Antidepressant-like mechanism of honokiol in a rodent model of corticosterone-induced depression

Abstract

Depression is closely linked to hypothalamus-pituitaryadrenal axis hyperactivity. Honokiol, a biphenolic lignan compound obtained from the traditional Chinese medicine Magnolia officinalis, can reduce the activity of the hypothalamus-pituitary-adrenal axis and improve depression-like behavior caused by hypothalamuspituitary-adrenal axis hyperactivity. The current study investigated the specific mechanism of action of this effect. A depression model was established by repeated injections of corticosterone to study the antidepressantlike effect of honokiol and its potential mechanism. Honokiol prevented the elevated activity of the hypothalamuspituitary-adrenal axis and the depression-like behavior induced by corticosterone. Treatment with honokiol resulted in greater glucocorticoid receptor mRNA expression, greater glucocorticoid receptor-positive expression, and a greater ratio of glucocorticoid receptor to the mineralocorticoid receptor in the hippocampus. Moreover, honokiol treatment led to lower levels of interleukin-1β in serum and the positive expression of the interleukin-1β receptor in the hippocampus. These results demonstrate that the antidepressant-like mechanism of honokiol, which has effects on inflammatory factors, may act through restoring the typical activity of the hypothalamus-pituitary-adrenal axis by regulating the glucocorticoid receptor-mediated negative feedback mechanism and the balance between glucocorticoid and mineralocorticoid receptors.

A System Biology Approach Reveals New Targets for Human Thyroid Gland Toxicity in Embryos and Adult Individuals

“…Its pharmacological effects include antiinflammatory, antithrombotic, antiarrhythmic, antioxidative, central depressant, muscle relaxant, and anxiolytic effects [82]. In the endocrine system, honokiol activates the ERK/cfos signaling pathway, increases levels [83], increases the mRNA expression of glucocorticoid receptors in the hippocampus [84], improves insulin resistance in type 2 diabetic db/db mice [85], and inhibits 5-alpha-reductase type 1, modulating testosterone levels in vitro [82]. Nevertheless, its effects on the thyroid gland have never been reported.…”

Honokiol improves depression-like behaviors in rats by HIF-1α- VEGF signaling pathway activation

“…The pathogenesis of depression was previously reported to be associated with synaptic plasticity disorders ( Pilar-Cuéllar et al, 2013 ; Li et al, 2020b ). Our previous studies have shown that honokiol exhibits significant antidepressant-like effects by affecting tryptophan metabolism and reducing the serum levels of corticosterone to improve neuronal plasticity ( Zhang et al, 2019 ; Zhang et al, 2020 ). Furthermore, honokiol was shown to bind to neural cell adhesion molecules to enhance neuronal survival and synaptic plasticity ( Xu et al, 2017 ).…”

Identification and Expression Analysis of the Magnolia officinalis AP2/ERF Gene Family Based on Different Age Groups

“…The medicinal Magnolia bark in the 'Chinese Pharmacopoeia' is commonly used to treat dampness injury, phlegm cough and other symptoms [1] . Lignans (including magnolol and honokiol), the main active components of M. officinalis, have many potential pharmacological effects, such as antitumor, antiviral, antibacterial, antiinflammatory, antioxidative, liver function-protective, and cardiovascular disease effects (Liao et al 2015;Pan et al 2024;Shen et al 2017;Xian et al 2015;Zhang et al 2020). Bioinformatics has previously investigated and discovered certain genes associated with the MVA pathway or the Dirigent gene family of M. officinalis, providing a theoretical basis for the molecular mechanism of M. officinalis biosynthesis (Zha et al 2015;Zhang et al 2024).…”