Bonaterra Gabriel A, Schwendler Anna, Hüther Julian, Schwarzbach Hans, Schwarz Anja, Kolb Christiane, Abdel-Aziz Heba, Kinscherf Ralf
Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Philipps-University of Marburg, Marburg, Germany.
Steigerwald Arzneimittelwerk GmbH, Scientific Department, Darmstadt, Germany.
Front Pharmacol. 2018 Jan 18;8:955. doi: 10.3389/fphar.2017.00955. eCollection 2017.
Since ancient times L. named St. John's wort (SJW), has been used in the management of a wide range of applications, including nervous disorders. Development of mood disorders are due to alterations in glutamate metabolism, initiation of inflammatory pathways, and changes of the neuronal plasticity. Previous studies suggest that the glutamatergic system contributes to the pathophysiology of depression. Extracts of SJW have been recommended for the treatment of depression. The aim of the present study was to evaluate the action of STW3-VI, a special SJW extract in differentiated mouse hippocampal HT-22 neurons. We evaluated the stimulation of neurogenesis, the protective effect against glutamate or N-methyl-D-aspartate receptor induced-excitotoxicity and its anti-inflammatory properties in LPS-activated human macrophages. After 48 h treatment, STW3-VI stimulated the neurite formation by 25% in comparison with the control and showed protective effects against glutamate- or NMDA-induced cytotoxicity by significantly increasing the viability about +25 or +50%. In conjunction with these effects, after pretreatment with STW3-VI, the intracellular reduced glutathione content was significantly 2.3-fold increased compared with the neurons incubated with glutamate alone. Additionally, pre-treatment of human macrophages with STW3-VI showed anti-inflammatory effects after 24 or 48 h concerning inhibition of LPS-induced TNF release by -47.3 and -53.8% (24 h) or -25.0 to -64.8% (48 h). Our data provide new evidence that STW3-VI protects hippocampal cells from NMDA- or glutamate-induced cytotoxicity. Moreover, our results indicate a morphological remodeling by increasing neurite outgrowth and activation of the anti-inflammatory defense by inhibition of the cytokine production in human macrophages after STW3-VI treatment. These protective, neurotrophic and anti-inflammatory properties may be beneficial in the treatment of depressive disorders.
自古以来，贯叶连翘（L.，又名圣约翰草，SJW）就被广泛应用于诸多领域，包括神经系统疾病的治疗。情绪障碍的发生是由于谷氨酸代谢改变、炎症通路激活以及神经可塑性变化。先前的研究表明，谷氨酸能系统在抑郁症的病理生理学中起作用。贯叶连翘提取物已被推荐用于治疗抑郁症。本研究的目的是评估一种特殊的贯叶连翘提取物STW3-VI对分化的小鼠海马HT-22神经元的作用。我们评估了其对神经发生的刺激作用、对谷氨酸或N-甲基-D-天冬氨酸受体诱导的兴奋性毒性的保护作用以及在脂多糖激活的人巨噬细胞中的抗炎特性。处理48小时后，与对照组相比，STW3-VI使神经突形成增加了25%，并通过显著提高约25%或50%的细胞活力，对谷氨酸或NMDA诱导的细胞毒性显示出保护作用。伴随这些作用，用STW3-VI预处理后，与仅用谷氨酸孵育的神经元相比，细胞内还原型谷胱甘肽含量显著增加了2.3倍。此外，用STW3-VI预处理人巨噬细胞24或48小时后，显示出抗炎作用，可使脂多糖诱导的肿瘤坏死因子释放分别减少47.3%和53.8%（24小时）或25.0%至64.8%（48小时）。我们的数据提供了新的证据，表明STW3-VI可保护海马细胞免受NMDA或谷氨酸诱导的细胞毒性。此外，我们的结果表明，STW3-VI处理后，通过增加神经突生长实现形态重塑，并通过抑制人巨噬细胞中的细胞因子产生激活抗炎防御。这些保护、神经营养和抗炎特性可能对抑郁症的治疗有益。
