Pharmacokinetics and Tissue Distribution of Anwuligan in Rats after Intravenous and Intragastric Administration by Liquid Chromatography-Mass Spectrometry

Abstract

Anwuligan, a natural 2,3-dibenzylbutane lignan from the nutmeg mace of Myristica fragans, has been proved to possess a broad range of pharmacological effects. A rapid, simple, and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been established and successfully applied to the study of pharmacokinetics and tissue distribution of anwuligan after intravenous or intragastric administration. Sample preparation was carried out through a liquid-liquid extraction method with ethyl acetate as the extraction reagent. Arctigenin was used as the internal standard (IS). A gradient program was employed with a mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile. The mass spectrometer was operated in a positive ionization mode with multiple reaction monitoring. The transitions for quantification were m/z 329.0→205.0 for anwuligan and m/z 373.0→137.0 for IS, respectively. Calibration curves were linear over the ranges of 0.5-2000 ng/mL for both plasma samples and tissue samples (r > 0.996). The absolute bioavailability is 16.2%, which represented the existing of the obvious first-pass effect. An enterohepatic circulation was found after the intragastric administration. Anwuligan could be distributed rapidly and widely in different tissues and maintained a high concentration in the liver. The developed and validated LC-MS/MS method and the pharmacokinetic study of anwuligan would provide reference for the future investigation of the preclinical safety of anwuligan as a candidate drug.

Pharmacokinetics and Main Metabolites of Anwulignan in Mice

“…The relative bioavailability of anwulignan was 23.8%, which may be due to the incomplete absorption in the gastrointestinal tract or the obvious first-pass effect on the liver. This result is also reflected by the distribution data of anwulignan in the main organs, which is consistent with that reported by Song et al (2020) .…”

Therapeutic, and pharmacological prospects of nutmeg seed: A comprehensive review for novel drug potential insights

“…Despite its promising therapeutic potential, yet some voids still exist and need to be filled by reviewing the recent finding behind its mechanism of action of nutmeg. Nutmeg seed possess exceptional pharmacokinetic characteristics, due to its active compounds metabolites such as myristicin, safrole, and elemicin ( Yang et al, 2015 , Song et al, 2019 ). Several pathways of metabolism have been suggested, including hydroxylation, demethylenation, and amination of the allyl group (Neukamm et al, 2022).…”

Anwuligan inhibits the progression of non‐small cell lung cancer via let‐7c‐3p/PI3K/AKT/mTOR axis

“…ANW has been shown to induce the apoptosis of human promyelocytic leukemia cells (HL‐60) through the activation of caspase‐3, demonstrating its anti‐cancer activity. In addition, ANW attenuated cisplatin‐induced hepatotoxicity 14 . Despite these evidence of the anti‐cancer properties of ANW, its therapeutic effect in lung cancer remains unclear.…”

“…In addition, ANW attenuated cisplatin‐induced hepatotoxicity. 14 Despite these evidence of the anti‐cancer properties of ANW, its therapeutic effect in lung cancer remains unclear. This study demonstrated inhibitory effect of ANW treatment in lung cancer in vivo and in vitro and explored the underlying mechanisms to clarify its importance in NSCLC treatment.…”