Pharmacokinetics and tissue distribution of dual PPARa/? agonist gigantol in mice

Gigantol is a bioactive compound in Dendrobium officinale with a wide range of pharmacological properties. This study developed an ultrahigh-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) method for quantifying gigantol, which was subsequently applied to assess its pharmacokinetics and tissue distribution in Kunming mice. Additionally, the effects of gigantol on peroxisome proliferator-activated receptors (PPARs) were investigated. The UHPLC-Q-TOF/MS method was validated following the guidelines provided by the FDA and EMA for bioanalytical methods. Pharmacokinetic analysis revealed that gigantol exhibits a non-linear kinetic profile. Tissue distribution studies demonstrated high concentrations of gigantol in the liver and lungs. RNA sequencing (RNA-seq) indicated significant enrichment of PPAR signaling pathways in the KEGG database during gigantol-induced gene expression changes in the liver of Kunming mice. Molecular fingerprinting, docking studies and dual luciferase reporter assays confirmed that gigantol is a dual PPARa/? agonist. These findings provide valuable insights for preclinical research on gigantol. Overall design: Six male Kunming mice (6–8 weeks old, 20–28 g) were randomly divided into two groups (Administration group (ADMG) and normal group (NG)). ADMG group received gigantol (10 mg/kg) via p.o., while NG group received an equivalent volume of vehicle as a control. Four hours post-administration, the mice were euthanized, and fresh liver tissues were collected. Total RNA was extracted according to the manufacturer's instructions. The purity and integrity of the RNA were assessed using a NanoDrop ND-100 (Wilmington, DE, USA) and an Agilent Bioanalyzer 2100 (Agilent, CA, USA), respectively.