Chu Xue1, Si-Xue Liu1, Jie Hu1, Jin Huang2, Hong-Min Liu1, Zhi-Xia Qiu1, Fang Huang3. 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. huangfang@cpu.edu.cn.
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.
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.
Authors: Yan Li; Pavel Adamek; Haijun Zhang; Claudio Esteves Tatsui; Laurence D Rhines; Petra Mrozkova; Qin Li; Alyssa K Kosturakis; Ryan M Cassidy; Daniel S Harrison; Juan P Cata; Kenneth Sapire; Hongmei Zhang; Ross M Kennamer-Chapman; Abdul Basit Jawad; Andre Ghetti; Jiusheng Yan; Jiri Palecek; Patrick M Dougherty Journal: J Neurosci Date: 2015-09-30 Impact factor: 6.167
Authors: Haijun Zhang; Jessica A Boyette-Davis; Alyssa K Kosturakis; Yan Li; Seo-Yeon Yoon; Edgar T Walters; Patrick M Dougherty Journal: J Pain Date: 2013-05-31 Impact factor: 5.820