Immediate and persistent antidepressant-like effects of Chaihu-jia-Longgu-Muli-tang are associated with instantly up-regulated BDNF in the hippocampus of mice

Abstract

Conventional antidepressants have a disadvantage in delayed onset of efficacy. Here, we aimed to evaluate the immediate and persistent antidepressant-like action of a classic herbal medicine Chaihu-jia-Longgu-Muli decoction (CLM) as well as the action of CLM on hippocampal brain-derived neurotrophic factor (BDNF) over time. CLM consists of Xiaochaihu decoction (XchD), Longgu-Muli (LM) and several other herbs. The contribution of constituent herbal formula XchD and other parts of CLM was also assessed. Following a single dose of CLM, tail suspension test (TST), forced swim test (FST), and novelty-suppressed feeding test (NSF) were performed. The antidepressant activity of XchD, its interaction with LM or remaining parts of CLM was also examined after a single administration. BDNF expression in the hippocampus was examined at 30 min and 24 hr post a single CLM. A single administration of half of clinical dose of CLM elicited antidepressant effects at TST 30 min post administration, and lasted for 72 hr. Furthermore, CLM also reduced the latency to eat in NSF test. A single proportional dose of XchD induced antidepressant effects at 30 min and lasted for 48 hr, whereas the effect lasted for 72 hr when combined with either LM or the remaining parts of CLM. BDNF expression increased at 30 min and persisted at least for 24 hr after a single dose of CLM. The results support that Chaihu-jia-Longgu-Muli decoction was capable to immediately and enduringly elicit antidepressant activity via enhancement of hippocampal BDNF expression, in which the constituent Xiaochaihu decoction played the primary role.

Efficacy and Safety of Chaihu Jia Longgu Muli Decoction in the Treatment of Poststroke Depression: A Systematic Review and Meta-Analysis

“…CLMD is one of the most common prescriptions used in the treatment of mental diseases in TCM. Clinical studies have found that CLMD has the effect of psychotropic drugs and have shown a significant antidepressant effect on animal models [37,38]. It can regulate the hypothalamopituitary-adrenal system dysfunction by preventing the dopaminergic and serotonergic transmission in the prefrontal cortex [39] and upregulate the expression of the brain-derived neurotrophic factor (BDNF) to alleviate the depression-like state induced by chronic stress [37].…”

“…It can regulate the hypothalamopituitary-adrenal system dysfunction by preventing the dopaminergic and serotonergic transmission in the prefrontal cortex [39] and upregulate the expression of the brain-derived neurotrophic factor (BDNF) to alleviate the depression-like state induced by chronic stress [37]. It also has immediate and long-lasting antidepressant effects by enhancing BDNF expression in the hippocampus [38]. Chaihu (Radix Bupleuri) and Huang Qin (Radix Scutellariae) are the key drugs in many prescriptions for mental disorders.…”

Bupleurum in Treatment of Depression Disorder: A Comprehensive Review

“…), and Da Zao ( Ziziphus jujuba Mill.). The researchers found that CLM produced immediate and lasting antidepressant activity by enhancing hippocampal BDNF expression, in which components of the Xiaochuhu decoction played a major role [ 94 ]. In addition, CLM induced rapid antidepressive-like effects in OB mice, which may be due to the reversal of abnormal expression of AMPA and NMDA receptors in the PFC and the related Akt-mTOR signaling [ 95 ].…”

Mechanism of Chaihu Longgu oyster adjusted decoction for the treatment of depression based on network pharmacology and molecular docking technology

“…Moreover, given its efficacy, it is also commonly used for the treatment of depression. Previous studies have established that the efficacy of the Chaihu Longgu Oyster Decoction is statistically significant (6)(7)(8)(9). Adjustments have been made to the Chaihu Longgu Oyster Decoction, with the removal of Qian Dan and replacing Ren Shen with Dang Shen, yielding a remarkable clinical effect.…”