Yu Hui, Shao Shumin, Xu Junnan, Guo Haibiao, Zhong Zhangfeng, Xu Jiangping
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
Macau Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, SAR, China.
Chin Med. 2022 Jun 6;17(1):65. doi: 10.1186/s13020-022-00609-4.
Fresh or dried Persimmon leaves (Diospyros kaki Thunb.) exhibit preventive effects on cardiovascular and cerebrovascular diseases. However, their antidepressant effects and underlying mechanisms are unclear. Thus, we investigated mechanisms responsible for Persimmon leaf extract (PLE) activity on chronic social defeat stress (CSDS)-induced depressive-like behaviors in mice.
CSDS was used as a mouse model of depression. We performed the sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) to identify depressive-like behavior. Spine density and dendritic morphology were assessed using Golgi staining. Neurochemicals were quantified by microdialysis, doublecortin by immunofluorescence, and cAMP using an ELISA kit. Finally, the levels of cortical proteins of phosphorylated cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), postsynaptic density synapsin-1 and protein 95 (PSD95) were quantified by western blot. 16S rRNA gene sequencing was used to detect fecal microbiota.
Treatment of CSDS-subjected mice with PLE (30.0-60.0 mg/kg, i.g.) enhanced sucrose preference, decreased immobility times in the TST and FST but did not affect locomotor activity. Furthermore, persistent social defeat stress decreased dendritic spine density and dendritic length in the brain, as well as decreased PSD95 and synapsin-1 expression. PLE, interestingly, inhibited dendritic spine loss and increased synaptic protein levels. PLE also increased brain levels of 5-HT, cAMP, phosphorylated (p)-CREB, BDNF, PSD95, and synapsin-1 in mice subjected to CSDS. Furthermore, PLE increased their doublecortin-positive cell count in the hippocampal dentate gyrus. CSDS mice represented a distinct fecal microbiota cluster which differed compared with normal C57BL/6J mice, and the phenotype was rescued by PLE.
PLE alleviated CSDS-induced depressive behaviors and spinal damage by suppressing serotonin reuptake and activating the cAMP/CREB/BDNF signaling pathway. Simultaneously, PLE influenced the composition of the fecal microbiota in CSDS-subjected mice.
新鲜或干燥的柿叶（柿树）对心脑血管疾病具有预防作用。然而，其抗抑郁作用及潜在机制尚不清楚。因此，我们研究了柿叶提取物（PLE）对慢性社会挫败应激（CSDS）诱导的小鼠抑郁样行为的作用机制。
将CSDS用作抑郁症小鼠模型。我们进行了蔗糖偏好试验（SPT）、强迫游泳试验（FST）和悬尾试验（TST）以识别抑郁样行为。使用高尔基染色评估树突棘密度和树突形态。通过微透析对神经化学物质进行定量，通过免疫荧光对双皮质素进行定量，使用ELISA试剂盒对cAMP进行定量。最后，通过蛋白质印迹法对磷酸化cAMP反应元件结合蛋白（CREB）、脑源性神经营养因子（BDNF）、突触后密度突触素-1和蛋白95（PSD95）的皮质蛋白水平进行定量。使用16S rRNA基因测序检测粪便微生物群。
用PLE（30.0 - 60.0 mg/kg，腹腔注射）处理CSDS诱导的小鼠可提高蔗糖偏好，减少TST和FST中的不动时间，但不影响运动活性。此外，持续的社会挫败应激会降低大脑中的树突棘密度和树突长度，以及降低PSD95和突触素-1的表达。有趣的是，PLE可抑制树突棘丢失并增加突触蛋白水平。PLE还可提高CSDS诱导小鼠大脑中5-羟色胺、cAMP、磷酸化（p）-CREB、BDNF、PSD95和突触素-1的水平。此外，PLE可增加海马齿状回中双皮质素阳性细胞计数。CSDS小鼠表现出与正常C57BL/6J小鼠不同的独特粪便微生物群簇，且该表型可被PLE挽救。
PLE通过抑制5-羟色胺再摄取和激活cAMP/CREB/BDNF信号通路减轻CSDS诱导的抑郁行为和脊髓损伤。同时，PLE影响CSDS诱导小鼠的粪便微生物群组成。
