2. Academic Validation
  3. Ferulic Acid Esters and Withanolides: In Search of Withania somnifera GABAA Receptor Modulators

Ferulic Acid Esters and Withanolides: In Search of Withania somnifera GABAA Receptor Modulators

  • J Nat Prod. 2019 May 24;82(5):1250-1257. doi: 10.1021/acs.jnatprod.8b01023.
Vijay P Sonar 1 2,  Benedetta Fois 1,  Simona Distinto 1,  Elias Maccioni 1,  Rita Meleddu 1,  Filippo Cottiglia 1,  Elio Acquas 1 3,  Sanjay Kasture 4,  Costantino Floris 5,  Daniele Colombo 1,  Claudia Sissi 6,  Enrico Sanna 1 3,  Giuseppe Talani 7
Affiliations

Affiliations

  • 1 Department of Life and Environmental Sciences , University of Cagliari , 09124 Cagliari , Italy.
  • 2 R. C. Patel Institute of Pharmaceutical Education and Research , Shirpur , 425404 India.
  • 3 Centre of Excellence on Neurobiology of Addiction , University of Cagliari , 09042 Cagliari , Italy.
  • 4 Department of Pharmacology , Sanjivani College of Pharmaceutical Education & Research , Kopargaon , 423603 India.
  • 5 Department of Chemical and Geological Sciences , University of Cagliari , 09042 Monserrato , Italy.
  • 6 Department of Pharmaceutical and Pharmacological Sciences , University of Padova , 35131 Padova , Italy.
  • 7 National Research Council (CNR) , Institute of Neuroscience , 09042 Monserrato , Italy.
PMID: 30998355 DOI: 10.1021/acs.jnatprod.8b01023
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 GABAA 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.

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