Part 3: Functions and Applications of Flavonoids
Plants produce a vast and diverse assortment of organic compounds, the great majority of which do not appear to participate directly in growth and development. These substances, traditionally referred to as secondary metabolites (flavonoids), often are differentially distributed among limited taxonomic groups within the plant kingdom. The flavonoids are categorised in different classes as alkaloids, terpenoids and phenolics. Flavonoids carry out a number of protective functions in the human body. Many flavonoids have evolved as bioactive compounds that interfere with nucleic acid or proteins and show antimicrobial or insecticidal and pharmacological properties.
Flavonoids are therefore of interest in medicine as therapeutics and at the same instance in agriculture as pesticides. In vitro technology has given new insight to explore the potency of plant cell tissue culture to produce the same valuable chemical compounds as those of the parent plant. The advancement in plant tissue culture methods for flavonoid production has bloomed beyond expectations. Plant tissue culture is an aseptic technique whereby proper manipulation of the nutrients, culture conditions, and phyto-hormone supply, one may be able to produce the desired quality and quantity of plants as well as metabolites. With the culture of differentiated cells it is possible to obtain production of the desired compounds in levels comparable with that of the plant.
Flavonoids are associated with a broad spectrum of health-promoting effects. They are an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their antioxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme functions. Flavonoids act in plants as antioxidants, antimicrobials, photoreceptors, visual attractors, feeding repellents, and for light screening. Many studies have suggested that flavonoids exhibit biological activities, including anti-allergenic, antiviral, anti-inflammatory and vasodilating actions. However, most interest has been devoted to the antioxidant activity of flavonoids which is due to their ability to reduce free radical formation and to scavenge free radicals.
The capacity of flavonoids to act as antioxidants in vitro has been the subject of several studies in the past years, and important structure–activity relationships of the antioxidant activity have been established. Ren et al., in their paper on flavonoids and anticancer agents, gave the major molecular mechanisms of actions in different situations. In preventing carcinogens they mentioned that flavonoids exert their effects on cytochrome P450 to inhibit the activities of certain P450 isozymes which are responsible for the production of a number of procarcinogens. Another mechanism of action they reported is that flavonoids help in the production of metabolising enzymes such as gluthione-S-transferase, quinone reductase and uridine 5-diphospho-glucuronyl transferase by which carcinogens are detoxified and thus eliminated from the body. This would also help in preventing the chemotherapy effect of flavonoids against carcinogens.
A number of studies have been carried out on properties of antioxidants in relation to different flavonoids and these studies emphasised that the flavonoids can be used as potential drugs to prevent oxidative stresses. Antioxidants are compounds that protect the cells against the oxidative effect of reactive oxygen species, and the impaired balance between these reactive oxygen species and antioxidants results in oxidative stress. The oxidative stress may lead to cellular damage which is related to various health ailments such as diabetes, cancer, CVD, neurodegenerative disorders and ageing. Oxidative stress can also damage many biological molecules and proteins and DNA molecules are significant targets of cellular injury. Antioxidants interfere with radical-producing systems and increase the function of endogenous antioxidants, protecting the cells from damage by these free radicals.
Pietta reviewed the current knowledge on structural aspects and in vitro antioxidant capacity of most common flavonoids as well as in vitro antioxidant activity and effects on endogenous antioxidants. Flavonoids have been found to be very effective in preventing lipid peroxidation and lipid peroxidation is responsible for various diseases such as atherosclerosis, diabetes, hepatotoxicity and inflammation, along with ageing. Studies have indicated that quercetin helps to suppress lipid peroxidation. In addition to quercetin, there are other flavonoids such as myricetin, quercetrin and rutin which help to inhibit the production of superoxide radicals.
Flavonoids have also been recognised for their antimicrobial activity and many researchers have isolated and identified the structures of flavonoids having properties of antifungal, antiviral and antibacterial activity. Because of this property, many flavonoids are now being used extensively in the fields of nutrition, food safety and health. The antiviral effect of flavonoids has been shown by Wang et al., particularly in therapy for viral infection. Flavonoids such as quercetin, naringin, hesperetin and catechin possess a variable degree of antiviral activity. They affect the replication and infectivity of certain RNA and DNA viruses. Quercetin and apigenin are among the most studied flavonoids which have been known to exhibit antibacterial activities. Li & Xu have reported that quercetin extracted from lotus leaves may be a promising antibacterial agent for periodontitis.
Some flavonoids show hormone-like activities and they bear a resemblance to steroid hormones, particularly with oestrogen. Such flavonoids are present in fruits and vegetables, tea, red wine and cereals. Hormone-like steroids are well known in protection against various chronic diseases, especially oestrogen, which has neuroprotective effects on the brain. A number of flavonoids such as genistein, daidzein and equol have been studied to assess their oestrogenic activity in clinical trials. The studies determined their potential for treatment of various chronic diseases such as cancer, cardiovascular disorders and osteoporosis. From their studies it is found that the flavonoid genistein has the most promising effect in preventing postmenopausal bone loss in women. A number of flavonoids of dietary significance have been shown to impart beneficial impact on parameters associated with atherosclerosis, including lipoprotein oxidation, blood platelet aggregation and cardiovascular reactivity.
Comalada et al. reviewed the effects of flavonoids, particularly quercetin, on a variety of inflammatory processes and immune functions and it has been shown that certain flavonoids help in inhibiting the initial process of inflammation and improve the immune system. Anti-inflammatory activity using flavonoids and tannins from the leaves of the plant Spilanthes paniculata has been recently reported. Anticancer effects of flavonoids such as tangeritin, 3-hydroxyflavone, 3?,4?-dihydroxyflavone, 2?,3?-dihydroxyflavone, fisetin, apigenin, luteolin daidzein and genistein have been carried out by a number of researchers.
Ren et al. and Huang et al., while working on natural phenolic compounds and their potential use for cancer prevention, reported that various flavonoids such as tannins, stilbenes, curcuminoids, coumarins, lignans, quinones and other flavonoids have chemopreventive properties and also contribute to induce apoptosis by arresting the cell cycle, regulating carcinogen metabolism and ontogenesis expression. While explaining the possible mechanism of flavonoids in cancer prevention they further mentioned that the flavonoids have complementary and overlapping mechanisms of action including antioxidant activity and scavenging free radicals, modulation of carcinogen metabolism, regulation of gene expression on oncogenes and tumour-suppressor genes in cell proliferation and differentiation, induction of cell cycle arrest and apoptosis, modulation of enzyme activities in detoxification, oxidation and reduction, anti-inflammatory properties and action on other possible targets.
Flavonoids and their effect of protection of the central nervous system are concerned particularly with those related to neurodegenerative disease caused by the combined effect of oxidative stress, inflammation and transition metal accumulation; a good amount of information is available. Alzheimer’s and related dementias are among some of the major disorders of neurodegeneration. Flavonoids, like flavonols, are associated with lower population rates of dementia. Similarly, Hwang & Yen and Jager & Saaby suggested that citrus flavanones such as hesperidin, hesperetin and naringenin could traverse the blood–brain barrier and may play an effective role in the intervention for neurodegenerative diseases. The role of flavonoids in antidiabetic activity and anti-ageing has also been reported.
Adapted from:
Panche, A. N., Diwan, A. D., & Chandra, S. R. (2016). Flavonoids: an overview. Journal of nutritional science, 5, e47. https://doi.org/10.1017/jns.2016.41