Hesperidin

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1957

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published literature which was conducted following the procedure which fulfills basically scientific principles.

Data source

Reference

Reference Type:

publication

Title:

Metabolic fate of hesperidin, eriodictyol, homoeriodictyol, and diosmin

Author:

ALBERT N. BOOTH, FRANCIS T. JONES, AND FLOYD DEEDS

Year:

1958

Bibliographic source:

J. Biol. Chem., 1958, pages 661-668

Report date:

1957

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

Breakdown products were identified after hesperidin was ingested by rabbit, rat and human using ascending two-dimensional paper chromatograms of the ether extracts of acid urines which were developed with bottom phase of a mixture of chloroform, acetic acid, and water (2:1L1) in the first
direction, followed by 20 per cent aqueous potassium chloride in the second direction.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Hesperidin

EC Number:

208-288-1

EC Name:

Hesperidin

Cas Number:

520-26-3

Molecular formula:

C28H34O15

IUPAC Name:

5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxo-3,4-dihydro-2H-chromen-7-yl 6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Hesperidin was purchased from The Sunkist Growers, Ontario, California and re-crystallized prior to use

Radiolabelling:

no

Test animals

Species:

other: rabbits, rats and humen

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on exposure:

Hesperidin (1 gm) was given by stomach tube to a rabbit (weight = 3 kilos) subsisting on a commercial pelleted ration. After a 5 day adjustment period, the same rabbit was given 1 gm of hesperetin. The same rabbit was adjusted to a purified diet consisting of starch, Cerelose, casein, Celluflour, salts’ (including potassium acetate and magnesium oxide), oil, and vitamins. Then 1 gm of hesperidin was given by stomach tube.
The administration by stomach tube of either 100 or 300 mg. of hesperidin per rat on a purified diet. The aglycon of hesperidin (hesperetin) was given to rats (150 mg per rat).Rats were given diosmin (400 mg per rat by stomach tube) while subsisting on a purified diet. Rats were given eriodictyol (300 mg per rat), Finally, rats on the purified diet were given homoeriodictyol (150 mg per rat).
Hesperidin (2 gm) was ingested by a human subsisting on an ordinary diet except for the exclusion of coffee and citrus products.

Duration and frequency of treatment / exposure:

Hesperidin (1 gm) was given by stomach tube to a rabbit (weight = 3 kilos) subsisting on a commercial pelleted ration. After a 5 day adjustment period, the same rabbit was given 1 gm of hesperetin. The same rabbit was adjusted to a purified diet consisting of starch, Cerelose, casein, Celluflour, salts’ (including potassium acetate and magnesium oxide), oil, and vitamins.
The administration by stomach tube of either 100 or 300 mg. of hesperidin per rat on a purified diet. The aglycon of hesperidin (hesperetin) was given to rats (150 mg per rat).Rats were given diosmin (400 mg per rat by stomach tube) while subsisting on a purified diet. Rats were given eriodictyol (300 mg per rat), Finally, rats on the purified diet were given homoeriodictyol (150 mg per rat).
Hesperidin (2 gm) was ingested by a human subsisting on an ordinary diet except for the exclusion of coffee and citrus products.

Doses / concentrations

Remarks:

Doses / Concentrations:
Hesperidin (1 gm) was given by stomach tube to a rabbit (weight = 3 kilos) subsisting on a commercial pelleted ration. After a 5 day adjustment period, the same rabbit was given 1 gm. of hesperetin. The same rabbit was adjusted to a purified diet consisting of starch, Cerelose, casein, Celluflour, salts’ (including potassium acetate and magnesium oxide), oil, and vitamins.
The administration by stomach tube of either 100 or 300 mg of hesperidin per rat on a purified diet. The aglycon of hesperidin (hesperetin) was given to rats (150 mg per rat).Rats were given diosmin (400 mg per rat by stomach tube) while subsisting on a purified diet. Rats were given eriodictyol (300 mg per rat), Finally, rats on the purified diet were given homoeriodictyol (150 mg per rat).
Hesperidin (2 gm) was ingested by a human subsisting on an ordinary diet except for the exclusion of coffee and citrus products.

No. of animals per sex per dose / concentration:

no data

Control animals:

other: rabbit: yes; rat and human: no data

Positive control reference chemical:

no

Statistics:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Hesperidin can be absorbed from the gastrointestinal tract after oral ingestion.

Details on distribution in tissues:

no data

Details on excretion:

no data

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

For rabbit: hesperetin and its glucuronide, 3,4-dihydroxyphenylpropionic acid, 3-methoxy-4-hydroxyphenylpropionic acid,m-coumaric acid (m-hydroxycinnamic acid), m-HPPA, m-hydroxyhippuric acid, m-hydroxybenzoic acid, and 3-methoxy-4-hydroxybenzoic acid.
For rat: m-HPPA, m-coumaric acid , hesperetin, and a conjugate of hesperetin.
For human: isoferulic acid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Hesperidin can be absorpted from the intestinal tract after oral ingested by rats and the cleavage of the middle ring of the hesperidin had taken place, accompanied by dehydroxylation, demethoxylation,or demethylation, followed by dehydroxylation to yield m-hydroxyphenylpropionic
acid. Other metabolites were m-coumaric acid and the aglycons. The aglycons were free and conjugated with glucuronic acid. A species difference was observed between the rat and human.

Executive summary:

The metabolic fate of six flavonoids (hesperidin, hesperetin, diosmin, diosmetin, eriodictyol, and homoeriodictyol) has been studied after oral ingestion by rats. In each case m-hydroxyphenylpropionic acid was found to be present in the urine, along with lesser amounts of m-coumaric acid and the aglycons. The aglycons were free and conjugated with glucuronic acid. This was proof not only that absorption from the intestinal tract had occurred but also that cleavage of the middle ring of the flavonoid had taken place, accompanied by dehydroxylation, demethoxylation, or demethylation, followed by dehydroxylation to yield m-hydroxyphenylpropionic acid. A species difference was observed between the rat and human when hesperidin was ingested. The composition of the diet exerted marked effects upon the absorption of hesperidin by rabbits.