Discussion on Allicin and Human Health

Allicin is an organic sulfur compound extracted from the bulb (garlic head) of garlic, a plant of the genus Allium in the Allium family. It is also found in onions and other Allium plants. Its scientific name is diallyl thiosulfinate. Allicin has a strong antibacterial effect and has a significant inhibitory effect on Escherichia coli and Shigella dysenteriae. It is widely used in feed, food, and medicine. Studies have shown that allicin can activate cells, promote energy production, increase disease resistance, and also has the effects of fat removal, blood pressure reduction, blood sugar reduction, cancer prevention, and gastrointestinal regulation. In view of the excellent effects of allicin, the development of allicin-related foods, medicines, health foods, functional foods, special medical foods, etc. provides corresponding references for the development of allicin.

Analysis of research results

1. Allicin activates AMPK in a muscle fiber-dependent manner through CSE/H2S-induced S-sulfation, thereby promoting glucose uptake in broilers

Abstract

Allicin is the product of enzymatic reaction after garlic damage and plays an important role in maintaining glucose homeostasis in mammals. However, the effect of allicin on glucose homeostasis in insulin resistance is still unclear. In this study, the effects of allicin on glucose metabolism in a chicken model were investigated using different muscle fibers.
Methods and Results: Male broilers were selected and randomly divided into three groups. Allicin was added to the basal diet at 0, 150, and 300 mg/kg, respectively, for 42 days. The results showed that allicin could improve the animal production performance of broilers during the fattening period. The glucose load test (2 g/kg) showed the regulatory effect of allicin on glucose homeostasis. In vitro experimental results showed that allicin increased glutathione (GSH) levels and the expression of cysteine ​​𝜸-cleavage enzyme (CSE), resulting in the production of endogenous hydrogen sulfide (H2S) in pectoralis major myotubes. Allicin stimulated adenosine monophosphate-activated protein kinase (AMPK)-sulfhydrylation and AMPK phosphorylation, promoting glucose uptake, which was inhibited in the presence of D,L-propylglycine (PAG, a CSE inhibitor). Conclusion: This study shows that allicin induces AMPKs-sulfhydrylation and AMPK phosphorylation, promoting glucose uptake through the CSE/H2S system in a muscle fiber-dependent manner.

Conclusion

Addition of allicin can improve the absorption and utilization of glucose in chicken skeletal muscle. Allicin stimulates AMPK sulfhydrylation, which in turn promotes glucose uptake through AMPK phosphorylation, a process regulated by the CSE/H2S pathway and intracellular GSH. Importantly, allicin stimulated glucose uptake in fast-contracting glycolytic muscle fibers, but not in slow-contracting oxidative muscle fibers. This indicates that the effect of allicin on glucose metabolism is muscle fiber-dependent and emphasizes the pharmacological importance of allicin on skeletal muscle glucose uptake and utilization. The in vivo mechanism of allicin needs further study to ensure its future application.

2. Aptamer-functionalized nanoflowers loaded with allicin improve obesity by regulating adipose tissue energy expenditure

Abstract

The aptamer-functionalized nanoflower-allicin delivery system (NFA) constructed with adipo-8 aptamers can load allicin and target adipose tissue. This delivery strategy is believed to have a more significant effect on promoting the formation of adipocytes. However, there are limited studies on the biological effects of NFA on brown adipose tissue (BAT). This study focused on the regulatory effects of NFA on the energy metabolism of brown adipose tissue. Compared with free allicin, NFA showed superior effects in upregulating genes related to BAT activation, thermogenesis, and Batokines, thereby promoting the yellowing of WAT. This suggests that NFA accelerates fatty acid catabolism by increasing the thermogenic activity of adipose tissue throughout the body. The results of the biosafety assessment showed that NFA has good biocompatibility and minimal side effects. In summary, the experimental data showed that NFA showed promise in the treatment of obesity and provided a theoretical basis for its application in obesity treatment.

Conclusion

An aptamer-functionalized DNA nanoflower was developed for the delivery of allicin to the target adipose tissue. The effects of NFA on thermogenesis and secretion of BAT were then studied. The results showed that NFA was more effective than free allicin in activating BAT and improving obesity. The strategy of loading allicin after the formation of DNA nanoflowers (NFs) was adopted. The successfully constructed NFA not only effectively overcomes the shortcomings of allicin, such as poor solubility, volatility and irritation, but also achieves targeted drug delivery, enhancing the potential of allicin in treating obesity. Compared with free allicin, NFA more effectively upregulates the expression of genes related to BAT activation and thermogenesis. NFA has a good effect on upregulating brown fat, suggesting that in addition to the direct effect of NFA on WAT, enhancing the secretion capacity of BAT may also be a way to promote WAT. DNA nanoflowers showed good biosafety through hematological examinations and pathological analysis of major organs. NFs are non-toxic to various blood cells, do not reduce oxygen transport capacity, do not affect hematopoiesis and immune response, and have good tissue compatibility.

