Abstract
Aims - The objective of this study was to investigate the effect of a berberine derivative, berberine8998, on serum cholesterol and lipid levels in-vivo and to explore the mechanisms involved.
Methods - Lipid lowering effect of berberine and berberine8998 was determined by high fat diet model on hamsters. Total cholesterol, low-density lipoprotein and triglycerides were analyzed. The potential target proteins on hamster liver were screened by iTRAQ labeled proteomics. The effect of berberine and berberine8998 on ACOX1 and ACSL1 was determined by western blot. Non-esterified fatty acids were analyzed to demonstrate its effect on triglyceride and fatty acid. Pharmacokinetics of berberine 8998 was conducted on SD rats.
Results - Berberine8998 significant lowered the total cholesterol, triglycerides (TG) and LDL-c levels in hamsters. Bioinformatics revealed that berberine and berberine8998 shared similar metabolic pathways where fatty acid metabolism was the most dominant one. Western blot validation results showed that peroxisomal acyl-coenzyme A oxidase 1 (ACOX1), Long-chain-fatty-acid—CoA ligase 1 (ACSL1) a protein involved in fatty acid metabolism, expressed differently in berberine8998 group comparing with both model group and berberine treatment group. Further biochemistry results showed that berberine8998 significantly lowered the non-esterified fatty acid (NEFA), which may lead to the reduction of TG levels in berberine8998 treatment groups and the difference in proteomics. Pharmacokinetic study showed that berberine8998, could remarkably improve absorption by 6.7 times, comparing with berberine.
Conclusion - These findings suggest that berberine8998 lowers both cholesterol and lipid with different mechanisms from berberine and is a promising therapeutic candidate for treating hypercholesterolemia and obesity.
Methods - Lipid lowering effect of berberine and berberine8998 was determined by high fat diet model on hamsters. Total cholesterol, low-density lipoprotein and triglycerides were analyzed. The potential target proteins on hamster liver were screened by iTRAQ labeled proteomics. The effect of berberine and berberine8998 on ACOX1 and ACSL1 was determined by western blot. Non-esterified fatty acids were analyzed to demonstrate its effect on triglyceride and fatty acid. Pharmacokinetics of berberine 8998 was conducted on SD rats.
Results - Berberine8998 significant lowered the total cholesterol, triglycerides (TG) and LDL-c levels in hamsters. Bioinformatics revealed that berberine and berberine8998 shared similar metabolic pathways where fatty acid metabolism was the most dominant one. Western blot validation results showed that peroxisomal acyl-coenzyme A oxidase 1 (ACOX1), Long-chain-fatty-acid—CoA ligase 1 (ACSL1) a protein involved in fatty acid metabolism, expressed differently in berberine8998 group comparing with both model group and berberine treatment group. Further biochemistry results showed that berberine8998 significantly lowered the non-esterified fatty acid (NEFA), which may lead to the reduction of TG levels in berberine8998 treatment groups and the difference in proteomics. Pharmacokinetic study showed that berberine8998, could remarkably improve absorption by 6.7 times, comparing with berberine.
Conclusion - These findings suggest that berberine8998 lowers both cholesterol and lipid with different mechanisms from berberine and is a promising therapeutic candidate for treating hypercholesterolemia and obesity.
| Original language | English |
|---|---|
| Pages (from-to) | 1473-1482 |
| Number of pages | 10 |
| Journal | Acta Pharmacologica Sinica |
| Volume | 39 |
| Early online date | 12 Apr 2018 |
| DOIs | |
| Publication status | Published - 1 Sept 2018 |
Access to Document
- Proteomics reveals potential new target protein
The final published version is available at DOI: 10.1038/aps.2017.200.