Nootropic Effects of 7-Isoprenyloxycoumarin and Herniarin from Tagetes lucida on Lipopolysaccharide-Induced Neuroinflammation

Tagetes lucida Cav., Asteraceae, is an essential cultural plant that is traditionally used to treat diseases involving inflammatory processes and is also widely used for treating “nervous” problems. Several pharmacological studies have addressed the effects of these compounds on different neurological and psychiatric disorders. The anti-inflammatory and neuroprotective activities of coumarins isolated from different plant extracts have been demonstrated. In this study, 7-isoprenyloxycoumarin (7- O -prenyl-umbelliferone) and herniarin (7-methoxycoumarin), isolated from a T. lucida hexane-soluble extract, were evaluated in a murine model of neuroinflammation and memory loss induced by lipopolysaccharide (1.25 µg/kg), which was administered via intraperitoneal injection for 7 days. In the following 7 days, the different groups received meloxicam (5 mg/kg), 7-isoprenyloxycoumarin, or herniarin at 0.25, 0.5, 1, or 2 mg/kg. Cognitive function, motor function, and cytokine concentrations were quantified. Coumarins induced a neuroprotective effect as they decreased platform time latency in animals exposed to Morris’s water maze. The total number of crosses in the open field test was significantly lower in the treatment groups than that in the group receiving only lipopolysaccharide (veh-treated), while rearing decreased only with herniarin treatment. In addition, concentrations of TNF-α, IL1, and IL-6 were significantly lower in the groups treated with coumarin as compared with the vehicle-treated group. The concentration of IL-10 in the spleen of mice with 7-isoprenyloxycoumarin and herniarin was high. In this work, we showed that the coumarins 7-isoprenyloxycoumarin and herniarin protect the central nervous system by counteracting inflammation and cognitive impairment secondary to the administration of lipopolysaccharide, and that these molecules can act as immunomodulators. Graphical Abstract