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    Home > Biochemistry News > Biotechnology News > Research progress on anti-HBV effects of natural compounds

    Research progress on anti-HBV effects of natural compounds

    • Last Update: 2022-05-24
    • Source: Internet
    • Author: User
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    Hepatitis B virus (HBV) is a hepatotropic DNA virus.
    HBV infection can cause viral hepatitis B.
    If there is no timely and effective treatment, it will lead to serious consequences such as liver fibrosis, liver cirrhosis and hepatocellular carcinoma.
    even endanger the patient's life

    .
    Although vaccines are effective in preventing HBV infection, they are ineffective in patients already infected with HBV

    .
    The anti-HBV drugs currently used clinically mainly include interferon (interferon, IFN) and nucleoside (acid) drugs, which play their roles by regulating immunity and interfering with the replication process of hepatitis B virus, respectively.
    Drug resistance occurs, interferon has certain side effects, and there is still a lack of effective drugs that can cure HBV infection

    .

    Natural compounds are an important source for the discovery of new drugs or new drug lead molecules because of their structural diversity and complexity
    .
    Chinese traditional medicine records the use of some Chinese herbal medicines for the treatment of hepatitis B virus.
    In the related research of modern pharmacy, there are also many studies reporting that natural compounds have the activity of inhibiting HBV

    .
    At present, many natural molecules with anti-HBV activity have been discovered, such as terpenes, lignans, alkaloids, phenolic acids and flavonoids

    .

    1.
    It exerts anti-HBV activity by regulating the life cycle of HBV itself

    1.
    It exerts anti-HBV activity by regulating the life cycle of HBV itself

    The study found that asiaticoside found in coriander (Hydrocotyle sibthorpioides) can significantly inhibit the formation of HBsAg, HBeAg, HBV DNA and cccDNA in a dose-dependent manner
    .
    Through preliminary exploration of its mechanism of action, it was found that asiaticoside can affect the transcription of corresponding genes and virus replication by inhibiting the activities of C, S and X gene promoters

    .

    The caudatin aglycone isolated from Cynanchum auriculatum has the activity of inhibiting the secretion of HBsAg and HBV DNA replication.
    A series of new compounds synthesized by chemical modification on the basis of caudatin aglycone were found.
    HBsAg, HBeAg secretion and HBV DNA replication by compound 3-O-( 3,4,5-trimethyl) cinnamoyl caudatin aglycone ( 3-O-( 3,4,5-trimethoxy) cinnamoyl caudatin) Has significant inhibitory activity

    .
    Preliminary mechanism exploration found that 3-O-( 3,4,5-trimethyl) cinnamoyl guldartin aglycone can affect the transcription of X gene by interfering with HBV X promoter and enhancer I to exert antiviral effect

    .

    HE-145 (helioxanthin) and its analogs isolated from Taiwania cryptomerioides can reduce the levels of HBV DNA and RNA, and reduce the expression of core protein
    .
    Further exploration of the anti-HBV mechanism of HE-145 revealed that HE-145 selectively inhibited S gene promoter II (SPII) and C gene promoter (CP)

    .
    In contrast, inhibition of SPII or CP promoters by HE-145 was not observed in non-hepatocytes such as 293T cells and HeLa cells, suggesting that the inhibition of SPII and CP by HE-145 was liver-specific

    .
    The HBV preC/C promoter/Enh II region contains many transcription factor binding sites, many of which have been shown to play critical roles in viral gene expression in cis-elements

    .
    Electrophoretic mobility assay (EMSA) showed that HE-145 reduced the DNA-binding activity of HepA2 nuclear extracts to several cis-acting elements on CP, including the α-fetoprotein transcription factor binding site, peroxisome proliferation Peroxisome proliferators-activated receptors (PPAR) binding site and transcription factor Sp1 binding site; overexpression of PPAR and hepatocyte nuclear factor 4α (HNF4α) can alleviate the inhibition of CP by HE-145

    .

