Wen-Luo-Tong Decoction Attenuates Paclitaxel-Induced Peripheral Neuropathy by Regulating Linoleic Acid and Glycerophospholipid Metabolism Pathways

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.

A Metabolomics Approach for Early Prediction of Vincristine-Induced Peripheral Neuropathy

“…Moreover, glutathione is a popular antioxidant tested as a therapeutic for chemotherapy-induced peripheral neuropathy, with various related studies mentioned in a review by Starobova and Vetter [46]. There is also evidence for the involvement of glycerophospholipid metabolism [47] which indicates that these metabolites may be biologically relevant to VIPN.…”

Analgesic effects of medicinal plants and phytochemicals on chemotherapy‐induced neuropathic pain through glial modulation

“…Topical application of WLT to the paws showed efficacy against oxaliplatin (total 36 mg/kg, 9 times)‐induced mechanical allodynia and hyperalgesia (4 and 15 g of von Frey filaments, respectively) in rats 45 . Moreover, the treatment with WLT had potency against paclitaxel (total 24 mg/kg, 3 times)‐induced mechanical allodynia (von Frey test) from day 6 onward 46 . On day 31, the WLT treatment inhibited the increase of GFAP and TNF‐α protein and mRNA levels in the rat spinal cord induced by oxaliplatin.…”

Integrating Metabolomics and Network Pharmacology to Explore the Protective Effect of Ginsenoside Re against Radiotherapy Injury in Mice

“…Glycerolipid metabolism is involved in the metabolism of serum samples, which are a special hydrolysis reaction existing in the body and an important metabolic pathway in the study of the pathogenesis of many diseases. It can be seen that glycerolipid metabolism is of great significance to the exploration of lipid metabolism in the body [23].…”

“…It holds the unique characteristics of polar and nonpolar parts. It can be inserted into its own cell membrane to prevent lipid peroxidation, inhibit the breakage of lipid disulfide bonds, prevent cells from being destroyed and apoptosis, and maintain their cell integrity [23]. Lysophosphatidylcholine in the blood is drawn from the hydrolysis of phosphatidylcholine by phospholipase A2 (PLA2).…”