520-26-3 Usage
Uses
Used in Pharmaceutical Industry:
Hesperidin is used as a vitamin P type medicine for enhancing the toughness of capillaries and reducing their fragility. It is particularly useful in the adjuvant treatment of hypertension.
Used in Food Industry:
Hesperidin is used as a flavoring agent and is a bioflavonoid found in citrus pulp. It has minor use as a flavorant and has been listed as a variety in Japan's "Japanese Standard of Food Additives."
Used in Nutraceutical Industry:
As a vitamin P, hesperidin promotes capillary health and increases resistance to collagen destruction. It can work in conjunction with vitamin C, helping prevent oxidation of the latter. Hesperidin is found in food sources such as apricots, broccoli, citrus fruit pulp, grapes, prunes, and spinach.
Used in Anticancer Applications:
Hesperidin has been shown to increase the cytotoxicity of doxorubicin on cancer cells in vitro by inhibiting cell cycle progression and upregulating apoptosis. It is also used in the development of novel drug delivery systems to enhance its applications and efficacy against cancer cells.
Used in Anti-inflammatory and Capillary Protection:
Hesperidin is used as an anti-inflammatory agent and capillary protectant, helping to maintain the health of blood vessels and reduce the risk of related health issues.
Chemical Properties:
Hesperidin is a light yellow crystalline powder with a melting point of 258-262 °C, softening at 250 °C. It is easily soluble in pyridine, sodium hydroxide solution, and dimethyl formamide. It is slightly soluble in methanol and hot glacial acetic acid and very slightly soluble in ether, acetone, chloroform, and benzene. Hesperidin is odorless and tasteless, with 1g of the product being soluble in 50L of water.
Hesperidin
Hesperidin (glycoside) is a flavonoid substance which has flavanone oxygen glycoside structure. It is weakly acidic with pure being white needle-like crystals. It is also the main component of vitamin P.
Figure 1 the molecular structure of hesperidin.
After the hydrogenation, hesperidin becomes a natural sweetener, dihydrochalcone, whose sweetness is 1,000 times as high as sucrose. It can be used as a functional food for application. Hesperidin has a variety of biological characteristics. Modern research has found that: hesperidin has various effects such as antioxidant, anti-cancer, anti-mildew, anti-allergy, lowering blood pressure, inhibiting oral cancer and esophageal cancer, maintenance of osmotic pressure, increasing capillary toughness, and lowering cholesterol. Related studies have shown that hesperidin has broad antibacterial spectrum on common food contamination. It has significant inhibitory effect on Bacillus subtilis, Salmonella typhimurium, Shigella bacteria, hemolytic streptococcus and Vibrio cholerae. Therefore, it is widely applied in food additives and food processing.
Pharmacological activity
1. Hesperidin is a kind of drug for treatment of hypertension and myocardial infarction. It is used as the pharmaceutical raw material in the pharmaceutical industry and is one of the main components of a Chinese patent medicine, beniol.
2. Hesperidin has various effects such as anti-lipid oxidation, scavenging oxygen free radicals, and anti-inflammatory, anti-viral, anti-bacterial. Long-term use can delay aging and cancer. In short, hesperidin is a kind of flavonoids with clear defined pharmacological activity as well as extensive function of flavonoids. In addition to its application in medicine, it also has wide application in sports pharmacy and sports nutrition and therefore has broad prospects of development and utilization. Its related research work is expected to subject to further deepening.
Industry Status
Hesperidin has various effects such as maintaining osmotic pressure, increasing capillary toughness, shortening the bleeding time, and reducing the cholesterol. It is clinically used for the adjuvant treatment of cardiovascular diseases. It can be used for cultivating various kinds of drugs for preventing arteriosclerosis and myocardial infarction. It is one of the major raw materials for synthesizing Chinese patent medicine “beniol”. It can be used as natural antioxidants in the food industry and can also be used in the cosmetics industry.
Hesperidin is mostly presented in the waste of citrus processing such as fruit skin and fruit bag with the highest content being presented in mature skin and tissue (30%-50% in the peel, orange envelope, nuclear, pulp contains 30%-50%, epicarp contains 10%-20%). Orange juice and capsule contain a relative low amount being 1% to 5%. Extraction methods of hesperidin include solvent extraction, alkaline extraction and acid precipitation, carbon adsorption, ion exchange, wherein the alkali extraction and acid precipitation method is simple, low-cost, and has a high extraction rate.
