Neuro-protective potential of a vesicular system of a standardized extract of a new chemotype of Withania somnifera Dunal (NMITLI118RT+) against cerebral stroke in rats

Drug Deliv. 2016 Sep;23(7):2630-2641. doi: 10.3109/10717544.2015.1041579. Epub 2015 May 28.

Abstract

Withania somnifera Dunal is an Indian medicinal plant with significant pharmacological properties, such as adaptogenic, anti-inflammatory, anti-oxidant, anti-platelet, anti-hypertensive, hypoglycemic and hypolipidemic effects. Several chemotypes of W. somnifera include NMITLI-101, NMITLI-118 and NMITLI-128. The present work elaborates the optimization and development of a liposomal delivery system for efficient delivery of NMITLI118RT+ [a standardized ethanolic extract of a new chemotype of W. somnifera Dunal (NMITLI-118) roots] against cerebral stroke in rats. Liposomal systems were prepared using thin-film hydration method and characterized on the basis of size, zeta potential, physical stability, FT-IR, DSC-TGA analysis and surface morphological studies by TEM. NMITLI118RT+ and its formulations (NMITLI118RT+LF) were evaluated for biological activity utilizing middle cerebral artery occlusion model in rats. The Z average of the developed liposomal formulation was about 142.6 ± 0.09 nm with a zeta potential of -31.20 ± 1.0 mV. Results of TEM revealed spherical particles in the range of 200 nm. The entrapment efficiency was found to be 94.603 ± 2%. The formulation was found to be physically stable over a 3-week period. Results were suggestive of the fact that both NMITLI118RT+ and its delivery system possess significant neuroprotective activity in cerebral ischemia. The liposomal system largely exhibits better performance over NMITLI118RT+ precisely in the post-treatment group. The present studies could elucidate the successful development of a delivery system for NMITLI118RT+ and demonstrate their beneficial neuro-protective potential in overcoming and reversing the consequences of I/R injury following stroke.

Keywords: Ashwagandha; Withania somnifera; Withanolide A; ischemia; liposome; stroke.

MeSH terms

  • Animals
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / chemistry
  • Antihypertensive Agents / pharmacology*
  • Infarction, Middle Cerebral Artery / drug therapy
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Plant Extracts / administration & dosage*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Roots
  • Rats
  • Spectroscopy, Fourier Transform Infrared
  • Stroke / drug therapy*
  • Stroke / pathology
  • Withania / chemistry*
  • Withania / drug effects*

Substances

  • Antihypertensive Agents
  • Neuroprotective Agents
  • Plant Extracts