The Analgesia Effect of Aucubin on CFA-Induced Inflammatory Pain by Inhibiting Glial Cells Activation-Mediated Inflammatory Response via Activating Mitophagy
Background: Inflammatory pain, characterized by sustained nociceptive hypersensitivity, represents one of the most prevalent conditions in both daily life and clinical settings. Aucubin, a natural plant iridoid glycoside, possesses potent biological effects, encompassing anti-inflammatory, antioxida...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/11/1545 |
| _version_ | 1827639074108735488 |
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| author | Dandan Yao Yongjie Wang Yeru Chen Gang Chen |
| author_facet | Dandan Yao Yongjie Wang Yeru Chen Gang Chen |
| author_sort | Dandan Yao |
| collection | DOAJ |
| description | Background: Inflammatory pain, characterized by sustained nociceptive hypersensitivity, represents one of the most prevalent conditions in both daily life and clinical settings. Aucubin, a natural plant iridoid glycoside, possesses potent biological effects, encompassing anti-inflammatory, antioxidant, and neuroprotective properties. However, its impact on inflammatory pain remains unclear. The aim of this study is to investigate the therapeutic effects and underlying mechanism of aucubin in addressing inflammatory pain induced by complete Freund’s adjuvant (CFA). Methods: The CFA-induced inflammatory pain model was employed to assess whether aucubin exerts analgesic effects and its potential mechanisms. Behavioral tests evaluated mechanical and thermal hyperalgesia as well as anxiety-like behaviors in mice. The activation of spinal glial cells and the expression of pro-inflammatory cytokines were examined to evaluate neuroinflammation. Additionally, RNA sequencing was utilized for the identification of differentially expressed genes (DEGs). Molecular biology experiments were conducted to determine the levels of the PINK1 gene and autophagy-related genes, along with PINK1 distribution in neural cells. Furthermore, mitophagy induced by carbonyl cyanide m-chlorophenylhydrazone (CCCP) was employed to examine the roles of PINK1 and mitophagy in pain processing. Results: Aucubin significantly ameliorated pain and anxiety-like behaviors induced by CFA in mice and reduced spinal inflammation. RNA sequencing indicated PINK1 as a pivotal gene, and aucubin treatment led to a significant downregulation of PINK1 expression. Further GO and KEGG analyses suggested the involvement of mitochondrial function in the therapeutic regulation of aucubin. Western blotting revealed that aucubin markedly decreased PINK1, Parkin, and p62 levels while increasing LC3B expression. Immunofluorescence showed the predominant co-localization of PINK1 with neuronal cells. Moreover, CCCP-induced mitophagy alleviated mechanical and thermal hyperalgesia caused by CFA and reversed CFA-induced mitochondrial dysfunction. Conclusions: In summary, our data suggest that aucubin effectively alleviates CFA-induced inflammatory pain, potentially through triggering the PINK1 pathway, promoting mitophagy, and suppressing inflammation. These results provide a novel theoretical foundation for addressing the treatment of inflammatory pain. |
| first_indexed | 2024-03-09T16:32:35Z |
| format | Article |
| id | doaj.art-af1c5c9ef5624326acb6441a2268b8a3 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T16:32:35Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-af1c5c9ef5624326acb6441a2268b8a32023-11-24T15:00:10ZengMDPI AGPharmaceuticals1424-82472023-11-011611154510.3390/ph16111545The Analgesia Effect of Aucubin on CFA-Induced Inflammatory Pain by Inhibiting Glial Cells Activation-Mediated Inflammatory Response via Activating MitophagyDandan Yao0Yongjie Wang1Yeru Chen2Gang Chen3Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, ChinaDepartment of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaDepartment of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaBackground: Inflammatory pain, characterized by sustained nociceptive hypersensitivity, represents one of the most prevalent conditions in both daily life and clinical settings. Aucubin, a natural plant iridoid glycoside, possesses potent biological effects, encompassing anti-inflammatory, antioxidant, and neuroprotective properties. However, its impact on inflammatory pain remains unclear. The aim of this study is to investigate the therapeutic effects and underlying mechanism of aucubin in addressing inflammatory pain induced by complete Freund’s adjuvant (CFA). Methods: The CFA-induced inflammatory pain model was employed to assess whether aucubin exerts analgesic effects and its potential mechanisms. Behavioral tests evaluated mechanical and thermal hyperalgesia as well as anxiety-like behaviors in mice. The activation of spinal glial cells and the expression of pro-inflammatory cytokines were examined to evaluate neuroinflammation. Additionally, RNA sequencing was utilized for the identification of differentially expressed genes (DEGs). Molecular biology experiments were conducted to determine the levels of the PINK1 gene and autophagy-related genes, along with PINK1 distribution in neural cells. Furthermore, mitophagy induced by carbonyl cyanide m-chlorophenylhydrazone (CCCP) was employed to examine the roles of PINK1 and mitophagy in pain processing. Results: Aucubin significantly ameliorated pain and anxiety-like behaviors induced by CFA in mice and reduced spinal inflammation. RNA sequencing indicated PINK1 as a pivotal gene, and aucubin treatment led to a significant downregulation of PINK1 expression. Further GO and KEGG analyses suggested the involvement of mitochondrial function in the therapeutic regulation of aucubin. Western blotting revealed that aucubin markedly decreased PINK1, Parkin, and p62 levels while increasing LC3B expression. Immunofluorescence showed the predominant co-localization of PINK1 with neuronal cells. Moreover, CCCP-induced mitophagy alleviated mechanical and thermal hyperalgesia caused by CFA and reversed CFA-induced mitochondrial dysfunction. Conclusions: In summary, our data suggest that aucubin effectively alleviates CFA-induced inflammatory pain, potentially through triggering the PINK1 pathway, promoting mitophagy, and suppressing inflammation. These results provide a novel theoretical foundation for addressing the treatment of inflammatory pain.https://www.mdpi.com/1424-8247/16/11/1545aucubininflammationpainPINK1mitophagy |
| spellingShingle | Dandan Yao Yongjie Wang Yeru Chen Gang Chen The Analgesia Effect of Aucubin on CFA-Induced Inflammatory Pain by Inhibiting Glial Cells Activation-Mediated Inflammatory Response via Activating Mitophagy Pharmaceuticals aucubin inflammation pain PINK1 mitophagy |
| title | The Analgesia Effect of Aucubin on CFA-Induced Inflammatory Pain by Inhibiting Glial Cells Activation-Mediated Inflammatory Response via Activating Mitophagy |
| title_full | The Analgesia Effect of Aucubin on CFA-Induced Inflammatory Pain by Inhibiting Glial Cells Activation-Mediated Inflammatory Response via Activating Mitophagy |
| title_fullStr | The Analgesia Effect of Aucubin on CFA-Induced Inflammatory Pain by Inhibiting Glial Cells Activation-Mediated Inflammatory Response via Activating Mitophagy |
| title_full_unstemmed | The Analgesia Effect of Aucubin on CFA-Induced Inflammatory Pain by Inhibiting Glial Cells Activation-Mediated Inflammatory Response via Activating Mitophagy |
| title_short | The Analgesia Effect of Aucubin on CFA-Induced Inflammatory Pain by Inhibiting Glial Cells Activation-Mediated Inflammatory Response via Activating Mitophagy |
| title_sort | analgesia effect of aucubin on cfa induced inflammatory pain by inhibiting glial cells activation mediated inflammatory response via activating mitophagy |
| topic | aucubin inflammation pain PINK1 mitophagy |
| url | https://www.mdpi.com/1424-8247/16/11/1545 |
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