Hesperidin can be dissolved in dilute alkali and pyridine as well as hot water (over 70 °C). It is also slightly soluble in methanol but almost insoluble in acetone, benzene and chloroform. The extraction of hesperidin mainly take advantage of its two phenolic hydroxyl groups which under alkaline conditions, has reaction with the sodium ion in the solution to generate sodium salt to be dissolved out; then acidify, cool to precipitate it from solution. Extraction of hesperidin from citrus peels commonly adopts heat extraction and soaks extraction method with a non-idea yield. In recent years, studies on the ultrasonic extraction of the effective components from natural plants (especially herbs) have been widely carried out, and have already obtained some progress. The extraction is first based on the hesperidins’ ring-opening dissolution under alkaline conditions and then further loop closure precipitation for being separated out under acidic conditions. During the extraction process, increasing the amount of the alkali can reduce the necessary amount of ethanol. But it is not recommended to apply a relative large amount of alkaline otherwise hesperidin is easily susceptible to oxidation damage.
Figure 2 Yellow powder of hesperidin
The above information is edited by the lookchem of Dai Xiongfeng.
Production method
The product is presented in the pericarp of lemon, citrus, and Citus aurantium. In citrus, the developed system of the mesocarp (white spongy tissue) mostly contains citrus glycosides.。 Instead thinner system of mesocarp mostly contains hesperidin. The product is mainly extracted from the dried, ripe orange peel. Crush the dry orange peel; add 3-6 times the amount of water to soak for about 0.5h to make it soft. Then add 4-10% of the amount of lime and 7-12 times the amount of water; stir uniformly and check the pH. The pH value should reach 11.5-12, otherwise we should supplement lime or sodium hydroxide. After soaking for 1.5-2h, centrifuge and filter with the residues adding 5-7 times the amount of water and further adjust to pH 11.5-12 with proper amount of lime; continue soaking and centrifuge and filter again. After the clarification of the filtrate, add diluted hydrochloric acid for adjusting pH to 5; stand for 2d; collect the precipitate and wash with water to nearly neutral which give the crude product. Add 1% of sodium hydroxide and 50% of ethanol to dissolve the crude product; filter and adjust the filtrate to pH 5 with dilute hydrochloric acid, stand overnight, and collect the precipitate; first wash once with 50% ethanol, and then wash with water to nearly neutral; dry at 70 °C; pulverize and sieve to obtain hesperidin with the total yield being 0.6-1.8%.
History
Hesperidin is the glycoside in the form of hesperidin and rubiose and is a derivative
of dihydroflavonoids. It widely exists in legume, birch, lip flower, butterfly flower,
Rutaceae, and citrus plants. Hesperidin is an important composition of citrus
pulp and peel; most of hesperidin exists in citrus processing waste such as skin and
fruit bag. Mature skin and tissue have the highest content of hesperidin (30–50% in
endocarp; 30–50% in orange collaterals, nuclear, and pulp; and 10–20% in exo_x005fcarp); the content of hesperidin is relatively low in juice and orange bag, which is
about 1–5%. The crude extracts of hesperidin was first discovered in 1827 by
Lebreton. Then the Hungarian scholar Albert Szent-Gyorgi discovered that the flavonoids have a protective microvascular effect in 1936, which is similar to that of
vitamin P. Preparation of vitamin P was made in 1938. It was not until 1949
that it was discovered that vitamin P was made up of two flavonoids, luteolin and
hesperidin, which are believed to be vitamin active. This substance, which was later
named as vitamin P, was designed to reduce blood vessel permeability and brittleness, as well as alleviate bad blood and vitamin C deficiency. It was later discovered
that the substance had an antioxidant effect, so the name of vitamin P was abandoned. Due to the widespread distribution of hesperidin in plant medicine, the
research and development have been widely followed.
Indications
Hesperidin can be used for cardiovascular disease prevention and treatment, blood
sugar and blood lipid and blood pressure regulation, circulatory system regulation,
and body regulation, and it can also be used as an antibacterial, anti-inflammatory,
and antiviral.
Flammability and Explosibility
Nonflammable
Pharmacology
The pharmacological effect of hesperidin is widespread, and people thought it was
vitamin P in the early days, but in recent years, people found that it has other functions such as controlling blood pressure, antiallergic, reducing bone mineral density
and cholesterol, improving enzyme activity and microcirculation, antibacterial,
anti-inflammatory, anti-hepatitis B, antitumor, and other pharmacological effects.Hesperidin has the function of vitamin P, which can reduce capillary permeability and prevent microvascular hemorrhage. Intraperitoneal injection of hesperidin at
175–250?mg/kg in mice could increase permeability of blood vessels by antihistamine and inhibiting hemolytic lecithin. Hesperidin has antiviral and antimicrobial
effect, and preincubation with hesperidin at 200? mg/ml protects the cells from
viruses. One to 10?μg/ml of hesperidin effectively inhibits the growth of the fungus.
