Absorption and metabolic transformation mechanisms of the interaction between salvianolic acids and tanshinones in DKD rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Salviae Miltiorrhizae Radix Et Rhizoma (SM) (The plant name has been checked with http://www.theplantlist.org) mainly contains water-soluble salvianolic acids and fat-soluble tanshinone components, which are often used to treat diabetic kidney disease (DKD) in clinical settings.

AIM OF THE STUDY: To investigate the absorption and metabolism regulation of salvianolic acid B and tanshinone IIA combination (Comb1) along with fraction of salvianolic acids and tanshinones combination (Comb2) in DKD rats.

METHODS

Plasma concentrations of 11 salvianolic acids and tanshinone compounds of Comb2 were determined using ultra-performance liquid chromatography in rats with DKD. The Caco-2 cell monolayer model was used to study the transmembrane transport of salvianolic acids and tanshinones and compatibility of the two compounds. Finally, we assessed the effects of cytochrome P450 (CYP450) enzyme on the metabolism of salvianolic acids and tanshinones as well as the compatibility of their components in normal and DKD rats using in vitro incubation of liver microsomes.

RESULTS

The results showed that danshensu, protocatechualdehyde, dihydrotanshinone I, cryptotanshinone, tanshinone I, and tanshinone IIA were well-absorbed in vivo. Salvianolic acid B and salvianolic acids promoted the absorption of tanshinone IIA, whereas tanshinones promoted the absorption of danshensu and inhibited the absorption of protocatechualdehyde. In vitro incubation of liver microsomes showed that salvianolic acids may not undergo phase I metabolism. The pathological status of DKD affected the metabolic rates of tanshinones not the content of total CYP450 enzymes.

CONCLUSION

The molecular compatibility of salvianolic acid B and tanshinone IIA as well as of salvianolic acids and tanshinones act synergistically to improve DKD by affecting drug absorption and metabolism. This study provides an experimental basis for research and development of new drugs related to salvianolic acids and tanshinones.