Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2

doi:10.1007/s13659-022-00325-4

应用天然产物 ›› 2022, Vol. 12 ›› Issue (1): 1-10.DOI: 10.1007/s13659-022-00325-4

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Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2

Wenting Liu¹, Weikang Zheng¹, Liping Cheng¹, Ming Li¹, Jie Huang², Shuzheng Bao³, Qiang Xu¹, Zhaocheng Ma¹

1 College of Horticulture and Forestry Sciences, Key Laboratory of Horticultural Plant Biology, Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China;
2 Network of Aquaculture Centres in Asia-Pacific, Bangkok 10903, Thailand;
3 China Association of Agricultural Science Societies, Beijing 100125, China

收稿日期:2021-11-09 修回日期:2021-12-31 出版日期:2022-02-24 发布日期:2022-03-12
通讯作者: Zhaocheng Ma
基金资助:
The study was supported by the National Key Research and Development Program (2018YFD1000200), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202005), the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources (2060302).

Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2

Wenting Liu¹, Weikang Zheng¹, Liping Cheng¹, Ming Li¹, Jie Huang², Shuzheng Bao³, Qiang Xu¹, Zhaocheng Ma¹

1 College of Horticulture and Forestry Sciences, Key Laboratory of Horticultural Plant Biology, Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China;
2 Network of Aquaculture Centres in Asia-Pacific, Bangkok 10903, Thailand;
3 China Association of Agricultural Science Societies, Beijing 100125, China

Received:2021-11-09 Revised:2021-12-31 Online:2022-02-24 Published:2022-03-12
Contact: Zhaocheng Ma
Supported by:
The study was supported by the National Key Research and Development Program (2018YFD1000200), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202005), the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources (2060302).

摘要/Abstract

摘要： The most recent outbreak of 2019 novel coronavirus, named as COVID-19, caused pneumonia epidemic in Wuhan with 2121 deaths cases as of February 20th 2020. Identification of effective antiviral agents to combat the novel coronavirus is urgently needed. Citrus fruit peel or wild citrus are rich in flavonoids, and clinically documented for roles in relief of cough and promotion of digestive health. Therefore, citrus fruits are assumed to possess antivirus activities or enhance the host immunity. A previous study found that hesperetin could act as a high potent inhibitor of SARS-CoV 3CLpro. We determined six flavonoid compounds' content in three citrus species by using LC-MS technique. The content of naringin and naringenin was at higher levels in pummelo. Hesperetin and hesperidin were highly accumulated in mandarin and sweet orange. The subsequent in vitro and in vivo experiments indicated that naringin could inhibit the expression of the proinflammatory cytokines (COX-2, iNOS, IL-1β and IL-6) induced by LPS in Raw macrophage cell line, and may restrain cytokine through inhibiting HMGB1 expression in a mouse model. The results revealed that naringin may have a potential application for preventing cytokine storm. We simulated molecular docking to predict the binding affinity of those flavonoids to bind Angiotensin-converting enzyme 2 (ACE 2), which is a receptor of the coronavirus. Consideration of the potential anti-coronavirus and anti-inflammatory activity of flavonoids, the citrus fruit or its derived phytochemicals are promising in the use of prevention and treatment of SARS-CoV-2 infection.

关键词: Citrus flavonoids, Naringin, Immunoregulation, ACE2, SARS-CoV-2

Abstract: The most recent outbreak of 2019 novel coronavirus, named as COVID-19, caused pneumonia epidemic in Wuhan with 2121 deaths cases as of February 20th 2020. Identification of effective antiviral agents to combat the novel coronavirus is urgently needed. Citrus fruit peel or wild citrus are rich in flavonoids, and clinically documented for roles in relief of cough and promotion of digestive health. Therefore, citrus fruits are assumed to possess antivirus activities or enhance the host immunity. A previous study found that hesperetin could act as a high potent inhibitor of SARS-CoV 3CLpro. We determined six flavonoid compounds' content in three citrus species by using LC-MS technique. The content of naringin and naringenin was at higher levels in pummelo. Hesperetin and hesperidin were highly accumulated in mandarin and sweet orange. The subsequent in vitro and in vivo experiments indicated that naringin could inhibit the expression of the proinflammatory cytokines (COX-2, iNOS, IL-1β and IL-6) induced by LPS in Raw macrophage cell line, and may restrain cytokine through inhibiting HMGB1 expression in a mouse model. The results revealed that naringin may have a potential application for preventing cytokine storm. We simulated molecular docking to predict the binding affinity of those flavonoids to bind Angiotensin-converting enzyme 2 (ACE 2), which is a receptor of the coronavirus. Consideration of the potential anti-coronavirus and anti-inflammatory activity of flavonoids, the citrus fruit or its derived phytochemicals are promising in the use of prevention and treatment of SARS-CoV-2 infection.

Key words: Citrus flavonoids, Naringin, Immunoregulation, ACE2, SARS-CoV-2

Wenting Liu, Weikang Zheng, Liping Cheng, Ming Li, Jie Huang, Shuzheng Bao, Qiang Xu, Zhaocheng Ma. Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2[J]. 应用天然产物, 2022, 12(1): 1-10.

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Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2

Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2

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