Research Progress in The Study Of Traditional Chinese Herbal Medicine Extracts Regulating Ferroptosis Thus Improving The Symptom Of Alzheimer's Disease Ⅲ

6 Summary and Outlook

Some ferroptosis-specific inhibitors have shown possible clinical benefits in clinical trials, all of which have improved AD to varying degrees. Representative metal ion chelators, such as deferoxamine (DFO) [79], can improve the learning and memory ability of AD animal models through intranasal administration. Its action pathway may be achieved through direct iron chelation, activation of HIF-1α, or inactivation of GSK-3β through phosphorylation. Another representative ferroptosis inhibitor, such as ferrostatin-1 (Fer-1), can effectively inhibit the production of cytoplasmic and lipid ROS and inhibit oxidative toxicity to protect HT-22 cells. Although these drugs currently have certain clinical efficacy in the treatment of AD, as new synthetic drugs, their long-term efficacy and pharmacodynamic stability are still unclear. Their specific targets and mechanisms involved in AD ferroptosis still need to be improved. In addition, long-term clinical observation is needed to determine whether they will destroy important iron-dependent physiological functions in cells and whether they will continue to be safe and effective in the case of AD combined with other diseases.

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In addition, the application of some traditional Chinese medicine compound prescriptions has also participated in regulating ferroptosis and improving AD symptoms. Icariin-astragaloside-puerarin (YHG) mixture [80], composed of effective monomers of epimedium, astragalus and pueraria, can improve the learning and memory ability of APP/PS1 mice, reduce the deposition of senile plaques in the brain, and reduce neuronal ferroptosis by enhancing the ferroptosis amino acid metabolism pathway and improving antioxidant capacity. Suanzaoren decoction [81] can alleviate ferroptosis and improve cognitive impairment in AD mice by activating the DJ-1/Nrf2 signaling pathway and alleviating Aβ deposition, neuronal loss and synaptic damage in AD mice. Compared with a single traditional Chinese medicine active ingredient, the clinical application of compound prescriptions is difficult to ensure the effectiveness of drug concentration and the convenience of administration. At present, most experimental studies focus on the mechanism of action of single herbs and their main active ingredients in AD, and there is little basic research on compound prescriptions, such as the material basis of efficacy, analysis of drug metabolic components and in-depth mechanism exploration in AD. Clinical research currently focuses on the observation of clinical efficacy of a single neurological disease, with less research on deep-level mechanisms and a lack of large-scale, multi-center, high-quality randomized controlled trials.

Iron is the most abundant metal element in the human brain and an important substance for maintaining human metabolism and life activities. Its excessive accumulation in the brain can further induce ferroptosis. Ferroptosis in the brain of AD patients has been the focus of researchers in recent years. In cells experiencing ferroptosis, ROS and lipids in the cytoplasm increase significantly, accompanied by a decrease in mitochondrial volume and an increase in cell membrane density. It is not difficult to find from previous studies that ferroptosis may play an important role in the occurrence and development of AD. Since the existing related research is still in its infancy, how to reduce ferroptosis without interfering with the physiological function of iron homeostasis requires further exploration of the best anti-ferroptosis targets with neuroprotection in the future. Previously, drug development with Aβ as a therapeutic target failed to succeed in the clinical trial stage. Ferroptosis, as a new potential target, has opened up a direction for the subsequent development of new AD therapeutic drugs. At present, although the first-line treatment drugs of Western medicine can improve the symptoms of AD to a certain extent, the therapeutic effect varies from person to person, and it cannot reduce and prevent neuronal damage caused by AD, and cannot reverse the progression of the disease.

In addition, there are problems of adverse reactions and drug resistance, and the clinical efficacy is not satisfactory. In this context, the article systematically introduces a series of Chinese medicines that treat AD by targeting ferroptosis, such as Rhodiola rosea, Polygala tenuifolia, Ginkgo biloba, Poria cocos, etc., which show obvious advantages such as significant efficacy and small adverse reactions during the treatment process. In the future, health researchers need to continue to study and improve the exact mechanism of ferroptosis in the pathogenesis of AD, enrich the corresponding clinical trial verification, and carry out more experimental studies on the intervention of Chinese medicine compound in ferroptosis prevention and treatment of AD. In addition, most of the research on the anti-AD mechanism of Chinese medicine is still in the in vitro and animal experimental stage. In the future, it is necessary to explore the experimental model of TCM syndrome differentiation and treatment to better play the characteristics of TCM.

Author contributions: Pei Jinying proposed the research topic, conceived and wrote the article; Song Jinzhou and Ma Daofeng searched and collected literature; Luo Xiaoting, Dong Xiaohong, and Cong Shuyuan revised the paper; Liu Bin was responsible for the quality control and review of the article, and was responsible for the article as a whole.

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