Identification of HMOX-1-Targeting Natural Compounds in <i>Camellia nitidissima</i> Chi for NSCLC Therapy: Integrating Bioassay and In Silico Screening Approaches
<b>Background/Objectives:</b> <i>Camellia nitidissima</i> Chi (<i>C. nitidissima</i>), a traditional Chinese “food and medicine homology” plant, has demonstrated potential anti-tumor properties. However, its mechanisms of anti-lung cancer activity via ferroptosis...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/6/824 |
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| Summary: | <b>Background/Objectives:</b> <i>Camellia nitidissima</i> Chi (<i>C. nitidissima</i>), a traditional Chinese “food and medicine homology” plant, has demonstrated potential anti-tumor properties. However, its mechanisms of anti-lung cancer activity via ferroptosis remain unclear. This study aimed to construct an integrated research system of “natural product extraction-purification, bioactivity evaluation, and computational drug screening” to explore the bioactive compounds in <i>C. nitidissima</i> leaves targeting HMOX-1-mediated ferroptosis and their anti-lung cancer mechanisms. <b>Methods:</b> Active fractions were prepared using ethanol extraction combined with polyamide column chromatography. The anti-lung cancer activity was evaluated using the NCI-H1975 cell model. Ferroptosis was verified via transmission electron microscopy (TEM), biochemical indicators, a PCR Array, and immunofluorescence. The bioactive compounds were identified using UPLC-Q Exactive MS, and their binding affinity to HMOX-1 was evaluated via molecular docking and dynamics simulations, followed by cellular validation. <b>Results:</b> The 95% F1 fraction from the extracts of <i>C. nitidissima</i> leaves exhibited the strongest anti-lung cancer activity, which could be significantly reversed by Ferrostatin-1. Furthermore, it induced typical ferroptosis-related structural damage in mitochondria, including shrinkage and a reduction in size, increased membrane density, and a reduction or even the disappearance of cristae structures. At the molecular level, this fraction significantly increased the levels of oxidative stress markers (ROS↑, MDA↑, Fe<sup>2+</sup>↑, and GSH↓) and upregulated the expression of key ferroptosis-related genes, including HMOX-1, CHAC1, and NOX1. Using UPLC-Q Exactive MS combined with computational simulation methods, four bioactive compounds with high affinity for HMOX1 were successfully identified, including isochlorogenic acid A (−8.4 kcal/mol), isochlorogenic acid C (−8.4 kcal/mol), apigenin (−7.8 kcal/mol), and chrysin (−7.3 kcal/mol). Cellular experiments validated that these compounds exhibited dose-dependent anti-proliferative effects. <b>Conclusions:</b> The leaves of <i>C. nitidissima</i> induce anti-lung cancer effects via HMOX-1-mediated ferroptosis. Isochlorogenic acid A/C, apigenin, and chrysin were identified as key bioactive components. These findings lay the foundation for the development of natural ferroptosis-targeted drugs. |
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| ISSN: | 1424-8247 |