<i>Phlomidis Radix</i> Extract Alleviates Paclitaxel-Induced Neuropathic Pain by Modulating Spinal TRPV1 in Mice
Paclitaxel is a chemotherapeutic drug reported to have excellent activity against tumors; however, various side effects, including peripheral neuropathy, limit its use in some cases. In this study, the effect of <i>Phlomidis radix</i> (<i>P.Radix</i>) extract was assessed on...
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MDPI AG
2023-11-01
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author | Keun-Tae Park Seong-Gyu Ko Woojin Kim |
author_facet | Keun-Tae Park Seong-Gyu Ko Woojin Kim |
author_sort | Keun-Tae Park |
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description | Paclitaxel is a chemotherapeutic drug reported to have excellent activity against tumors; however, various side effects, including peripheral neuropathy, limit its use in some cases. In this study, the effect of <i>Phlomidis radix</i> (<i>P.Radix</i>) extract was assessed on paclitaxel-induced cold and mechanical peripheral neuropathy in mice. Multiple paclitaxel injections (accumulative dose of 8 mg/kg, i.p.) induced increased behavioral responses to cold and mechanical stimuli in mice from D10 to D21 after the first paclitaxel injection. Cold and mechanical stimuli were performed by acetone drop and von Frey filament, respectively. Oral administrations of 25% ethanol extract of <i>P.Radix</i> (300 and 500 mg/kg) relieved cold and mechanical pain in a dose-dependent manner. Furthermore, among the various transient receptor potential (TRP) cation channel subfamilies, paclitaxel upregulated the spinal gene expression of transient receptor potential vanilloid 1 (<i>TRPV1</i>) and melastatin 4 (<i>TRPM4</i>), but not ankyrin 1 (<i>TRPA1</i>). However, 500 mg/kg but not 300 mg/kg of <i>P.Radix</i> extract significantly downregulated the gene expression of <i>TRPV1</i> but not <i>TRPM4</i>. Among the components of <i>P.Radix</i>, sesamoside was identified and quantified by high-performance liquid chromatography (HPLC), and the administration of sesamoside (7.5 mg/kg, i.p.) showed a similar analgesic effect to 300 mg/kg <i>P.Radix</i>. These results suggest that <i>P.Radix</i> and sesamoside should be considered when treating paclitaxel-induced neuropathic pain. |
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spelling | doaj.art-2fe79136c3c146f49161ed7b9fd395002023-11-24T15:01:54ZengMDPI AGPlants2223-77472023-11-011222381910.3390/plants12223819<i>Phlomidis Radix</i> Extract Alleviates Paclitaxel-Induced Neuropathic Pain by Modulating Spinal TRPV1 in MiceKeun-Tae Park0Seong-Gyu Ko1Woojin Kim2Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02453, Republic of KoreaKorean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02453, Republic of KoreaPaclitaxel is a chemotherapeutic drug reported to have excellent activity against tumors; however, various side effects, including peripheral neuropathy, limit its use in some cases. In this study, the effect of <i>Phlomidis radix</i> (<i>P.Radix</i>) extract was assessed on paclitaxel-induced cold and mechanical peripheral neuropathy in mice. Multiple paclitaxel injections (accumulative dose of 8 mg/kg, i.p.) induced increased behavioral responses to cold and mechanical stimuli in mice from D10 to D21 after the first paclitaxel injection. Cold and mechanical stimuli were performed by acetone drop and von Frey filament, respectively. Oral administrations of 25% ethanol extract of <i>P.Radix</i> (300 and 500 mg/kg) relieved cold and mechanical pain in a dose-dependent manner. Furthermore, among the various transient receptor potential (TRP) cation channel subfamilies, paclitaxel upregulated the spinal gene expression of transient receptor potential vanilloid 1 (<i>TRPV1</i>) and melastatin 4 (<i>TRPM4</i>), but not ankyrin 1 (<i>TRPA1</i>). However, 500 mg/kg but not 300 mg/kg of <i>P.Radix</i> extract significantly downregulated the gene expression of <i>TRPV1</i> but not <i>TRPM4</i>. Among the components of <i>P.Radix</i>, sesamoside was identified and quantified by high-performance liquid chromatography (HPLC), and the administration of sesamoside (7.5 mg/kg, i.p.) showed a similar analgesic effect to 300 mg/kg <i>P.Radix</i>. These results suggest that <i>P.Radix</i> and sesamoside should be considered when treating paclitaxel-induced neuropathic pain.https://www.mdpi.com/2223-7747/12/22/3819CIPNpaclitaxel<i>Phlomidis radix</i>TRPV1 |
spellingShingle | Keun-Tae Park Seong-Gyu Ko Woojin Kim <i>Phlomidis Radix</i> Extract Alleviates Paclitaxel-Induced Neuropathic Pain by Modulating Spinal TRPV1 in Mice Plants CIPN paclitaxel <i>Phlomidis radix</i> TRPV1 |
title | <i>Phlomidis Radix</i> Extract Alleviates Paclitaxel-Induced Neuropathic Pain by Modulating Spinal TRPV1 in Mice |
title_full | <i>Phlomidis Radix</i> Extract Alleviates Paclitaxel-Induced Neuropathic Pain by Modulating Spinal TRPV1 in Mice |
title_fullStr | <i>Phlomidis Radix</i> Extract Alleviates Paclitaxel-Induced Neuropathic Pain by Modulating Spinal TRPV1 in Mice |
title_full_unstemmed | <i>Phlomidis Radix</i> Extract Alleviates Paclitaxel-Induced Neuropathic Pain by Modulating Spinal TRPV1 in Mice |
title_short | <i>Phlomidis Radix</i> Extract Alleviates Paclitaxel-Induced Neuropathic Pain by Modulating Spinal TRPV1 in Mice |
title_sort | i phlomidis radix i extract alleviates paclitaxel induced neuropathic pain by modulating spinal trpv1 in mice |
topic | CIPN paclitaxel <i>Phlomidis radix</i> TRPV1 |
url | https://www.mdpi.com/2223-7747/12/22/3819 |
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