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Open AccessArticle

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

1
Instituto de Biología y Genética Molecular, Universidad de Valladolid-CSIC, 47003 Valladolid, Spain
2
Instituto de Productos Naturales y Agrobiología (IPNA-CSIC), Avenida Astrofísico F. Sánchez, 3, 38206 La Laguna, Tenerife, Spain
3
Departamento de Ciencias y Recursos Naturales, Facultad de Ciencias, Universidad de Magallanes, Avenida Bulnes 01855, Punta Arenas, Chile
4
Departamento de Biología Marina y Limnología, Universidad de Panamá, Panama 3366, Panama
5
Smithsonian Tropical Research Institute, STRI, Box 0843-03092 Balboa, Panama
6
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Present address: Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez 2, 38206 La Laguna, Tenerife, Spain.
§
Present address: Departamento de Bioquímica, Microbiología, Biología Celular y Genética, Facultad de Farmacia, Universidad de La Laguna (ULL), 38206 La Laguna, Tenerife, Spain.
Mar. Drugs 2020, 18(8), 378; https://doi.org/10.3390/md18080378
Received: 11 June 2020 / Revised: 9 July 2020 / Accepted: 20 July 2020 / Published: 22 July 2020
(This article belongs to the Special Issue Marine Compounds and Inflammation II)
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 (15), 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. View Full-Text
Keywords: Leptogorgia; furanocembranolides; leptolide; microglia; astrocytes; gliosis; anti-inflammatory compounds; bioactive natural products; drug discovery; high-fat diet Leptogorgia; furanocembranolides; leptolide; microglia; astrocytes; gliosis; anti-inflammatory compounds; bioactive natural products; drug discovery; high-fat diet
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MDPI and ACS Style

Corraliza-Gómez, M.; Gallardo, A.B.; Díaz-Marrero, A.R.; de la Rosa, J.M.; D’Croz, L.; Darias, J.; Arranz, E.; Cózar-Castellano, I.; Ganfornina, M.D.; Cueto, M. 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. Mar. Drugs 2020, 18, 378.

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