桑叶中的类黄酮通过调节 GABA 和 5-HT 受体发挥改善睡眠的作用。

Flavonoids from mulberry leaves exhibit sleep-improving effects via regulating GABA and 5-HT receptors.

机构信息

School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China; Food Laboratory of Zhongyuan, Zhengzhou University, Luohe, Henan, 462300, China.

Systems Engineering Institute, Academy of Military Sciences (AMS), Beijing, 100010, China.

出版信息

J Ethnopharmacol. 2025 Jan 30;337(Pt 3):118734. doi: 10.1016/j.jep.2024.118734. Epub 2024 Oct 5.

DOI:10.1016/j.jep.2024.118734

PMID:39374877

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Mulberry leaf (Folium Mori) is a dried leaf of the dicotyledonous mulberry tree and is a homologous food and medicine. Treating insomnia with it is a common practice in traditional Chinese medicine. But still, its potential sleep-improving mechanism remains to be elucidated.

AIM OF REVIEW

Potential bioactive components and mechanisms of the sleep-improving effect of purified flavone from mulberry leaves (MLF) were explored through in vivo experiments, network pharmacology analysis, and molecular experimental validation.

MATERIALS AND METHODS

The mice model was established by pentobarbital sodium induction to evaluate the sleep-improving effect of MLF. The MLF's chemical composition was identified through a liquid chromatograph quadrupole time-of-flight mass spectrometer (Q-TOF LC/MS) to elucidate its sleep-improving active ingredient. At last, the underlying mechanism of MLF's sleep-improving effect was elucidated through neurotransmitter detection (ELISA), network pharmacology analysis, and molecular experimental validation (quantitative real-time PCR and western blotting).

RESULTS

MLF could dramatically reduce sleep latency by 35%, prolong sleep duration by 123%, and increase the sleep rate of mice through increasing γ-aminobutyric acid (GABA) and serotonin (5-HT) release in serum, hypothalamus, and hippocampus. Q-TOF LC/MS identified 17 flavonoid components in MLF. Network pharmacological analysis suggested that the key sleep-improving active ingredients in MLF might be quercetin, kaempferol, morin, and delphinidin. The key path for MLF to improve sleep might be the tryptophan metabolism and neuroactive ligand-receptor interaction, and the key targets might be gamma-aminobutyric acid type A receptor subunit alpha2 Gene (GABRA2) and serotonin 1A (5-HT1A) receptors.

CONCLUSIONS

MLF has shown significant sleep-improving effects in mice and may take effect through regulating the GABA and 5-HT receptors.

摘要

药食同源

桑叶为桑科植物桑的干燥叶，既是食物又是药物。中医常以桑叶治疗失眠。然而，其潜在的改善睡眠的机制仍有待阐明。

目的

通过体内实验、网络药理学分析和分子实验验证，探讨从桑叶中提取的纯化黄酮（MLF）改善睡眠的潜在生物活性成分和机制。

材料与方法

采用戊巴比妥钠诱导建立小鼠模型，评价 MLF 的改善睡眠作用。采用液质联用四级杆飞行时间质谱（Q-TOF LC/MS）鉴定 MLF 的化学成分，阐明其改善睡眠的活性成分。最后，通过神经递质检测（ELISA）、网络药理学分析和分子实验验证（实时定量 PCR 和 Western blot）阐明 MLF 改善睡眠的作用机制。

结果

MLF 可显著降低睡眠潜伏期 35%，延长睡眠时间 123%，并通过增加血清、下丘脑和海马中的γ-氨基丁酸（GABA）和 5-羟色胺（5-HT）释放来提高小鼠的睡眠率。Q-TOF LC/MS 鉴定出 MLF 中的 17 种黄酮类成分。网络药理学分析表明，MLF 改善睡眠的关键活性成分可能是槲皮素、山奈酚、杨梅素和矢车菊素。MLF 改善睡眠的关键途径可能是色氨酸代谢和神经活性配体-受体相互作用，关键靶点可能是γ-氨基丁酸 A 型受体亚基α2 基因（GABRA2）和 5-羟色胺 1A（5-HT1A）受体。