Grape seeds are the seeds of Vitis vinifera L. in the family Vitis, which are dried and separated from the skins and stems of the grapes. As one of the oldest tree species in the world, grapes are native to Western Asia and distributed all over the world, with about 95% concentrated in the Northern Hemisphere. The roots of grapes are well developed and can adapt to all kinds of soil. China's grape planting area and annual output have always ranked first in the world, mainly concentrated in Xinjiang, Shandong, Hebei, Henan and Liaoning and other regions.

In recent years, through continuous research, it has been found that grape seeds not only have high nutritional value, but also have outstanding medicinal value. The polyphenol compounds proanthocyanidins contained in grape seeds have strong antioxidant, free radical scavenging, blood lipid lowering, cardiovascular protection and anti-tumor effects.

In this paper, the current researches on the pharmacodynamic components and pharmacological effects of grape seeds were reviewed.

1 Chemical Composition

Polyphenols

Grape seeds contain polyphenols, mainly catechins and proanthocyanidins. Catechin compounds, including catechin, epicatechin and gallate, are the main monomers in grape seeds, and also the component units of oligomers and polymers of proanthocyanidins.

Oils and fats

Grape seeds are rich in oil, accounting for about 12% to 15% of its weight, and oil contains a large number of unsaturated fatty acids, of which the content of linoleic acid is between 58% and 78%.

Volatile component

Grape seeds also contain a small amount of volatile components, which are mostly alcohols, phenols, terpenoids, and have high biological activities.

Other components

In addition to the above substances, grape seeds also contain crude protein, amino acids and vitamins A, E, D, K, P and a variety of trace elements, such as calcium, zinc, iron, magnesium, copper, potassium, sodium, manganese, cobalt and so on.

2 Pharmacological Effects

2.1 Antioxidant

Zhou Jianshe et al. confirmed through clinical experiments that the experimental group taking PC capsule (grape seed extract) was peroxidized by double-blind control method

The content of lipid (MDA) was significantly different from that of the control group and before the experiment (P<0.01), and the mean percentage of decrease was significantly different from that of the control group (-1.8±11.0)% (P<0.01), indicating that PC had strong antioxidant capacity. Sun Yun et al. also confirmed through research that PC in linoleic acid and liposome systems has strong antioxidant capacity. PC had higher antioxidant activity than Vc and VE, and showed significant synergistic enhancement effect with both. PC also had significantly higher scavenging ability of DPPH· free radicals than Vc and VE, and the semi-inhibitory concentrations were: PC1.8μg /mL, Vc2.5μg /mL, and Vε 6.3μg /mL, respectively. The ability of PC to clear O₂ is close to Vc but significantly higher than V, and the semi-inhibitory concentrations are :PC15.4μg/mL, Vc 14.5 μg/mL, and Vε177μg/mL, respectively.

2.2 Lowering blood lipids

Yan Shaofang et al. "showed through experimental studies that PC can reduce the levels of TC, TG, LDL-C, liver cholesterol and triglyceride in serum of high-fat rats, and increase the activity of lecithin lipoprotein acyltransferase in serum of high-fat rats, which helps to accelerate the reversal of cholesterol transport and thus promote the liver metabolism of cholesterol. It can also increase the excretion of total bile acid in high-fat rats, which also plays an indirect role in promoting the excretion of cholesterol in vitro. This study provides a further theoretical basis for PC to reduce human blood lipids.

2.3 Anti-Diabetes

Through experimental studies, Tomaru et al. found that dietary supplementation of PC can effectively prevent the occurrence of hyperglycemia in diabetic mice in a dose-dependent manner, which indicates that PC also has a positive effect on stabilizing blood sugar in type 2 diabetes. Pesta et al. and Stepien et al. found that metabolic disorders such as obesity, insulin resistance, fatty liver, type 2 diabetes, and hyperlipidemia all have reactive oxygen species (ROS) surplus, lipid peroxidation, and abnormal changes in MAPK and JNK signal transduction. Patients with metabolic disorders such as diabetes often have abnormal markers of oxidative stress (OS) in their serum. In a type 2 diabetes cell model, glucose-induced ROS accumulation and OS caused damage to cardiomyocytes, endothelial cells, and nerve cells. El-Alfy et al. have demonstrated that PC can significantly improve various tissue damage caused by type 2 diabetes by increasing pancreatic glutathione and reducing lipid peroxidation and nitrite levels in the pancreas. Therefore,PC plays an extremely important role in the prevention and treatment of type 2 diabetes and its complications.

