Effects of diosmetin on nine cytochrome P450 isoforms, UGTs and three drug transporters in vitro

Chen, Junjun; Zhang, Jingxian; Zhang, Xiangqi; Qi, Mei-Juan; Shi, Mei-Zhi; Jiao, Yang; Zhang, Kezhi; Guo, Cheng; Han, Yonglong

doi:10.1016/j.taap.2017.08.020

Cited by 21 publications

(12 citation statements)

References 21 publications

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“…The hepatoprotective phytoconstituents of CH might include flavonoids, such as silibinin diastereomers and phenylethanoid glycosides, because the hepatoprotective ingredients of C. japonicum are flavonoids and the hepatoprotective ingredients of C. setosum are phenylethanoid glycosides [ 11 , 12 ]. The efficacy of CJF, which showed the best hepatoprotective effects among the four Cirsium species, might be due to silibinin diastereomers and diosmetin because diosmetin could inhibit CYP 2E1 [ 38 ] and it possesses antioxidant and anti-inflammatory activities against endotoxin-induced acute liver injury [ 39 ]. Therefore, the hepatoprotective phytoconstituents of CH against CCl 4 -induced acute liver damage must be clarified.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Hepatoprotective Effects of Four Endemic Cirsium Species Extracts from Taiwan on CCl4-Induced Acute Liver Damage in C57BL/6 Mice

Zhao

Chang

Lin

et al. 2018

IJMS

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Species of Cirsium (Asteraceae family) have been used in folk hepatoprotective medicine in Taiwan. We collected four Cirsium species—including the aerial part of Cirsium arisanense (CAH), the aerial part of Cirsium kawakamii (CKH), the flower part of Cirsium japonicum DC. var. australe (CJF), and Cirsii Herba (CH)—and then made extractions from them with 70% methanol. We compared the antioxidant contents and activities of these four Cirsium species extracts by a spectrophotometric method and high-performance liquid chromatography–photodiode array detector (HPLC-DAD). We further evaluated the hepatoprotective effects of these extracts on CCl4-induced acute liver damage in C57BL/6 mice. The present study found CAH possesses the highest antioxidant activity among the four Cirsium species, and these antioxidant activities are closely related to phenylpropanoid glycoside (PPG) contents. The extracts decreased serum ALT and AST levels elevated by injection with 0.2% CCl4. However, only CJF and CH decreased hepatic necrosis. Silibinin decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and hepatic necrosis caused by CCl4. CJF and CH restored the activities of hepatic antioxidant enzymes and decreased hepatic malondialdehyde (MDA) levels. CJF further restored the expression of hepatic antioxidant enzymes including Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), and glutathione S-transferase (GST) proteins. HPLC chromatogram indicated that CKH, CJF, and CH contained silibinin diastereomers (α and β). Only CJF contained diosmetin. Hence, the hepatoprotective mechanism of CJF against CCl4-induced acute liver damage might be involved in restoring the activities and protein expression of the hepatic antioxidant defense system and inhibiting hepatic inflammation, and these hepatoprotective effects are related to the contents of silibinin diastereomers and diosmetin.

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Section: Discussionmentioning

confidence: 99%

Comparison of the Hepatoprotective Effects of Four Endemic Cirsium Species Extracts from Taiwan on CCl4-Induced Acute Liver Damage in C57BL/6 Mice

Zhao

Chang

Lin

et al. 2018

IJMS

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“…CYP450 superfamilies include CYP1, CYP2 and CYP3. CYP3A4 is the most abundant enzyme in CYP subtype and accounts for approximately 34% of drug metabolism, which is followed by 2D6, 2C8, 2C9, 2C19 and 1A2 [17]. Inhibition or induction of any isoforms of CYP450 has been recognized as the pivotal cause of DDIs and HDIs.…”

Section: Discussionmentioning

confidence: 99%

Effects of Shaoyao-Gancao-Fuzi Decoction on the Pharmacokinetics of CYP3A4-Mediated Tofacitinib in Rats

Li¹,

Wang²,

Shao³

et al. 2020

Preprint

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Background: The combination of traditional Chinese medicine and western medicine is commonly accepted in clinics in China. Shaoyao-Gancao-Fuzi decoction (SGFD) has been extensively used to dispel wind, eliminate dampness and treat paralysis. Tofacitinib is approved for the treatment of rheumatoid arthritis. SGFD and tofacitinib could be used together for the treatment of rheumatoid arthritis.Methods: A cocktail approach was employed to assess the effects of SGFD on the activities of CYP450s. After pretreatment for 2 weeks with SGFD, a cocktail solution was given to rats 24 h after the last dose of saline or SGFD. Additionally, the pharmacokinetic profiles of oral administration of tofacitinib in rats, with or without SGFD pre-treatment were investigated.Results: The results showed that SGFD could induce the activity of CYP1A2 and inhibit the activity of CYP3A4. Furthermore, SGFD could significantly affect the pharmacokinetics of tofacitinib. Compared with control group, the AUC0-∞ of tofacitinib was increased from 13669.53 ± 4986.83 to 28706.69 ± 9563.13 ng/mL*h (p < 0.01), and the Cmax was increased from 8359.66 ± 1512.22 to 11332.51 ± 2791.90 ng/mL (p < 0.05).Conclusions: The system exposure of tofacitinib was increased by SGFD. The mechanism might be through inhibiting the activity of CYP3A4 and reducing the metabolism of tofacitinib in rats. The study will provide better guidance for the safe clinical use of SGFD and tofacitinib.

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“…The CYP450 enzymes are involved in the metabolism of endogenous substances (such as fatty acids, vitamins, cholic acid), detoxification of exogenous substances (such as drugs) and activation of precarcinogens (such as aromatic substances). There are more than 50 CYP450 enzymes, most of which are CYP3A4, CYP2C9, CYP2C19, CYP2D6, CYP1A2 CYP2A6 and CYP2E1 enzymes (Chen et al 2017). These enzymes are mainly expressed in the liver, though they are also expressed in the pancreas, brain, lung, adrenal gland, small intestine and bone marrow (Wilkinson 2005).…”

Section: Analytementioning

confidence: 99%

Effects of naringenin on the pharmacokinetics of tofacitinib in rats

Wang

Shen

Zhou

et al. 2020

Pharmaceutical Biology

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Context: Naringenin and tofacitinib are often used together for treatment of rheumatoid arthritis in Chinese clinics. Objective: This experiment investigates the effect of naringenin on the pharmacokinetics of tofacitinib in rats. Materials and methods: Twelve Sprague-Dawley rats were randomly divided into two groups (experimental group and control group). The experimental group was pre-treated with naringenin (150 mg/kg/ day) for two weeks before dosing tofacitinib, and equal amounts of CMC-Na solution in the control group. After a single oral administration of 5 mg/kg of tofacitinib, 50 lL blood samples were directly collected into 1.5 mL heparinized tubes via the caudal vein at 0.083, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h. The plasma concentration of tofacitinib was quantified by UPLC/MS-MS. Results: Results indicated that naringenin could significantly affect the pharmacokinetics of tofacitinib. The AUC 0-24 of tofacitinib was increased from 1222.81 ± 222.07 to 2016.27 ± 481.62 ng/mL/h, and the difference was significant (p < 0.05). