Preliminary exploration of the mechanism by which Angelica volatile oil improves learning and memory in Alzheimer’s disease model rats
Alzheimer’s disease (AD), as a neurodegenerative disease characterized by progressive cognitive impairment and behavioral damage, is induced by multiple factors, including biological and psychosocial factors. Among them, changes in neurotransmitters, oxidative stress, and deposition of beta amyloid protein have become clear triggers, forming a cascading deterioration reaction that further promotes and stimulates the occurrence and development of AD.
As one of the “Top Ten Longyao” and an authentic medicinal herb in Gansu, the research team has preliminarily explored its role in preventing and treating AD. In order to promote the refinement of effective components and parts of Angelica sinensis for the prevention and treatment of Alzheimer’s disease, the research team will select clear parts (components) of Angelica sinensis, polysaccharides, volatile oils, and ferulic acid for effective component and component compatibility studies, and further select the core parts or components of Angelica sinensis for the prevention and treatment of Alzheimer’s disease. This experiment is based on the pathogenesis theories of neurotransmitter changes, oxidative stress, and β – amyloid protein deposition to study the effect and preliminary mechanism of Angelica sinensis volatile oil, the main active component of Angelica sinensis, in preventing and treating AD.

AD, as a common degenerative disease of the nervous system, has risen to become one of the top ten causes of death worldwide. Traditional Chinese medicine has a long history of preventing and treating AD, with abundant literature records. Modern research has shown that traditional Chinese medicine has significant efficacy and safety in treating AD. Danggui Gan Bu Xin San has a gentle temperament and can not only nourish blood and promote blood circulation, but also regulate liver qi and smooth qi flow. As pointed out in the “Compendium of Jing Yue: Materia Medica”, “Angelica sinensis has a sweet and heavy taste, so it is specialized in nourishing blood; its qi is light and spicy, so it can also nourish blood. There is movement in the tonifying process, and there is tonifying in the action, which is the qi medicine in the blood and also the holy medicine in the blood… When combined with it, it can nourish the blood, nourish qi and produce essence, calm the five organs, strengthen the body, benefit the mind. For any disease with visible deficiency, there is nothing inappropriate.” The “Medical Mirror” says: “Angelica sinensis has a warm and sweet taste, a light odor, can rise or fall, and is also yang. It is widely used and greatly beneficial to the blood family. It is used for all blood syndromes. However, it is widely circulated. And without stability, the taste of Angelica sinensis is accompanied by sweetness and smooth qi, and it follows the guidance to reach its destination. Starting from Shaoyin, the heart controls the blood; entering Taiyin, the spleen wraps the blood; entering Jueyin, the liver stores the blood. It can be seen that Angelica sinensis regulates qi and blood, replenishes deficiency and promotes stagnation, and is beneficial for nourishing blood and activating blood circulation The essential medicine for regulating liver and promoting stagnation is in line with the three major mechanisms of AD: phlegm and blood stasis deficiency. Modern research has also shown that Angelica sinensis has anti free radical oxidation and anti-aging effects, which can alleviate cell apoptosis after cerebral ischemia, alleviate memory loss in dementia mice, and demonstrate potential preventive and therapeutic effects on AD. The volatile oil of Angelica sinensis is an important active ingredient, containing compounds such as phthalates, phenols, terpenes, etc. It has been confirmed that various compounds have the ability to protect neurons and improve learning and memory. For example, research on the common benzophenone compound, ligustilide, has shown that it can protect neurons by promoting the clearance of A β deposits. Liu et al. predicted the quality markers of Angelica sinensis volatile oil and believed that the core targets of Angelica sinensis volatile oil are located in the hippocampus, cerebral cortex, basal ganglia, and other areas, and are related to neuroprotection and immune regulation. Due to the instability of some compounds in the volatile oil of Angelica sinensis, which are prone to isomerization and degradation reactions, in order to ensure the stability of Angelica sinensis volatile oil as much as possible and minimize its effects on the brain and nerves, this experiment used Angelica sinensis volatile oil gavage to explore its effects on AD rats.

