Views: 1 Author: 熊雯宇,何君强,黄梓芮,等. Publish Time: 2022-09-20 Origin: 食药用菌活性成分对酒精性肝损伤防护作用研究进展[J].食品工业,2022,43(4):221-225.
The liver is the organ in the body that detoxifies and metabolizes and can break down alcohol. Most of the non-nutritive substances are broken down by the liver, and the toxic substances are metabolized into non-toxic or low-toxic substances and excreted from the body. There are many reasons for liver damage, such as excessive alcohol, drugs or other toxic substances, and the degree of damage is related to conditions such as time, dose, and toxicity. Among them, alcohol is the most important factor. In recent years, the incidence of alcoholic liver injury (ALD) has been increasing in China, the United States and European countries. Early symptoms of ALD include stomach pain, vomiting, loss of appetite, etc. Severe ALD will eventually develop into liver cirrhosis and even worsen into liver cancer. Studies have shown that the active ingredients of edible and medicinal fungi have great potential in the protection of ALD, and their medicinal and edible safety has also been proved by history, which is an important development direction of health food in my country. The study found that the main active components of edible and medicinal fungi on liver protection are flavonoids, polyphenols, sterols, polysaccharides, terpenes and alkaloids, and the mechanism of action is anti-oxidation, scavenging free radicals and regulating lipid metabolism. Wait.
The pathogenesis and research status of alcoholic liver injury
Metabolism of alcohol in the body
In the liver, alcohol is oxidized to acetaldehyde by alcohol dehydrogenase, and acetaldehyde is metabolized to acetic acid by acetaldehyde dehydrogenase, which is decomposed into CO2 and H2O through a series of metabolism and excreted. When the body ingests alcohol, the liver stops normal fat metabolism and breaks down alcohol. Alcohol and its metabolites have strong toxic and side effects on the liver, coupled with the formation of acetaldehyde adducts, which are metabolites of alcohol, resulting in the death and injury of a large number of liver cells and causing hepatitis. After the liver is damaged, a large amount of fibrous tissue grows and gradually hardens, eventually leading to cirrhosis. After severe liver cirrhosis, the body's various abilities decline rapidly, and the continuous deterioration leads to the occurrence of liver cancer - liver cancer.
Pathogenesis of alcoholic liver injury
Oxidative damage is one of the main hazards of alcohol and a key target for the pathogenesis of ALD. Excessive drinking leads to the accumulation of alcohol and acetaldehyde in the blood and liver, and the liver will form a lot of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the process of decomposing alcohol and metabolizing it, resulting in a decrease in antioxidant levels. It further causes excessive oxidative stress to generate oxidative products, destroys the antioxidant system, causes mitochondrial damage, and leads to liver cell damage and liver dysfunction. Oxidative stress and inflammatory responses induced by alcohol metabolism can lead to mitochondria-dependent apoptosis and accelerate the progression of ALD. During the development of ALD, mitophagy plays an important role in protecting hepatocytes. After alcohol metabolism damages mitochondria, autophagy selectively removes damaged mitochondria, thereby reducing oxidative stress and preventing cell death.
The formation mechanism of ALD is complex, mainly including abnormal lipid metabolism, imbalance of intestinal flora and disorder of alcohol metabolizing enzymes. In recent years, it has been gradually recognized that the imbalance of intestinal flora is an important pathological feature of certain metabolic diseases, especially liver injury diseases. Dysbacteriosis and liver injury are closely related and interacting vicious cycle processes. Long-term excessive drinking can lead to dysbiosis of intestinal flora and further aggravate the condition of liver injury, which is also one of the pathogenic mechanisms of chronic ALD.
Active ingredients of edible and medicinal fungi and their efficacy
According to scientific research, edible and medicinal mushrooms are a kind of precious delicacies and medicinal materials, with the characteristics of "one high, two no, three low, and four more", that is, high protein, no cholesterol, no starch, low sugar, low energy, Low in fat, high in minerals, high in amino acids, high in dietary fiber, and high in vitamins. Most edible and medicinal fungi can be used as edible and medicinal raw materials, often in fresh or dry state, giving them a unique aroma and delicious taste. Rich in a full range of nutrients necessary for maintaining human health, it has the functions of scavenging free radicals, improving immunity, improving blood circulation, maintaining internal environment balance, protecting liver, strengthening stomach, and inhibiting tumors. As shown in Table 1, it was found in scientific research that edible and medicinal fungi contain biologically active substances such as polysaccharides, polypeptides, terpenes, flavonoids, polyphenols, sterols and alkaloids.
A large number of studies have shown that edible and medicinal fungi have a great effect on reducing hypertension, high cholesterol, protecting liver damage, enhancing immunity and inhibiting tumor activity. Shi Yanling's research results show that the peptides, polysaccharides and triterpenoids in Ganoderma lucidum have antioxidant and hepatoprotective effects, can effectively inhibit hydroxyl free radicals and anti-phospholipid oxidation, and have auxiliary protective effects on ethanol-induced liver damage; Wang Wei etc. showed that the fruiting body extract or deep liquid fermentation broth of 4 rare bacteria Agaricus blazei, Grifola frondosa, Boletus, and Bamboo fungus had antitumor activity, improved immunity, immunomodulatory activity and antioxidant activity.
