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. 2022 Jun 21;13:879690. doi: 10.3389/fphar.2022.879690

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Copyright © 2022 Zhang, Chen, Jia, Liu, Wang, Zhang and Zhen.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Pharmacokinetic profiles of metformin in microglial cells in vitro and rats in vivo. (A) BV-2 microglial cells were incubated with different concentration of SHY-01 (SHY) or metformin hydrochloride (Met) for the indicated periods, supernatants were discarded and cells were lysed for intracellular metformin analysis by LC-MS. Data were expressed as mean ± SD (n = 3). (B) Uptake of metformin (15 min) into BV-2 microglia cells incubated with different concentrations of SHY-01 (SHY) or metformin hydrochloride (Met). The Michaelis-Menten equation with one saturable component was fit to the corrected uptake rate and the estimated Km and Vmax values are presented. (C) Plasma and brain concentration-time profile of metformin after intraperitoneal injection of SHY-01 in rats. SHY-01 (SHY, 50 mg/kg) or metformin hydrochloride (Met, 50 mg/kg) were administrated (i.p.) to rats. Blood samples were taken from fundus venous plexus at 0, 15, 30, and 60 min, 2, 4, 8, 12, and 24 h after injections. Concentrations of metformin in plasma was analyzed by LC-MS/MS. (D) Rats were sacrificed and brains were assessed at 0, 15, 30, and 60 min, 2, 4, 8, 12, and 24 h after injections. Concentrations of metformin in brain tissue were analyzed by LC-MS/MS. Results are expressed as mean ± SD (n = 3 rats/group). Two-tailed unpaired Students’ t-test was used to analyzing the difference between SHY- and Met-treated groups in each time point. ^∗ p < 0.05, ^∗∗ p < 0.01 versus the Met-treated group.