This study replicated an AD model by injecting A β 25-35 solution into the hippocampal CA1 region, and explored the effects of Angelica volatile oil on learning and memory in AD rats from the perspectives of neurotransmitter changes, oxidative stress, and β – amyloid protein deposition. The results showed that the volatile oil of Angelica sinensis could significantly shorten the escape latency of model rats, prolong the retention time in the target quadrant, shorten the latency time of the first arrival at the original escape platform, increase the number of crossings across the original platform, and significantly increase the serum ACh content and ChAT, SOD activity, reduce the serum AChE activity, MDA level, and hippocampal APP, A β 1-42 content. It effectively improved the learning and memory ability of model rats, indicating that it has a certain preventive and therapeutic effect on AD.

Numerous studies have shown that senile plaques (SP) are the core pathological manifestation of AD, formed by the fragmentation of APP into A β and further aggregation. A β 1-42 and A β 1-40 are the cleavage products of APP, among which A β 1-42 is more prone to aggregation and has strong cytotoxicity. When the balance between the production and clearance mechanisms of A β 1-42 in the brain is disrupted, it leads to excessive accumulation of A β 1-42 in the brain, resulting in diffuse plaques or SP; The accumulation of A β 1-42 can also promote oxidative stress, damage the cholinergic system of the body, and further induce or accelerate the occurrence and development of AD. Due to the large accumulation of APP, A β, especially A β 1-42, which will stimulate multiple mechanisms and promote the occurrence of AD through multiple pathways, the determination of APP and A β content has become one of the indicators for measuring the severity of AD. This study shows that the volatile oil of Angelica sinensis can reduce the content of APP and A β 1-42, and there is a dose-response relationship between the volatile oil of Angelica sinensis and the content of APP. The dosage of Angelica sinensis volatile oil has the strongest inhibition on A β 1-42. The high-dose Danggui volatile oil has the best effect on reducing the content of APP, but at this time, the content of A β 1-42 is higher than that of the low and medium dose groups of Danggui volatile oil. In future research, the optimal concentration of Danggui volatile oil to inhibit APP and A β 1-42 content, whether high-dose Danggui volatile oil activates other pathways that promote the production of A β 1-42 while inhibiting APP expression, and whether there is an effective range for reducing APP content can be further explored.

During the natural aging process of the body, neurons produce a large amount of free radicals, which act on lipids to undergo peroxidation reactions, forming the ultimate cytotoxic product MAD, causing cross-linking and polymerization of life macromolecules such as proteins and nucleic acids. It can also promote the toxicity and aggregation of A β, leading to the formation of AD age spots. The cholinergic nervous system is closely related to the formation and storage of brain memory, directly affecting the ability to learn and remember. Acetylcholine (ACh) is an important neurotransmitter that promotes learning and memory, widely distributed in brain tissue. It is synthesized by choline and acetyl CoA under the catalysis of ChAT and broken down under the cleavage of AChE. It can be seen that the activity of ChAT and AchE reflects the rate of ACh synthesis and metabolism in the brain, and is a contradictory binary that maintains the dynamic balance of Ach content. Therefore, the decrease in ChAT catalytic activity and the increase in AChE cleavage activity can lead to a reduction or even loss of acetylcholine, which will inevitably result in a decline in cognitive function and memory loss in the body. This study indicates that the volatile oil of Angelica sinensis can significantly increase serum ACh content and ChAT, while reducing serum AChE activity. The effect of medium dose Angelica sinensis volatile oil on ChAT is weaker than that of low and high dose groups, but there is a dose-response relationship between Angelica sinensis volatile oil and Ach levels. High dose Angelica volatile oil has the best effect on enhancing SOD activity and reducing MDA levels. From the perspective of cholinergic neurotransmitters and oxidation, it has been confirmed that the volatile oil of Angelica sinensis has an effect on Alzheimer’s disease, which is consistent with the previous results of using Angelica sinensis decoction to intervene in AD model mice. Therefore, Angelica sinensis volatile oil may be one of the main components that take effect. This experiment only explored the therapeutic effect of Danggui volatile oil on AD, and its absorption and metabolism patterns in vitro and in vivo, as well as the mechanisms of improving cholinergic neurotransmitters and enhancing anti free radical oxidation ability, need further investigation.

In summary, the volatile oil of Angelica sinensis can effectively improve the learning and memory abilities of AD model rats, and its mechanism may be related to the promotion of A β metabolism, improvement of cholinergic neurotransmitters, and enhancement of anti free radical oxidation ability through multiple pathways and cascading interactions.