AIM OF THE REVIEW: The present review aims to compile an up-to-date information on the progress made in the protective role of swertiamarin in cardiac and metabolic diseases with the objective of providing a guide for future research on this bioactive molecule.
MATERIALS AND METHODS: Information on the swertiamarin was collected from major scientific databases (Pubmed, Springer, google scholar, and Web of Science) for publication between1974-2016. In this review, the protective role of swertiamarin on cardiac and metabolic diseases was discussed.
RESULTS: Swertiamarin reported to exhibit a wide range of biological activities such as anti-atherosclerotic, antidiabetic, anti-inflammatory and antioxidant effects. These activities were mainly due to its effect on various signaling pathways associated with cardiac remodeling events such as inhibition of NF-kB expression, LDL oxidation, apoptosis, inflammatory and lipid peroxidation markers and stimulation of antioxidant enzymes.
CONCLUSION: Sweriamarin exhibit a wide range of biological activities. This review presents evidence supporting the point of view that swertiamarin should be considered a potential therapeutic agent against cardiac and metabolic diseases, giving rise to novel applications in their prevention and treatment.
METHODS: Subjects (n = 121) received oral repaglinide (4 mg). Blood samples were taken at 0, 30, 60, 120, 180 and 240 min and serum concentrations of repaglinide were determined using high-performance liquid chromatography. Subjects were also genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for CYP3A4*4, *5 and*18 and by an allele-specific multiplex PCR for CYP2C8*2, *3, *4 and *5 alleles.
RESULTS: The allele frequencies of CYP2C8*1, *2, *3, *4 and *5 were 95.04, 0.40, 0.40, 0 and 4.13%, respectively. The frequencies of the CYP3A4*1, *4, *5 and *18 alleles were 97.93, 0, 0 and 2.07%, respectively. CYP2C8 and CYP3A4 genotypes were not significantly associated with repaglinide's blood glucose-lowering effect. However, the CYP3A4 genotype significantly influenced some of repaglinide's pharmacokinetics, where the mean elimination rate constant was 44.0% lower (p = 0.04) and the mean half-life was 33.8% higher (p = 0.04) in subjects with the CYP3A4*1/*18 genotype as compared to those with the normal CYP3A4*1/*1 genotype. This result confirms that CYP3A4 plays a large role in metabolizing repaglinide.
CONCLUSION: Genetic polymorphisms of CYP3A4, specifically CYP3A4*18, play a major role in contributing to the interindividual variability in repaglinide's pharmacokinetics.