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Identification and Mechanism Investi...
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Zhang, Tianbo.
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Identification and Mechanism Investigation of Anti-Influenza Virus Agents from Chinese Prescriptions and Herbs.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Identification and Mechanism Investigation of Anti-Influenza Virus Agents from Chinese Prescriptions and Herbs./
作者:
Zhang, Tianbo.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:
154 p.
附註:
Source: Dissertations Abstracts International, Volume: 81-09, Section: B.
Contained By:
Dissertations Abstracts International81-09B.
標題:
Alternative medicine. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27783961
ISBN:
9781392800782
Identification and Mechanism Investigation of Anti-Influenza Virus Agents from Chinese Prescriptions and Herbs.
Zhang, Tianbo.
Identification and Mechanism Investigation of Anti-Influenza Virus Agents from Chinese Prescriptions and Herbs.
- Ann Arbor : ProQuest Dissertations & Theses, 2019 - 154 p.
Source: Dissertations Abstracts International, Volume: 81-09, Section: B.
Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 2019.
Annual influenza is estimated to cause 3 to 5 million cases of illness, and claims more than 250000 deaths every year. Many strains of influenza virus have developed resistance against the existing anti-influenza drugs, thus it is essential to develop new drugs against this virus. Traditional Chinese Medicine has its own unique advantages over modern medicine and has historically been invaluable as a source of therapeutic agents. In this study, aqueous extracts of ten single herbs and ten multi-herb formulations for antiviral activity against influenza virus were screened. As a result, prescription Sheng Jiang San (SJS) and single herb Radix Paeoniae Alba (BS) and Folium Hibisci Mutabilis (FRY) have been found to have anti-influenza activities, and their mechanisms were also investigated.Chinese prescription SJS could inhibit various of influenza viral strains in vitro. The 50% inhibitory concentration of SJS against A/WSN/33 (H1N1) (WSN) was even lower than 35 μg/ml. SJS also protected 50% of mice from A/PR/8/34 (H1N1) infection. Decline of viral titers in the lungs of mice and the lung index was obviously observed in groups administrated with SJS, compared with untreated mice. SJS was found to exert anti-influenza efficacy through targeting on the influenza neuraminidase (NA) protein and down-regulating significantly TNF-α and up-regulated IL-2 of influenza virus induced mice.BS and FRY are categorized in "heat clearing and blood cooling herb". These two Chinese medicinal herbs were identified anti-influenza efficacy. A bioassay-guided isolation led to the discovery of three tannin compounds gallic acid (GA), methyl gallate (MG) and pentagalloyglucose (PGG) in BS aqueous extract. The IC50 of these compounds against WSN virus in MDCK cells were 50, 46 and 20 μM, respectively. PGG was found to inhibit both influenza virus receptor binding and NA activity, while MG and GA inhibited NA but not hemagglutinin (HA). GA was found to target on residue R152 of NA protein by molecular docking. After generating the recombinant virus carrying single mutation R152A, the resistance of R152A virus against GA as IC50 of GA was increased to 200 μM, confirming the docking site of R152 may be one of the target NA residues for GA. FRY herbal extract was further isolated to a refined fraction F3-3-2-1, the major components were characterized as flavonoid compounds by HR-MS analysis, F3-3-2-1 could suppress 100% WSN virus growth in plaque reduction assay at only 15 μg/ml. Results showed F3-3-2-1 did not act on HA or NA, but it could significantly regulate certain cytokines/chemokines TNF-α, IL-6, IL-8, MCP-1, IP-10 expression induced by virus in host cells. Fraction F3-3-2-1 may contribute to alleviate inflammatory response in lung tissue.Our work has substantiated SJS is an effective anti-influenza prescription. It is also the first in vitro study pointed out that tannin compounds and flavonoid compounds are the reason of BS and FRY aqueous extract, respectively, exerting anti-flu activity. The work enhances the confidence of using medicinal herbs to combat influenza virus and concerned herbs and prescription may be further developed by the herbal industry.
ISBN: 9781392800782Subjects--Topical Terms:
536195
Alternative medicine.
Subjects--Index Terms:
Molecular biotechnology
Identification and Mechanism Investigation of Anti-Influenza Virus Agents from Chinese Prescriptions and Herbs.
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Annual influenza is estimated to cause 3 to 5 million cases of illness, and claims more than 250000 deaths every year. Many strains of influenza virus have developed resistance against the existing anti-influenza drugs, thus it is essential to develop new drugs against this virus. Traditional Chinese Medicine has its own unique advantages over modern medicine and has historically been invaluable as a source of therapeutic agents. In this study, aqueous extracts of ten single herbs and ten multi-herb formulations for antiviral activity against influenza virus were screened. As a result, prescription Sheng Jiang San (SJS) and single herb Radix Paeoniae Alba (BS) and Folium Hibisci Mutabilis (FRY) have been found to have anti-influenza activities, and their mechanisms were also investigated.Chinese prescription SJS could inhibit various of influenza viral strains in vitro. The 50% inhibitory concentration of SJS against A/WSN/33 (H1N1) (WSN) was even lower than 35 μg/ml. SJS also protected 50% of mice from A/PR/8/34 (H1N1) infection. Decline of viral titers in the lungs of mice and the lung index was obviously observed in groups administrated with SJS, compared with untreated mice. SJS was found to exert anti-influenza efficacy through targeting on the influenza neuraminidase (NA) protein and down-regulating significantly TNF-α and up-regulated IL-2 of influenza virus induced mice.BS and FRY are categorized in "heat clearing and blood cooling herb". These two Chinese medicinal herbs were identified anti-influenza efficacy. A bioassay-guided isolation led to the discovery of three tannin compounds gallic acid (GA), methyl gallate (MG) and pentagalloyglucose (PGG) in BS aqueous extract. The IC50 of these compounds against WSN virus in MDCK cells were 50, 46 and 20 μM, respectively. PGG was found to inhibit both influenza virus receptor binding and NA activity, while MG and GA inhibited NA but not hemagglutinin (HA). GA was found to target on residue R152 of NA protein by molecular docking. After generating the recombinant virus carrying single mutation R152A, the resistance of R152A virus against GA as IC50 of GA was increased to 200 μM, confirming the docking site of R152 may be one of the target NA residues for GA. FRY herbal extract was further isolated to a refined fraction F3-3-2-1, the major components were characterized as flavonoid compounds by HR-MS analysis, F3-3-2-1 could suppress 100% WSN virus growth in plaque reduction assay at only 15 μg/ml. Results showed F3-3-2-1 did not act on HA or NA, but it could significantly regulate certain cytokines/chemokines TNF-α, IL-6, IL-8, MCP-1, IP-10 expression induced by virus in host cells. Fraction F3-3-2-1 may contribute to alleviate inflammatory response in lung tissue.Our work has substantiated SJS is an effective anti-influenza prescription. It is also the first in vitro study pointed out that tannin compounds and flavonoid compounds are the reason of BS and FRY aqueous extract, respectively, exerting anti-flu activity. The work enhances the confidence of using medicinal herbs to combat influenza virus and concerned herbs and prescription may be further developed by the herbal industry.
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