It has the effect of maintaining the normal osmotic pressure of the blood vessels,
reducing the shortness of blood vessels, shortening bleeding time, reducing blood
fat, and preventing atherosclerosis; hesperidin has an effect on the gastrointestinal
tract, which can excite the smooth muscle transiently and then inhibit it, and it is a
major component of the diet drug; hesperidin has an effect of anti-lipid peroxidation
and scavenging hydroxyl radical. Hesperidin is a newly discovered flavonoid compound which has an effect in the central nervous system; it has a sedative effect. At
the same time, hesperidin has the effect of lowering cholesterol, curing rheumatism,
and inhibiting skin pigmentation. Hesperidin is a strong affinity for estrogen receptors, which can be used in estrogen receptors to prevent bone loss and reduce the
number of osteoblasts. Hesperidin has a significant inhibitory effect on human lung
cancer, colorectal cancer, kidney cancer, and human breast cancer cells, which can
be used for cancer prevention.
Clinical Use
Hesperidin has the effect to maintain osmotic pressure, strengthen the capillary
toughness, shorten the bleeding time, lower cholesterol, and so on. Although hesperidin cannot be used as independent medication, it is recorded in the pharmacopoeia that hesperidin, as auxiliary materials, is widely used to aid in the treatment
of cardiovascular system; it can be configured as a variety of drugs to prevent hardening of the arteries and myocardial infarction. It is one of the main raw materials
of medicine “pulse.” Hesperidin is used as auxiliary materials for the treatment of
vascular brittleness, bedsore, rheumatoid arthritis, vitamin C deficiency disease,
trauma, obstetric disease, gum inflammation, edema, and gastrointestinal tract disease in the world. Hesperidin can be used to produce an anticancer drug called
diosmin. Natural antioxidant is available in the food industry. It is also used in
the cosmetics industry.
Purification Methods
Dissolve hesperidine in dilute aqueous alkali and precipitate it by adjusting the pH to 6-7. [Beilstein 18 III/IV 3219, 18/5 V 218.]
Check Digit Verification of cas no
The CAS Registry Mumber 520-26-3 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 5,2 and 0 respectively; the second part has 2 digits, 2 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 520-26:
(5*5)+(4*2)+(3*0)+(2*2)+(1*6)=43
43 % 10 = 3
So 520-26-3 is a valid CAS Registry Number.
InChI:InChI=1/C28H34O15/c1-10-21(32)23(34)25(36)27(40-10)39-9-19-22(33)24(35)26(37)28(43-19)41-12-6-14(30)20-15(31)8-17(42-18(20)7-12)11-3-4-16(38-2)13(29)5-11/h3-7,10,17,19,21-30,32-37H,8-9H2,1-2H3/t10?,17-,19?,21-,22+,23-,24-,25?,26?,27+,28+/m0/s1
520-26-3Relevant articles and documents
Preparation and evaluation of a triazole-bridged bis(β-cyclodextrin)–bonded chiral stationary phase for HPLC
Shuang, Yazhou,Liao, Yuqin,Wang, Hui,Wang, Yuanxing,Li, Laisheng
, p. 168 - 184 (2019/11/25)
A triazole-bridged bis(β-cyclodextrin) was synthesized via a high-yield Click Chemistry reaction between 6-azido-β-cyclodextrin and 6-propynylamino-β-cyclodextrin, and then it was bonded onto ordered silica gel SBA-15 to obtain a novel triazole-bridged bis (β-cyclodextrin)–bonded chiral stationary phase (TBCDP). The structures of the bridged cyclodextrin and TBCDP were characterized by the infrared spectroscopy, mass spectrometry, elemental analysis, and thermogravimetric analysis. The chiral performance of TBCDP was evaluated by using chiral pesticides and drugs as probes including triazoles, flavanones, dansyl amino acids and β-blockers. Some effects of the composition in mobile phase and pH value on the enantioseparations were investigated in different modes. The nine triazoles, eight flavanones, and eight dansyl amino acids were successfully resolved on TBCDP under the reversed phase with the resolutions of hexaconazole, 2′-hydroxyflavanone, and dansyl-DL-tyrosine, which were 2.49, 5.40, and 3.25 within 30 minutes, respectively. The ten β-blockers were also separated under the polar organic mode with the resolution of arotinolol reached 1.71. Some related separation mechanisms were discussed preliminary. Compared with the native cyclodextrin stationary phase (CDSP), TBCDP has higher enantioselectivity to separate more analytes, which benefited from the synergistic inclusion ability of the two adjacent cavities and bridging linker of TBCDP, thereby enabling it a promising prospect in chiral drugs and food analysis.
