Scutellarin inhibits pyroptosis via selective autophagy degradation of p30/GSDMD and suppression of ASC oligomerization
Most of the pyroptosis inhibitors targeted Gasdermin D (GSDMD) are functioning by restraining GSDMD-N (p30) oligomerization. For the first time, this work discovered a pyroptosis inhibitor taking effect by degrading p30 and GSDMD. As the principal bioactive constituent in Erigeron breviscapus, scute...
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Elsevier
2025-02-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825000301 |
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| author | Danyue Li Weilv Xu Suhui He Xinyue Li Yumeng Wang Qian Lv Nan Chen Lu Dong Feng Guo Fushan Shi |
| author_facet | Danyue Li Weilv Xu Suhui He Xinyue Li Yumeng Wang Qian Lv Nan Chen Lu Dong Feng Guo Fushan Shi |
| author_sort | Danyue Li |
| collection | DOAJ |
| description | Most of the pyroptosis inhibitors targeted Gasdermin D (GSDMD) are functioning by restraining GSDMD-N (p30) oligomerization. For the first time, this work discovered a pyroptosis inhibitor taking effect by degrading p30 and GSDMD. As the principal bioactive constituent in Erigeron breviscapus, scutellarin (SCU) assumes a pivotal role in the realm of anti-inflammatory processes. In this study, SCU demonstrated efficacy in hindering pyroptosis mediated by the NOD-like receptor protein 3 (NLRP3) inflammasome, absent in melanoma 2 (AIM2) inflammasome, NLR-family CARD-containing protein 4 (NLRC4) inflammasome, and that activated through the non-canonical pathway. The inhibitory effect is achieved by thwarting apoptosis-associated speck-like protein containing CARD (ASC) oligomerization and inducing the ubiquitin-dependent selective autophagy of p30/GSDMD. Throughout the autophagic process, SCU facilitates selective autophagy of the pyroptosis executor p30/GSDMD through K33-linked polyubiquitination at Lys51 catalyzed by the E3 ligase tripartite motif-containing 21 (TRIM21). This process contributes to the recognition of p30/GSDMD by the cargo receptor sequestosome 1 (SQSTM1)/p62. The characteristic positions SCU as a prospective clinical intervention for a broader spectrum of inflammatory-related disorders. |
| format | Article |
| id | doaj-art-4b0b09f23eed4b0f83a3bef33a851a18 |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-4b0b09f23eed4b0f83a3bef33a851a182025-02-08T04:59:49ZengElsevierPharmacological Research1096-11862025-02-01212107605Scutellarin inhibits pyroptosis via selective autophagy degradation of p30/GSDMD and suppression of ASC oligomerizationDanyue Li0Weilv Xu1Suhui He2Xinyue Li3Yumeng Wang4Qian Lv5Nan Chen6Lu Dong7Feng Guo8Fushan Shi9MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou 310058, China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaMOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou 310058, ChinaMOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou 310058, ChinaMOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou 310058, ChinaMOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou 310058, ChinaMOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou 310058, ChinaMOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou 310058, ChinaMOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310012,ChinaMOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou 310058, China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; Corresponding author at: MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou 310058, China.Most of the pyroptosis inhibitors targeted Gasdermin D (GSDMD) are functioning by restraining GSDMD-N (p30) oligomerization. For the first time, this work discovered a pyroptosis inhibitor taking effect by degrading p30 and GSDMD. As the principal bioactive constituent in Erigeron breviscapus, scutellarin (SCU) assumes a pivotal role in the realm of anti-inflammatory processes. In this study, SCU demonstrated efficacy in hindering pyroptosis mediated by the NOD-like receptor protein 3 (NLRP3) inflammasome, absent in melanoma 2 (AIM2) inflammasome, NLR-family CARD-containing protein 4 (NLRC4) inflammasome, and that activated through the non-canonical pathway. The inhibitory effect is achieved by thwarting apoptosis-associated speck-like protein containing CARD (ASC) oligomerization and inducing the ubiquitin-dependent selective autophagy of p30/GSDMD. Throughout the autophagic process, SCU facilitates selective autophagy of the pyroptosis executor p30/GSDMD through K33-linked polyubiquitination at Lys51 catalyzed by the E3 ligase tripartite motif-containing 21 (TRIM21). This process contributes to the recognition of p30/GSDMD by the cargo receptor sequestosome 1 (SQSTM1)/p62. The characteristic positions SCU as a prospective clinical intervention for a broader spectrum of inflammatory-related disorders.http://www.sciencedirect.com/science/article/pii/S1043661825000301Gasgermin DP30ScutellarinAutophagyUbiquitin-dependentTRIM21 |
| spellingShingle | Danyue Li Weilv Xu Suhui He Xinyue Li Yumeng Wang Qian Lv Nan Chen Lu Dong Feng Guo Fushan Shi Scutellarin inhibits pyroptosis via selective autophagy degradation of p30/GSDMD and suppression of ASC oligomerization Pharmacological Research Gasgermin D P30 Scutellarin Autophagy Ubiquitin-dependent TRIM21 |
| title | Scutellarin inhibits pyroptosis via selective autophagy degradation of p30/GSDMD and suppression of ASC oligomerization |
| title_full | Scutellarin inhibits pyroptosis via selective autophagy degradation of p30/GSDMD and suppression of ASC oligomerization |
| title_fullStr | Scutellarin inhibits pyroptosis via selective autophagy degradation of p30/GSDMD and suppression of ASC oligomerization |
| title_full_unstemmed | Scutellarin inhibits pyroptosis via selective autophagy degradation of p30/GSDMD and suppression of ASC oligomerization |
| title_short | Scutellarin inhibits pyroptosis via selective autophagy degradation of p30/GSDMD and suppression of ASC oligomerization |
| title_sort | scutellarin inhibits pyroptosis via selective autophagy degradation of p30 gsdmd and suppression of asc oligomerization |
| topic | Gasgermin D P30 Scutellarin Autophagy Ubiquitin-dependent TRIM21 |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825000301 |
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