Neuroprotective Effect of Natural Compounds in Paclitaxel-Induced Chronic Inflammatory Pain

Molecules. 2022 Aug 2;27(15):4926. doi: 10.3390/molecules27154926.

Abstract

The current study explored the effects of natural compounds, berbamine, bergapten, and carveol on paclitaxel-associated neuroinflammatory pain. Berbamine, an alkaloid obtained from BerberisamurensisRuprhas been previously researched for anticancer and anti-inflammatory potential. Bergapten is 5-methoxsalenpsoralen previously investigated in cancer, vitiligo, and psoriasis. Carveol obtained from caraway is a component of essential oil. The neuropathic pain model was induced by administering 2 mg/kg of paclitaxel (PTX) every other day for a week. After the final PTX injection, a behavioral analysis was conducted, and subsequently, tissue was collected for molecular analysis. Berbamine, bergapten, and carveol treatment attenuated thermal hypersensitivity, improved latency of falling, normalized the changes in body weight, and increased the threshold for pain sensation. The drugs increased the protective glutathione (GSH) and glutathione S-transferase (GST) levels in the sciatic nerve and spinal cord while lowering inducible nitric oxide synthase (iNOS) and lipid peroxidase (LPO). Hematoxylin and eosin (H and E) and immunohistochemistry (IHC) examinations confirmed that the medication reversed the abnormal alterations. The aforementioned natural substances inhibited cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κb) overexpression, as evidenced by enzyme-linked immunosorbant assay (ELISA) and Western blot and hence provide neuroprotection in chronic constriction damage.

Keywords: ELISA; Western blot; berbamine; bergapten; carveol; paclitaxel.

MeSH terms

  • 5-Methoxypsoralen / therapeutic use
  • Chronic Pain* / drug therapy
  • Humans
  • NF-kappa B / metabolism
  • Neuralgia* / chemically induced
  • Neuralgia* / drug therapy
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Nitric Oxide Synthase Type II / metabolism
  • Paclitaxel / adverse effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • NF-kappa B
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • 5-Methoxypsoralen
  • Nitric Oxide Synthase Type II
  • Paclitaxel

Grants and funding

Shenzhen-Hong Kong Institute of Brain Sciences No: 2019SHIBS0004.