Phosphatidylserine, also known as compound nervous acid, referred to as PS, is a kind of phospholipid, and its chemical structure is shown in Figure 1. Phosphatidylserine consists of three parts: two long chains of fatty acids, a glycerol backbone, and a phospholipid headgroup. Among them, the phospholipid head group is composed of serine and phosphoric acid, and the phospholipid head group has a negative charge. The phospholipid head group of PS is hydrophilic, and the tail containing fatty acid is lipophilic, so PS is amphiphilic, both hydrophilic and lipophilic. In addition, because of the difference in long-chain fatty acids, PS refers to a class of compounds rather than a single component.

PS exists in the biofilms of all animals, higher plants, and microorganisms, and is one of the important components of cell membrane phospholipids. It accounts for 10%-20% of all phospholipids in the mammalian brain and is important for many cell metabolism processes. Regulatory effect. In particular, it plays an important role in regulating the memory and emotional stability of the brain. At present, phosphatidylserine has been certified as a nutritional supplement by the Food and Drug Administration of many countries and is widely used abroad. In South Korea, PS was allowed by the Korean Food and Drug Administration (KFDA) to be prominently displayed in products added with PS in May 2006, and publicized that related products have the functions of "improving bad mood, enhancing memory" and preventing senile dementia; in the United States , PS was recognized as GRAS by the US Food and Drug Administration (FDA) in October 2006, which means that PS can be added as a nutritionally fortified functional food material in yogurt, milk powder, bread, powder drinks and other foods; in Japan , PS was included in the food (non-drug) list by Japanese food and drug HBM, and passed the individual review of food additives on February 5, 2010; in China, PS was listed by the former Ministry of Health ( Now renamed as the National Health and Family Planning Commission) was added to the new resource food catalog, allowing it to be used as a new resource food. However, in China, people do not know much about phosphatidylserine. This article will briefly introduce the clinical efficacy and application of phosphatidylserine.

1. Improve brain function, focus attention, improve cognitive ability, especially learning and memory ability

Suzuki et al. [1] studied the Morris (Morris) underwater maze escape test in older rats with memory impairment. After feeding 60 mg/kg·d soybean phosphatidylserine (SB-tPS) for 60 days, the results showed that male The behavioral performance of older rats was significantly improved, and SB-tPS was found to promote the release of acetylcholine and the activity of Na+/K+-ATPase. When acetylcholine enters the brain with the blood, the speed of information transmission between brain nerve cells is accelerated, thereby promoting brain function and enhancing the ability of memory, thinking and analysis.

Tang Yong, Zhang Qianyong et al. [2] took high school students aged 17-18 as the research objects, and studied the improvement effect of drinking fresh milk with 0.08% phosphatidylserine with a purity of 50% on human memory. The results showed that milk added with PS It can significantly improve and improve the memory of students.

2. Improve brain function and improve Alzheimer's disease in the elderly

As we grow older, phosphatidylserine and other important chemicals that affect brain function will gradually decrease. This chemical change leads to a decrease in enzyme activity and transport energy in normal cell membranes. Lead to decline in memory and cognitive ability. Supplementing PS can increase the number of brain synapses, enhance the fluidity of brain cell membranes, and promote glucose metabolism in brain cells, thereby making brain cells more active. PS supplementation is now widely used in many countries to treat aging-induced dementia and senile memory loss.

In 1986, Delwaide et al. [3] reported for the first time that oral administration of bovine brain PS (BC-PS) (300 mg/d) to Alzheimer's patients could improve the cognitive function of the patients. Since then, multiple double-blind and placebo-controlled studies in Europe and the United States have confirmed the efficacy of this phospholipid. Crook et al [4] reported that 51 Alzheimer's patients took BC-PS or placebo for 12 weeks and found that patients taking PS had improved cognitive ability, while the control group taking placebo had no such results. The effect was even more pronounced in patients with less severe cognitive impairment. The results of this experiment suggest that PS may be a promising drug candidate in the early stages of Alzheimer's disease.

