Researchers in China identified and analyzed garlic's active components and their targets in atherosclerosis while investigating the underlying pharmacological mechanisms. They found that garlic lowers the expression of ferroptosis-related genes, indicating its potential application in treating atherosclerosis by regulating ferroptosis and reducing lipid peroxidation.
Study
Experimental verification involved cell experiments with mouse cells for cytotoxicity, biochemical assays, Oil red O staining, and Western blotting. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was conducted to measure gene expression levels. Further, mouse models were divided into four groups: sham operation group, model group, allicin treatment group, and negative control group. Biochemical assays were performed on serum samples, and histological changes were observed.
Findings and Discussion
A total of 16 active garlic components and 503 potential targets were identified. Additionally, 3,033 key targets for atherosclerosis were found. By intersecting garlic's targets with atherosclerosis targets, 230 potential therapeutic targets were identified. Pathway enrichment analyses revealed 2017 biological processes, 78 cellular components, and 200 molecular functions. Significant processes included response to oxidative stress and inflammation. Potential targets were found to be enriched in lipid metabolism and atherosclerosis pathways.
Molecular docking studies demonstrated that garlic components like sobrol A, benzaldoxime, allicin, and (+)-L-alliin interact strongly with ferroptosis-related proteins such as GPX4 (glutathione peroxidase), DPP4 (dipeptidyl peptidase 4), and ALOX5 (arachidonate 5-lipoxygenase). In animal models, specifically, apolipoprotein E knockout and C57BL/6 mice, allicin was shown to significantly reduce plaque formation and lipid deposition in the carotid artery. Allicin was also found to improve lipid profiles, given by the lower concentrations of low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides in the treated group as compared to the untreated group. Allicin was found to mitigate lipid peroxidation and iron death, as shown by reduced levels of malondialdehyde and increased GPX4 in the serum.
In in vitro experiments, Allicin was found to decrease oxidative damage caused by ox-LDL. The protein expression of ferroptosis-related genes DPP4 and ALOX5 was found to reduce with allicin treatment, while GPX4 expression was found to increase. Additionally, allicin was found to lower ALOX5 messenger ribonucleic acid (mRNA) levels and increased GPX4 mRNA levels compared to the ox-LDL group. These findings suggest that garlic, especially allicin, may improve atherosclerosis by regulating ferroptosis, highlighting its potential therapeutic value in CVD management.
Conclusion
In conclusion, the study highlights the potential of garlic and its active compounds, such as sobrol A, allicin, (+)-L-alliin, and benzaldoxime, in treating atherosclerosis by targeting ferroptosis-related mechanisms. The specific gene targets identified in the study provide a basis for designing targeted therapies that could enhance treatment outcomes in the future. The findings warrant further research into garlic-based therapies, which could potentially lead to more effective, natural treatment options for CVDs.