College of Pharmacy, Department of Pharmaceutics, University of Florida, PO Box 100494, Gainesville, FL 32610, USA.
Neuropharmacology. 2010 Mar-Apr;58(4-5):767-73. doi: 10.1016/j.neuropharm.2009.12.014. Epub 2009 Dec 28.
Chronic stress is a contributing risk factor for the development of psychiatric illnesses such as anxiety and depression disorders. The aim of the present study was to evaluate the mechanisms of action of the standardized St. John's wort extract (STW3-VI; SJW) in a chronic restraint stress model. Markers of antioxidant capacity such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the hippocampus and hypothalamus, and plasma levels of ACTH and corticosterone as well as the inflammatory markers IL-6 and TNF-alpha were determined in rats exposed to chronic restraint stress for 21 consecutive days. In addition, total body and relative organ weights as well as behavioral changes in the open field test were evaluated on the last day. The results show that stressed animals decreased in open field activity compared to unstressed animals, which could be reversed by fluoxetine (10mg/kg, p.o.) and SJW (125-750mg/kg, p.o.) treatment. In addition, chronic restraint stress significantly decreased thymus and spleen indices in the stressed control group. However, treating stressed rats with fluoxetine or STW3-VI produced a significant and dose dependent increase in both thymus and spleen indices compared to stressed controls. Additionally, SJW and fluoxetine significantly reduced stress-induced increases in plasma ACTH and corticosterone levels. Furthermore, the administration of SJW significantly reduced the stress-induced increase in TNF-alpha levels. Our data provide new evidence for the hypothesis that the mechanism of action of STW3-VI is mediated by the interrelationship between the immune, oxidative defense and neuroendocrine system.
慢性应激是焦虑和抑郁等精神疾病发展的一个致病因素。本研究的目的是评估标准化贯叶连翘提取物（STW3-VI；SJW）在慢性束缚应激模型中的作用机制。在连续 21 天暴露于慢性束缚应激的大鼠中，测定海马体和下丘脑的抗氧化能力标志物，如超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和过氧化氢酶（CAT），以及血浆中促肾上腺皮质激素（ACTH）和皮质酮水平，以及炎症标志物白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）。此外，在最后一天评估了大鼠的总体和相对器官重量以及在开阔场试验中的行为变化。结果表明，与未应激动物相比，应激动物在开阔场活动中减少，这可以通过氟西汀（10mg/kg，po）和 SJW（125-750mg/kg，po）治疗得到逆转。此外，慢性束缚应激显著降低了应激对照组的胸腺和脾脏指数。然而，用氟西汀或 STW3-VI 治疗应激大鼠可显著增加胸腺和脾脏指数，且呈剂量依赖性，与应激对照组相比。此外，SJW 和氟西汀可显著降低应激引起的血浆 ACTH 和皮质酮水平升高。此外，SJW 的给药可显著降低应激引起的 TNF-α水平升高。我们的数据为 STW3-VI 的作用机制是通过免疫、氧化防御和神经内分泌系统之间的相互关系介导的假说提供了新的证据。