Chiral separation of hesperidin and naringin and its analysis in a butanol extract of Launeae arborescens
Belboukhari, Nasser,Cheriti, Abdelkrim,Roussel, Christian,Vanthuyne, Nicolas
scheme or table, p. 669 - 681 (2010/08/20)
Two flavanone glycosides were isolated from the aerial part of Launeae arborescens (Asteraceae), which were identified as hesperidin and naringin. They are the most abundant flavonoids in the edible parts of many species of citrus fruits. In this study, we were interested in the chiral separation and determination of the diastereomerisation barriers of hesperidin and naringin by HPLC methods. The chiral separation HPLC screening of diastereomers of hesperidin and naringin by HPLC methods was accomplished in the normal-phase mode using 11 chiral stationary phases and various n-hexane/alcohol mobile phases. The rate constants and activation energy of diastereomerisation (G#) of flavanones, naringin and hesperidin were determined, respectively, on Chiralpak IC and Chiralpak IA. The analysis of flavanones isolated in butanol extracts of Launeae arborescens were confirmed by HPLC on Chiralpak IC.
Bioavailability of glucosyl hesperidin in rats
Yamada, Mika,Tanabe, Fujimi,Arai, Norie,Mitsuzumi, Hitoshi,Miwa, Yoshikatsu,Kubota, Michio,Chaen, Hiroto,Kibata, Masayoshi
, p. 1386 - 1394 (2008/02/11)
Glucosyl hesperidin (G-hesperidin) is a water-soluble derivative of hesperidin. We compared the absorption and metabolism of G-hesperidin with those of hesperidin in rats. After oral administration of G-hesperidin or hesperidin to rats, hesperetin was detected in sera hydrolyzed with β-glucuronidase, but it was not detectable in unhydrolyzed sera. Serum hesperetin was found more rapidly in rats administered G-hesperidin than in those administered hesperidin. The area under the concentration-time curve for hesperetin in the sera of rats administered G-hesperidin was approximately 3.7-fold greater than that of rats administered hesperidin. In the urine of both administration groups, hesperetin and its glucuronide were found. Urinary excretion of metabolites was higher in rats administered G-hesperidin than in those administered hesperidin. These results indicate that G-hesperidin presents the same metabolic profile as hesperidin. Moreover, it was concluded that G-hesperidin is absorbed more rapidly and efficiently than hesperidin, because of its high water solubility.
Reduction potentials of flavonoid and model phenoxyl radicals. Which ring in flavonoids is responsible for antioxidant activity?
Jovanovic, Slobodan V.,Steenken, Steen,Hara, Yukihiko,Simic, Michael G.
, p. 2497 - 2504 (2007/10/03)
Model phenoxyl and more complex flavonoid radicals were generated by azide radical induced one-electron oxidation in aqueous solutions. Spectral, acid-base and redox properties of the radicals were investigated by the pulse radiolysis technique. The physicochemical characteristics of the flavonoid radicals closely match those of the ring with the lower reduction potential. In flavonoids which have a 3,5-dihydroxyanisole (catechins), or a 2,4-dihydroxyacetophenone (hesperidin, rutin, quercetin)-like A ring and a catechol- or 2-methoxyphenol-like B ring, the antioxidant active moiety is clearly the B ring [reduction potential difference between the model phenoxyls is ΔE(A-B ring models) > 0.1 V]. In galangin, where the B ring is unsubstituted phenyl, the antioxidant active moiety is the A ring. Even though the A ring is not a good electron donor, E7, > 0.8/NHE V, it can still scavenge alkyl peroxyl radicals, E7, = 1.06 V, and the Superoxide radical, E7 > 1.06 V. Quercetin is the best electron donor of all investigated flavonoids (measured E10.8 = 0.09 V, and calculated E7 = 0.33 V). The favourable electron-donating properties originate from the electron donating O-3 hydroxy group in the C ring, which is conjugated to the catechol (B ring) radical through the 2,3-double bond. The conjugation of the A and B rings is apparently minimal, amounting to less than 2.5% of the substituent effect in either direction. Thus, neglecting the acid-base equilibria of the A ring, and using those of the B ring and the measured values of the reduction potentials at pH 3,7 and 13.5, the pH dependence of the reduction potentials of the flavonoid radicals can be calculated. In neutral and slightly alkaline media (pH 7-9), all investigated flavonoids are inferior electron donors to ascorbate. Quercetin, E7 = 0.33 V, and gallocatechins, E7 = 0.43 V, can reduce vitamin E radicals (assuming the same reduction potential as Trolox C radicals, E7 = 0.48 V). Since all investigated flavonoid radicals have reduction potentials lower than E7 = 1.06 V of alkyl peroxyl radicals, the parent flavonoids qualify as chain-breaking antioxidants in any oxidation process mediated by these radicals.
Conversion of hesperidin into hesperetin
-
, (2008/06/13)
An improved procedure for the conversion of commercial hesperidin into high-purity, crystalline hesperetin is disclosed. This procedure comprises purifying the crude starting material by insolubles removal and precipitation, followed by cleaving the saccharides with a strong mineral acid in lower primary alkanol. The use of lower alkanol in this transformation facilitates the isolation of a high purity product uncontaminated by resinified sugars.
