSIC)
Ganfornina, Maria D.
Consejo Superior de Investigaciones Cientificas (CSIC)
Cueto, Mercedes
Consejo Superior de Investigaciones Cientificas (CSIC)
Journal
Marine Drugs
ISSN
1660-3397
Open Access
gold
Volume
18
Neurodegenerative diseases are age-related disorders caused by progressive neuronal death in different regions of the nervous system. Neuroinflammation, modulated by glial cells, is a crucial event during the neurodegenerative process; consequently, there is an urgency to find new therapeutic products with anti-glioinflammatory properties. Five new furanocembranolides (1-5), along with leptolide, were isolated from two different extracts ofLeptogorgiasp., and compound6was obtained from chemical transformation of leptolide. Their structures were determined based on spectroscopic evidence. These seven furanocembranolides were screened in vitro by measuring their ability to modulate interleukin-1 beta (IL-1 beta) production by microglial BV2 cells after LPS (lipopolysaccharide) stimulation. Leptolide and compounds3,4and6exhibited clear anti-inflammatory effects on microglial cells, while compound2presented a pro-inflammatory outcome. The in vitro results prompted us to assess anti-glioinflammatory effects of leptolide in vivo in a high-fat diet-induced obese mouse model. Interestingly, leptolide treatment ameliorated both microgliosis and astrogliosis in this animal model. Taken together, our results reveal a promising direct biological effect of furanocembranolides on microglial cells as bioactive anti-inflammatory molecules. Among them, leptolide provides us a feasible therapeutic approach to treat neuroinflammation concomitant with metabolic impairment.