Pharmacokinetics, tissue distribution and excretion of luteolin and its major metabolites in rats: Metabolites predominate in blood, tissues and are mainly excreted via bile

Deng, Chenglong; Gao, Chunying; Tian, Xiaoqing; Chao, Bo; Wang, Fang; Zhang, Ying; Zou, Jingtao; Liu, Dongchun

doi:10.1016/j.jff.2017.05.056

Cited by 53 publications

(44 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mean plasma concentration-time curve and pharmacokinetic parameters of naringin and total naringenin for aged rats were presented in Figure 1 and Table 1, respectively. Similar to reported pharmacokinetic studies concerning other flavonoid compounds (Li et al, 2012; Xiong et al, 2015), double-peak phenomenon was observed in the plasma profile of naringin and total naringenin after an oral administration of naringin, probably flowed from enterohepatic circulation or gastric emptying-regulated absorption (Deng et al, 2017). The concentration level of naringenin at the first peak was much lower than that at the second peak, revealed that just little naringin could be rapidly metabolized into naringenin and then absorbed into circulatory system.…”

Section: Resultssupporting

confidence: 84%

Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Naringin in Aged Rats

Zeng

Zheng

et al. 2019

Front. Pharmacol.

View full text Add to dashboard Cite

Aging is an inevitable biological process characterized by the loss of functional capacity and associated with changes in all phases of pharmacokinetic processes. Naringin, a dietary flavanone glycoside, has been proved to be beneficial for the treatment of multiple age-associated chronic diseases. To date, the pharmacokinetic processes of naringin in aged individuals are still unknown. Thus, a rapid resolution liquid chromatography tandem triple quadrupole mass spectrometry (RRLC-QQQ-MS/MS) method was established for the determination of naringin and its metabolite naringenin in rat plasma, urine, feces, and tissue homogenate. The pharmacokinetic parameters were calculated and a higher exposure of naringin and naringenin were observed in aged rats. Naringin and naringenin were mostly distributed in gastrointestinal tract, liver, kidney, lung, and trachea. Furthermore, a total of 39 flavonoid metabolites (mainly glucuronides and sulfates) and 46 microbial-derived phenolic catabolites were screened with ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). Naringenin, hippuric acid, and 3-(4’-hydroxyphenyl)propionic acid were predominated metabolites. This study systemically investigated the pharmacokinetics, tissue distribution, metabolism, and excretion of naringin in aged rats, revealing age- and gender-related changes in the in vivo behavior of naringin. These results would be helpful for the interpretation of pharmacokinetics and pharmacodynamics of naringin in aged population.

show abstract

Section: Resultssupporting

confidence: 84%

Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Naringin in Aged Rats

Zeng

Zheng

et al. 2019

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…1.5 nM/mL. In contrast, luteolin ( 9 ) itself reached only a 0.6 nM/mL peak plasma concentration in that study, and its concentration in the organs was also typically below that of 9c . Unlike luteolin, its glycosides reach the large intestine where the sugar moieties can efficiently be cleaved by gut bacteria.…”

Section: Metabolism Of Antioxidants In View Of Their Bioactivitymentioning

confidence: 66%

“…DHED was successfully applied in vivo as a brain-targeted neuroprotective pro-drug of estradiol [147][148][149] HUNYADI | 2515 0.6 nM/mL peak plasma concentration in that study, and its concentration in the organs was also typically below that of 9c. 124 Unlike luteolin, its glycosides reach the large intestine where the sugar moieties can efficiently be cleaved by gut bacteria. Subsequent bacterial metabolism of luteolin involves the reduction of the 2,3-double bond to form the flavanone eriodictyol (9n) whose cleavage to phloroglucinol (9o) and 3-(3,4-dihydroxyphenyl)propionic acid (9p) can also take place.…”

Section: Metabolism Of Luteolinmentioning

confidence: 99%

The mechanism(s) of action of antioxidants: From scavenging reactive oxygen/nitrogen species to redox signaling and the generation of bioactive secondary metabolites

