The limitations of traditional antiviral regimens for hepatitis B are becoming increasingly significant, and although existing treatments can be used to control hepatitis B virus (HBV), they require long-term use and may develop drug-resistant strains. Flavonoids are a diverse polyphenolic compound found in various plant foods with anti-hepatitis B activity that can interfere with multiple stages of the hepatitis B virus life cycle, and flavonoid compounds combined with antiviral therapy provide a promising approach to enhance anti-hepatitis B virus efficacy and reduce drug resistance. This article reviews the types, sources, and mechanisms of action of flavonoid compounds for clinicians' reference.
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Types and sources of flavonoid compounds
Flavonoids are a variety of polyphenolic compounds found in a variety of plant foods and can be divided into several different subclasses, including flavonoids, flavonols, flavanols, isoflavones, anthocyanins, and chalcones. Citrus fruits, especially oranges and grapefruits, are a rich source of flavanones. Naringenin and hesperetin are flavanoones of the week and have antioxidant and anti-inflammatory properties.
Anthocyanins are water-soluble flavonoids that have antioxidant and anti-inflammatory effects that give many fruits and vegetables their vivid red, blue, and purple colors. Berries, red grapes, and red cabbage are rich in anthocyanins. Flavonoids are another subclass of flavonoids that are commonly found in leafy greens like spinach and spices like parsley and celery and have potential anti-inflammatory and anti-cancer properties.
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Mechanism of action of flavonoids in the treatment of hepatitis B
Flavonoids exhibit multiple antiviral mechanisms (Figure 1), which contributes to their potential against the hepatitis B virus. One of the key mechanisms includes inhibition of viral entry.
Fig.1 Multiple antiviral mechanisms of flavonoid compounds
表没食子儿茶素没食子酸酯（Epigallocatechin gallate，EGCG）和原花青素分别通过干扰病毒的内吞作用和细胞融合来抑制HBV感染，通过阻断病毒与特定细胞表面受体钠离子-牛磺胆酸共转运蛋白(sodium taurocholate cotransporting polypeptide，NTCP)的附着，阻止病毒进入，从而减少HBV抗原和乙肝病毒的脱氧核糖核酸（Hepatitis B virus deoxyribonucleic acid，HBV-DNA）。
EGCG is one of the most studied flavonoids, and EGCG inhibits HBV infection in different viral replication states, including entry, DNA synthesis, gene expression, and replication. EGCG primarily blocks HBV entry into hepatocytes by blocking viral interactions with NTCP, clathrin-mediated endocytosis, and cell fusion in a dose- and time-dependent manner. In addition, EGCG reduces HBV infection by decreasing the levels of circular DNA molecules (covalently closed circularDNA, cccDNA) and mRNA, affecting the levels of core protein and HBsAg protein.
Known for their antioxidant properties, flavonoids play a vital role in regulating oxidative stress associated with HBV infection, with flavonoids protecting liver cells and liver tissue from oxidative damage by reducing reactive oxygen species levels and inhibiting lipid peroxidation. These antioxidant effects help reduce liver inflammation and damage associated with chronic hepatitis B infection. Flavonoids can also enhance the immune response, induce endogenous pro-inflammatory response to HBV, produce autocrine IFN-γ response and promote the expression of IFNα/β and IFN-γ, contributing to the antiviral response of host cells.
summary
In conclusion, flavonoids are a diverse class of polyphenolic compounds found in a variety of plant foods that have shown great potential for antiviral activity, particularly against hepatitis B virus infection. This group of natural compounds includes different subclasses, each with unique variations and potential health benefits. Understanding the different classes of flavonoids and their dietary sources is essential to capitalize on their potential health benefits.
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Source: Yimaitong Hepatology