Hesperidin
(hesperidin-7-rhamnoglucoside, hesperidin-7-b-rutinoside) is a substance with a flanonoid structure, similar in properties to rutin and quercetin. Soluble in acids and alkalis.
Venotopic. Angioprotector. It is not produced in the human body.
It works in combination with vitamin C, which is found in nature. Natural C-complex has a pronounced antioxidant effect, reduces inflammation, strengthens collagen and connective tissue in general. Clinical trials have shown that vitamin C and hesperidin alone do not have the same therapeutic effect as they do when taken together. Vitamin C, as an antioxidant, protects bioflavonoids from destruction, allowing them to exhibit their healing properties.
Natural springs
Hesperidin is found in various citrus fruits. Most of the compound is found in the skin of the fruit, and about 10-15% is in the pericarp and seeds. The largest amount of hesperidin contains:
- unripe oranges;
- tangerines;
- hybrid fruits obtained by crossing oranges and tangerines.
Small concentrations of the substance contain extracts of valerian, Condopsis flowers, white bomeria, etc. These natural sources are not used for the industrial production of medicinal supplements. Diosmin is not found in nature and can only be obtained by processing hesperidin.
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Impact on the body
The beneficial effects and properties of natural hesperidin and the synthetic compound diosmin are greatly enhanced when these substances are used simultaneously. Therefore, individual nutrients are practically not used. Flavonoids enhance the vasoconstrictor effects of the hormone and neurotransmitter norepinephrine. As a result, the tone of the vein walls increases, venous capacity decreases and blood stagnation in the distal parts of the lower extremities decreases. Bioflavonoids reverse vascular damage observed in patients with chronic venous insufficiency.
In addition to the venotonic effect, flavonoid compounds have other effects:
- increase the intensity of contraction of lymphatic vessels and improve the outflow of lymph, due to which swelling of the legs goes away faster;
- reduce the permeability of capillaries and reduce their fragility, so the vessels of the microvasculature maintain their integrity;
- make venous walls more resistant to the harmful effects of free radicals and reactive oxygen species;
- reduce the concentration of pro-inflammatory prostaglandins and cytokines, reduce pain;
- prevent the risk of bleeding in women using an intrauterine device as a contraceptive.
Attention! Hesperidin is similar in structure to estrogens, so it prevents bone loss and the development of genital tumors in women during menopause.
Description:
Hesperidin is one of the most important flavonoids with a low molecular weight (610.57 Da). Its molecular formula is C28H34O15. Hesperidin belongs to flavanone, a class of flavonoids. Chemically, it consists of an aglycone (a form without sugar residues called hesperitin) and a sugar rutinoside: hesperetin-7-rutinoside or IUPAC name: (2S)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl) - 7-[(2S, 3R, 4S, 5S, 6R) -3,4,5-trihydroxy-6 - [[(2R, 3R, 4R, 5R, 6S) - 3,4,5-trihydroxy-6-methyloxan -2-yl] oxymethyl] oxan-2-yl] oxy-2,3-dihydrochromen-4-one.
Hesperidin is a flavan glycoside found in citrus fruits. It is a naturally occurring glucoside in most citrus fruits, found mostly in the fruit's albedo (the inner white, loose layer of citrus peel). Its aglycone form is called hesperetin. The name comes from the word Hesperidium or “hesperidium” - the fruit of plants of the orange subfamily. Hesperidin was first isolated in 1828 by the French chemist Lebreton from the white inner layer of citrus peel (mesocarp, albedo). Hesperidin is believed to play a role in plant defense.
Application:
In medicine, hesperidin is used as a venoprotective and antioxidant agent. For medicinal purposes it is often used in combination with diosmin. Included in drugs for the treatment of venous insufficiency, hemorrhoids, and lymphedema. There are studies that show the positive effects of hesperidin on rheumatoid arthritis and lowering diastolic blood pressure, as well as its ability to inhibit the spread and growth of cancer cells in cancer.
The use of hesperidin in infections is being studied. Antibacterial and antifungal activity of ethanol extract of grapefruit seeds and pulp against bacteria and yeast strains. The strongest antibacterial effect was observed against Salmonella enteritidis with a minimum inhibitory concentration (MIC) of 2.06% (extract concentration), and MICs for other bacteria and yeasts tested ranging from 4.13% to 16.5%. A recent study with Aeromonas hydrophila, a human pathogen that causes intestinal and extraintestinal infections, demonstrated that hesperidin has bactericidal and immunomodulatory effects. Other observations have shown that hesperidin is effective against human rotavirus, which causes diarrhea in infants and young children. Hesperidin also inhibited influenza virus (flu) replication in vitro and reduced the number of infected cells. Both in vitro and in vivo experiments show that hesperidin exhibits antiparasitic activity against adult Schistosoma mansoni worms, which cause the tropical disease schistosomiasis, which affects millions of people, especially children, worldwide.