3. Explore the lipid-lowering mechanism of allicin based on the CSE/H2S pathway

Abstract

The mechanism of allicin regulating lipid metabolism in mice fed a high-fat diet through the CSE/H2S pathway is clarified. Allicin intervention (120 mg/kg) significantly reduced the body weight, serum total cholesterol (TC) and triglyceride (TG) levels of mice, and increased the antioxidant level of the liver. Liver transcriptomic analysis showed that allicin affected several key metabolic pathways, including lipid metabolism (steroid hormone synthesis, unsaturated fatty acid synthesis, and PPAR signaling pathway) and antioxidant pathways (chemical carcinogenesis-reactive oxygen pathway and glutathione metabolic pathway). RT-qPCR experiments confirmed that the expression of CD36 in the liver of the HA group (high-dose allicin, 120 mg/kg) was downregulated, and the expression of LPL, GST, GPX, and GCLC was upregulated. In addition, metabolomics analysis identified core differential metabolites mainly related to sulfate/sulfite metabolism and glutathione metabolic pathways. This was demonstrated by changes in the levels of sulfur-containing compounds such as H2S, L-glutathione (reduced), G-glutamate-formylcysteine, and methionine. In the constructed HepG2 hyperlipidemia cell model, after treatment with DL-Propargylglycine (PAG, H2S synthesis inhibitor), lipid content was significantly increased, and the expression levels of antioxidant genes such as GST, GPX, and GCLC were reduced compared with the Allicin-600 group. This further validates the key role of the CSE/H2S pathway in the lipid-lowering effect of allicin. In conclusion, when used as an H2S donor, allicin exhibits a strong lipid-lowering activity, laying the foundation for the development of a wider range of allicin-related health products.

Conclusion

In the context of hyperlipidemia, the link between the lipid-lowering effect of allicin and H2S has been established, indicating that the CSE/H2S pathway plays a vital role in mediating the lipid-lowering effect of allicin. Sulfur-containing compounds, such as methionine, L-cysteine ​​glycine, and L-glutamate, can release H2S through the action of CSE enzymes. On the one hand, H2S molecules reduce lipid uptake and utilization by regulating the expression of genes such as CD36 and LPL, while upregulating the expression of antioxidant genes GPX, GCLC, and GST, thereby enhancing the body's antioxidant capacity and preventing the aggravation of hyperlipidemia and liver damage. It reveals an important opportunity to develop and apply health-promoting dietary products using allicin as a natural H2S donor.

4. Allicin inhibits the biological activity of cervical cancer cells by inhibiting circEIF4G2

Abstract

The anti-tumor effect of allicin on cervical cancer was explored through cell experiments. This study took Hela and Siha as the research targets. In the first step, Hela and Siha cell lines were treated with different concentrations of allicin (20, 40, 80 μmol/L), and then the role of circEIF4G2 in the anti-tumor effect of allicin on Hela and Siha cell lines was explored; CCK-8 and EdU staining of cell proliferation and EdU-positive cell number; flow cytometry to determine cell apoptosis rate; transwell method to determine the number of invasive cells; wound healing rate determination; qRT-PCR and WB methods to determine relative mRNA and protein levels. The experimental results showed that allicin supplementation can significantly inhibit cell proliferation and the number of EdU-positive cells, significantly increase the cell apoptosis rate; the number of invasive cells and wound healing rate were significantly inhibited, and circEIF4G2 mRNA expression was significantly downregulated. However, there were no significant differences in cell biological activities such as cell proliferation, apoptosis, invasion and migration, as well as the expression of related genes and proteins between allicin, si-circEIF4G2 and allicin + si-circEIF4G2. In summary, allicin can inhibit the biological activity of cervical cancer cells by downregulating circEIF4G2/HOXA1/AKT/mTOR.

Conclusion

This study found that allicin can significantly reduce the invasion and metastasis rates of Hela and Siha cells, and has a good inhibitory effect at high concentrations. After allicin treatment, the proliferation, invasion and migration abilities of Hela and Siha cells were significantly inhibited, and the apoptosis rate was significantly increased. Among them, high-dose allicin had the best inhibitory effect. Further detection found that the expression of the circEIF4G2 gene was significantly inhibited, and reducing the expression of circEIF4G2 can effectively reduce the biological activity of CC cells. In addition, transfection of Hela and Siha cells with si-circEIF4G2 can significantly reduce the activity of these cells, but when this transfection was combined with allicin intervention, the anticancer effect was not enhanced. Therefore, allicin may exert its anticancer effect by inhibiting circEIF4G2. circEIF4G2 was reduced in Hela and Siha cells, CC cell activity was inhibited, and the HOXA1/AKT/mTOR signaling pathway was significantly inhibited. In summary, allicin can inhibit the biological activity of CC cells by inhibiting circEIF4G2 and downregulating the activity of the downstream HOXA1/AKT/mTOR signaling pathway.