Red Ginger Extract Prevents the Development of Oxaliplatin-Induced Neuropathic Pain by Inhibiting the Spinal Noradrenergic System in Mice
Oxaliplatin is a well-known chemotherapeutic drug that is widely used to treat colorectal cancer. However, it can induce acute side effects in up to 90% of patients. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are used as first-choice drugs; however, even SNRIs are known to be effective...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/2/432 |
| _version_ | 1797622177387773952 |
|---|---|
| author | Keun-Tae Park Heejoon Jo Bonglee Kim Woojin Kim |
| author_facet | Keun-Tae Park Heejoon Jo Bonglee Kim Woojin Kim |
| author_sort | Keun-Tae Park |
| collection | DOAJ |
| description | Oxaliplatin is a well-known chemotherapeutic drug that is widely used to treat colorectal cancer. However, it can induce acute side effects in up to 90% of patients. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are used as first-choice drugs; however, even SNRIs are known to be effective only in treatment and not for prevention. Therefore, finding a drug that can prevent the development of cold and mechanical forms of allodynia induced by oxaliplatin is needed. This study demonstrated that multiple oral administrations of 100 mg/kg and 300 mg/kg of red ginger extract could significantly prevent pain development in mice. The role of the noradrenergic system was investigated as an underlying mechanism of action. Both the spinal α1- and α2-adrenergic receptors were significantly downregulated after treatment. Furthermore, the noradrenaline levels in the serum and spinal cord were upregulated and downregulated after treatment with paclitaxel and red ginger, respectively. As the active sub-component of red ginger, ginsenoside Rg3 (Rg3) was identified and quantified using HPLC. Moreover, multiple intraperitoneal injections of Rg3 prevented the development of pain in paclitaxel-treated mice, suggesting that RG3 may induce the effect of red ginger extract. |
| first_indexed | 2024-03-11T09:06:38Z |
| format | Article |
| id | doaj.art-0ffe6de8bf32427ebbe267fed3aaa9d4 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T09:06:38Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-0ffe6de8bf32427ebbe267fed3aaa9d42023-11-16T19:18:07ZengMDPI AGBiomedicines2227-90592023-02-0111243210.3390/biomedicines11020432Red Ginger Extract Prevents the Development of Oxaliplatin-Induced Neuropathic Pain by Inhibiting the Spinal Noradrenergic System in MiceKeun-Tae Park0Heejoon Jo1Bonglee Kim2Woojin Kim3Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02453, Republic of KoreaDepartment 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 KoreaOxaliplatin is a well-known chemotherapeutic drug that is widely used to treat colorectal cancer. However, it can induce acute side effects in up to 90% of patients. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are used as first-choice drugs; however, even SNRIs are known to be effective only in treatment and not for prevention. Therefore, finding a drug that can prevent the development of cold and mechanical forms of allodynia induced by oxaliplatin is needed. This study demonstrated that multiple oral administrations of 100 mg/kg and 300 mg/kg of red ginger extract could significantly prevent pain development in mice. The role of the noradrenergic system was investigated as an underlying mechanism of action. Both the spinal α1- and α2-adrenergic receptors were significantly downregulated after treatment. Furthermore, the noradrenaline levels in the serum and spinal cord were upregulated and downregulated after treatment with paclitaxel and red ginger, respectively. As the active sub-component of red ginger, ginsenoside Rg3 (Rg3) was identified and quantified using HPLC. Moreover, multiple intraperitoneal injections of Rg3 prevented the development of pain in paclitaxel-treated mice, suggesting that RG3 may induce the effect of red ginger extract.https://www.mdpi.com/2227-9059/11/2/432noradrenalineoxaliplatin-induced neuropathic painred ginseng |
| spellingShingle | Keun-Tae Park Heejoon Jo Bonglee Kim Woojin Kim Red Ginger Extract Prevents the Development of Oxaliplatin-Induced Neuropathic Pain by Inhibiting the Spinal Noradrenergic System in Mice Biomedicines noradrenaline oxaliplatin-induced neuropathic pain red ginseng |
| title | Red Ginger Extract Prevents the Development of Oxaliplatin-Induced Neuropathic Pain by Inhibiting the Spinal Noradrenergic System in Mice |
| title_full | Red Ginger Extract Prevents the Development of Oxaliplatin-Induced Neuropathic Pain by Inhibiting the Spinal Noradrenergic System in Mice |
| title_fullStr | Red Ginger Extract Prevents the Development of Oxaliplatin-Induced Neuropathic Pain by Inhibiting the Spinal Noradrenergic System in Mice |
| title_full_unstemmed | Red Ginger Extract Prevents the Development of Oxaliplatin-Induced Neuropathic Pain by Inhibiting the Spinal Noradrenergic System in Mice |
| title_short | Red Ginger Extract Prevents the Development of Oxaliplatin-Induced Neuropathic Pain by Inhibiting the Spinal Noradrenergic System in Mice |
| title_sort | red ginger extract prevents the development of oxaliplatin induced neuropathic pain by inhibiting the spinal noradrenergic system in mice |
| topic | noradrenaline oxaliplatin-induced neuropathic pain red ginseng |
| url | https://www.mdpi.com/2227-9059/11/2/432 |
| work_keys_str_mv | AT keuntaepark redgingerextractpreventsthedevelopmentofoxaliplatininducedneuropathicpainbyinhibitingthespinalnoradrenergicsysteminmice AT heejoonjo redgingerextractpreventsthedevelopmentofoxaliplatininducedneuropathicpainbyinhibitingthespinalnoradrenergicsysteminmice AT bongleekim redgingerextractpreventsthedevelopmentofoxaliplatininducedneuropathicpainbyinhibitingthespinalnoradrenergicsysteminmice AT woojinkim redgingerextractpreventsthedevelopmentofoxaliplatininducedneuropathicpainbyinhibitingthespinalnoradrenergicsysteminmice |