Virtual screening analysis of natural flavonoids as trimethylamine ( TMA )‐lyase inhibitors for coronary heart disease

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.

Mitochondria as novel mediators linking gut microbiota to atherosclerosis that is ameliorated by herbal medicine: A review

“…Herbal medicine has been used to treat CVDs in China for many years because of the advantages of multi-target, synergistic, and systemic therapy. Herbs are closely related to gut microbiota and mitochondria ( Zhou et al, 2022 ). Gut microbiota converts herbs into active metabolites with higher bioavailability, and herbs regulate gut microbiota biodiversity to ameliorate CVD in the host, similar to prebiotics ( Table 2 ) ( Ma et al, 2022 ; Qi et al, 2022 ).…”

“…Herbal medicines have been widely used to treat AS, and a possible therapeutic target is to regulate gut microbiota homeostasis, which is regarded as prebiotics ( Anlu et al, 2019 ). Herbal medicines and their natural compounds can effectively improve mitochondrial function to protect vascular cell homeostasis and survival ( Zhou et al, 2022 ). In this review, we discussed the emerging mechanisms of mitochondria as the key mediator linking gut microbiota to AS and systematically reviewed the role of herbal medicine and their natural compounds in improving AS through the microbiota–mitochondrial axis.…”

Inflammatory Response: A Crucial Way for Gut Microbes to Regulate Cardiovascular Diseases

“…Targeted regulation of intestinal metabolites is also a therapeutic strategy for cardiovascular disease. Gut microbiota originated from metabolite trimethylamine- N -oxide (TMAO) is closely related to the pathophysiology of coronary heart disease and is formed when trimethylamine (TMA) is converted by flavin-containing monooxygenases in hepatocytes [ 120 ]. Therefore, inhibiting the production of TMA might effectively reduce TMAO production and alleviate the inflammatory response.…”

Gut Microbiota and Coronary Artery Disease: Current Therapeutic Perspectives

“…Flavonoids, a large class of polyphenolic compounds, are present in tea, citrus fruit, citrus fruit juices, berries, red wine, apples, and legumes. In flavonoid aglycones, baicalein, fisetin, acacetin, and myricetin exhibited a decent binding effect with TMA-lyase, as did baicalin, naringin, and hesperidin in flavonoid glycosides [ 103 ]. Therefore, inhibition of TMA-lyase activity is another method of reducing TMAO concentration.…”