Protective effect of active ingredients of edible and medicinal fungi on alcoholic liver injury
Studies have confirmed that edible and medicinal fungi such as shiitake mushrooms, chicken leg mushrooms, black fungus, Xiuzhen mushrooms, Yunzhi, Agaricus, Grifola frondosa, Cordyceps militaris, etc. have a good effect on ALD protection. Oxidation, etc. Studies have shown that the active ingredients of edible and medicinal fungi, as a natural product, can effectively relieve ALD, and can regulate the occurrence and development of ALD through various mechanisms, and play a relieving effect. Edible and medicinal fungi have shown their clinical value in the treatment of ALD because of their strong antioxidant activity. The active components of edible and medicinal fungi can affect liver indexes and liver morphological histology, improve liver function and ethanol metabolism, improve liver fat metabolism and the expression of related genes, reduce oxidative stress, and have anti-inflammatory and liver-protecting effects on ALD. Inhibits apoptosis.
Affects liver indexes and improves liver function
Liver index is a very important clinical index, which can better reflect the degree of liver disease. The commonly used clinical indicators of liver function mainly include alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triacylglycerol (TG), and high-density lipoprotein cholesterol (HDL-C). , low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C). The contents of peroxidase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) can better reflect the antioxidant level of liver. Interleukin-6 (IL-6) reflects the degree of liver cell inflammation, and lipopolysaccharide (LPS) reflects the degree of liver cell toxicity. Among them, ALT and AST are the most direct and sensitive indicators reflecting hepatocyte damage. When hepatocyte damage occurs, the permeability of hepatocyte membrane increases, and the concentrations of ALT and AST also increase. SOD protects the body by scavenging free radicals, and plays an important role in the body's oxidative balance. The content of MDA reflects the degree of liver cell damage and the repair of liver cells after treatment. Clinically, these indicators have a good indication of the degree of ALD. Song et al. found that the mushroom polysaccharide (IMPP) can significantly reduce the levels of TC, TG, LDL-C and VLDL-C in ALD mice, and increase the level of HDL-C, suggesting that IMPP has the potential to improve dyslipidemia. Zhang Jing explored the hepatoprotective activity of the composite aqueous extract of Boletus and Morchella by establishing a mouse ALD model, and prepared the technological formula for the development of oral liquid. The active ingredients of the composite water extract were determined, and active ingredients such as polysaccharides, reducing sugars, proteins, amino acids, fatty acids, and organic acids were detected. The results showed that the composite water extract significantly reduced the contents of ALT and AST, and increased the contents of MDA, TG and SOD, indicating that it can not only improve the antioxidant function of the body, but also improve the degree of liver cell damage.
Regulates hepatic lipid metabolism
Under the intervention of a large amount of alcohol for a long time, the synthesis and metabolism of fatty acids in the liver lose the steady state balance, and ROS inhibit the autophagy of hepatocytes, resulting in the accumulation of a large amount of fatty acids in the body to form fatty liver. Its pathogenesis is related to various factors such as mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptors (PPARs). MAPKs inhibit fatty acid and cholesterol synthesis, and PPARs regulate fatty acid transport and oxidation and cholesterol metabolism. Ren et al. studied the preventive effect of Yunzhi polysaccharide polypeptide (PSP) on ALD in mice. PSP supplementation reduced ethanol-induced ALT, AST, trace MDA, TC, TG levels and endotoxin concentrations. Mechanistically, PSP treatment upregulates alcohol-stimulated intrahepatic expression of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and peroxisome proliferator-activated receptor alpha (PPARα), by reducing fatty liver development. Process lipid accumulation and alleviation of endotoxin-mediated inflammatory responses ameliorates ethanol-induced hepatic steatosis and injury. The findings suggest that PSP has the potential to be prescribed as a dietary supplement or ALD, and provide a theoretical basis for the future direction of PSP development.
Regulation of Keap1-Nrf2/ARE signaling pathway alleviates oxidative stress
Oxidative stress refers to the fact that when the body is stimulated by alcohol, the body cannot remove excessive ROS and RNS produced by metabolism in time, which further causes the imbalance of the redox system to cause oxidative stress, which eventually leads to apoptosis and liver damage. The study found that the key pathway for cells to resist oxidative stress is Kelch-like epichlorohydrin-related protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE). The active ingredients of edible and medicinal fungi can detoxify alcohol by regulating this pathway, and at the same time regulate antioxidant enzymes to remove harmful substances such as ROS and RNS, and enhance the body's antioxidant capacity, thereby reducing oxidative stress, so as to achieve the effect of treating and preventing ALD. . Hou Ruolin established a mouse acute ALD model, and its liver index, ALT and AST, CAT, SOD and MDA showed that black fungus melanin could significantly improve the antioxidant capacity of ALD mice. The study also confirmed that black fungus melanin can activate the Nrf2 signaling pathway and increase the expression of downstream related antioxidant enzymes, providing a direction for exploring its pharmacological mechanism.
Restoring gut homeostasis regulates ALD-related metabolic disorders
Studies have shown that a large amount of alcohol intake can cause intestinal flora imbalance, increase intestinal permeability, and some of the microorganisms and metabolites in the intestinal tract will circulate to the liver through the blood, causing secondary damage to the liver and aggravating alcoholic liver damage. degree. Probiotics can improve liver damage diseases, strengthen immunity, reduce the carcinogenicity of poisons, and prevent the deterioration of liver damage. Therefore, the use of hepatoprotective drugs or probiotics to improve or treat the imbalanced state of intestinal flora to treat liver injury diseases has received extensive attention. Many animal model experiments and clinical studies have shown that liver damage diseases can be improved through the regulation of intestinal flora. The active ingredients of edible and medicinal fungi maintain the intestinal microecological balance by regulating the bacterial structure composition and microbial metabolites in the intestinal flora, and have a significant protective effect on ALD. With the advancement of detection technology, more systematic and in-depth research will be carried out on the mechanism of the active ingredients of edible and medicinal fungi in regulating intestinal flora. New breakthroughs have been made in this regard, and it is of great significance to promote the modernization of edible and medicinal fungi.
