Is Astragalus Extract Antiviral？

The Pharmacopoeia of the People's Republic of China clearly states that the traditional Chinese medicine Astragalus is the dried root of Astragalus membranaceus (Fisch.) Bge. and Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hisao from the legume family [1], and that it has the functions of tonifying the middle Jiao, benefiting Qi, inducing diuresis and reducing swelling. [Astragalus membranace (Fisch.) Bge. var. mongholicus (Bge.) Hisao] dried root [1], which has the effects of tonifying the middle Jiao, benefiting Qi, promoting urination to reduce swelling, etc.

Studies shows that the main chemical components of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hisao are flavonoids, saponins, polysaccharides, amino acids and trace elements [2], and it has been confirmed that various components of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hisao have a good inhibitory effect on herpes virus, hepatitis B virus, influenza A virus and other human infection viruses, as well as avian and livestock viruses such as duck flu virus and porcine circovirus. This study study of the main chemical components and antiviral effects of astragalus to provide a reference for research in this area.

1 Main chemical components of astragalus

1.1 Polysaccharides

Astragalus polysaccharides (APS) is one of the main components of astragalus. Currently, there is a wide range of research on astragalus polysaccharides, and there are various methods of isolation and purification. Astragalus polysaccharides can be purified using a simple solvent method with an aqueous solution, an alkaline solution or an alcohol solution; they can also be separated and purified by physical adsorption to separate and purify astragaloside. It can also be purified from astragalus by biological methods such as microbial fermentation or enzyme-assisted methods [3, 4]. After years of research, molecular testing of purified astragalus polysaccharide samples has shown that the monosaccharides that make up astragalus polysaccharides mainly include glucose, mannose, rhamnose, galactose, glucuronic acid, galacturonic acid, xylose, etc. [5]. According to current research, astragalus polysaccharides have great effects on improving immunity, anti-oxidation and lowering blood sugar, and have been formulated into various dosage forms and widely used in medical [6, 7].

1.2 Flavonoids

Flavonoids compounds (Astragalus Flavonoids, AFS) are a type of chemical component that is abundant in astragalus. The extraction methods for astragalus flavonoids are also diverse. In addition to the common solvent extraction method, physical adsorption method and other conventional extraction and purification methods, the response surface method can also be used to optimize the separation and purification of astragalus flavonoids [8, 9]. At present more than 80 types of flavonoids have been isolated from various medicinal Astragalus plants [10]. There are many different types, which can be classified according to their structure as flavones, isoflavones, isoflavanones, prunetin, dihydroisoflavones, and prunetin [11]. Astragalus flavonoids have obvious effects in improving immunity, anti-tumor, anti-necrosis, etc. [12, 13].

1.3 Saponins

Saponins compounds (Astragalus Membranaceus Sapo⁃ nins, AMS) are one of the important components of Astragalus membranaceus. The purification method of astragaloside is similar to that of astragalus polysaccharide and astragalus flavonoids, but it can also be separated and purified by biomimetic method, supercritical fluid method, flash extraction method and other methods [14]. So far more than 40 types of saponin compounds have been extracted [10], of which the main types are the four major types of astragaloside, isomucronulatol, acetyl-astragaloside and soyasaponin [15]. Astragalus saponin compounds, especially astragaloside IV, have significant antiviral, antitumor, immune-modulating, and organ-protecting effects [16, 17].

1. 4 Other substances

In addition to the three main types of compounds mentioned above, Astragalus also contains various alkaloids, mainly the six types Astragaloside A–F [10]; various amino acids, such as γ-aminobutyric acid, glycine, serine and lysine; various trace elements such as Sc, Se, Cr, Fe, Ca, K, etc. [18]; and substances such as vitamin D, linoleic acid, and folic acid [19]. Among them, the astragaloside compound can also delay cell aging through p16 [20].

2 Research on the antiviral effect of astragalus extract

Astragalus has a wealth of medicinal value, and its antiviral effect has attracted attention. The antiviral effects of various components in Astragalus have been extensively studied. A comprehensive review of existing reports reveals that Astragalus extracts with antiviral effects are mainly composed of astragalosides, astragalosides IV and astragalus polysaccharides. Therefore, the antiviral effects of these three Astragalus extracts are summarized.

2. 1. Antiviral effect of astragaloside

Astragaloside is one of the main components of astragalus. According to current research, astragaloside has a relatively simple antiviral effect, mainly inhibiting Coxsackievirus B group. Coxsackievirus Coxsackievirus B (CVB) is one of the most important human pathogens of subacute, acute and chronic viral myocarditis, dilated cardiomyopathy (DCM), meningitis and severe pancreatitis [21]. Studies  have shown that the astragalus flavonoid calycosin-7-O-β-D-gluco⁃  pyranoside (CCGR) effectively inhibits CVB3-mediated cytopathic effects. CCGR exhibits significant antiviral activity against CV B3. It reduces the viral titer in the heart and improves the survival rate of mice infected with CVB3. CCGR also protects the heart muscle and reduces the pathological damage to the heart muscle of myocarditis mice, thereby improving the left ventricular function of mice [22]. There are also studies have also shown that astragaloside IV can exert antiviral effects by protecting cell proliferation, directly inactivating CVB5 or hindering the CVB5 cell adsorption process [23].

