Pharmacokinetic Interaction of Green Rooibos Extract With Atorvastatin and Metformin in Rats

Abstract

An aspalathin-rich green rooibos extract (Afriplex GRT™) has demonstrated anti-diabetic and hypolipidemic properties, while also moderately inhibiting CYP3A4 activity, suggesting a potential for herb–drug interaction. The present study, therefore, evaluated the effects of orally administered GRT on the pharmacokinetics of atorvastatin and metformin in Wistar rats. Wistar rats were orally treated with GRT (50 mg/kg BW), atorvastatin (40 mg/kg BW) or metformin (150 mg/kg BW) alone or 50 mg/kg BW GRT in combination with 40 mg/kg BW atorvastatin or 150 mg/kg BW metformin. Blood samples were collected at 0, 10, and 30 min and 1, 2, 4, 6, and 8 h and plasma samples obtained for Liquid chromatography-mass spectrometry (LC-MS/MS) analyses. Non-compartment and two-compartment pharmacokinetic parameters of atorvastatin and metformin in the presence or absence of GRT were determined by PKSolver version 2.0 software. Membrane transporter proteins, ATP-binding cassette sub-family C member 2 (Abcc2), solute carrier organic anion transporter family, member 1b2 (Slco1b2), ATP-binding cassette, sub-family B (MDR/TAP), member 1A (Abcb1a), and organic cation transporter 1 (Oct1) mRNA expression were determined using real-time PCR expression data normalized to β-actin and hypoxanthine-guanine phosphoribosyltransferase (HPRT), respectively. Co-administration of GRT with atorvastatin substantially increased the maximum plasma concentration (Cmax) and area of the plasma concentration–time curve (AUC0-8) of atorvastatin by 5.8-fold (p = 0.03) and 5.9-fold (p = 0.02), respectively. GRT had no effect on the plasma levels of metformin. GRT increased Abcc2 expression and metformin downregulated Abcb1a expression while the combination of GRT with atorvastatin or metformin did not significantly alter the expression of Slco1b1 or Oct1 did not significantly alter the expression of Sclo1b2 or Oct1. Co-administration of GRT with atorvastatin in rats may lead to higher plasma concentrations and, therefore, to an increase of the exposure to atorvastatin.

Therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice

“…These results confirm that although we established moderate glucose and lipoprotein lowering biological effects of GRT and atorvastatin co-therapy, mechanistically, the increased expression of genes involved in fat accumulation and storage could enhance the hepatotoxic effects of atorvastatin. This corresponds with a previous study that showed increased plasma concentrations of atorvastatin after GRT supplementation increasing the likelihood of a herbdrug interaction [62].…”

Potential Pharmacokinetics and Pharmacodynamics (PK-PD) Drug-Herbs Interactions (DHI) from Metformin and Traditional Medicines: A Literature Review

“…It showed reducing in Tmax, Cmax, and AUC insignificantly and also increased insignificantly in T 1 / 2 . 37 GRT could increase mRNA Abcc2 expression significantly, while metformin downregulated the mRNA Abcc2 expression. Combination metformin and GRT made mRNA Abcc2 downregulated its expression.…”

“…The AMPactivated protein kinase was activated and glucose translocated to the cell membrane through GLUT-4 by asphalathin. 36,37 When combined with metformin the pharmacokinetics parameters did not showed affected significantly and also the concentrations of metformin did not change significantly. It showed reducing in Tmax, Cmax, and AUC insignificantly and also increased insignificantly in T 1 / 2 .…”

“…[38][39][40] The combination of both not affected of metformin pharmacokinetics profile specifically, and for the pharmacodynamic effect also insignificantly affected by combination compared to given metformin alone. 37…”

A new perspective to improve the treatment of Lianhuaqingwen on COVID-19 and prevent the environmental health risk of medication

“…Studies have shown that the interaction of TCM multiple compounds could affect the absorption, distribution, metabolism, and other drug stages in humans. It is also the main reason for clinical drug treatment failure and an important factor for side effects (Lu and Di 2019 ; Patel et al 2019 ). LH is composed of 13 TCM (Wu 2005 ), but the material basis of its efficacy is still unclear.…”