Flavonoids: A treasure house of prospective pharmacological potentials

Abstract

Flavonoids are organic compounds characterized by a range of phenolic structures, which are abundantly present in various natural sources such as fruits, vegetables, cereals, bark, roots, stems, flowers, tea, and wine. The health advantages of these natural substances are renowned, and initiatives are being taken to extract the flavonoids. Apigenin, galangin, hesperetin, kaempferol, myricetin, naringenin, and quercetin are the seven most common compounds belonging to this class. A thorough analysis of bibliographic records from reliable sources including Google Scholar, Web of Science, PubMed, ScienceDirect, MEDLINE, and others was done to learn more about the biological activities of these flavonoids. These flavonoids appear to have promising anti-diabetic, anti-inflammatory, antibacterial, antioxidant, antiviral, cytotoxic, and lipid-lowering activities, according to evidence from in vitro, in vivo, and clinical research. The review contains recent trends, therapeutical interventions, and futuristic aspects of flavonoids to treat several diseases like diabetes, inflammation, bacterial and viral infections, cancers, and cardiovascular diseases. However, this manuscript should be handy in future drug discovery. Despite these encouraging findings, a notable gap exists in clinical research, hindering a comprehensive understanding of the effects of flavonoids at both high and low concentrations on human health. Future investigations should prioritize exploring bioavailability, given the potential for high inter-individual variation. As a starting point for further study on these flavonoids, this review paper may promote identifying and creating innovative therapeutic uses.

Keywords: Antioxidants; Apigenin; Flavone; Flavonoids; Flavonol; Flavonone; Galangin; Hesperetin; Kaempferol; Myricetin; Naringenin; Quercetin.

Graphical abstract

Fig. 1

Chemical structures of important bioactive flavonoids.

Fig. 2

Antidiabetic effect of flavonoids results from glycation, gluconeogenesis, and glycolytic enzyme activity. Flavonoids reduce the glucose level in the body by interfering with gluconeogenesis. Also, flavonoids reduce advanced glycolation end products along with glycolytic enzyme overexpression; Reactive oxygen species (ROS).

Fig. 3

Antidiabetic effect of flavonoids involving glucokinase, hexokinase, and aldose reductase enzyme activities.Flavonoids reduce blood glucose level by reducing glycokinase and hexokinase activities. They also interfere with aldose reductase actvity which hampered fructose production from glucose; glutathione disulfide (GSSG); glutathione (GSH); nicotinamide adenine dinucleotide (NAD); nicotinamide adenine dinucleotide phosphate (NADP); nicotinamide adenine dinucleotide phosphate hydrogen (NADPH).

Fig. 4

Anti-inflammatory effect of flavonoids through reduction of inflammatory markers, supression of inflammatory genes, and increasing expression of antiinflammatory genes. Flavonoids prohibit growth related oncogene and phosphorylase enzyme responsible for inflammation, increase expression of inflammatory suppressive genes like IkBα, vascular cell adhesion module-1, endothelial cell resulting in decreased antiinflammatory markers like tumer necrosis factor (TNF), Interleukin (IL), peroxisome proliferator-activated receptors (PPARs).

Fig. 5

Antibacterial effect of flavonoids by interfearing bacterial central dogma as well as cell wall synthesis. Flavonoids reduce mRNA expression of glycotransferase which hampers bacterial translation process. Flavonoids also interfere with bacterial mRNA to block bacterial transcription process and arrest cell wall synthesis by blocking conversion of d-alanine.

Fig. 6

Antifungal effect of flavonoids involves fungal intracellular redox imbalance, free radical activity, and mitochondrial ion exchange. Flavonoids interfere with the fungal intracellular electron transport system by overexpressing the glutathione reductase enzyme, which inhibits the production of lethal hydrogen peroxide. Flavonoids are also capable of creating fungal mitochondrial dysfunction by increasing mitochondrial calcium uptake: Nicotinamide adenine dinucleotide phosphate (NADP); Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH); Glutathione (GSH); Glutathione disulfide (GSSH), Adenosine triphosphate (ATP), Free fatty acids (FFA).

Fig. 7

Antioxidant effect of flavonoids by reducing free radical-mediated neurotoxicity and lipid peroxidation. Flavonoids block the conversion of free radicals, resulting in protection from frradical-mediated cell damage. Moreover, flavonoids can block lactate dehydrogenase, which is responsible for the conversion of pyruvate from lactate, in relation to the oxidative reactions: Aspartate transaminase (AST); Alkaline phosphatase (ALP); Alanine transmitase (ALT); Tricarboxylic acid cycle (TCA).

Fig. 8

Antiviral effect of flavonoids by interfearing viral protein synthesis as well as viral replication. Flavonoids inhibit the intracellular replication of virus along with reverse transcriptase enzyme which is responsible for viral multiplication. They can also hamper central dogma of virus.

Fig. 9

Cytotoxic effect of flavonoids related to MAPK and PI3KAkt pathways. Flavonoids reduced cell proliferation by blocking Mitogen-activated protein kinase (MAPK). They are also capable to stimulate PI3KAkt expression which reduced tumer cell survival. Besides, flavonoids result in reduction of metastases by increasing pro-apoptic protein.

Fig. 10

Cytotoxic effect of flavonoids resulted from nuclear factor erythroid 2 (Nerf-2), Ak strain transforming (Akt), and nuclear factor kappa B (NFƙB) pathways. Flavonoids interfere with Nrf-2 signaling pathway to arrest tumor cell growth, increase immune response by elevating nuclear translocation of nuclear factor kappa B (NFƙB) and reduce cell survival by decreasing Akt phosphorylation; cyclooxygenase-2 (COX-2).

Fig. 11

Lipid-lowering effect of flavonoids hindering autophagic and LOX-related pathways. Flavonoids interfere with LOX-1 (Lectin-like oxidized low density lipoprotein receptor 1) resulting in reduction of low density lipoprotein. They also increase activity of autophagic process which helps to inhibit fat cells.