Daidzein attenuated paclitaxel-induced neuropathic pain via the down-regulation of TRPV1/P2Y and up-regulation of Nrf2/HO-1 signaling

Sana Zafar, Yong Luo, Li Zhang, Chang Hu Li, Adnan Khan, Muhammad Ibrar Khan, Kifayatullah Shah, Eun Kyoung Seo, Feng Wang, Salman Khan

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Paclitaxel (PTX) is an anti-microtubule agent, used for the treatment of various types of cancers; however, it produces painful neuropathy which limits its use. Many neuroprotective agents have been introduced to mitigate PTX-induced neuropathic pain (PINP), but they pose many adverse effects. The purpose of this study was to evaluate the pharmacological characteristics of soy isoflavone, and daidzein (DZ) in attenuating PINP. At the beginning of the investigation, the effect of DZ was confirmed through behavioral analysis, as it reduced pain hypersensitivity. Moreover, changes in the histological parameters were reversed by DZ administration along with vascular permeability. PTX administration upregulated transient receptor potential vanilloid 1 (TRPV1) channels and purinergic receptors (P2Y), contributing to hyperalgesia; but administration of DZ downregulated the TRPV1 and P2Y, thus reducing hyperalgesia. DZ increased nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), playing a pivotal role in the activation of the antioxidant pathway. DZ also decreased neuronal apoptosis by decreasing caspase-3 and Bcl2-associated X-protein (Bax), while simultaneously, increasing Bcl-2. PTX administration produced severe DNA damage, which was mitigated by DZ. Similarly, DZ administration resulted in inhibition of neuroinflammation by increasing antioxidant enzymes and reducing oxidative stress markers. PTX caused increased in production of pro-inflammatory mediators such as the cytokines production, while DZ inhibited the pro-inflammatory mediators. Additionally, in silico pharmacokinetic and toxicodynamic study of DZ was also conducted. In summary, DZ demonstrated significant neuroprotective activity against PTX induced neuropathic pain.

Original languageEnglish
Pages (from-to)1977-1992
Number of pages16
JournalInflammopharmacology
Volume31
Issue number4
DOIs
StatePublished - Aug 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Keywords

  • Daidzein
  • Hyperalgesia
  • Neuropathic pain
  • Neuroprotective
  • Oxidative stress
  • Paclitaxel

Fingerprint

Dive into the research topics of 'Daidzein attenuated paclitaxel-induced neuropathic pain via the down-regulation of TRPV1/P2Y and up-regulation of Nrf2/HO-1 signaling'. Together they form a unique fingerprint.

Cite this