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

Marine Drugs

Luis D’Croz¹  María D. Ganfornina²  Eduardo Arranz²  Irene Cózar-Castellano²  Miriam Corraliza-Gómez²  Ana R. Díaz-Marrero³  José M. de la Rosa³  José Darias³  Mercedes Cueto³  Amalia B. Gallardo³ 

[1] Departamento de Biología Marina y Limnología, Universidad de Panamá, Panama 0801, Panama;Instituto de Biología y Genética Molecular, Universidad de Valladolid-CSIC, 47003 Valladolid, Spain;Instituto de Productos Naturales y Agrobiología (IPNA-CSIC), Avenida Astrofísico F. Sánchez, 3, 38206 La Laguna, Tenerife, Spain;

关键词: Leptogorgia;    furanocembranolides;    leptolide;    microglia;    astrocytes;    gliosis;   

DOI  :  10.3390/md18080378

来源: DOAJ

【 摘 要 】

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 of Leptogorgia sp., and compound 6 was 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-1β (IL-1β) production by microglial BV2 cells after LPS (lipopolysaccharide) stimulation. Leptolide and compounds 3, 4 and 6 exhibited clear anti-inflammatory effects on microglial cells, while compound 2 presented 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.

【 授权许可】

Unknown