1. Academic Validation
  2. Corydalis saxicola Bunting total alkaloids attenuate paclitaxel-induced peripheral neuropathy through PKCε/p38 MAPK/TRPV1 signaling pathway

Corydalis saxicola Bunting total alkaloids attenuate paclitaxel-induced peripheral neuropathy through PKCε/p38 MAPK/TRPV1 signaling pathway

  • Chin Med. 2021 Jul 19;16(1):58. doi: 10.1186/s13020-021-00468-5.
Chu Xue 1 Si-Xue Liu 1 Jie Hu 1 Jin Huang 2 Hong-Min Liu 1 Zhi-Xia Qiu 1 Fang Huang 3
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, China.
  • 2 Shenzhen Pingle Orthopedic Hospital (Shenzhen Pingshan Traditional Chinese Medicine Hospital), Shenzhen, 518001, China.
  • 3 Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, China. [email protected].
Abstract

Background: Corydalis saxicola Bunting, affiliated with the Papaveraceae Juss., has been proven to work well in anti-inflammation, hemostasis, and analgesia. This study was designed to observe the effect and potential mechanism of Corydalis saxicola Bunting total Alkaloids (CSBTA) on paclitaxel-induced peripheral neuropathy (PIPN).

Materials and methods: Rats were injected 2 mg/kg paclitaxel 4 times and administrated with 30 or 120 mg/kg CSBTA. Mechanical and thermal allodynia and hyperalgesia were tested. After 40 days, serum was collected to detect PGE2, TNF-α, and IL-1β by ELISA. The L4-L6 segment spinal cord, DRG, and plantar skin were harvested, and Western-blot or RT-qPCR analyzed protein and gene levels of pro-inflammatory cytokines, p38 MAPK, PKCε, and TRPV1. The PIPN cell model was established with paclitaxel (300 nM, 5 d) in primary DRG neurons. We examined the effect of CSBTA (25 μg/ml or 50 μg/ml) by measuring the mRNA levels in PGE2, TNF-α and CGRP, and the protein expression on the PKCε/p38 MAPK/TRPV1 signaling pathway in the PIPN cell model.

Results: The results showed that CSBTA effectively ameliorated allodynia and hyperalgesia, and regulated cytokines' contents (PGE2, TNF-α, and IL-1β) and neuropeptides (CGRP and SP) in different tissues in vivo. In addition, CSBTA significantly decreased cytokine gene levels of DRG neurons (PGE2, TNF-α, and CGRP) and the protein expressions of PKCε/p38 MAPK/TRPV1 signaling pathway in vivo and in vitro.

Conclusion: Therefore, CSBTA has a perspective therapeutic effect on the treatment of paclitaxel-induced peripheral neuropathy.

Keywords

Corydalis saxicola Bunting total alkaloids; DRG neurons; Paclitaxel; Paclitaxel-induced peripheral neuropathy.

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