Quercetin And Isorhamnetin Form’ Metabolism Distribution In Mice Plasma And Tissues After Long Term Administration

Quercetin (quercetin;3,5,7,3’,4’-five hydroxyflavone) is a multi-hydroxy flavonoids, quercetin and its derivatives are rich in human botanical dietary. Studies found that quercetin was prone to decomposition and conjugation reactions such as methylation, hydroxylation, sulfation and glucuronidation in the body, transformed into small molecule compounds or more water-solubility metabolites, then excreted. Many literatures reported the quercetin water-solubility metabolites in vivo, while its lipid-solubility metabolic research was less. The research almost focused on the extraction and detection of plant and quercetin’water-solubility metabolites in plasma after short-term gavage, reports about long-term gavage and distribution of quercetin’ metabolism in tissues were rarely.In order to investigate the mechanisms and metabolic pathways of quercetin biological effects in the human body further. To explore quercetin other possible metabolites and mesostate existed in vivo metabolic processes, quercetin’metabolism distribution in mice tissues and plasma was investigated. According to its distribution in tissue and plasma to speculate which position quercetin may effect on. Then provide theoretical basis for how it develop anti-tumor, anti-cancer, anti-fibrosis and other functions in vivo superiorly. Studies were as follows:1. A method was established to detect quercetin and isorhamnetin in plasma and tissues. A method was established to separate and detect the quercetin’ water-solubility and lipid-solubility metabolites in plasma and tissues. A series standard curve of quercetin’ and isorhamnetin’ water-solubility and lipid-solubility were set up, including plasma, uterine, ovarian, mammary gland, hypothalamus, matrix, fat, muscle, brain and liver, required for experiments. This method had higher sensitivity, higher precision and lower detection limit.2. Quercetin’ water-solubility and lipid-solubility metabolites distribution in plasma were investigated during the long term gavage. Quercetin metabolites were not detected in blank control group, indicating that the feed was fit for this experimental study. During the period of animal experiment study, quercetin and isorhamnetin in plasma without hydrolysis were failed to detected, indicating that quercetin and isorhamnetin content was very low and even none. Quercetin’ lipid-solubility and water-solubility metabolites in plasma except1day0h were detected, speculated that as the gavage time growed, the quercetin and isorhamnetin form metabolites accumulated in vivo.0h plasma isorhamnetin form fatty acid ester concentration was higher than quercetin form under the same conditions. Quercetin’ water-solubility and lipid-solubility metabolites were detected, showed a certain dose and time dependent. Plasma metabolites content increased as the gavage dosage increased, while the metabolites concentration also increased with metabolite time in vivo. Under the same conditions of dosage and gavage time, quercetin form’fatty acid ester was higher than the isorhamnetin form slightly, isorhamnetin form’ water-solubility metabolites was higher than quercetin form generally, total quercetin’ metabolism quercetin form metabolism was significantly higher than isorhamnetin form.3.The distribution of quercetin’ water-solubility and lipid-solubility metabolites in mice tissues was investigated. Corresponding metabolites was not detected in tissues in blank control group throughout, indicating that the test feed was fit for this experimental study. Quercetin and isorhamnetin were not detected in not enzyme solution. Tissues of three groups could be detected quercetin and isorhamnetin form’ water-solubility and lipid-solubility metabolites, showed a dose dependent. Distribution in these tissues such as hypothalamus, mammary gland, uterus, ovary and adrenal gland were higher than other organs obviously, comtent were not so high in muscle and fat, whlie were very low in liver and brain. Toal quercetin form metabolites were higher than isorhamnetin form. Compare to both quercetin form metabolites among tissues, lipid-solubility was higher than water-solubility slightly, on the contrary isorhamnetin form metabolites water-solubility was higher than lipid-solubility slightly, total lipid-solubility metabolites was higher than total water-solubility in both metabolites slightly.As gavage dosage increased, the content of water-solubility metabolites was significantly increased in the mammary gland, indicating that water-solubility metabolites was accumulated in mammary gland. Previous studies found that quercetin played the role in inmammary gland cancer treatment, inferd that quercetin water-solubility metabolites may assume the role of active factors in the treatment of mammary gland cancer. Quercetin’ lipid-solubility metabolites content in the secretory organ such as adrenal gland, hypothalamus, mammary gland, uterine and ovarian was higher than other organs significantly. Considerd that it may be related to anti-cancer effect in the treatment of breast cancer and uterine fibroids, which can be inferred that quercetin may act on body’s endocrine and reproductive organs to achieve its physiological function. The liver is the largest organ of metabolic transformation organ in the human body, we found both quercetin’ metabolites content were very low in liver, indicating that quercetin converted in liver but not accumulated.