Molecular mechanism underlying Oleum Cinnamomi-induced ferroptosis in MRSE via covalent modification of AhpC
文献类型：期刊论文
| 作者 | Wang, Jianchao2; Wu, Ziqi2; Chen, Qianying1; Yan, Danna1; Ling, Yuanqiang4; He, Yuan2; Jin, Lu3; Zhao, Guomin1; Peng, Huayong1,2; Yang, Depo1 |
| 刊名 | FRONTIERS IN PHARMACOLOGY
 |
| 出版日期 | 2025-07-22 |
| 卷号 | 16页码:18 |
| 关键词 | Oleum Cinnamomi (OC) MRSE covalent inhibitors AhpC ROS metabolic pathways |
| DOI | 10.3389/fphar.2025.1554294 |
| 通讯作者 | Peng, Huayong(penghy29@163.com) ; Yang, Depo(lssydp@mail.sysu.edu.cn) |
| 英文摘要 | Introduction Oleum Cinnamomi (OC) is a volatile oil extracted by steam distillation from the dried branches and leaves of Cinnamomum cassia Presl, a plant belonging to the Lauraceae family. For centuries, OC has been utilized as a food preservative and flavoring agent, demonstrating potent inhibitory effects against bacteria and fungi. It is particularly effective in controlling infections caused by Methicillin-Resistant Staphylococcus epidermidis (MRSE), which often parasitizes the skin surface. To uncover the target and molecular mechanism by which OC eradicates MRSE, this study initially assessed the impact of OC and its primary constituents on oxidative stress in MRSE cells.Methods Mass spectrometry was employed to identify the target and covalent binding sites of OC, while a kit was used to monitor changes in key biomolecules of MRSE cells exposed to OC. Additionally, the efficacy of OC in inhibiting MRSE adhesion and infection of RAW 264.7 mouse macrophages was evaluated.Results The findings revealed that OC's main components, cinnamaldehyde and 2-methoxycinnamaldehyde, covalently modify MRSE and AhpC. This modification disrupts the AhpC-AhpE regeneration cycle, thereby disturbing both enzymatic and non-enzymatic redox homeostasis. It leads to intracellular ROS accumulation and effectively prevents MRSE from adhering to RAW 264.7 mouse macrophages. In response to ROS detoxification, MRSE attempts to upregulate the expression of TCA cycle-related proteins. However, the continuous accumulation of ROS inactivates the [Fe-S] protein of Aconase (ACO), hindering ACO's catalytic conversion of citric acid to isocitrate. This results in sustained intracellular accumulation of citric acid, limiting the TCA cycle and ATP generation. Simultaneously, enzymes involved in reduction catalysis, such as superoxide dismutase (SOD), peroxidase reductase (Prx), and glutathione synthase (GCL), are collectively inactivated. OC induces oxidative stress in MRSE, depleting GSH and triggering lipid peroxidation, which in turn induces MRSE to undergo ferroptosis.Discussion This covalent inhibition strategy targeting AhpC to induce ferroptosis offers a promising approach for effectively treating and preventing MRSE infections, thereby opening new avenues for combating drug-resistant pathogen infections. |
| WOS关键词 | ESCHERICHIA-COLI ; STRESS ; GLUTATHIONE |
| 资助项目 | National Key Research and Development Program of China[2022YFD1600304] ; Project for Provincial Agricultural Science and Technology Innovation and Promotion in Guangdong[2023KJ142] ; Scientific and Technological Project of Yunfu[2021020605] ; National Natural Science Foundation of China Youth Program[82304804] ; Yunnan Science and Technology Talents and Platform Program[202205AF150071] ; Natural Science Foundation of Hunan Province of China[2024JJ7415] ; Education Department of Hunan Province of China[24B0501] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001543592900001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321174]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Peng, Huayong; Yang, Depo |
| 作者单位 | 1.Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou, Peoples R China 2.Jishou Univ, Sch Pharmaceut Sci, Jishou, Peoples R China 3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Peoples R China 4.Guangdong L Med Biotechnol Co Ltd, Guangzhou, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Jianchao,Wu, Ziqi,Chen, Qianying,et al. Molecular mechanism underlying Oleum Cinnamomi-induced ferroptosis in MRSE via covalent modification of AhpC[J]. FRONTIERS IN PHARMACOLOGY,2025,16:18. |
| APA | Wang, Jianchao.,Wu, Ziqi.,Chen, Qianying.,Yan, Danna.,Ling, Yuanqiang.,...&Yang, Depo.(2025).Molecular mechanism underlying Oleum Cinnamomi-induced ferroptosis in MRSE via covalent modification of AhpC.FRONTIERS IN PHARMACOLOGY,16,18. |
| MLA | Wang, Jianchao,et al."Molecular mechanism underlying Oleum Cinnamomi-induced ferroptosis in MRSE via covalent modification of AhpC".FRONTIERS IN PHARMACOLOGY 16(2025):18. |
入库方式： OAI收割
来源：上海药物研究所
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