<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...

Full description

Bibliographic Details
Main Authors: Keun-Tae Park, Seong-Gyu Ko, Woojin Kim
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Plants
Subjects:
Online Access:https://www.mdpi.com/2223-7747/12/22/3819
_version_ 1797457954403778560
author Keun-Tae Park
Seong-Gyu Ko
Woojin Kim
author_facet Keun-Tae Park
Seong-Gyu Ko
Woojin Kim
author_sort Keun-Tae Park
collection DOAJ
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.
first_indexed 2024-03-09T16:31:09Z
format Article
id doaj.art-2fe79136c3c146f49161ed7b9fd39500
institution Directory Open Access Journal
issn 2223-7747
language English
last_indexed 2024-03-09T16:31:09Z
publishDate 2023-11-01
publisher MDPI AG
record_format Article
series Plants
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
work_keys_str_mv AT keuntaepark iphlomidisradixiextractalleviatespaclitaxelinducedneuropathicpainbymodulatingspinaltrpv1inmice
AT seonggyuko iphlomidisradixiextractalleviatespaclitaxelinducedneuropathicpainbymodulatingspinaltrpv1inmice
AT woojinkim iphlomidisradixiextractalleviatespaclitaxelinducedneuropathicpainbymodulatingspinaltrpv1inmice