Oral Delivery of Honokiol Microparticles for Nonrapid Eye Movement Sleep

Abstract

Honokiol (HNK) is a small-molecule lignin extracted from Magnolia Officinalis, demonstrating high potency in promoting nonrapid eye movement (NREM) sleep by modulating the benzodiazepine site of the GABAA receptor. However, the clinical use of HNK in the treatment of insomnia is restricted by its extremely low oral bioavailability. In the present work, enhanced oral bioavailability of HNK was achieved by loading it into poly lactide–glycolide acid microparticles (HNK-MP). After oral administration, HNK-MP demonstrated 15-fold increase of AUC0–12 h in comparison to free HNK. The maximum blood concentration (C max) of HNK in HNK-MP-treated rats was 3.6 μg/mL at 2 h after oral administration, which was 6.5-fold of that in free HNK-treated rats. Oral administration of HNK-MP (20 mg/kg) efficiently increased NREM sleep by 60% by enhancing the transition from wakefulness to NREM sleep in rats. The biosafety of HNK-MP was assessed in vivo, and no damage occurred in the gastrointestinal tract. The present study provides a promising oral HNK formulation for the treatment of insomnia.

Integrated Screening of Effective Anti-Insomnia Fractions of Zhi-Zi-Hou-Po Decoction via Drosophila melanogaster and Network Pharmacology Analysis of the Underlying Pharmacodynamic Material and Mechanism

“…Insomnia is commonly regarded as a disturbance in the dynamic balance of molecules in the brain that promote either sleepiness or wakefulness. Based on the reports about the mechanism of insomnia, we can learn that insomnia is influenced by various factors which are involved in disorder of hyperarousal; the relationship between stimulants associated with sleep promotion, abnormal regulation of the hypothalamic–pituitary–adrenal axis (HPA), the effects of inflammatory cytokine on slow-wave sleep, involvement of multiple neurotransmitters in the CNS, , and circadian rhythm. Prolonged exposure to light decreases the release of melatonin (MT), which is closely related to the regulation of sleep cycle, antioxidant damage, sedative, and hypnotic effects .…”

“…In addition, honokiol possesses antioxidant, anti-inflammatory, anticancer, antidepressant, and neuroprotective activities . It is reported that honokiol has a high potency in promoting nonrapid eye movement sleep by modulating the benzodiazepine site of the GABA A receptor. ,− …”