2.4 Prevention and treatment of cardiovascular diseases

OS is considered to be an essential pathogenesis of cardiovascular diseases such as atherosclerosis, hypertension, heart failure and restenosis after interventional surgery. ROS disrupts myocardial calcium homeostasis, causing a cascade of abnormal signaling pathways and gene expression, leading to arrhythmia and myocardial remodeling. Lipid peroxidation induced by ROS runs through the whole process of atherosclerosis and promotes its occurrence and development. Deoxycorticosterone acetate can promote the progression of hypertension, cardiovascular remodeling and cardiac dysfunction by increasing the phosphorylation of p38 MAPK and JNK1/2. In contrast,PC can reduce hypertension and improve cardiovascular remodeling and cardiac function by inhibiting ROS gene and p38 MAPK pathway activation. At the same time,PC can not only improve cardiovascular disease damage, but also reduce cardiovascular disease hypertension, hyperlipidemia, peroxidation and other risk factors. Therefore,PC plays an important role in the prevention and treatment of cardiovascular diseases.

2.5 Anti-tumor

Gao et al. showed that the survival activity of MDA-MB-231 cells in the PC treatment group decreased by 9%-19% within 48 hours (P<0.05), by 30%-41% within 72 hours (P<0.05), and by 13%-35% within 48 hours of MCF-7PC cells (P<0.05), decreased by 28% to 44% in 72h (P<0.05). It was confirmed that PC could significantly inhibit the activity of human breast cancer cells by inhibiting MDA-MB-231 and MCF-7. Katiyar et al. showed through experimental studies that dietary supplementation of mice in the PC group effectively prevented the occurrence of UV-radiation-induced non-melanoma skin cancer, and the mechanism may be caused by the repair of DNA-dependent activity that enhances damage and controls immune sensitivity.

2.6 Antibacterial

Savickiene et al. confirmed through experiments that PC can selectively target oral pathogenic microorganisms - gram-negative bacteria, such as porphyromonas gingivalis, and has no killing effect on beneficial symbiotic bacteria, such as Streptococcus salivarius. Due to the mild antibacterial effect of PC and the multiple targeted effects, PC is not at risk of developing drug resistance. Therefore, PC is regarded as an excellent alternative for the treatment of oral diseases and other infections, and is a very promising natural antibacterial substance.

2.7 Other Effects

Liu et al. showed through experimental studies that PC can significantly extend the weight-bearing swimming time of mice and reduce fatigue of mice. Experimental finding

After exercise, the serum lactic acid level in mice decreased and the glycogen content in liver cells increased. Therefore, the anti-fatigue effect of PC may be realized through the scavenging of free radicals and the protection of tissue peroxidation damage caused by free radicals. Nair et al. have shown that PC can inhibit the activity of HIV-1 virus in monocytes, inhibit its expression and replication, and the mechanism is that PC can significantly reduce the expression of a variety of chemotactic receptors such as CCR2b, CCR3 and CCR5 in a dose-dependent manner, which has certain significance for the prevention and treatment of HIV. In addition,PC also has resistance to ultraviolet radiation, aging, ulcers and immune rejection.

3 Outlook

In short, grape seeds contain rich nutrients and pharmacodynamic components, with high nutritional and medicinal value. Pharmacological studies have shown that PC has a variety of pharmacological effects, and it plays an important role in antioxidant, lipid-lowering, diabetes prevention, cardiovascular protection and anti-tumor, which is particularly worthy of attention. Therefore, the application prospect of PC is also very broad.

Although some achievements have been made in some aspects of grape seed research, the pharmacodynamic components, efficacy and mechanism of grape seed are not clear so far. Therefore, it is necessary to further study the pharmacodynamic components and pharmacological effects of grape seeds, clarify its active components, clarify the mechanism of action, fully tap its use value, and make it better benefit mankind.