🌴 Flavonoids

Introduction

Flavonoids help regulate cellular activity and fight off free radicals that cause oxidative stress on your body. In simpler terms, they help your body function more efficiently while protecting it against everyday toxins and stressors.

Flavonoids are also powerful antioxidant agents. Antioxidants help your body fight off potentially harmful molecules that can be introduced to the body. Your body produces antioxidants naturally, but they’re also found in dark chocolate, legumes, and many fruits and vegetables.

Inflammation is one of your body’s immune responses. Allergens, germs, toxins, and other irritants can trigger inflammation that results in uncomfortable symptoms. Flavonoids may help your body dismiss that inflammatory reaction so that those symptoms are reduced.

Different flavonoids can help the body in different ways. For one, including foods with flavonoids in your diet may be an effective way to help manage high blood pressure.

A diet high in flavonoids may also decrease your risk of type 2 diabetes

The anti-inflammatory and antioxidant effects of flavonoids have also encouraged researches to study their potential as anticancer drugs. Research has shownTrusted Source that certain flavonoids may help stop cancer cells from multiplying. Including foods with flavonoids and keeping a healthy diet may decrease your risk of getting certain cancers.

Research Paper Notes

abstract

In many molecular mechanisms of action for prevention against cancer, flavonoids play a major role by interacting between different types of genes and enzymes.

Many mechanisms of action have been identified, including

• carcinogen inactivation,
• antiproliferation,
• cell cycle arrest,
• induction of apoptosis,
• inhibition of angiogenesis,
• antioxidation, and
• reversal of multidrug resistance or a combination of these mechanisms.

This review also highlights some advanced derivatives of flavonoids, which play an important role against cancer.

intorduction

8000 different compounds of polyphenols have been known and that can be further divided into 10 different general classes. Flavonoids are part of this family & have more than 4000 varieties.

They have been classified according to their molecular structure that consists of two benzene rings joined by a linear three-carbon chain and forms an oxygenated heterocycle (C6-C3-C6) and their large number arises from the various combinations of multiple hydroxyl, methoxyl, and O-glycoside group substituents on the basic benzo--pyrone (C6-C3-C6) moiety.

They interact with number of cellular targets, such as anti-oxidant and free-radical scavenger activities also the anti-inflammatory, antiviral, and especially anti-cancer properties.

It may be controlled by various means,

• including suppression,
• blockage, and
• transformation.

Suppressing agents prevent the formation of new cancers from procarcinogens,

Blocking agents prevent carcinogenic compounds from reaching critical initiation sites, and

Transformation agents facilitate the metabolism of carcinogenic components into less toxic materials or prevent their biological actions.

Flavonoids can act in all the three ways.

Major Molecular Mechanism of Action

One of the most exciting discoveries is the identification of oncogenes.More than 40 oncogenes have been identified and their protein products have been characterized.

These include protein kinases, GTP-binding proteins, and nuclear transcription factors.

A unique hypothesis that the activation of transformation might act via protein phosphorylation came into existence. Protein- tyrosine kinases (PTKs) are the group of enzymes that catalyze the transfer of the phosphate of ATP to the hydroxyl group of tyrosine on many key proteins, which in turn induce the cascade of altered cell parameters, a characteristic of transformed cells.

1. Activated PTKs have been identified to be the products of approximately half of the known viral transforming genes (oncogenes)

2. The plasma-membrane receptors for several polypeptide growth factors, such as epidermal growth factor (EGF), transforming growth factor-α (TGF-α), platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-l), macrophage colony stimulating factor-1 (CSF-l), fibroblast growth factors (FGF-1 and FGF-2), nerve growth factor (NGF), and hepatocyte growth factor (HGF) are ligand-activated PTKs

Biomolecular activites of flavonoids

• Antioxidative effects: inactivation of oxygen radicals
• Binding of electrophils
• Induction of protective enzymes: phase 2 with conjugating activities (GT, GST)
• Apoptosis rate increase
• Cell proliferation inhibition
• Lipid peroxidation inhibition
• Angiogenesis inhibition
• H-Donation (e.g. GSH-peroxidases)
• DNA oxidation inhibition

Preventing carcinogen metabolic activation

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One of the most important mechanism by which flavonoids can exert their effects is through their interaction with phase I metabolizing enzymes (eg, cytochrome P450), which metabolically activate a large number of procarcinogens to reactivate intermediates that can interact with cellular nucleophiles and ultimately trigger carcinogenesis.

Flavonoids inhibit the activities of certain P450 isozymes, such as CYP1A1 and CYP1A2, thus they are likely to have a protective role against the induction of cellular damage by the activation of carcinogens.

Another mechanism of action is the induction of phase II metabolizing enzymes (eg, GST, quinone reductase, and UDP-GT) by which carcinogens are detoxified & eliminated from the body.

This helps in explaining the chemopreventive effects of flavonoids against carcinogenesis

Antiproliferation

Flavonoids are effective in inhibiting xanthine oxidase, COX or LOX55, and therefore inhibit tumor cell proliferation.

Reference

1. Healthline article on Flavonoid (opens in a new tab)

2. Flavonoids: A versatile source of anticancer drugs (opens in a new tab)