3. Relieve tension, depression and physical fatigue

The dysfunction of noradrenergic system and serotonergic system in the brain may be the cause of stress and depression. Phosphatidylserine can significantly reduce the level of excessive stress hormones in the body, reduce stress, relieve brain fatigue, promote concentration, improve alertness and memory, and relieve bad emotions.

In a double-blind controlled trial[5], one group of subjects took 800mg of phosphatidylserine per day, and the other group took the same dose of placebo. After 10 days, the two groups performed the same high-intensity training, and tested the subjects blood cortisol concentration. It was found that the cortisol levels in the control group were significantly higher than before training, while the subjects in the PS group were controlled at a lower level of cortisol. If it can effectively inhibit the increase of cortisol during intensive training of athletes, it will provide a good hormone environment for improving training performance. The researchers speculate that PS may be involved in the response process of the hypothalamus-pituitary-gonad axis to stress. PS will be a sports nutrition strengthening substance with development potential.

Hellhammer used a mixture of soybean phosphatidic acid (PA) and phosphatidylserine (PS) (PAS) to conduct a social stress test on 20 subjects, and found that the subjects who took PAS (at a dose of 400mg/d) for 3 weeks had a serum stimulating effect. The levels of adrenaline and cortisone were significantly suppressed, and the physical tension of the subjects was significantly relieved without affecting heart rate changes [6].

4. Treatment of depression

Brambilla[7] used bovine brain PS (BC-PS) to study the efficacy of cognitive and behavioral symptoms on 10 elderly female patients with depression. The patient received BC-PS treatment (300mg/d) for 30 days after receiving placebo treatment for 15 days. Mood, memory and general sexual behavior were monitored before and after placebo and BC-PS treatment. The results show that phosphatidylserine can regulate the level of neurotransmitter hormones in the brain that control emotions, and the depression of patients is reduced by an average of 70%, and symptoms such as mood disorders, abnormal behavior, anxiety, and irritability have been significantly improved. There was basically no change in symptoms before and after, and no side effects were found during the BC-PS trial.

5. Application of phosphatidylserine in michalum peptide liposomes

In the field of liposomes, phosphatidylserine also has its unique effects. Studies have found that liposomes containing negatively charged phosphatidylserine (PS) and phosphatidylglycerol (PG) are easily recognized by macrophages, so liposomes containing PS are more likely to target the reticuloendothelial system. The experiment compared the uptake of neutral phosphatidylcholine (PC) and negatively charged PS liposomes in macrophages, and the results showed that the uptake of liposomes containing negative charges (DOPS-Chol) was higher than that of neutral liposomes ( DOPC-Chol) intake is 5.3 times [8]. Taking advantage of the property of dioleoylphosphatidylserine DOPS to easily target macrophages, Mepact® liposome injection (Mepact®) developed by IDM Pharma Inc of the United States was approved for marketing in the European Union in 2009. Peptide liposomes kill tumor cells by stimulating certain white blood cells such as macrophages, and are used for the treatment of lung metastatic osteosarcoma [9]. Mepact® is ingested by macrophages and releases miphatide, which kills cancer cells by activating monocytes, macrophages and cytokines. Patients received Mepact® combined with other chemotherapy drugs after surgical resection of osteosarcoma. Chemotherapy is like a bomb destroying tumors, and Mepact® can completely remove residual cancer cells in the tumor site. Clinical data show that its combination with cisplatin, doxorubicin and other chemotherapy drugs can reduce the mortality rate of patients by 30%, and the survival rate of patients with a survival period of more than 6 years can reach 78%. The formulation composition of Mepact® is relatively simple, using phospholipids DOPS and POPC with a molar ratio of 3:7 (Figure 3). Each bottle of Mepact® lyophilized powder contains 4mg of MTP-PE and 1g of total phospholipids.

At present, the preparation methods of PS mainly include extraction method, enzymatic synthesis method and chemical synthesis method. Food-grade PS is usually extracted from soybeans or animal organs, but the purity of PS produced in this way is not high and the structure is not a single component. High-purity PS with a single chemical structure needs to be produced by chemical synthesis.