School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, P. R. China.
School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, P. R. China.
J Integr Neurosci. 2020 Sep 30;19(3):459-467. doi: 10.31083/j.jin.2020.03.172.
Depression is closely linked to hypothalamus-pituitary-adrenal axis hyperactivity. Honokiol, a biphenolic lignan compound obtained from the traditional Chinese medicine , can reduce the activity of the hypothalamus-pituitary-adrenal axis and improve depression-like behavior caused by hypothalamus-pituitary-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 antidepressant-like effect of honokiol and its potential mechanism. Honokiol prevented the elevated activity of the hypothalamus-pituitary-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.
抑郁症与下丘脑-垂体-肾上腺轴的过度活跃密切相关。厚朴酚是一种从传统中药中提取的双酚类木脂素化合物，能够降低下丘脑-垂体-肾上腺轴的活性，并改善由下丘脑-垂体-肾上腺轴过度活跃引起的抑郁症样行为。本研究探讨了这种作用的具体机制。通过重复注射皮质酮来建立抑郁症模型，研究厚朴酚的抗抑郁样作用及其潜在机制。厚朴酚可预防皮质酮引起的下丘脑-垂体-肾上腺轴活性升高和抑郁症样行为。厚朴酚治疗导致海马中糖皮质激素受体 mRNA 表达增加、糖皮质激素受体阳性表达增加以及糖皮质激素受体与盐皮质激素受体的比值增加。此外，厚朴酚治疗还导致血清中白细胞介素-1β水平降低，以及海马中白细胞介素-1β受体的阳性表达降低。这些结果表明，厚朴酚的抗抑郁样机制可能通过调节糖皮质激素受体介导的负反馈机制以及糖皮质激素和盐皮质激素受体之间的平衡来恢复下丘脑-垂体-肾上腺轴的典型活性，对炎症因子产生作用。
