Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting toxicity of many anti-neoplastic agents, especially paclitaxel, and oxaliplatin. Up to 62% of patients receiving paclitaxel regimens turn out to develop CIPN. Unfortunately, there are so few agents proved effective for prevention or management of CIPN. The reason for the current situation is that the mechanisms of CIPN are still not explicit. Traditional Chinese Medicine (TCM) has unique advantages for dealing with complex diseases. Wen-Luo-Tong (WLT) is a TCM ointment for topical application. It has been applied for prevention and management of CIPN clinically for more than 10 years. Previous animal experiments and clinical studies had manifested the availability of WLT. However, due to the unclear mechanisms of WLT, further transformation has been restricted. To investigate the therapeutic mechanisms of WLT, a metabolomic method on the basis of UPLC- MS was developed in this study. Multivariate analysis techniques, such as principal component analysis (PCA) and partial least squares discriminate analysis (PLS-DA), were applied to observe the disturbance in the metabolic state of the paclitaxel-induced peripheral neuropathy (PIPN) rat model, as well as the recovering tendency of WLT treatment. A total of 19 significant variations associated with PIPN were identified as biomarkers. Results of pathway analysis indicated that the metabolic disturbance of pathways of linoleic acid (LA) metabolism and glycerophospholipid metabolism. WLT attenuated mechanical allodynia and rebalanced the metabolic disturbances of PIPN by primarily regulating LA and glycerophospholipid metabolism pathway. Further molecular docking analysis showed some ingredients of WLT, such as hydroxysafflor yellow A (HSYA), icariin, epimedin B and 4-dihydroxybenzoic acid (DHBA), had high affinity to plenty of proteins within these two pathways.
Highlights
Chemotherapy-induced peripheral neuropathy (CIPN) is a common treatment-related adverse effect of many anti-neoplastic agents
Our study aimed to investigate the metabolic disturbances of peripheral neuropathy (PIPN) through untargeted metabolomic assays
It had been revealed that up-regulation of CX3CL1 was involved with the neuropathic pain induced by nerve injury
Summary
Chemotherapy-induced peripheral neuropathy (CIPN) is a common treatment-related adverse effect of many anti-neoplastic agents. It is a serious dose-limiting toxicity characterized by distal, symmetrical, sensory peripheral neuropathy. These sensory neuropathy symptoms generally present as paraesthesia, numbness and/or pain, which severely affect the patient’s quality of life (QOL). Recent advances in cancer treatment have led to prolonged survival of patients, many treatmentrelated adverse effects remain unsolved (Wolf et al, 2008; Hershman et al, 2011, 2014). An explicit mechanism is the precondition of discovery for eutherapeutic drug or treatment, it’s very important and urgent to understand its mechanism
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