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It has been found that OCM has a significant inhibitory effect against Cutibacterium acnes (C. acnes), but the precise target and molecular mechanism are still not fully understood. In this study, the antibacterial activity of OCM against C. acnes and its potential effect on cell membranes were elucidated. Metabolomics methods were used to reveal metabolic pathways, and proteomics was used to explore the targets of OCM inhibiting C. acnes. The yield of the OCM was 3.3% (w\/w). A total of 19 compounds were identified, representing 96.213% of the total OCM composition, with the major constituents being phenylpropanoids (36.84%), sesquiterpenoids (26.32%), and monoterpenoids (15.79%). The main component identified was trans-cinnamaldehyde (85.308%). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of OCM on C. acnes were 60 \u00b5g\/mL and 180 \u00b5g\/mL, respectively. The modified proteomics results indicate that cinnamaldehyde was the main bioactive ingredient within OCM, which covalently modifies the ABC transporter adenosine triphosphate (ATP)-binding protein and nicotinamide adenine dinucleotide (NADH)-quinone oxidoreductase, hindering the amino acid transport process, and disrupting the balance between NADH and nicotinamide adenine dinucleoside phosphorus (NAD+), thereby hindering energy metabolism. We have reported for the first time that OCM exerts an antibacterial effect by covalent binding of cinnamaldehyde to target proteins, providing potential and interesting targets to explore new control strategies for gram-positive anaerobic bacteria.<\/jats:p>","DOI":"10.3390\/molecules29133165","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T06:04:18Z","timestamp":1719986658000},"page":"3165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Study on Oleum cinnamomi Inhibiting Cutibacterium acnes and Its Covalent Inhibition Mechanism"],"prefix":"10.3390","volume":"29","author":[{"given":"Huayong","family":"Peng","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 511400, China"},{"name":"School of Pharmaceutical Sciences, Jishou University, Jishou 416000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenliang","family":"Chu","sequence":"additional","affiliation":[{"name":"School of Food and Pharmaceutical Engineering, Zhaoqing University, Zhaoqing 526060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 511400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 511400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilei","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 511400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longping","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 511400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Depo","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 511400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3384-2365","authenticated-orcid":false,"given":"Zhimin","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 511400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, C.L., Fan, L.H., Fan, S.M., Wang, J.Q., Luo, T., Tang, Y., Chen, Z.M., and Yu, L.Y. 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