2. 2. Antiviral effect of astragaloside

Astragaloside is one of the saponin compounds in astragalus, which has been widely used in various studies. It has the ability to resist many viruses and is a popular medicinal astragalus extract.

Studies has been shown to have an inhibitory effect on influenza A virus. Influenza virus belongs to the genus Influenzavirus in the family Orthomyxoviridae. It is a type of RNA virus that mainly causes acute upper respiratory tract infections in humans, seriously affecting people's lives and health. Influenza A virus is one of these viruses. Astragaloside Astragaloside IV can significantly inhibit the synthesis of influenza virus nucleoprotein (NP), thereby inhibiting the replication of the progeny virus, thereby producing an effect against H1N1, H5N1, and PR8 influenza viruses [24, 25]. Through mouse model experiments found that astragaloside can treat influenza A virus infection, significantly improving the survival time and survival rate of mice, and significantly improving weight loss [25]. Studies have also shown that astragaloside also has anti-Coxsackie virus effects. Astragaloside can significantly reduce serum creatine kinase-mb (CK-MB) and lactate dehydrogenase (LDH) levels, inhibit the FAS/FASL signaling pathway, thereby inhibiting CVB3-induced cardiomyocyte apoptosis, and improve CVB3-induced myocardial damage and myocardial fibrosis [26]. In addition , Astragaloside IV inhibits CVB3 by upregulating IFN-γ mRNA expression [27].

Studies have also shown that astragaloside IV has the ability to resist hepatitis B virus. Hepatitis B virus (HBV) is a DNA virus, and HBV infection can manifest as acute/severe hepatitis or various chronic diseases, including chronic hepatitis, cirrhosis, and liver cancer. It has a varying degree of inhibitory effect on surface antigen, hepatitis B E antigen and HBV DNA production all exhibit different degrees of inhibition, and this inhibition is concentration-dependent [28]. In addition to its inhibitory effect on HBV in cell experiments, astragaloside IV also exhibits a significant anti-HBV effect in animal experiments using ducks [29].

Astragaloside IV also has an anti-adenovirus effect. Human adenovirus viruses (HAdVs) are common pathogens that cause a variety of diseases, including pneumonia, acute gastroenteritis, and epidemic keratoconjunctivitis. HAdVs infections are also associated with severe adenovirus syndrome in patients with immunodeficiency following stem cell transplantation. HAdVs are classified into 7 species (HAdV-A-G) and 65 subtypes based on DNA genomic homology [30]. Some studies studies have shown that astragaloside can directly kill HAdV3, inhibit virus adsorption by destroying the filopodia of HAdV3, and also inhibit the replication of HAdV3. At the same time, astragaloside inhibit HAdVs by suppressing the expression of bax and caspase-3 proteins and promoting the expression of bcl-2 protein, thereby inhibiting apoptosis and reducing the damage caused by HAdVs infection [31, 32].

2.3 Astragalus Astragalus polysaccharide antiviral effect

Astragalus polysaccharide, as one of the main extracts of astragalus, also has a wide range of antiviral effects. Astragalus polysaccharide not only inhibits human infection with viruses, but also has a significant inhibitory effect on a variety of animal viruses.

2.3.1 Studies on the inhibition of human infection with viruses

Studies have found that astragalus polysaccharide has an anti-Coxsackie virus effect. Astragalus polysaccharide can not only inhibit CVB3 binding to target cells by competitive inhibition at the in vitro cellular level, thereby inhibiting virus replication and in turn CVB3 infection, but also protect mouse cardiomyocytes from CVB3 infection [33].

Astragalus polysaccharide can also resist the hepatitis B virus, effectively inhibit the production of hepatitis B surface antigen, and significantly inhibit the proliferation of liver cancer cells containing HBV DNA [34]. Further studies have shown that astragalus polysaccharide exerts an anti-HBV effect by producing a lasting inhibitory effect on HBV replication in the body [35].

Astragalus polysaccharide also has a significant antiviral effect against herpes viruses.

