1. Ferulic Acid Esters and Withanolides: In Search of Withania somnifera GABA A Receptor Modulators.
- Author
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Sonar VP, Fois B, Distinto S, Maccioni E, Meleddu R, Cottiglia F, Acquas E, Kasture S, Floris C, Colombo D, Sissi C, Sanna E, and Talani G
- Subjects
- Animals, Coumaric Acids chemical synthesis, Esters chemical synthesis, Esters pharmacology, GABA Modulators chemical synthesis, In Vitro Techniques, Inhibitory Postsynaptic Potentials drug effects, Magnetic Resonance Spectroscopy, Male, Molecular Structure, Plant Extracts chemistry, Plant Roots chemistry, Rats, Rats, Sprague-Dawley, Withanolides chemical synthesis, Xenopus, Coumaric Acids pharmacology, GABA Modulators pharmacology, Receptors, GABA-A drug effects, Withania chemistry, Withanolides pharmacology
- Abstract
Nine compounds, including two undescribed withanolides, withasomniferolides A and B (1 and 2), three known withanolides (3-5), a ferulic acid dimeric ester (6), and an inseparable mixture of three long alkyl chain ferulic acid esters (7-9), were isolated from a GABA
A receptor positive activator methanol extract of the roots of Withania somnifera. The structures of the isolated compounds were elucidated based on NMR, MS, and ECD data analysis. In order to bioassay the single ferulic acid derivatives, compounds 6-9 were also synthesized. The most active compound, docosanyl ferulate (9), was able to enhance the GABAA receptor inhibitory postsynaptic currents with an IC50 value of 7.9 μM. These results, by showing an ability to modulate the GABAA receptor function, cast fresh light on the biological activities of the secondary metabolites of W. somnifera roots.- Published
- 2019
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