Receipt:
Hesperidin will be obtained from the albedo of fruits. According to one of the methods (owned by R.H. HIGBI), the following occurs: after coagulation of the mucous components, the concentration of hydrogen ions in the mass is adjusted to a pH of approximately 11.0 to 11.5 using a suitable alkalizing agent. The suspension or slurry is agitated for a period of time to allow extraction of hesperidin from the starting material, after which the mass is subjected to a pressing operation to separate the hesperdin-containing liquid from the leached peel. The hesperedin solution is then adjusted to a pH below 9.0 using a suitable acid. At a pH below about 9.0, hesperidin crystallizes from solution. However, since crystallization may be slow at this point, centrifuge or filter the neutralized solution soon after neutralization to separate fine pulp particles, undissolved lime, and other foreign matter that tend to contaminate the hesperidin. Crystallization of hesperidin from liquid, after separation of foreign materials, is allowed to proceed to near completion at room temperature, which is usually accomplished approximately 43 hours after acidification. The resulting hesperidin is not purified because it usually contains some impurities. It is separated from the mother liquor and dissolved in a relatively weak alkali, then mixed with a quantity of alcohol to coagulate certain impurities in the form of pectic substances, which are subsequently removed by filtration. The filtrate is retained and acidified to a pH below about 9 and preferably to a pH of about 6.0, at which point ApI-I crystallizes hesperidin from solution. These crystals are then separated from the solution.
Effect on the body:
Hesperidin 6-O-alpha-L-rhamnosyl-beta-D-glucosidase enzyme, which uses hesperidin to convert and H2O to produce hesperetin and rutinose, is found as Ascomycete. Hesperdin itself is absorbed from the intestine intact, like a glycoside. Its aglycone hesperitin appears in plasma 3 hours after oral administration, reaching a peak around 5 and 7 hours. The circulating forms of hesperitin are glucuronides (87%) and sulfoglucuronides (13%). For hesperedin, urinary excretion is almost complete 24 hours after ingestion of orange or juice and is not dose-dependent. Although hesperidin does not have the usual structural elements to properly scavenge free radicals and act as a chelator, the ability to chelate metal ions has been confirmed in some studies (Faculty of Pharmacy, Department of Physical Chemistry, University of Belgrade, Belgrade, Serbia, 2014). Other scientific observations have discovered hesperidin's antioxidant activity and radical scavenging properties using various assay systems (Jovanovic et al). In addition, hesperidin was found to be effective in protecting liposomes from peroxidation caused by ultraviolet radiation. Numerous studies have confirmed the powerful biological activity of hesperidin: effects on the vascular system (reduces capillary permeability), anti-inflammatory effect, antioxidant effect, effect on enzymes, antimicrobial (antibacterial, antifungal, antiviral) and anticarcinogenic activity, inhibition of cell aggregation, antiallergic effects. The possible anti-inflammatory effect of hesperidin is likely due to the anti-inflammatory effect of its aglycone hesperetin. Hesperetin appears to influence arachidonic acid metabolism as well as histamine release. It inhibits phospholipase A2, lipoxygenase and cyclooxygenase. There is evidence that hesperetin inhibits the release of histamine from mast cells, which may explain the possible antiallergic activity. The lipid-lowering effects of hesperidin are likely related to the possible lipid-lowering effects of hesperetin. Hesperetin may reduce plasma cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase as well as acyl coenzyme A cholesterol acytransferase (ACAT). Inhibition of these enzymes by hesperetin has been demonstrated in rats fed a high-cholesterol diet.
The mechanism of the possible vasoprotective effect of hesperidin is unclear.
Animal studies have shown that it reduces microvascular permeability. Hesperidin alone or through hesperetin may protect endothelial cells from hypoxia by stimulating certain mitochondrial enzymes such as succinate dehydrogenase. The mechanism of the possible anticarcinogenic effect of hesperidin is also unclear. One explanation may be inhibition of polyamine synthesis. Inhibition of lipoxygenase and cyclooxygenase is another possibility.
Application in medicine
Doctors use drugs containing the flavonoids hesperidin and diosmin for various lesions of the venous vessels. There are venotonics for topical use - in the form of gels and ointments. Next we will talk mainly about products for oral use. They are available in 3 forms: hard tablets, gelatin-coated capsules and suspension.
For varicose veins
Drugs are prescribed to eliminate unpleasant symptoms of varicose veins, such as:
- feeling of heaviness and fatigue in the legs;
- pain in the calf muscles;
- swelling of the feet and legs in the evening;
- the appearance of spider veins;
- swelling of veins.
With regular use of drugs containing hesperidin and diosmin, the venous wall is strengthened and the progression of varicose veins is slowed down. Patients get rid of painful symptoms and can return to normal life.
Watch a video about what supplements can be used for varicose veins and lymphostasis:
Dietary supplements for varicose veins and lymphostasis
For hemorrhoids
The main effect of flavonoids is to increase the tone of hemorrhoids. After taking the drugs, the blood supply to the veins in the anus decreases, and problems with defecation disappear. With prolonged use of the active substance hesperidin, the walls of the veins become strong, and bleeding occurs much less frequently. The drugs also stop the inflammatory process and have a pronounced analgesic effect.
