Yueju Pill Rapidly Induces Antidepressant-Like Effects and Acutely Enhances BDNF Expression in Mouse Brain

Abstract

The traditional antidepressants have a major disadvantage in delayed onset of efficacy, and the emerging fast-acting antidepressant ketamine has adverse behavioral and neurotoxic effects. Yueju pill, an herb medicine formulated eight hundred years ago by Doctor Zhu Danxi, has been popularly prescribed in China for alleviation of depression-like symptoms. Although several clinical outcome studies reported the relative short onset of antidepressant effects of Yueju, this has not been scientifically investigated. We, therefore, examined the rapid antidepressant effect of Yueju in mice and tested the underlying molecular mechanisms. We found that acute administration of ethanol extract of Yueju rapidly attenuated depressive-like symptoms in learned helpless paradigm, and the antidepressant-like effects were sustained for at least 24 hours in tail suspension test in ICR mice. Additionally, Yueju, like ketamine, rapidly increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, whereas the BDNF mRNA expression remained unaltered. Yueju rapidly reduced the phosphorylation of eukaryotic elongation factor 2 (eEF2), leading to desuppression of BDNF synthesis. Unlike ketamine, both the BDNF expression and eEF2 phosphorylation were revered at 24 hours after Yueju administration. This study is the first to demonstrate the rapid antidepressant effects of an herb medicine, offering an opportunity to improve therapy of depression.

Optimization of Supercritical Fluid Extraction of Oil from the Fruit of Gardenia jasminoides and Its Antidepressant Activity

“…The chemical composition of OFG was analyzed by GC-MS. Furthermore, the antidepressant activity of OFG was determined by means of a tail suspension test (TST) and a forced swimming test (FST), which have been used as primary screening tests for antidepressant drugs [15].…”

Rapid-Acting Antidepressants and Underlying Mechanisms

“…Yueju, similar to ketamine, rapidly increased the expression of BDNF in the hippocampus, whereas the BDNF mRNA expression remained unaltered [13]. This is likely to have resulted from posttranscriptional regulation.…”

“…It significantly reduced the number of escape failures. The latency to escape also showed a trend to decrease in Yueju-treated mice [13]. Many active components in Yueju are essential oils that may be extracted with ethanol, such as α-cyperone and β-cyperone in Xiang Fu and atractylin and hinesol in Cang Zhu [15], [29].…”

“…Yueju is composed of five equal amount of herbs, Xiang Fu, Chuan Xiong, Zhi zi, Cang Zu, and Shen Qu. Animal preclinical studies have shown that Yueju is an effective antidepressant [13][14][15]. It has been previously reported that ethanol extract of Yueju has antidepressant effect after a week-long administration [15].…”

“…Scopolamine was found to reduce symptoms of depression within three days of the first administration [10][11][12]. The Yueju pill, an ancient Chinese herbal formula designed to treat mood disorders, is still popular today and found to be a rapid-onset antidepressant working through NMDA receptors and BDNF expression [13][14][15]. The level of magnesium, another NMDA-receptor antagonist, is found to be lower than normal in Treatment-resistant individuals [16][17].…”