Rowe Karon, Gray Nora E, Zweig Jonathan A, Law Alexander, Techen Natascha, Maier Claudia S, Soumyanath Amala, Kretzschmar Doris
BENFRA Botanical Dietary Supplements Research Center, Oregon Health and Science University, Portland, OR, United States.
Oregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR, United States.
Front Aging. 2024 Jul 11;5:1374905. doi: 10.3389/fragi.2024.1374905. eCollection 2024.
(CA) is known in Ayurvedic medicine as a rejuvenating herb with particular benefits in the nervous system. Two groups of specialized metabolites found in CA and purported to contribute to its beneficial effects are triterpenes (TTs) and caffeoylquinic acids (CQAs). In order to evaluate the role and interactions of TTs and CQAs in the effects of CA, we examined the neurotrophic effects of a water extract of CA (CAW) and combinations of its TT and CQA components in mouse primary hippocampal neurons and in flies .
Primary hippocampal neurons were isolated from mouse embryos and exposed for 5 days to CAW (50 μg/mL), mixtures of TTs, CQAs or TT + CQA components or to 4 TTs or 8 individual CQA compounds of CAW. Dendritic arborization was evaluated using Sholl analysis. flies were aged to 28 days and treated for 2 weeks with CAW (10 mg/mL) in the food, mixtures of TTs, CQAs or TT + CQA and individual TT and CQA compounds. TTs and CQAs were tested at concentrations matching their levels in the CAW treatment used. After 2 weeks of treatment, aged 42 days were evaluated for phototaxis responses.
In mouse primary hippocampal neurons, CAW (50 μg/mL), the TT mix, CQA mix, all individual TTs and most CQAs significantly increased dendritic arborization to greater than control levels. However, the TT + CQA combination significantly decreased dendritic arborization. In a marked age-related decline in fast phototaxis response was observed in both males and females over a 60 days period. However, resilience to this decline was afforded in both male and female flies by treatment from 28 days onwards with CAW (10 mg/mL), or equivalent concentrations of mixed TTs, mixed CQAs and a TT + CQA mix. Of all the individual compounds, only 1,5-diCQA slowed age-related decline in phototaxis in male and female flies.
This study confirmed the ability of CAW to increase mouse neuronal dendritic arborization, and to provide resilience to age-related neurological decline in . The TT and CQA components both contribute to these effects but do not have a synergistic effect. While individual TTs and most individual CQAs increased dendritic arborization at CAW equivalent concentrations, in the model, only 1,5-diCQA was able to slow down the age-related decline in phototaxis. This suggests that combinations (or potentially higher concentrations) of the other compounds are needed to provide resilience in this model.
在阿育吠陀医学中，（某植物）被认为是一种具有恢复活力功效的草药，对神经系统有特殊益处。在该植物中发现的两类特定代谢产物，即三萜类化合物（TTs）和咖啡酰奎宁酸（CQAs），被认为有助于其产生有益效果。为了评估TTs和CQAs在该植物作用中的作用及相互作用，我们在小鼠原代海马神经元和果蝇中研究了该植物水提取物（CAW）及其TT和CQA成分组合的神经营养作用。
从小鼠胚胎中分离出原代海马神经元，并将其暴露于CAW（50μg/mL）、TTs混合物、CQAs混合物或TT + CQA成分混合物中，或暴露于该植物的4种TTs或8种单独的CQA化合物中5天。使用Sholl分析评估树突分支。将果蝇饲养至28天，并在食物中用CAW（10mg/mL）、TTs混合物、CQAs混合物或TT + CQA以及单独的TT和CQA化合物处理2周。以与CAW处理中其水平相匹配的浓度测试TTs和CQAs。处理2周后，对42日龄的果蝇进行趋光反应评估。
在小鼠原代海马神经元中，CAW（50μg/mL）、TT混合物、CQA混合物、所有单独的TTs以及大多数CQAs均显著增加树突分支，使其高于对照水平。然而，TT + CQA组合显著降低了树突分支。在果蝇中，在60天的时间里，雄性和雌性果蝇的快速趋光反应均出现明显的与年龄相关的下降。然而，从28天起用CAW（10mg/mL）或等效浓度的混合TTs、混合CQAs和TT + CQA混合物处理，雄性和雌性果蝇对这种下降均具有恢复能力。在所有单独的化合物中，只有1,5 - 二CQA减缓了雄性和雌性果蝇趋光反应中与年龄相关的下降。
本研究证实了CAW能够增加小鼠神经元树突分支，并为果蝇中与年龄相关的神经功能衰退提供恢复能力。TT和CQA成分均对这些作用有贡献，但没有协同作用。虽然在与CAW等效浓度下，单独的TTs和大多数单独的CQAs增加了树突分支，但在果蝇模型中，只有1,5 - 二CQA能够减缓趋光反应中与年龄相关的下降。这表明在该模型中需要其他化合物的组合（或可能更高的浓度）来提供恢复能力。
