Han Rui, Han Guoying, Yan Yiqi, Han Lifeng, Li Lin, Zhang Han
Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Ministry of Education, Tianjin, China.
Front Pharmacol. 2023 Feb 27;14:1038492. doi: 10.3389/fphar.2023.1038492. eCollection 2023.
High concentrations of glucocorticoids (GC) can cross the blood-brain barrier into the brain parenchyma, triggering a stress state that can lead to a range of physiological changes. This study investigated whether Erzhi formula has neuroprotective effects against glucocorticoid damage by establishing a dexamethasone-induced primary cortical neuron injury model . The results showed that Erzhi formula could reduce dexamethasone-induced apoptosis in primary cultured cortical neurons and improve synaptic damage. Further, network pharmacological analysis revealed that Erzhi formula may exert antidepressant effects by multi-component, multi-target, and multi-pathway characteristics, in which Salidroside, Biochanin-A and other ingredients are key components, HSD11B1, NR3C1, and other proteins are key targets, and steroid metabolism may be a key process in its action. Moreover, our study found that the neuroprotective effect of Erzhi formula might be related to the 11β-HSD1-GC/glucocorticoid receptor (GR) signaling pathway. The Erzhi formula could significantly inhibit the activity of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) using homogeneous time-resolved fluorescence. In addition to providing evidence for the pharmacological effects of the Erzhi formula, the present study lays down the foundation for subsequent experiments.
高浓度的糖皮质激素（GC）可穿过血脑屏障进入脑实质，引发应激状态，进而导致一系列生理变化。本研究通过建立地塞米松诱导的原代皮质神经元损伤模型，探讨二至丸对糖皮质激素损伤是否具有神经保护作用。结果表明，二至丸可减少地塞米松诱导的原代培养皮质神经元凋亡，并改善突触损伤。此外，网络药理学分析显示，二至丸可能通过多成分、多靶点、多途径发挥抗抑郁作用，其中红景天苷、染料木素等成分是关键成分，11β-羟基类固醇脱氢酶1（HSD11B1）、核受体亚家族3成员C1（NR3C1）等蛋白是关键靶点，类固醇代谢可能是其作用的关键过程。此外，本研究发现二至丸的神经保护作用可能与11β-羟基类固醇脱氢酶1（11β-HSD1）-GC/糖皮质激素受体（GR）信号通路有关。采用均相时间分辨荧光法，二至丸可显著抑制11β-羟基类固醇脱氢酶1（11β-HSD1）的活性。本研究除为二至丸的药理作用提供证据外，还为后续实验奠定了基础。
