Comparative Pharmacokinetic Study of Mangiferin in Normal and Alloxan-Induced Diabetic Rats after Oral and Intravenous Administration by UPLC-MS/MS

Abstract

Backgrounds: Diabetes mellitus (DM)-induced morphological and/or functional complications may alter the pharmacokinetic profiles of mangiferin. This study aims to compare pharmacokinetic profiles of mangiferin in normal and alloxan-induced diabetic rats after oral and intravenous administration. Methods: Mangiferin was administered orally (10 mg/kg) and intravenously (2 mg/kg) to normal and alloxan-induced diabetic Sprague-Dawley (SD) rats (n = 8). Blood samples were collected at different time points post-dose. Mangiferin and esculentoside (internal standard) were analyzed by Waters Acquity ultra-performance liquid chromatography system and TSQ Quantum Ultra triple quadrupole mass spectrometer (UPLC-MS/MS). Results: Mangiferin in normal and alloxan-induced diabetic rats experienced serious first-pass effect, which resulted in 1.71 and 0.80% of oral bioavailability respectively. Meanwhile, mangiferin was predominantly restricted to blood but not extensively distributed to organ tissues after intravenous administration. Compared with normal rats, the diabetic condition induced 53.26 and 50.90% decreases in C_max and AUC_0–t, respectively, for mangiferin after oral administration, and 63.08% decreases in C_max after intravenous administration. Conclusions: Compared to normal rats, pharmacokinetic parameters of mangiferin were altered in diabetic condition induced by alloxan. The findings might help to provide useful evidence for modeling of diabetic rats and the clinical applications of mangiferin.

Simultaneous determination of five alkaloids from Rauvolfia vomitoria in rat plasma by LC‐MS/MS: Application to a comparative pharmacokinetic study in normal and type 2 diabetic rats

“…The reasons for these discrepancies could be attributed to the changed activity of drug‐metabolizing enzymes and drug transporters under the pathological state of diabetes mellitus [26, 38, 39]. This is in accordance with several publications showing that diabetes mellitus significantly altered the pharmacokinetic characteristics of drugs in vivo [11, 40, 41]. Results presented a meaningful basis for the clinical applications of R. vomitoria when used in the treatment of diabetes mellitus.…”

Physicochemical Stability of Enriched Phenolic Fractions of Cyclopia genistoides and ex vivo Bi-directional Permeability of Major Xanthones and Benzophenones

“…Further context in terms of the present results and previous cell-based studies is the confirmed low oral bioavailability and tissue disposition of many dietary polyphenols (i.e., their tendency to not reach target tissues at the required concentrations following interaction with microbiota, absorption, and phase II metabolism) [27]. For example, oral bioavailability of mangiferin in normal and alloxan-induced diabetic rats amounted to just 1.71 % and 0.80 %, respectively [28], while the peak plasma concentra-▶ Table 1 Apparent permeability coefficients and efflux ratios for the 2 major xanthones, mangiferin and isomangiferin, and the 2 major benzophenones, IDG and I3G, in Cyclopia genistoides fractions, tested individually or in combination, for ex vivo intestinal permeability.…”

Role of Mangiferin in Management of Cancers through Modulation of Signal Transduction Pathways

“…Even though there are very significant potential health benefits of mangiferin, this compound shows substantial restrictions for its clinical use in cancer management due to poor water solubility, low absorption and rapid elimination [124]. Mangiferin led to an exhaustive hepatic first-pass metabolism, reducing the fraction of the dose reaching the systemic circulation, which is a reason causing the low oral bioavailability, leading to limitation of the efficacy [125]. An HPLC/MS method for the measurement of mangiferin in rat plasma was performed.…”