    2.
    Anti-HBV activity by regulating host cell-related factors

    2.
    Anti-HBV activity by regulating host cell-related factors

    Epigallocatechin-3-gallate (EGCG) in green tea can significantly inhibit the secretion of HBsAg and HBeAg from HepG2.
    2.
    15 cells in a dose- and time-dependent manner; EGCG can also significantly reduce extracellular HBV DNA expression level

    .
    Treatment of Huh7 cells expressing HA-NTCP with EGCG resulted in a decrease in the expression of HA-NTCP protein.
    Further analysis of the expression of HA-NTCP on the cell membrane found that EGCG treatment significantly induced the transport of NTCP from the cell membrane to the cytoplasm, indicating that EGCG May induce endocytosis and degradation of NTCP

    .

    Betulinic acid (BetA) extracted from Pulsatilla chinensis has the effect of inhibiting HBV DNA replication
    .
    Animal experiments found that in hepatocytes from HBV transgenic mice, betulinic acid can significantly inhibit HBV replication by downregulating the expression of superoxide dismutase 2 (SOD2), and lead to the generation of reactive oxygen species and mitochondrial Dysfunction

    .

    Curcumin, a natural phenolic compound, can inhibit the expression and replication of HBV genes
    .
    Studies have found that this inhibitory effect is mediated by down-regulating peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α)

    .
    PGC-1α is a starvation-inducible protein that initiates the gluconeogenesis cascade and has been shown to efficiently synergistically activate HBV transcription

    .
    It was shown that curcumin affects PGC-1α at the protein level and inhibits HBV by promoting the degradation of PGC-1α protein

    .
    In addition, the study also found that curcumin can work synergistically with anti-HBV nucleotide/nucleoside analogs to enhance the inhibition of HBV gene expression

    .
    Curcumin as a host-targeted therapy for HBV infection can complement current virus-specific treatments

    .

    Oxymatrine (OMTR) from the Sophora japonica plant has been used for decades in the treatment of hepatitis B patients in China, and its safety has been proven
    .
    Heat shock homologous protein 70 (Hsc70) is a host protein necessary for HBV replication

    .
    Studies have found that OMTR can significantly down-regulate the expression of host Hsc70 mRNA at the post-transcriptional level by destroying the stability of Hsc70 mRNA, thereby inhibiting the de novo synthesis of HBV from pgRNA to DNA at the reverse transcription stage, thus showing anti-HBV effect

    .
    Since this target is not a viral protein, OMTR is active against both wild-type HBV and strains resistant to reverse transcriptase (RT) inhibitors

    .
    In addition, the mice with knockout of the Hsc70 gene did not show abnormality, indicating that the inhibition of Hsc70 has good safety, which also provides a good basis for the further development of OMTR as an anti-HBV drug

    .

    Cepharanthine hydrochloride (CH) is a natural alkaloid derivative
    .
    Studies have found that the compound can inhibit DNA replication and HBeAg secretion in wild-type or lamivudine-resistant HBV clinical isolates in a dose-dependent manner, indicating that the compound may be useful in the treatment of lamivudine-resistant chronic hepatitis B.
    A new alternative medicine for patients

    .
    Further research found that the effect of CH on inhibiting the expression of host Hsc70 mRNA is parallel to the inhibition of intracellular HBV replication, indicating that CH may inhibit HBV replication by down-regulating the expression of host Hsc70

    .

    So far, there is no clinically effective drug or method to cure hepatitis B virus infection
    .
    Therefore, the research and development of anti-HBV drugs is still a top priority

    .
    According to the anti-HBV mechanism of natural compounds found in current research, most active compounds inhibit virus replication in cells by acting on host-related factors, or by regulating the activities of viral S, C and X gene promoters.
    It regulates the virus's own factors and affects the replication of the virus

    .
    However, there are very few reports on the direct target of anti-HBV active compounds, and the research focused on discovering the inhibition of a certain life cycle stage of the virus is also relatively lacking

    .
    In addition, there is no structure-activity relationship discussion or further structural modification and transformation of natural compounds with potential anti-HBV activity, which is difficult to provide support for the subsequent in-depth study of targets and mechanisms of action

    .
    Therefore, as a drug R&D worker, it is very necessary to conduct in-depth and systematic research on the target and mechanism of action of natural active products by means of interdisciplinary methods such as chemical biology, and promote the discovery of new natural anti-HBV lead molecules and new targets of hepatitis B virus.
    's discovery

    .

    References

    [1] Xiang Jiayao, Xu Min, Feng Yang.
    Research progress on the mechanism of anti-HBV natural compounds [J].
    Chinese Pharmacological Bulletin, 2021, 37(10): 1346-1351.

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