Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Pharmacol Biochem Behav. 2014 Jan;116:1-8. doi: 10.1016/j.pbb.2013.10.026. Epub 2013 Nov 4.
Perillaldehyde (PAH), a major component of essential oil of Perilla Frutescens, has antidepressant-like effects and anti-inflammatory effects. The present study was designed to determine whether PAH is effective in treating lipopolysaccharide (LPS)-induced depression-like behavior in mice and to explore the possible mechanism between its antidepressant-like effect and anti-inflammatory activity. PAH (60 and 120 mg/kg) and fluoxetine (20mg/kg) were administered intragastrically once daily for 7 consecutive days. In the 7th day, LPS (0.5mg/kg) was injected intraperitoneally 30 min after drug administration. Blood samples were collected 90 min after LPS injection to evaluate serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels by enzyme-linked immunosorbent assay (ELISA). Behavioral tests were measured 24h after LPS injection. After the behavioral tests the prefrontal cortex was rapidly dissected from the brain of the sacrificed mice, then the 5-hydroxytryptamine (5-HT) and norepinephrine (NE) levels in prefrontal cortex were determined by HPLC-MS, and IL-6 and TNF-α mRNA expression was measured using quantitative real-time PCR. Our results showed that a single administration of LPS significantly increased the levels of TNF-α and IL-6 in both the serum and the prefrontal cortex and decreased 5-HT and NE levels in the prefrontal cortex in mice. Pretreatment with fluoxetine (20mg/kg) or PAH (60 and 120 mg/kg) could effectively reverse the alterations in the concentrations of 5-HT and NE, and attenuate LPS-induced increases in TNF-α and IL-6 levels. Besides, LPS administration increased the immobility time in tail suspension test (TST) and forced swimming test (FST) without affecting spontaneous locomotor activity. Fluoxetine (20mg/kg) or PAH (60 and 120 mg/kg) significantly shortened LPS-induced increases of immobility time in both TST and FST. In conclusion, PAH exhibited significant antidepressant-like effects in mice with LPS-induced depression. The antidepressant activity of PAH might be related to the alteration of monoaminergic responses and the anti-inflammatory effects.
紫苏醛（PAH）是紫苏精油的主要成分，具有抗抑郁和抗炎作用。本研究旨在确定 PAH 是否能有效治疗脂多糖（LPS）诱导的小鼠抑郁样行为，并探讨其抗抑郁作用与抗炎活性之间的可能机制。PAH（60 和 120mg/kg）和氟西汀（20mg/kg）每天灌胃一次，连续 7 天。在第 7 天，药物给药后 30 分钟腹腔内注射 LPS（0.5mg/kg）。LPS 注射后 90 分钟采集血样，通过酶联免疫吸附试验（ELISA）检测血清白细胞介素（IL）-6 和肿瘤坏死因子（TNF）-α水平。LPS 注射后 24h 进行行为测试。行为测试后，迅速从处死小鼠的大脑中取出前额叶皮质，然后通过 HPLC-MS 测定前额叶皮质中 5-羟色胺（5-HT）和去甲肾上腺素（NE）的水平，并使用定量实时 PCR 测量 IL-6 和 TNF-αmRNA 的表达。结果显示，单次 LPS 给药可显著增加小鼠血清和前额皮质中 TNF-α和 IL-6 的水平，降低前额皮质中 5-HT 和 NE 的水平。氟西汀（20mg/kg）或 PAH（60 和 120mg/kg）预处理可有效逆转 5-HT 和 NE 浓度的变化，并减轻 LPS 诱导的 TNF-α和 IL-6 水平升高。此外，LPS 给药增加了悬尾试验（TST）和强迫游泳试验（FST）中的不动时间，而不影响自发运动活动。氟西汀（20mg/kg）或 PAH（60 和 120mg/kg）显著缩短了 LPS 诱导的 TST 和 FST 中不动时间的增加。总之，PAH 对 LPS 诱导的抑郁小鼠表现出显著的抗抑郁作用。PAH 的抗抑郁活性可能与单胺能反应的改变和抗炎作用有关。
