Thymol Improves Brain Functional Outcomes after Cerebral Ischemia-Reperfusion Injury by Regulating p38 MAPK Associated Apoptosis Signalling Pathway

Indian Journal of Pharmaceutical Education and Research

  • Hima Saila Mukkudiahgari1Department of Pharmacology, Sri Padmavathi School of Pharmacy, Tiruchanoor, Tirupati (Affiliated to JNTU), Anantapur, Andhra Pradesh, INDIA.
  • Ramesh Reddy Kudamala2Department of Pharmaceutics, Sri Padmavathi School of Pharmacy, Tiruchanoor, Tirupati (Affiliated to JNTU), Anantapur, Andhra Pradesh, INDIA.
  • Santhrani Thakur3Department of Pharmacology, Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visva Vidyalayam, Tirupati, Andhra Pradesh, INDIA.

Volume 59 Issue 2 Pages 790-799

DOI: 10.5530/ijper.20257027

Abstract

Background: Thymol, a monoterpene phenolic compound and an essential oil extracted from Tachyspermum ammi (ajwain) has been shown to possess multiple therapeutic potentials as anti-inflammatory, antioxidant, antihyperlipidemic, antiapoptotic, antitumor agent against neurological, cardiovascular, gastrointestinal and malignant diseases. Objectives: The current investigation aimed to determine whether thymol could protect rats from cerebral ischemia reperfusion injury by preventing Bilateral Common Carotid Artery Occlusion (BCCAO). Materials and Methods: After 14 days of pretreatment with thymol at the doses of 50 mg/kg, p.o and 100 mg/kg, p.o. respectively, Albino Wistar rats (200-250 g) were subjected to BCCAO for 1 hr followed by 22 hr reperfusion (I/R). The levels of protein carbonyl content, Myeloperoxidase (MPO) were measured in brain tissue homogenate. Utilising western blotting, the expression levels of TNF-α, Interleukin 10 (IL-10) anti-inflammatory cytokines, pro-apoptotic mediators Bax and Caspase 3 and anti-apoptotic mediator Bcl-2 were assessed. Results and Discussion: Reduction in levels of protein carbonyl content and Myeloperoxidase (MPO) was observed in thymol groups. Thymol pretreated rats showed significant (p<0.01) downregulation in the expressions of TNF-α and inhibited phosphorylation of p38 MAPK. In parallel, the expressions of IL-10 were upregulated significantly (p<0.01). Thymol exerted anti-apoptotic effect as reflected by decreased expression of the key downstream executioner caspase-3 and Bax, which is probably mediated by significant upregulation of expression of Bcl-2. Conclusion: Thymol is endowed with neuroprotection against global cerebral ischemia reperfusion injury which may be probably mediated by attenuation of inflammatory and apoptotic mechanism via p38 MAPK signaling pathway.

Keywords

  • Anti-inflammatory activity
  • p38 MAPK
  • Anti-apoptotic activity
  • Ischemic reperfusion injury
  • Thymol.
IJOPP

Loading…