An Insight Into The Alzheimer's Breakthrough New Drug

Alzheimer's disease (AD) is an irreversible neurodegenerative disease with clinical manifestations such as memory impairment, aphasia, impairment of visuospatial skills, executive dysfunction and personality changes. Its pathogenesis has not been fully clarified, and there is no complete cure so far, which has brought a heavy burden to the family and society.

Saponins are a class of oligosaccharides whose aglycones are triterpenoids or spirostane compounds. They are divided into triterpenoid saponins and steroid saponins and have various biological activities. It is currently being used as an alzheimer's breakthrough new drug. A number of studies have shown that saponins can prevent the occurrence and development of AD through multiple targets and multiple mechanisms. There are many types of saponins with therapeutic effects on AD, but there is no systematic review on them. Therefore, this paper systematically summarizes the effects and mechanisms of the alzheimer's breakthrough new drug in inhibiting β-amyloid（Aβ）activity, inhibiting neuronal oxidative stress, and inhibiting inflammatory factors on the basis of animal experiments.

Inhibits Aβ cascade activity

Aβ is a normal metabolite formed by the hydrolysis of amyloid precursor protein (APP), and abnormal accumulation of Aβ in the brain is one of the hallmarks of AD. At present, there are two main ways to target Aβ to improve AD: ①reduce Aβ production; ②inhibit Aβ aggregation and accelerate Aβ clearance. Pseudo-ginsenoside PF11 can promote the transport of APP from the cytoplasm to the plasma membrane, inhibit the amyloid processing of APP, and reduce the production of Aβ; PF11 can also promote the binding of APP to circulating inclusion bodies to reduce the production of Aβ. Ginsenoside Rg1 has estrogen-like activity, can promote the metabolism of APP, reduce the Aβ content in the hippocampus of ovariectomized rats, and has a good potential for preventing AD in menopausal women.

Inhibits neuronal oxidative stress

Elevated levels of free radicals and dysfunction of the antioxidant system may damage brain cells, eventually leading to the occurrence and progression of AD, which in turn promotes the aggregation of Aβ and the phosphorylation of microtubule-related protein tau, aggravating the imbalance of redox reactions in AD brains , and excessive Aβ deposition and tau protein phosphorylation accelerate AD process. Panax notoginseng saponins can increase the activities of total superoxide dismutase, glutathione peroxidase and catalase in the brain of SAMP8 mice and reduce the expression level of 8-hydroxydeoxyguanosine, a DNA damage marker Rat brain tissue is damaged by oxidative stress and activates the Nrf2/HO-1 pathway to reduce oxidative stress damage.

Inhibit inflammatory factors

A large number of activated microglia exist around senile plaques in AD patients. Aβ can activate astrocytes and microglia and induce the production of a large number of inflammatory mediators; inflammatory mediators directly damage nerve cells, promote the production of Aβ, and then trigger AD. Ginsenosides can inhibit the excessive activation of microglia, reduce the expression of inflammatory factors such as interleukin-1β and tumor necrosis factor-α in hippocampal CA1 region, improve oxidative stress and inflammatory response, and reduce memory damage.

Regulates apoptosis and protects neurons

Neuronal cell death in the brain of AD patients occurs in the form of apoptosis, and the active expression of various gene products plays a role in AD neuronal apoptosis, such as Bcl-2, Bax, Caspase gene, etc. Saponins protect neurons by regulating the expression of apoptosis genes.

Inhibit cholinergic neuron degeneration

In the course of AD, the degeneration of cholinergic neurons is considered to be an important pathological factor causing dementia. Most saponins reduce the degradation of acetylcholine by reducing the activity of acetylcholinesterase, such as notoginsenoside Rg1, timosaponin AIII, ginsenoside Rh2, ginsenoside Rh3, thereby enhancing the function of the cholinergic system.

Others

Regulation of gut microbiota

The gut microbiota plays a key role in the regulation of brain function by maintaining homeostatic regulation of innate and adaptive immunity. Studies have found that modulating gut microbiota can protect neural pathways that delay the progression of AD. Ginsenoside Rg1 can regulate the intestinal core microbiota of AD model animals and improve the intestinal flora disturbance of AD animals. Panax notoginseng saponins combined with icariin can reverse the decrease in the microflora in AD mice and improve the memory impairment caused by AD.

Enhance energy metabolism

Mitochondrial dysfunction and abnormal energy metabolism in the brain of AD patients are earlier than conventional Aβ deposition and Tau protein phosphorylation. Therefore, abnormal energy metabolism is also considered to be the main cause and hallmark of AD. Experiments have shown that this alzheimer's breakthrough new drug can enhance energy metabolism in AD mice, significantly increase the protein expression levels of insulin receptor, glucose transporter and GLUT3, improve energy imbalance, increase the level of adenosine triphosphate, and improve cognitive impairment.

This article summarizes the mechanism of action of the alzheimer's breakthrough new drug-saponin in the treatment of AD. This kind of alzheimer's breakthrough new drug will undergo a series of structural changes in the intestine, mainly based on gradual deglycosylation. Therefore, it is necessary to change the traditional mode of administration, develop new dosage forms, and increase the gastrointestinal tract to saponins. Absorption of ingredients to reduce losses.