含有睡茄内酯A的南非醉茄（Withania somnifera (L.) dunal）根提取物通过在意外慢性轻度应激下增强脑源性神经营养因子途径来减轻小鼠的抑郁样行为。
Ashwagandha (Withania somnifera (L.) dunal) root extract containing withanolide a alleviates depression-like behavior in mice by enhancing the brain-derived neurotrophic factor pathway under unexpected chronic mild stress.
作者信息
Kim Hyeongyeong, Choi Hyeon-Son, Han Kisoo, Sim Wansup, Suh Hyung Joo, Ahn Yejin
机构信息
Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul 02841, Republic of Korea; Transdisciplinary Major in Learning Health Systems, Graduate School, Korea University, Seoul 02841, Republic of Korea.
Department of Food Nutrition, Sangmyung University, Seoul 03016, Republic of Korea.
出版信息
J Ethnopharmacol. 2025 Jan 31;340:119224. doi: 10.1016/j.jep.2024.119224. Epub 2024 Dec 12.
ETHNOPHARMACOLOGICAL RELEVANCE
Ashwagandha (Withania somnifera (L.) Dunal) root or whole-plant extracts are used to treat anxiety, insomnia, and other nervous system disturbances.
AIM OF THE STUDY
We evaluated the neuroprotective and antidepressant effects of ashwagandha root extract (ARE) on corticosterone-exposed HT-22 cells and unpredictable chronic mild stress (UCMS)-challenged mice.
MATERIALS AND METHODS
The neuroprotective properties of ARE containing withanolide A were assessed in HT-22 cells subjected to corticosterone-induced oxidative stress. Additionally, the effects of ARE on depression-like behavior, stress-related hormones, and inflammatory cytokine levels were evaluated in a mouse model of UCMS.
RESULTS
In HT-22 cells, ARE (100 and 200 μg/mL) and its constituent, withanolide A (1.56 and 3.12 μg/mL), mitigated corticosterone-induced increases in MAO activity, ROS, and MDA levels. Treatment also reversed corticosterone-induced reductions in BDNF, TrkB, p-AKT, p-ERK, and p-CREB and normalized Nrf2 and Keap1 levels, thereby elevating HO-1 expression. In UCMS mice, ARE improved behavioral outcomes, increased sucrose preference, and reduced immobility in the forced swimming test while enhancing activity in the open field test and elevated plus maze. ARE decreased the levels of stress hormones (corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone) and increased the levels of neurotransmitters (L-DOPA, 5-HTP, and serotonin). Histological analysis revealed that ARE reduced hippocampal cell loss. Additionally, ARE (60 and 100 mg/kg) restored decreased levels of p-AKT, p-ERK, and p-CREB and lowered inflammation-related proteins (Cox2, iNOS, IL-6, IL-1β, TNF-α).
CONCLUSION
These results indicate that ARE containing withanolide A exhibits notable neuroprotective and antidepressant properties.
民族药理学相关性
印度人参（Withania somnifera (L.) Dunal）根或全株提取物用于治疗焦虑、失眠和其他神经系统紊乱。
研究目的
我们评估了印度人参根提取物（ARE）对皮质酮处理的HT-22细胞和不可预测的慢性轻度应激（UCMS）刺激的小鼠的神经保护和抗抑郁作用。
材料与方法
在经受皮质酮诱导的氧化应激的HT-22细胞中评估含有睡茄内酯A的ARE的神经保护特性。此外，在UCMS小鼠模型中评估ARE对抑郁样行为、应激相关激素和炎性细胞因子水平的影响。
结果
在HT-22细胞中，ARE（100和200μg/mL）及其成分睡茄内酯A（1.56和3.12μg/mL）减轻了皮质酮诱导的MAO活性、ROS和MDA水平的升高。处理还逆转了皮质酮诱导的BDNF、TrkB、p-AKT、p-ERK和p-CREB的降低，并使Nrf2和Keap1水平正常化，从而提高了HO-1表达。在UCMS小鼠中，ARE改善了行为结果，增加了蔗糖偏好，并减少了强迫游泳试验中的不动时间，同时增强了旷场试验和高架十字迷宫中的活动。ARE降低了应激激素（促肾上腺皮质激素释放激素、促肾上腺皮质激素和皮质酮）的水平，并增加了神经递质（L-多巴、5-羟色氨酸和血清素）的水平。组织学分析显示ARE减少了海马细胞损失。此外，ARE（60和100mg/kg）恢复了降低的p-AKT、p-ERK和p-CREB水平，并降低了炎症相关蛋白（Cox2、iNOS、IL-6、IL-1β、TNF-α）。
结论
这些结果表明含有睡茄内酯A的ARE具有显著的神经保护和抗抑郁特性。
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