8-shogaol derived from dietary ginger alleviated acute and inflammatory pain by targeting TRPV1
Copyright © 2024. Published by Elsevier GmbH..
Ginger, a well-known spice plant, has been used widely in medicinal preparations for pain relief. However, little is known about its analgesic components and the underlying mechanism. Here, we ascertained, the efficacy of ginger ingredient 8-Shogaol (8S), on inflammatory pain and tolerance induced by morphine, and probed the role of TRPV1 in its analgesic action using genetic and electrophysiology approaches. Results showed that 8S effectively reduced nociceptive behaviors of mice elicited by chemical stimuli, noxious heat as well as inflammation, and antagonized morphine analgesic tolerance independent on opioid receptor function. Genetic deletion of TRPV1 significantly abolished 8S' analgesia action. Further calcium imaging and patch-clamp recording showed that 8S could specifically activate TRPV1 in TRPV1-expressing HEK293T cells and dorsal root ganglion (DRG) neurons. The increase of [Ca2+]i in DRG was primarily mediated through TRPV1. Mutational and computation studies revealed the key binding sites for the interactions between 8S and TRPV1 included Leu515, Leu670, Ile573, Phe587, Tyr511, and Phe591. Further studies showed that TRPV1 activation evoked by 8S resulted in channel desensitization both in vitro and in vivo, as may be attributed to TRPV1 degradation or TRPV1 withdrawal from the cell surface. Collectively, this work provides the first evidence for the attractive analgesia of 8S in inflammatory pain and morphine analgesic tolerance mediated by targeting pain-sensing TRPV1 channel. 8S from dietary ginger has potential as a candidate drug for the treatment of inflammatory pain.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:128 |
|---|---|
| Enthalten in: |
Phytomedicine : international journal of phytotherapy and phytopharmacology - 128(2024) vom: 29. Feb., Seite 155500 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Cheng, Xiao-Lan [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
8-shogaol |
|---|
| Anmerkungen: |
Date Revised 14.03.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1016/j.phymed.2024.155500 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369743148 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369743148 | ||
| 003 | DE-627 | ||
| 005 | 20240315234432.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240315s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.phymed.2024.155500 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1330.xml |
| 035 | |a (DE-627)NLM369743148 | ||
| 035 | |a (NLM)38484627 | ||
| 035 | |a (PII)S0944-7113(24)00164-8 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Cheng, Xiao-Lan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 8-shogaol derived from dietary ginger alleviated acute and inflammatory pain by targeting TRPV1 |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 14.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2024. Published by Elsevier GmbH. | ||
| 520 | |a Ginger, a well-known spice plant, has been used widely in medicinal preparations for pain relief. However, little is known about its analgesic components and the underlying mechanism. Here, we ascertained, the efficacy of ginger ingredient 8-Shogaol (8S), on inflammatory pain and tolerance induced by morphine, and probed the role of TRPV1 in its analgesic action using genetic and electrophysiology approaches. Results showed that 8S effectively reduced nociceptive behaviors of mice elicited by chemical stimuli, noxious heat as well as inflammation, and antagonized morphine analgesic tolerance independent on opioid receptor function. Genetic deletion of TRPV1 significantly abolished 8S' analgesia action. Further calcium imaging and patch-clamp recording showed that 8S could specifically activate TRPV1 in TRPV1-expressing HEK293T cells and dorsal root ganglion (DRG) neurons. The increase of [Ca2+]i in DRG was primarily mediated through TRPV1. Mutational and computation studies revealed the key binding sites for the interactions between 8S and TRPV1 included Leu515, Leu670, Ile573, Phe587, Tyr511, and Phe591. Further studies showed that TRPV1 activation evoked by 8S resulted in channel desensitization both in vitro and in vivo, as may be attributed to TRPV1 degradation or TRPV1 withdrawal from the cell surface. Collectively, this work provides the first evidence for the attractive analgesia of 8S in inflammatory pain and morphine analgesic tolerance mediated by targeting pain-sensing TRPV1 channel. 8S from dietary ginger has potential as a candidate drug for the treatment of inflammatory pain | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 8-shogaol | |
| 650 | 4 | |a DRG | |
| 650 | 4 | |a Ginger | |
| 650 | 4 | |a Inflammatory pain | |
| 650 | 4 | |a Morphine analgesic tolerance | |
| 650 | 4 | |a TRPV1 | |
| 700 | 1 | |a Ruan, Yong-Lan |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Jing-Ya |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Hai-Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Ling, Jin-Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jiao |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Wu-Guang |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Xue-Jiao |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Peng |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Phytomedicine : international journal of phytotherapy and phytopharmacology |d 1994 |g 128(2024) vom: 29. Feb., Seite 155500 |w (DE-627)NLM093820402 |x 1618-095X |7 nnns |
| 773 | 1 | 8 | |g volume:128 |g year:2024 |g day:29 |g month:02 |g pages:155500 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.phymed.2024.155500 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 128 |j 2024 |b 29 |c 02 |h 155500 | ||