For the treatment of trophic ulcers
Flavonoid compounds have pronounced regenerative properties. They reduce the area of distribution and depth of trophic ulcers. Hesperidin also improves blood flow in the affected area, making wound healing much faster and eliminating acute pain.
Before and after vein surgery
Bioflavonoid complexes are used during the period of preparation for vein operations or the elimination of hemorrhoids. The products accelerate tissue healing and prevent relapses of the disease.
Hesperidin is also used in the postoperative period. The drugs increase peripheral vascular resistance, prevent orthostatic hypotension, reduce swelling of the legs, and are used after prolonged bed rest and to prevent venous insufficiency. The ability of flavonoids to prevent bleeding in patients after phlebectomy has been proven.
Hesperidin
Hesperetin has been noted to inhibit aromatase with an IC50 of 1 μg/ml (comparable to apigenin at 0.9 μg/ml and chrysin at 1.1 μg/ml), and other studies have reported inhibitory activity (IC50) of 4-5 μM ( inferior to apigenin by 1 µM). 25) 500-5000 ppm of hesperetin was added to the food for mice with estrogen-responsive tumors (with no dose-dependent effect, but 1000 ppm was required for statistical significance of the result), which was associated with a decrease in serum estrogen concentrations. This content (million-1 corresponds to µg/g, therefore, the content of hesperetin in the food was 0.5-5 mg/g) is approximately 120-500 mg/kg (based on the assumption that 3 g of food is consumed by a mouse weighing 25 g). Hesperetin is an aromatase inhibitory flavonone; its inhibitory potential is either equal to or slightly inferior to that of apigenin. Hesperetin (0.1%) inhibits the ability of aromatase to stimulate androstenedione production, but other studies have shown an increase in messenger RNA at 5 µM and above. This study revealed dose-dependent inhibition by luteolin (a flavonoid that also inhibits aromatase). There is ambiguous information about the transformation of aromatase protein molecules by hesperidin. As for other enzymes, cytochrome CYP2C8 is weakly to moderately inhibited by hesperetin, with an IC50 value of 68-168 µM26), while the inhibitory potency of hesperidin is attenuated at 209-274 µM; both have less inhibitory capacity than flavonoids such as quercetin and luteolin. The structurally similar diosmetin is 16 times more potent, suggesting that the flavanone configuration essentially blocks CYP2C8 inhibition. As for CYP2C9, this enzyme is more susceptible to inhibition by hesperetin with an IC50 value of 21.50+/-3.62 µM, which is again inferior to diosmetin (1.71+/-0.58 µM). Hesperidin was orally administered to rats at a daily dose of 5-15 mg/kg rather than 1 mg/kg. Subsequently, this revealed that hesperidin alters the pharmacokinetics of diltiazem and its metabolite (desacetyldiltiazem) by increasing Cmax (46.7-62.4%) and AUC (48.9-65.3%), suggesting the possibility of inhibition of CYP3A4 or inhibition of P-glycoprotein efflux protein. At the same time, attention should be paid to the fact that (due to the IC50 value of 2.7 μM relative to intestinal soluble CYP3A4) hesperidin is not the main component of grapefruit juice responsible for the inhibition of CYP3A4 (the main component in this case is bergamottin27 )). Following hesperidin administration or incubation, hesperetin is blocked by CYP2C8 and CYP3A4, indicating that the extent of their inhibitory properties allows for interactions with other drugs. ==== Phase II of biotransformation ==== It was noted that hesperidin stimulates the activity of the Nrf2 gene, which, in turn, leads to an increase in the expression of heme oxygenase 1 (oxidative stress protein HO-1) in liver cells at 40-80 μM, this is minor in MAPK signaling pathways because hesperidin activates ERK1/2. Although the known antioxidant properties of hesperidin are not mediated by direct antioxidant chelation effects, it appears that the concentration of hesperidin required to stimulate the Nrf2 gene is high enough that it is not a suitable signaling pathway. Isolated hesperetin is glucuronidated by UDP-GT enzymes, particularly at the 3′ and 7 positions (hesperetin 3′-O-glucuronide and hesperetin 7-O-glucuronide, respectively). This entire process is mediated by a large number of UDP-GT enzymes, such as UDP-GT1A9, UDP-GT1A1, UDP-GT1A7 and UDP-GT1A3. 28) Hesperetin (and eridictyol) has been noted to inhibit sulfotransferase; hesperetin inhibits intestinal sulfotransferase with clear IC50 values against hCYP1A1 (23.4+/-5.75µM), hCYP1A3 (20.8+/-8.1µM), hCYP1E1 (90.4+/-11.5µM), and hCYP2A1 (152+/-14.9 µM). The inhibitory effect directed against the formation of sulfates in the cytoplasm of intestinal cells was more powerful; inhibition of estrogen sulfates occurred with an IC50 of 3.6 μM.29) Hesperetin is also able to inhibit a number of sulfotransferase enzymes (which sulfate molecules and signal their elimination from the body), but this information has not yet been practically confirmed, since inhibition of these enzymes requires high concentration of hesperetin.
