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      Dietary Flavonoids: Cardioprotective Potential with Antioxidant Effects and Their Pharmacokinetic, Toxicological and Therapeutic Concerns

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          Abstract

          Flavonoids comprise a large group of structurally diverse polyphenolic compounds of plant origin and are abundantly found in human diet such as fruits, vegetables, grains, tea, dairy products, red wine, etc. Major classes of flavonoids include flavonols, flavones, flavanones, flavanols, anthocyanidins, isoflavones, and chalcones. Owing to their potential health benefits and medicinal significance, flavonoids are now considered as an indispensable component in a variety of medicinal, pharmaceutical, nutraceutical, and cosmetic preparations. Moreover, flavonoids play a significant role in preventing cardiovascular diseases (CVDs), which could be mainly due to their antioxidant, antiatherogenic, and antithrombotic effects. Epidemiological and in vitro/in vivo evidence of antioxidant effects supports the cardioprotective function of dietary flavonoids. Further, the inhibition of LDL oxidation and platelet aggregation following regular consumption of food containing flavonoids and moderate consumption of red wine might protect against atherosclerosis and thrombosis. One study suggests that daily intake of 100 mg of flavonoids through the diet may reduce the risk of developing morbidity and mortality due to coronary heart disease (CHD) by approximately 10%. This review summarizes dietary flavonoids with their sources and potential health implications in CVDs including various redox-active cardioprotective (molecular) mechanisms with antioxidant effects. Pharmacokinetic (oral bioavailability, drug metabolism), toxicological, and therapeutic aspects of dietary flavonoids are also addressed herein with future directions for the discovery and development of useful drug candidates/therapeutic molecules.

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          Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.

          Although more than 80% of the global burden of cardiovascular disease occurs in low-income and middle-income countries, knowledge of the importance of risk factors is largely derived from developed countries. Therefore, the effect of such factors on risk of coronary heart disease in most regions of the world is unknown. We established a standardised case-control study of acute myocardial infarction in 52 countries, representing every inhabited continent. 15152 cases and 14820 controls were enrolled. The relation of smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins (Apo), and psychosocial factors to myocardial infarction are reported here. Odds ratios and their 99% CIs for the association of risk factors to myocardial infarction and their population attributable risks (PAR) were calculated. Smoking (odds ratio 2.87 for current vs never, PAR 35.7% for current and former vs never), raised ApoB/ApoA1 ratio (3.25 for top vs lowest quintile, PAR 49.2% for top four quintiles vs lowest quintile), history of hypertension (1.91, PAR 17.9%), diabetes (2.37, PAR 9.9%), abdominal obesity (1.12 for top vs lowest tertile and 1.62 for middle vs lowest tertile, PAR 20.1% for top two tertiles vs lowest tertile), psychosocial factors (2.67, PAR 32.5%), daily consumption of fruits and vegetables (0.70, PAR 13.7% for lack of daily consumption), regular alcohol consumption (0.91, PAR 6.7%), and regular physical activity (0.86, PAR 12.2%), were all significantly related to acute myocardial infarction (p<0.0001 for all risk factors and p=0.03 for alcohol). These associations were noted in men and women, old and young, and in all regions of the world. Collectively, these nine risk factors accounted for 90% of the PAR in men and 94% in women. Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity account for most of the risk of myocardial infarction worldwide in both sexes and at all ages in all regions. This finding suggests that approaches to prevention can be based on similar principles worldwide and have the potential to prevent most premature cases of myocardial infarction.
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            Flavonoids: an overview

            Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD. Information on the working mechanisms of flavonoids is still not understood properly. However, it has widely been known for centuries that derivatives of plant origin possess a broad spectrum of biological activity. Current trends of research and development activities on flavonoids relate to isolation, identification, characterisation and functions of flavonoids and finally their applications on health benefits. Molecular docking and knowledge of bioinformatics are also being used to predict potential applications and manufacturing by industry. In the present review, attempts have been made to discuss the current trends of research and development on flavonoids, working mechanisms of flavonoids, flavonoid functions and applications, prediction of flavonoids as potential drugs in preventing chronic diseases and future research directions.
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              Chemistry and Biological Activities of Flavonoids: An Overview

              There has been increasing interest in the research on flavonoids from plant sources because of their versatile health benefits reported in various epidemiological studies. Since flavonoids are directly associated with human dietary ingredients and health, there is need to evaluate structure and function relationship. The bioavailability, metabolism, and biological activity of flavonoids depend upon the configuration, total number of hydroxyl groups, and substitution of functional groups about their nuclear structure. Fruits and vegetables are the main dietary sources of flavonoids for humans, along with tea and wine. Most recent researches have focused on the health aspects of flavonoids for humans. Many flavonoids are shown to have antioxidative activity, free radical scavenging capacity, coronary heart disease prevention, hepatoprotective, anti-inflammatory, and anticancer activities, while some flavonoids exhibit potential antiviral activities. In plant systems, flavonoids help in combating oxidative stress and act as growth regulators. For pharmaceutical purposes cost-effective bulk production of different types of flavonoids has been made possible with the help of microbial biotechnology. This review highlights the structural features of flavonoids, their beneficial roles in human health, and significance in plants as well as their microbial production.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                30 June 2021
                July 2021
                : 26
                : 13
                : 4021
                Affiliations
                [1 ]Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia; j.khan@ 123456mu.edu.sa
                [2 ]Life Sciences Division, Institute of Advanced Study in Science and Technology, Guwahati 781035, Assam, India; shaandeb2010@ 123456gmail.com (P.K.D.); rajlakshmi@ 123456iasst.gov.in (R.D.)
                [3 ]Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India
                [4 ]University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India; somipriya99@ 123456gmail.com
                [5 ]Food Technology Unit, Centre for Research and Assistance in Technology and Design of Jalisco State A.C., Camino Arenero 1227, El Bajío del Arenal, Zapopan 45019, Jalisco, Mexico; karla.damian03@ 123456gmail.com
                [6 ]Rasiklal M. Dhariwal Institute of Pharmaceutical Education & Research, Chinchwad, Pune 411019, Maharashtra, India; sanjuwalode@ 123456rediffmail.com
                Author notes
                [* ]Correspondence: rsmrpal@ 123456gmail.com ; Tel.: +91-8638724949
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-3778-6540
                https://orcid.org/0000-0002-8172-6633
                Article
                molecules-26-04021
                10.3390/molecules26134021
                8272101
                34209338
                0075736e-7c60-4578-a639-19da1fc90971
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 09 June 2021
                : 23 June 2021
                Categories
                Review

                dietary flavonoids,cardioprotective effects,ros scavenging,myocardial dysfunction,bioavailability and drug metabolism,toxicity,drug discovery

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