Siwei Jianbu decoction improves painful paclitaxel-induced peripheral neuropathy in mouse model by modulating the NF-κB and MAPK signaling pathways

Jinshuai Suo; Man Wang; Peng Zhang; Yuting Lu; Rong Xu; Ling Zhang; Siyan Qiu; Qiuyan Zhang; Yangyan Qian; Jing Meng; Jing Zhu

doi:10.1051/rmr/200001

Siwei Jianbu decoction improves painful paclitaxel-induced peripheral neuropathy in mouse model by modulating the NF-κB and MAPK signaling pathways

Regen Med Res. 2020:8:2. doi: 10.1051/rmr/200001. Epub 2020 Oct 20.

Authors

Jinshuai Suo¹, Man Wang¹, Peng Zhang¹, Yuting Lu¹, Rong Xu¹, Ling Zhang¹, Siyan Qiu¹, Qiuyan Zhang¹, Yangyan Qian¹, Jing Meng¹, Jing Zhu²

Affiliations

¹ Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Department of pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
² Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Department of pharmacy, Nanjing University of Chinese Medicine, Nanjing, China - Department of Neurology and Neuroscience, Johns Hopkins School of Medicine, Baltimore, USA.

Abstract

Background: Paclitaxel, a commonly used chemotherapeutic agent, is usually associated with peripheral neuropathy. Paclitaxel induced peripheral neuropathy (PIPN) can be dose limiting and may have detrimental influence on patients' quality of life. However, the mechanism of PIPN remains unclear. Medicinal herbs and their formulas might offer neuronal protection with their multitarget and integrated benefits in chemotherapy-induced peripheral neuropathy (CIPN). Siwei Jianbu decoction (J12) is a classic formula of traditional Chinese medicine which can promote blood circulation and treat diabetic nephropathy in clinical with the symptoms of weakness and pain.

Methods: The effects of J12 were treated in C57BL/6 mice before injected with Paclitaxel.Behaviour studies: Measurement of mechanical hyperalgesia, thermal nociception and cold allodynia. On the last day at the end of week 6, DRGs were obtained from mice for western blot and immunohistochemical analysis containing NF-κB, p-ERK1/2 and p-SAPK/JNK protein expression. Quantitative real-time polymerase chain reaction: mRNA expression of NF-κB, IL-1β and TNF-α was analyzed. Additionally, the blood samples collected from the eye socket of the mouse were prepared to examine the levels of NF-κB, TNF-α, IL-6 and IL-1β using ELISA assay kits.

Results: Hypersensitivity tests and pathology analysis have demonstrated that J12 could improve paclitaxel-induced peripheral pain. J12 acts by inhibiting the activation of (C-Jun N-terminal kinases) JNK, (extracellular signal-regulated kinase) ERK1/2 phosphorylation in (Mitogen-activated protein kinases) MAPK signaling pathway and the nuclear factor-κB (NF-κB) in C57BL/6 mice model, J12 also inhibits the production of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and IL-6.

Conclusion: The present study showed that J12 ameliorates paclitaxel-induced peripheral neuropathic pain.

Keywords: MAPK signaling pathway; NF-κB; Siwei Jianbu decoction; paclitaxel; peripheral neuropathic pain.