Hunyadi

2019

Medicinal Research Reviews

164

View full text Add to dashboard Cite

Small molecule, dietary antioxidants exert a remarkably broad range of bioactivities, and many of these can be explained by the influence of antioxidants on the redox homeostasis. Such compounds help to modulate the levels of harmful reactive oxygen/nitrogen species, and therefore participate in the regulation of various redox signaling pathways. However, upon ingestion, antioxidants usually undergo extensive metabolism that can generate a wide range of bioactive metabolites. This makes it difficult, but otherwise a need, to identify the ones responsible for the different activities of antioxidants. By better understanding their ways of action, the use of antioxidants in therapy can be improved. This review provides a summary on the role of the in vivo metabolic changes and the oxidized metabolites on the mechanisms behind the bioactivity of antioxidants. A special attention is given to metabolites described as products of biomimetic oxidative chemical reactions, which can be considered as models of free radical scavenging. During such reactions a wide variety of metabolites are formed, and they can exert completely different specific bioactivities as compared to their parent antioxidants. This implies that exploring the free radical scavenging‐related metabolite fingerprint of each antioxidant molecule, collectively defined here as the scavengome, will lead to a deeper understanding of the bioactivity of these compounds. Furthermore, this paper aims to be a working tool for systematic studies on oxidized metabolic fingerprints of antioxidants, which will certainly reveal an often‐neglected segment of chemical space that is a treasury of bioactive compounds.

show abstract

“…Chrysoeriol is generated by the methoxylation of luteolin at the C3’ atom (luteolin-3′-methoxy ether) by catechol-O-methyltransferase (COMT) [ 66 ]. Chrysoeriol has been detected in rat plasma samples after oral administration of luteolin [ 63 ] and is broadly distributed to the lungs, kidney, spleen, muscle, and heart, but found to be undetectable in the brain, within 1 h after oral administration [ 67 ], suggesting that circulating chrysoeriol can reach various target tissues. The anti-breast cancer efficacy of chrysoeriol in vivo is closely related to its concentration in breast cancer tissues.…”

Section: Discussionmentioning

confidence: 99%

Chrysoeriol Prevents TNFα-Induced CYP19 Gene Expression via EGR-1 Downregulation in MCF7 Breast Cancer Cells

Min

Jung

Ahn

et al. 2020

IJMS

View full text Add to dashboard Cite

Estrogen overproduction is closely associated with the development of estrogen receptor-positive breast cancer. Aromatase, encoded by the cytochrome P450 19 (CYP19) gene, regulates estrogen biosynthesis. This study aimed to identify active flavones that inhibit CYP19 expression and to explore the underlying mechanisms. CYP19 expression was evaluated using reverse transcription PCR, quantitative real-time PCR, and immunoblot analysis. The role of transcription factor early growth response gene 1 (EGR-1) in CYP19 expression was assessed using the short-hairpin RNA (shRNA)-mediated knockdown of EGR-1 expression in estrogen receptor-positive MCF-7 breast cancer cells. We screened 39 flavonoids containing 26 flavones and 13 flavanones using the EGR1 promoter reporter activity assay and observed that chrysoeriol exerted the highest inhibitory activity on tumor necrosis factor alpha (TNFα)-induced EGR-1 expression. We further characterized and demonstrated that chrysoeriol inhibits TNFα-induced CYP19 expression through inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated EGR-1 expression. Chrysoeriol may be beneficial as a dietary supplement for the prevention of estrogen receptor-positive breast cancer, or as a chemotherapeutic adjuvant in the treatment of this condition.

show abstract

Pharmacokinetics, tissue distribution and excretion of luteolin and its major metabolites in rats: Metabolites predominate in blood, tissues and are mainly excreted via bile

Cited by 53 publications

References 33 publications

Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Naringin in Aged Rats

Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Naringin in Aged Rats

The mechanism(s) of action of antioxidants: From scavenging reactive oxygen/nitrogen species to redox signaling and the generation of bioactive secondary metabolites

Chrysoeriol Prevents TNFα-Induced CYP19 Gene Expression via EGR-1 Downregulation in MCF7 Breast Cancer Cells

Contact Info

Product

Resources

About