Lec # 3 Flavonoids Fall 2024 PDF

Biochemistry of Natural products 040817311 Lec. # 3. Flavonoids Dr. SamarR.Saleh Assistant Prof., BiochemistryDepartment Fall 2024 ❖ Characterized by the presence of more than one phenolic group. ❖ Phenolic compounds are phytochemicals which pla...

Biochemistry of Natural products 040817311 Lec. # 3. Flavonoids Dr. SamarR.Saleh Assistant Prof., BiochemistryDepartment Fall 2024 ❖ Characterized by the presence of more than one phenolic group. ❖ Phenolic compounds are phytochemicals which play a major role in the protection of oxidation processes. ❖ The antioxidant properties of phenolic compounds  Air pollution Free Radicals Alcohol Pesticides (1O2, O−, HO2, OH) Food additives Tobacco smoking Fried food 5  Antioxidant defense Systems There are several enzyme systems that catalyze reactions to neutralize free radicals and ROS. These enzymes include: Superoxide dismutase (SOD) Glutathione peroxidase (GPx) Glutathione reductase (GR) Catalases (CAT) ▣ Antioxidants are compounds that protect cells against the damaging effects of reactive oxygen species (ROS), such as singlet oxygen (1O2), superoxide ( O−2), peroxyl radicals (HO2), hydroxyl radicals ( OH) and peroxynitrite ( ONOO−). An imbalance between antioxidants and ROS results in oxidative stress, leading to cellular damage ❖ The antioxidant properties of phenolic compounds can act as: ❑ Free radical scavengers, ❑ Singlet oxygen quenchers. ❑ Hydrogen donators, ❑ Metal chelators. ❖ Flavonoids are polyphenolic secondary plant metabolites ❖ comprise: 15 carbons (2 aromatic rings connected with 3 carbon bridge) and many hydroxyl groups (OH) Basic structure of flavonoids 14  Structure and classification of flavonoids and their dietary sources.  Flavonoids classification and their possible chemical structure The basic Flavonoid skeleton can have a large no. of substitutions on it: (OH, sugar, Methylation, acetylation) Flavonoids: source Tea: Fruit and vegetables: (Flavanols) (All classes) Red wine: Citrus: (Flavanol, Flavonols) (Flavanone) Cocoa: (Flavanols Berries: and procyanidins) (Anthocyanins)  Physicochemical Properties, Extraction, Characterization, and Quantitation ✓ Glycosides are water-soluble and soluble in alcohols. ✓ Glycosides can be extracted, most often at high temperature, by acetone or by alcohols (ethanol, methanol) mixed with water. ✓ Aglycones are soluble in apolar organic solvents (dichloromethane).  Extraction and Characterization of flavonoids (Solvent evaporation Extraction methods: under ▪ Maceration vacuum) ▪ Soxhlet Chromatographic ▪ UAE ▪ SFE techniques (HPLC,…) ▪ ASE Extraction of flavonoids Detection and Quantitation of flavonoids  Biological properties 1-Flavonoids as antioxidants: The flavones, catechins, epicatechin and rutin seem to be the most powerful flavonoids for protecting the body against ROS (powerful radical scavengers). Because of the high reactivity of the hydroxyl groups of Flavonoids the flavonoids, radicals are made inactive Catechin Oxidized by radicals More stable, less- reactive radical Epicatechin Rutin Quercetin (FlavOnols) ▪ Onion rich in quercetin  2- Anti ulcer effect: ▪ Helicobacter pylori, a spiral-shaped bacterium that lives in the acidic environment of the stomach. ▪ Helicobacter pylori is a human pathogen associated with: ▪ Gastritis, ▪ Peptic ulceration and ▪ Gastric cancer. 2- Anti ulcer effect: Quercetin plays a very important role in the prevention and treatment of peptic ulcer by: 1. Promoting mucus secretion, thereby serves as gastroprotective agent 2. Inhibiting the growth of H. pylori bacterium. Occurs in apples, onions, tea, red The D-alanine- D-alanine ligase (Ddl) enzymes is important wines and berries in bacterial cell wall peptidoglycan assembly Quercetin Ddl has been considered as a putative antimicrobial drug target  3- Anti atherosclerotic effects: Atherosclerosis is a condition that results from the gradual build-up of fatty substances (plaque), including cholesterol, on the walls of the arteries. This plaque ❖ Reduces the blood flow to the heart, brain and other tissues and ❖ Hardening of the arteries (heart attack or stroke). An elevated plasma LDL concentration is a primary risk factor for the development of atherosclerosis and coronary artery disease. 3- Anti atherosclerotic effects: An elevated plasma LDL concentration: ▪ The oxidation of LDL occurs when it reacts with free radicals. ▪ The oxi LDL itself becomes more reactive and can produce tissue damage. ▪ OxLDL promotes the accumulation of the immune and inflammatory cells, such as macrophages, and platelets to the damaged area. OxLDL promotes the immune and inflammatory reactions that characterize atherosclerosis and associated with the risk of acute CVD events 3- Anti atherosclerotic effects: Flavonoids seems to suppress LDL oxidation and inflammatory progression in the artery wall. There is an inverse correlation between flavonoid intake and total plasma cholesterol concentrations and coronary heart disease. ▪A glass of red wine has ~200 mg of flavonoids (mainly quercetin and rutin). One –two glasses of red wine daily can protect against heart disease and reducing the risk of CVD (cardiovascular disease). ▣ The oxidation of LDL is thought to occur when the LDL cholesterol particles in your body react with free radicals. The oxidized LDL itself then becomes more reactive with the surrounding tissues, which can produce tissue damage. Some of the things that appear to increase levels of oxidized LDL include: ◾ Consuming a diet that is high in trans fats ◾ Smoking ◾ Having poorly controlled diabetes ▣ Once LDL becomes oxidized, it goes directly within the inner lining (endothelium) of any artery in the body, including the carotid artery, coronary artery or the arteries that supply your legs and arms with blood. ▣ Once there, it encourages the accumulation of inflammatory cells, such as macrophages, and platelets at the site of the vessel and promotes their adhesion to the damaged area. More macrophages, cholesterol and other lipids begin to accumulate at the site, forming a plaque that begins to grow thicker. ▣ Over time, this can slow -- or completely restrict -- the amount of blood flow that travels to one or more areas of the body. This can result in a variety of health conditions, including coronary heart disease, peripheral vascular disease or dementia. 4- Anti-inflammatory effect: Cyclooxygenase (COX) is an inflammatory mediator and is involved in the release of arachidonic acid. The release of arachidonic acid can be considered starting point for a general inflammatory response. Flavonoids like quercetin are shown to inhibit COX pathway and inflammatory mediators 5-Hepatoprotective activity: Many flavonoids (silymarin, apigenin, quercetin and naringenin) possess hepato-protective activity. 6. Memory improvement properties 6. Memory improvement properties 6. Memory improvement properties