TITLE:
Sodium Aescinate Alleviates Neuropathic Pain in Rats by Suppressing the TLR4/NF KB Pathway Activation after Paclitaxel Chemotherapy
AUTHORS:
Miao Huo, Qian Zhang, Ziyu Zhao, Ruifen Xu, Xingxing Zheng, Guang Yang, Jiao Guo
KEYWORDS:
Chemotherapy-Induced Peripheral Neuropathy, Sodium Aescinate,
JOURNAL NAME:
Yangtze Medicine,
Vol.7 No.2,
June
30,
2023
ABSTRACT: Background: Emerging evidence suggests that chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of chemotherapeutic drugs. Many experiments have proved that sodium aescinate (SA) has definite pharmacological effects such as anti-infection, anti-exudation, anti-edema, anti-tumor as well as neuroprotection, and the drug side effects are mild. However, no study has explored whether SA is involved in the analgesic effect of paclitaxel (PAC) induced neuropathic pain in rats. Methods: Rats were given an intraperitoneal injection of PAC (2.5 mg/Kg intraperitoneally on days 1, 3, 5, and 7), while SA 25 mg/kg intraperitoneally was administered daily for 14 consecutive days. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats were examined on experimental days 3, 5, 7, 11, 14. All rats were sacrificed on day 15 of the experiment, and L4-6 spinal cords were removed. Subsequently, immunohistochemistry, HE staining, ELISA, RT-qPCR, Western blotting were applied to evaluate cytoskeletal protein expression (NF-L and NF-M), spinal nerve structural integrity, proinflammatory factor contents (TNF-α, IL-1β, and IL-6), and protein content of the TLR4/NF-κB pathway, respectively. Results: After the rats developed PAC induced pain behaviors, multiple injections of SA rendered the rats with elevated MWT and TWL values, decreased expression of NF-L and NF-M in the spinal cord, materially downregulated content of proinflammatory factors, and reduced amounts of TLR4 and p-NF-κB protein levels. Conclusions: The results of the present study preliminarily indicate that SA has an analgesic effect on rats with CIPN induced by PAC injection, and the mechanism may be related to blocking the TLR4/NF-κB signaling pathway, inhibiting the expression of proinflammatory factors, and alleviating cytoskeletal disorders.