Possible Interaction: Berberine and Metformin

“Consistent with pharmacokinetic findings, … vitro incubations of MET … BBR in both rat intestinal content and human fecalase demonstrated significant increase on MET persisted after 24-h incubation in G3R/…/H. Moreover, post-dose (G3B) and pre-dose (G4B) of BBR decreased the MET degradation significantly in most selected bacteria.”

“Furthermore, metformin could increase anti-proliferative effects of mTORC1 and PI3K/mTOR inhibitors as well as natural products such as berberine and the anti-malarial drug chloroquine in certain PDAC lines.”

“ Berberine inhibited the transport activity of OCT1 and OCT2 and showed significant potential drug–drug interactions with metformin in in vivo rats.”

“Co-administration of berberine increased the initial plasma concentration and AUC of metformin and decreased systemic clearance and volume of distribution of metformin in rats, suggesting that berberine inhibited disposition of metformin, which is governed by OCT1 and OCT2.”

“In HEK293 cells, berberine inhibited OCT1- and OCT2-mediated metformin uptake in a concentration dependent manner and IC50 values for OCT1 and OCT2 were 7.28 and 11.3 μM, respectively.”

“Thus, we assessed the potential drug–drug interactions between berberine and metformin.”

“Interestingly, the effects of metformin could be enhanced by BBR and certain modified BBRs.”

“Finally, metformin enhanced the effects of BBR both in vitro and in vivo.”

“In addition, there is a synergy of BBR and metformin.”

“As revealed by comparison with the metformin‐only group, berberine significantly decreased the maximum plasma concentration (Cmax), area under the curve from 0 to 4 h (AUC0–4h), and urinary and bile excretion, and increased the kidney tissue concentration of metformin in rats.”

“Furthermore, metformin increased kidney and liver concentrations and reduced the urinary and biliary excretion of berberine.”

“In contrast, co‐administration of metformin increased the Cmax and AUC0‐4h of berberine with no significant difference in pharmacokinetics parameters between co‐administration and berberine‐only groups.”

“ Metformin (≥1 or ≥0.3 mM) decreased berberine transport in MDCK‐rOCT1, MDCK‐rOCT2, and MDCK‐rMATE1 cells.”

“These results suggest that the combination of metformin and berberine induced a pharmacokinetic interaction by cooperatively inhibiting OCT and MATE1‐mediated transport.”

“… berberine … metformin , and in transfected Madin‐Darby canine kidney (MDCK)‐rat organic cation transporter 1 (MDCK‐rOCT1), MDCK‐rat organic cation transporter 2 (MDCK‐rOCT2), and … in a concentration‐dependent manner with half‐maximal inhibitory concentration (IC50) values of 18.8, 1.02, and 10.7 &mgr;M, respectively.”

“Whereas, berberine , in combination with either metformin or THZ, has shown an additive effect with maximum 2DG uptake of 4.1- and 4.7-times from the base value, respectively.”

“ Metformin (mM) and berberine (µM) at combination ratios of 2:40, 1:20, 0.5:10, and 0.25:5 exhibited a synergistic lipid-lowering effect on HepG2 cells.”

“The combination of Metformin and berberine exerted synergistic lipid-lowering effects on HepG2 cells by reducing total lipid content, triglyceride level, and the expression of the genes involved in lipogenesis.”

“The lowest dose of the combination Metformin (0.25 mM) and berberine (5 μM)] also synergistically reduced the expression of the FAS and SREBP-1c genes in HepG2 cells treated with high glucose.”