Abstract
Tilianin was obtained from the medicinal plant Agastache mexicana (Kunth) Lint & Epling, Lamiaceae, a compound that is candidate to develop new multitarget drug for the treatment of metabolic syndrome–related diseases. The main aim of this work is to determine the pharmacokinetic parameters of tilianin after oral administration in Wistar rats to clarify its absorption pattern, distribution, metabolism, excretion, and permeability. A validated sensitive, selective, and reproducible high-performance liquid chromatography method was developed: r2 = 0.9992, 5.8 min of retention time, recovery of 100.2%, and LOD and LOQ were 1.86 and 5.63 μg/ml, respectively. By non-compartmental analysis, pharmacokinetic parameters were obtained, such as Tmax (1.00 h), Cmax (29.01 μg/ml), T1/2 (3.33 h), MRT (2.91 h), AUC0–t (62.25 µg h/ml), AUC0–∞ (92.47 µg h/ml), Kel (0.21 1/h), and Vd/F (2,788.05 ml). It was also determined that tilianin is deposited at 5 h in the pancreas, liver, and lung. The protonated [M + H]+ ion peaks of main metabolites were obtained by LC–MS at m/z 285.1 and 625.2, corresponding to acacetin and tilianin-glucuronic acid conjugation, respectively. In addition, tilianin was not excreted and metabolized through urine. Tilianin had a lower permeability pattern than furosemide and naproxen using everted gut model (1.43 × 10−6 cm/s). The pharmacokinetic study showed a long-lasting terminal half-life, and rapid absorption of tilianin in rodents. These results support the search to develop tilianin as a new drug for the treatment of metabolic syndrome.
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This work was supported by SEP-CONACYT (Ciencia Básica A1-S-13540), CONACYT FORDECYT-PRONACES (Ciencia de Frontera 377882/2020), and IN210222, PAPIIT, DGAPA, UNAM.
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OH-A: performed the experiments, data analysis, drafted the manuscript; SE-S: project design, drafted and revised the final manuscript, funding acquisition; JCR-L: conceptualization, supervision in the validation of the analytical method by HPLC; AP-L: performed the LC–MS analysis; GÁ-V: data analysis and interpretation, technical assistance, and revised the manuscript; RV-M: drafted and revised the final manuscript, funding acquisition.
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In memory of Professor Ismael León-Rivera, may he rest in peace.
Taken in part from the PhD thesis of O. Hernández-Abreu.
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Hernández-Abreu, O., Estrada-Soto, S., Rivera-Leyva, J.C. et al. Pharmacokinetic Study of Tilianin After Oral Administration in Wistar Rats by HPLC. Rev. Bras. Farmacogn. (2024). https://doi.org/10.1007/s43450-024-00541-8
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DOI: https://doi.org/10.1007/s43450-024-00541-8