State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China.
Phytomedicine. 2024 Nov;134:155977. doi: 10.1016/j.phymed.2024.155977. Epub 2024 Aug 22.
Ligusticum chuanxiong hort. (Chuanxiong, CX) is a well-known traditional edible-medicinal herb, especially in brain diseases. However, there is a lack of studies focusing on the action of CX in metabolites of migraine.
HYPOTHESIS/PURPOSE: To investigate the action of the aqueous extract of CX (LCH) on nitroglycerin (NTG)-induced migraine.
The effects and mechanisms of LCH on migraine were evaluated in NTG-induced mice and rats. Laser speckle contrast imaging was performed to detect the cerebral blood flow. Metabolomic analysis in serum and mass spectrometry imaging in brain tissue from NTG-induced rats were conducted to explore the metabolites. The techniques including RT-qPCR, immunohistochemistry, and immunofluorescence were employed to estimate the molecular changes.
Totally, 1480 metabolites were identified, among which, 50 and 49 differential metabolites were identified by t-test, fold change, and VIP score for NTG vs. CON and LCH+NTG vs. NTG, respectively. Next, 13 common real difference metabolites were revealed by comparative analysis, and KEGG annotation and enrichment analysis showed that the glutathione (GSH) metabolism pathway played important roles in migraine, whereas the glutamate could be metabolized to γ-glu-cys and converted to GSH. Molecular exploring further confirmed that LCH treatment increased the expression of essential components of GSH synthetase, such as GCLC and GCLM, and elevated the expression levels of Nrf-2 and its downstream targets including HO1 and NQO1. Moreover, the mass spectrometry imaging results found that LCH treatment promoted the synthesis of GSH and the spatial distribution of glucose as well as ATP metabolites to normal levels.
To sum up, the present study firstly reveals that LCH plays a therapeutic role for migraine through glucose-glutamate-Nrf-2 axis, which might represent a promising approach in the development of advanced therapeutic strategies for migraine, and the LCH may be an effective drug or dietary supplement for relieving headache.
川芎（川芎，CX）是一种著名的传统食用药用植物，特别是在脑部疾病方面。然而，目前缺乏针对 CX 在偏头痛代谢物中作用的研究。
假说/目的：研究川芎水提物（LCH）对硝酸甘油（NTG）诱导偏头痛的作用。
采用 NTG 诱导的小鼠和大鼠模型评价 LCH 对偏头痛的作用及机制。采用激光散斑对比成像技术检测脑血流。对 NTG 诱导的大鼠血清代谢组学和脑组织质谱成像进行分析，以探讨代谢物。采用 RT-qPCR、免疫组织化学和免疫荧光技术评估分子变化。
共鉴定出 1480 种代谢物，其中 NTG 与 CON 相比，t 检验、倍数变化和 VIP 得分分别鉴定出 50 种和 49 种差异代谢物；LCH+NTG 与 NTG 相比，分别鉴定出 13 种共同的真实差异代谢物。KEGG 注释和富集分析表明，谷胱甘肽（GSH）代谢途径在偏头痛中起重要作用，谷氨酸可代谢为γ-谷氨酰半胱氨酸并转化为 GSH。分子研究进一步证实，LCH 处理增加了 GSH 合成的关键组成部分，如 GCLC 和 GCLM 的表达，并提高了 Nrf-2 及其下游靶标 HO1 和 NQO1 的表达水平。此外，质谱成像结果发现，LCH 处理促进了 GSH 的合成以及葡萄糖和 ATP 代谢物的空间分布恢复到正常水平。
综上所述，本研究首次揭示了 LCH 通过葡萄糖-谷氨酸-Nrf-2 轴对偏头痛发挥治疗作用，这可能为偏头痛的先进治疗策略的发展提供新的思路，并且 LCH 可能是缓解头痛的有效药物或膳食补充剂。