Herpesvirus (Herpesvirus) is a double-stranded DNA virus with an envelope. Human herpesviruses can be further subdivided into three subfamilies, α, β, and γ, based on biological and genetic differences. The α subfamily includes herpes simplex virus 1 and 2 (HSV-1 and HSV-2) and varicella-zoster virus (VZV). The β subfamily human cytomegalovirus (HCMV) and human herpesviruses 6a, 6b and 7 (HHV6a, 6b, 7). The γ subfamily include the Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV). These viruses can cause a variety of herpes and skin rashes, and in severe cases, they can even cause malignant diseases such as tumors and encephalitis [36]. Studies have found that astragalus polysaccharide has a significant antiviral effect against herpes virus. It can promote the secretion of TNF-α and IL-6 by astrocytes and protect astrocytes from HSV-1 infection by activating the TLR3/NF-κB signaling pathway [37]. Astragalus polysaccharide can also inhibit the expression of Epstein-Barr virus (EBV) early proteins ZTA, RTA and EA-D in RAJI cells, blocking the EBV replication cycle and thus exerting its anti-EBV effect [38].

2.3. 2 Inhibition of animal virus-related research

Porcine circovirus 2 (PCV2) is one of the smallest DNA viruses that infect mammals. It belongs to the genus Circovirus in the family Circoviridae and is an important factor in porcine circovirus-associated diseases (PCVADS) [39]. Astragalus polysaccharide inhibits PCV2 replication by reducing oxidative stress and endoplasmic reticulum stress, while activating the NF-κB signaling pathway, thereby exerting an inhibitory effect on PCV2 infection

[40, 41].

Duck viral hepatitis (DVH) is a fatal infectious disease caused by duck hepatitis virus (DHV), which is characterized by high morbidity and mortality. In addition, duck hepatitis A virus is a perfect animal model for the human hepatitis A virus [42]. Studies have shown that the phosphorylated form of astragalus polysaccharide has a good inhibitory effect on duck hepatitis A virus, but the effect of natural astragalus polysaccharide against duck hepatitis A virus is not obvious

[43, 44].

Avian infectious bronchitis virus (IBV) is a member of the coronavirus family that causes mild to acute respiratory disease in chickens and is a major cause of huge economic losses in the poultry industry worldwide. Astragalus polysaccharides inhibit the intracellular replication of IBV, and the mechanism is related to the decrease in the mRNA levels of the pro-inflammatory cytokines IL-1β, IL-6, IL-8 and TNF-α [45].

Avian influenza ( AI is a highly contagious disease that generally causes acute disease and death in poultry and other animals. Due to its high morbidity and mortality, AI has a significant impact on both the farming economy and social health. The AI subtype H9N2 belongs to the group of low pathogenic avian influenza viruses (AIV) and is a common cause of disease affecting the poultry farming industry. Astragalus polysaccharides can significantly reduce the proliferation of the H9N2 virus. Its mechanism of action is to promote the expression of cytokines IL-2, IL-4, IL-6, IL-10, LITAF and IL-12, thereby promoting the proliferation of immune cells and thus enhancing the body's cellular immune capacity [46].

In addition to inhibitory effect on the above viruses, the main active ingredients of Astragalus also have anti-respiratory syncytial virus, cytomegalovirus, rhinovirus, porcine parvovirus, pseudorabies virus, Newcastle disease virus and other effects [47, 48].

3    Prospects

From current research, the main chemical components of Astragalus have a wide range of antiviral effects and are used in both experimental and practical medicine. Among these, the chemical components with antiviral properties are mainly astragalosides, astragaloside IV and astragalus polysaccharides. Astragaloside IV has a significant antiviral effect and can inhibit both RNA and DNA viruses. Astragalus polysaccharides also have very good antiviral effects and are widely used. They have corresponding antiviral abilities against a variety of human and animal viruses and are effective antiviral drugs.

Although the antiviral ability of astragalus flavonoids is not very outstanding, and there have only been reports of their inhibitory effect on Coxsackievirus B, it also reflects the potential of astragalus flavonoids as antiviral drugs. The antiviral mechanism of astragalus is mainly reflected in its ability to inhibit viral proliferation by activating multiple immune pathways, promoting the secretion of multiple immune factors, promoting the proliferation of immune cells, and enhancing the body's specific or non-specific immune capacity. It can also inhibit viral proliferation by preventing the virus from contacting receptor cells, inhibiting the synthesis of virus-related proteins, and preventing viral proliferation. Although much progress has been made in the study of the antiviral properties of various chemical components of Astragalus, the inhibition mechanism is still not very clear, and there is still broad scientific research prospects and development space.

Now with the widespread spread of the new coronavirus worldwide, antiviral research is even more important and urgent. Traditional Chinese medicine, as the crystallization of China's outstanding scientific and technological culture, has accumulated a wealth of experience in the prevention of various diseases, and should be applied to the research of combating the new coronavirus pneumonia. Among them, the antiviral effect of Astragalus has attracted the attention of scientific researchers and has been reported [49, 50]. This research review provides a basis for the use of Astragalus in research related to the novel coronavirus and provides a reference for the selection of antiviral components of Astragalus.

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