Atractylenolide I Inhibits Nicotine-Induced Macrophage Pyroptosis and Alleviates Atherogenesis by Suppressing the TLR4/ROS/TXNIP/NLRP3 Pathway
<b>Background/Objectives:</b> Studies have shown that Atractylenolide I (AT-I) can exert anti-inflammatory and anti-oxidative effects, protecting against the development of various kinds of cardiovascular diseases. However, whether AT-I prevents nicotine-induced atherogenesis is unknown....
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2025-05-01
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| author | Huan-Huan Li Xian Liu Yu-Ping Wang Xi Xu Lin Zhu Wei Zhang Kun Ren |
| author_facet | Huan-Huan Li Xian Liu Yu-Ping Wang Xi Xu Lin Zhu Wei Zhang Kun Ren |
| author_sort | Huan-Huan Li |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Studies have shown that Atractylenolide I (AT-I) can exert anti-inflammatory and anti-oxidative effects, protecting against the development of various kinds of cardiovascular diseases. However, whether AT-I prevents nicotine-induced atherogenesis is unknown. This study was designed to explore the effects of AT-I on nicotine-induced macrophage pyroptosis and the progression of atherosclerosis. <b>Methods:</b> RT-qPCR and Western blot were used to detect the mRNA and protein levels of TXNIP and pyroptosis-related factors in THP-1-derived macrophages. ELISA was used to detect the secretion of pro-inflammatory cytokines. Hoechst/PI double-staining assay was used to assess plasma membrane integrity. The ROS assay kit, LDH release assay kit, and caspase-1 activity assay kit were used to detect ROS production, LDH release, and caspase-1 activity. Oil Red O, HE, and Masson staining were used to evaluate lipid accumulation, lesion size, and plaque stability in HFD-fed apoE<sup>−/−</sup> mice. <b>Results:</b> AT-I treatment significantly decreased pyroptosis-related factors expression, disrupted plasma membrane integrity, and down-regulated pro-inflammatory cytokines secretion, thereby inhibiting nicotine-induced pyroptosis of THP-1-derived macrophages. In addition, AT-I decreased ROS production and the expression of TLR4 and TXNIP. Lentivirus overexpression of TLR4 or TXNIP, or pre-treatment with ROS agonist, mainly reversed the anti-pyroptotic effects of AT-I in nicotine-treated THP-1-derived macrophages. Additionally, administering AT-I to HFD-fed apoE<sup>−/−</sup> mice markedly decreased nicotine-induced up-regulation of pyroptosis-related proteins in the aortas. Enzymatic methods and ELISA assay suggested that AT-I improved dyslipidemia and inflammation in vivo. Oil Red O, HE, and Masson staining showed that AT-I alleviated lipid accumulation, decreased plaque size, and increased plaque stability. <b>Conclusions:</b> Taken together, AT-I can be regarded as a potential phytomedicine that protects against macrophage pyroptosis and atherosclerosis triggered by nicotine. |
| format | Article |
| id | doaj-art-1cde72fecf3f4814b9a61b37c2022931 |
| institution | Kabale University |
| issn | 2218-1989 |
| language | English |
| publishDate | 2025-05-01 |
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| series | Metabolites |
| spelling | doaj-art-1cde72fecf3f4814b9a61b37c20229312025-08-20T03:47:58ZengMDPI AGMetabolites2218-19892025-05-0115532910.3390/metabo15050329Atractylenolide I Inhibits Nicotine-Induced Macrophage Pyroptosis and Alleviates Atherogenesis by Suppressing the TLR4/ROS/TXNIP/NLRP3 PathwayHuan-Huan Li0Xian Liu1Yu-Ping Wang2Xi Xu3Lin Zhu4Wei Zhang5Kun Ren6College of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230012, ChinaCollege of Nursing, Anhui University of Chinese Medicine, Hefei 230012, ChinaCollege of Nursing, Anhui University of Chinese Medicine, Hefei 230012, ChinaCollege of Nursing, Anhui University of Chinese Medicine, Hefei 230012, ChinaCollege