Title:Ameliorative Potential of Ethyl Gallate in a Rat Model of Chronic Constriction Injury-Induced Neuropathic Pain
Volume: 22
Issue: 5
Author(s): Harshal D. Pawar, Sayali Chaudhari, Purvaj G. Barote, Kartik T. Nakhate, Abdulla Sherikar and Sameer N. Goyal*
Affiliation:
- Department of Pharmacology, Shri Vile Parle Kelavani Mandal’s Institute of Pharmacy, Dhule, 424001, India
Keywords:
Ethyl gallate, neuropathic pain, chronic constriction injury, neuroinflammation, oxidative stress, nuclear factor erythroid 2-related factor 2, nuclear factor kappa-light-chain-enhancer of activated B cells.
Abstract:
Introduction: Neuropathic pain (NP), a chronic and debilitating condition resulting
from nerve injury, remains a significant clinical challenge due to limited effective therapies.
Ethyl gallate (EG), a natural ester of gallic acid, possesses potent antioxidant and antiinflammatory
properties; however, its role in NP management has not been previously explored.
Methods: This study investigated the neuroprotective potential of EG in a chronic constriction
injury (CCI)-induced NP model in rats. EG was administered intraperitoneally at doses of 10,
15, and 20 mg/kg/day for 14 days. Behavioral assessments, including thermal hyperalgesia, mechanical
allodynia, and motor nerve conduction velocity (MNCV), were performed. Biochemical
evaluations, such as oxidative stress markers (SOD, GSH, catalase, MDA) and pro-inflammatory
cytokines (TNF-α, IL-1β, and IL-6) were conducted. Histopathological analysis of the sciatic
nerve was performed to assess structural integrity. Additionally, molecular docking was employed
to evaluate the binding interactions of EG with key redox and inflammatory regulators,
Nrf2 and NF-κB, in comparison with the standard drug gabapentin (GBP).
Results: EG significantly alleviated CCI-induced pain behaviors, demonstrated by increased
paw withdrawal latency, enhanced mechanical threshold, and improved MNCV. EG treatment restored
antioxidant enzyme activities and reduced MDA levels, indicating decreased oxidative
stress. Additionally, EG markedly lowered pro-inflammatory cytokine levels. Histological findings
revealed preserved nerve fiber integrity and reduced structural damage in EG-treated groups. Molecular
docking revealed stronger binding affinity of EG (–6.8 kcal/mol with Nrf2; -5.1 kcal/mol
with NF-κB) compared to GBP (–5.9 kcal/mol and –4.3 kcal/mol, respectively), supporting its
potential mechanistic role in modulating oxidative stress and inflammatory pathways.
Discussion: These results suggest that EG mitigates NP symptoms by modulating oxidative
stress and inflammation. Its ability to enhance endogenous antioxidant defenses and suppress
pro-inflammatory responses underlies its neuroprotective action.
Conclusion: EG demonstrates promising therapeutic potential in the management of NP through
its antioxidant, anti-inflammatory, and neuroprotective properties. Further molecular studies are
warranted to elucidate its underlying mechanisms.
