Title:Caffeic Acid Phenethyl Ester (CAPE) Attenuates Paclitaxel-induced
Peripheral Neuropathy: A Mechanistic Study
Volume: 19
Issue: 3
Author(s): Namrata Pramod Kulkarni, Bhupesh Vaidya, Acharan S. Narula and Shyam Sunder Sharma*
Affiliation:
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER),
S.A.S. Nagar, Sector 67, Punjab 160062, India
Keywords:
Chemotherapy-induced peripheral neuropathy, paclitaxel, Wnt signalling, β-catenin, MMP2, Nrf2.
Abstract:
Background: Chemotherapy-induced peripheral neuropathy is a debilitating pain syndrome
produced as a side effect of antineoplastic drugs like paclitaxel. Despite efforts, the currently
available therapeutics suffer from serious drawbacks like unwanted side effects and poor efficacy
and provide only symptomatic relief. Hence, there is a need to find new therapeutic alternatives for
the treatment of chemotherapy-induced peripheral neuropathy.
Objective: The objective of this study was to explore the protective potential of caffeic acid
phenethyl ester in paclitaxel-induced neuropathic pain.
Methods: We examined the effects of caffeic acid phenethyl ester by administering paclitaxel (2
mg/kg, intraperitoneal) to female Sprague Dawley rats on four alternate days to induce neuropathic
pain, followed by the administration of caffeic acid phenethyl ester (10 and 30 mg/kg, intraperitoneally).
Results: Rats that were administered paclitaxel showed a substantially diminished pain threshold
and nerve functions after 28 days. A significantly increased protein expression of Wnt signalling
protein (β-catenin), inflammatory marker (matrix metalloproteinase 2) and a decrease in endogenous
antioxidant (nuclear factor erythroid 2–related factor 2) levels were found in paclitaxel administered
rats in comparison to the naïve control group. Caffeic acid phenethyl ester (10 and 30 mg/kg, intraperitoneal)
showed improvements in behavioural and nerve function parameters along with reduced
expression of β-catenin, matrix metalloproteinase 2 and an increase in nuclear factor erythroid 2–
related factor 2 protein expression.
Conclusion: The present study suggests that caffeic acid phenethyl ester attenuates chemotherapyinduced
peripheral neuropathy via inhibition of β-catenin and matrix metalloproteinase 2 and increases
nuclear factor erythroid 2–related factor 2 activation.