of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, ChinaCollege of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, ChinaCollege of Nursing, Anhui University of Chinese Medicine, Hefei 230012, China<b>Background/Objectives:</b> Studies have shown that Atractylenolide I (AT-I) can exert anti-inflammatory and anti-oxidative effects, protecting against the development of various kinds of cardiovascular diseases. However, whether AT-I prevents nicotine-induced atherogenesis is unknown. This study was designed to explore the effects of AT-I on nicotine-induced macrophage pyroptosis and the progression of atherosclerosis. <b>Methods:</b> RT-qPCR and Western blot were used to detect the mRNA and protein levels of TXNIP and pyroptosis-related factors in THP-1-derived macrophages. ELISA was used to detect the secretion of pro-inflammatory cytokines. Hoechst/PI double-staining assay was used to assess plasma membrane integrity. The ROS assay kit, LDH release assay kit, and caspase-1 activity assay kit were used to detect ROS production, LDH release, and caspase-1 activity. Oil Red O, HE, and Masson staining were used to evaluate lipid accumulation, lesion size, and plaque stability in HFD-fed apoE<sup>−/−</sup> mice. <b>Results:</b> AT-I treatment significantly decreased pyroptosis-related factors expression, disrupted plasma membrane integrity, and down-regulated pro-inflammatory cytokines secretion, thereby inhibiting nicotine-induced pyroptosis of THP-1-derived macrophages. In addition, AT-I decreased ROS production and the expression of TLR4 and TXNIP. Lentivirus overexpression of TLR4 or TXNIP, or pre-treatment with ROS agonist, mainly reversed the anti-pyroptotic effects of AT-I in nicotine-treated THP-1-derived macrophages. Additionally, administering AT-I to HFD-fed apoE<sup>−/−</sup> mice markedly decreased nicotine-induced up-regulation of pyroptosis-related proteins in the aortas. Enzymatic methods and ELISA assay suggested that AT-I improved dyslipidemia and inflammation in vivo. Oil Red O, HE, and Masson staining showed that AT-I alleviated lipid accumulation, decreased plaque size, and increased plaque stability. <b>Conclusions:</b> Taken together, AT-I can be regarded as a potential phytomedicine that protects against macrophage pyroptosis and atherosclerosis triggered by nicotine.https://www.mdpi.com/2218-1989/15/5/329Atractylenolide Inicotinemacrophagepyroptosisatherosclerosis |
| spellingShingle | Huan-Huan Li Xian Liu Yu-Ping Wang Xi Xu Lin Zhu Wei Zhang Kun Ren Atractylenolide I Inhibits Nicotine-Induced Macrophage Pyroptosis and Alleviates Atherogenesis by Suppressing the TLR4/ROS/TXNIP/NLRP3 Pathway Metabolites Atractylenolide I nicotine macrophage pyroptosis atherosclerosis |
| title | Atractylenolide I Inhibits Nicotine-Induced Macrophage Pyroptosis and Alleviates Atherogenesis by Suppressing the TLR4/ROS/TXNIP/NLRP3 Pathway |
| title_full | Atractylenolide I Inhibits Nicotine-Induced Macrophage Pyroptosis and Alleviates Atherogenesis by Suppressing the TLR4/ROS/TXNIP/NLRP3 Pathway |
| title_fullStr | Atractylenolide I Inhibits Nicotine-Induced Macrophage Pyroptosis and Alleviates Atherogenesis by Suppressing the TLR4/ROS/TXNIP/NLRP3 Pathway |
| title_full_unstemmed | Atractylenolide I Inhibits Nicotine-Induced Macrophage Pyroptosis and Alleviates Atherogenesis by Suppressing the TLR4/ROS/TXNIP/NLRP3 Pathway |
| title_short | Atractylenolide I Inhibits Nicotine-Induced Macrophage Pyroptosis and Alleviates Atherogenesis by Suppressing the TLR4/ROS/TXNIP/NLRP3 Pathway |
| title_sort | atractylenolide i inhibits nicotine induced macrophage pyroptosis and alleviates atherogenesis by suppressing the tlr4 ros txnip nlrp3 pathway |
| topic | Atractylenolide I nicotine macrophage pyroptosis atherosclerosis |
| url | https://www.mdpi.com/2218-1989/15/5/329 |
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