FLAVONOIDS: BIOCHEMISTRY, BIOPHYSICS, MEDICINE - Tarakhovsky Yu. S. - 2013

CHAPTER 1. MAJOR FLAVONOIDS

1.3. Flavones

The name "flavones" originates from the Latin word flavus, meaning yellow or golden. Flavones are primarily found in cereal plants and grain crops (Fig. 9). Citrus peels, parsley leaves, and celery are particularly rich in these compounds. In Western countries, the average daily intake of flavones typically ranges from 20 to 50 mg. Many of these substances are of significant medical interest due to their antioxidant activity.

Class="center">Fig. 9. Principal flavones.

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However, their biological effects are considerably more diverse and extend far beyond simple free radical scavenging. For instance, Baikal skullcap (Scutellaria baicalensis Georgi) is one of the most popular herbs in traditional Chinese medicine. It is used to treat inflammatory conditions, Hypertension, cardiovascular disorders, as well as bacterial and viral infections. In Russia, folk medicine employs the common skullcap (Scutellaria galericulata L.) for similar purposes (http://www.litmir.net). Nevertheless, it is the Baikal skullcap—growing predominantly in Buryatia, the Irkutsk Region, and Mongolia—that attracts particular attention from researchers. Baikal skullcap is rich in Phenolic Compounds, with flavones occupying a prominent position among them.

1.3.1. Baicalein and Wogonin

It has been discovered that baicalein, a flavone present in the roots of the skullcap, can hinder The Development of age-related neurodegenerative diseases (such as Alzheimer's disease) by virtue of its ability to prevent Cell death.

Oroxylin A, also found in skullcap roots, significantly enhances cognitive function, as demonstrated in animal experiments. Wogonin, another flavone present in the same plant, stimulates tissue regeneration following Brain injury by accelerating the differentiation of neural progenitor Cells. Furthermore, wogonin exhibits substantial antifungal activity against pathogenic Fungi such as Alternaria alternata, which are implicated in respiratory diseases and asthma.

Wogonin Glycosides, known as "wogoninosides," are incorporated into various traditional medicines. For example, oroxyloside, a wogonin glucuronide, is extracted from the fruits of Oroxylium indicum (a tree species belonging to the Bignoniaceae family, widespread in Eastern countries). The fruits and roots of this tree are utilized in traditional Indian (Ayurvedic) medicine as an astringent, tonic, digestive aid, and analgesic. The anti-inflammatory action of this glycoside is believed to stem from its ability to inhibit arachidonic acid METABOLISM, although its potency is considerably lower than that of established non-steroidal anti-inflammatory drugs such as indomethacin.

1.3.2. Apigenin (Apiin)

Apigenin is widely distributed in numerous fruits and vegetables, with parsley, celery, and lemons being particularly rich sources. It is a vital component of medicinal plants such as German chamomile (Matricaria recutita) and feverfew (Tanacetum parthenium). Apigenin possesses anti-inflammatory and anticarcinogenic properties. Although extensive clinical trials are yet to be conducted, preliminary findings from cell culture and animal studies suggest that an apigenin-rich diet reduces the risk of breast, digestive tract, Skin, and prostate cancers, as well as certain hematological malignancies. Apigenin inhibits thyroid Cancer cell growth by suppressing the phosphorylation of the epidermal growth factor receptor (EGF-R) and mitogen-activated protein kinase (MAP). This flavone is capable of upregulating the expression of the p53 tumor suppressor protein and the retinoblastoma (Rb) tumor suppressor protein. Additionally, animal experiments indicate that apigenin may help prevent airway inflammation in asthma patients.

1.3.3. Luteolin

Luteolin, extracted from weld (Reseda luteola), has long been used as a yellow-orange dye for fabrics. Preliminary studies indicate that luteolin—found not only in weld but also in a wide array of vegetables, fruits, and herbs (carrots, bell peppers, celery, mint, rosemary, chamomile, and foxglove)—exhibits anti-inflammatory and anticarcinogenic properties. It not only hinders tumor development but also potentiates the efficacy of anticancer drugs and displays cytotoxicity against tumor cells. As a potent antioxidant, luteolin lowers Lipid Peroxidation levels, inhibits topoisomerases I and II, and suppresses The activity of NF-κB and AP-1 Transcription factors, which are linked to the expression of Immune Response, apoptosis, and Cell Cycle genes. Luteolin also modulates the activity of the p53 tumor suppressor and XIAP apoptosis factors, inhibits the STAT3 transcription factor, and modulates phosphoinositide 3-kinase activity, which may account for its multifaceted biological activity. Compared to other flavonoids, luteolin is one of the most potent anticarcinogenic agents. It can inhibit tumor cell proliferation in vitro with an IC₅₀ concentration ranging from 3 to 50 µM, whereas its effective in vivo concentration is 5–10 µg/kg of body weight, corresponding to a daily intake of 0.1–0.3 mg/kg/day.

Beyond its anticarcinogenic activity, luteolin has been found to prevent mast cell stimulation and T-lymphocyte activation, which is hypothesized to confer therapeutic benefits in the Treatment of multiple sclerosis, a neurodegenerative disease associated with autoimmune processes. Luteolin also exerts neuroprotective effects on the Central Nervous system. Specifically, it has been demonstrated that luteolin prevents the expression of inflammatory markers and suppresses excessive microglial activation in the hippocampus of Aging mice down to the levels seen in young animals, a change that was accompanied by improved memory performance.

1.3.4. Flavoxate

Synthetic compounds belonging to the class of flavones are also utilized in clinical practice. For instance, flavoxate is an antimuscarinic agent possessing myotropic and antispasmodic properties. It preferentially relaxes the smooth Muscle of the Urinary Tract and is prescribed for urinary frequency and incontinence. Its therapeutic efficacy is thought to stem from enhancing the inhibitory Influence of the brain's reticular formation Neurons on Micturition centers. This action is mediated, at least in part, by modulating cellular signaling pathways, particularly involving certain G Proteins.