REVIEW
Virtual screening analysis of natural flavonoids as trimethylamine (TMA)-lyase inhibitors for coronary heart disease
Peng Zhou,
Xiao-Ni Zhao,
Yao-Yao Ma,
Tong-Juan Tang,
Shu-Shu Wang,
Liang Wang,
Jin-Ling Huang,
Peng Zhou
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, People's Republic of China
Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, People's Republic of China
Search for more papers by this authorXiao-Ni Zhao
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Search for more papers by this authorYao-Yao Ma
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Search for more papers by this authorTong-Juan Tang
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Search for more papers by this authorShu-Shu Wang
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Search for more papers by this authorCorresponding Author
Liang Wang
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, People's Republic of China
Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, People's Republic of China
Correspondence
Liang Wang and Jin-Ling Huang, Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, People's Republic of China.
Email: [email protected] (L. W.); [email protected] (J.-L. H.)
Search for more papers by this authorCorresponding Author
Jin-Ling Huang
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, People's Republic of China
Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, People's Republic of China
Correspondence
Liang Wang and Jin-Ling Huang, Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, People's Republic of China.
Email: [email protected] (L. W.); [email protected] (J.-L. H.)
Search for more papers by this authorPeng Zhou,
Xiao-Ni Zhao,
Yao-Yao Ma,
Tong-Juan Tang,
Shu-Shu Wang,
Liang Wang,
Jin-Ling Huang,
Peng Zhou
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, People's Republic of China
Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, People's Republic of China
Search for more papers by this authorXiao-Ni Zhao
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Search for more papers by this authorYao-Yao Ma
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Search for more papers by this authorTong-Juan Tang
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Search for more papers by this authorShu-Shu Wang
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Search for more papers by this authorCorresponding Author
Liang Wang
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, People's Republic of China
Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, People's Republic of China
Correspondence
Liang Wang and Jin-Ling Huang, Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, People's Republic of China.
Email: [email protected] (L. W.); [email protected] (J.-L. H.)
Search for more papers by this authorCorresponding Author
Jin-Ling Huang
Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, People's Republic of China
Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, People's Republic of China
Correspondence
Liang Wang and Jin-Ling Huang, Department of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, People's Republic of China.
Email: [email protected] (L. W.); [email protected] (J.-L. H.)
Search for more papers by this authorPeng Zhou and Xiao-Ni Zhao contributed equally to this work.
Abstract
Coronary heart disease (CHD) is defined by atherosclerosis, which can result in stenosis or blockage of the arterial cavity, leading to ischemic cardiac diseases such as angina and myocardial infarction. Accumulating evidence indicates that the gut microbiota plays a vital role in the beginning and progression of CHD. The gut microbial metabolite, trimethylamine-N-oxide (TMAO), is intimately linked to the pathophysiology of CHD. TMAO is formed when trimethylamine (TMA) is converted by flavin-containing monooxygenases in the hepatocytes. Therefore, inhibition of TMA production is essential to reduce TMAO levels. Flavonoids may reduce the risk of death from cardiovascular disease. In this article, we reviewed and evaluated twenty-two flavonoids for the therapy of CHD based on their inhibition of TMA-lyase by molecular docking. Docking results revealed that baicalein, fisetin, acacetin, and myricetin in flavonoid aglycones, and baicalin, naringin, and hesperidin in flavonoid glycosides had a good binding effect with TMA-lyase. This indicates that these chemicals were the most active and could be used as lead compounds for structural modification in the future.
Practical applications
Flavonoids are a large class of polyphenolic compounds found in fruits, vegetables, flowers, tea, and herbal medicines, which are inexorably metabolized and transformed into bioactive metabolites by α-rhamnosidase, β-glucuronidase, β-glucosidase, and nitroreductase produced by the gut microbiota, which plays a beneficial role in the prevention and treatment of cardiovascular diseases. Because flavonoids protect the cardiovascular system and regulate the gut microbiota, and the gut microbiota is directly connected to TMAO, thus, reducing TMAO levels involves blocking the transition of TMA to TMAO, which may be performed by reducing TMA synthesis. Molecular docking results found that baicalein, fisetin, acacetin, and myricetin in flavonoid aglycones, and baicalin, naringin, and hesperidin in flavonoid glycosides had good binding effects on TMA-lyase, which were the most active and could be used as lead compounds for structural modification.
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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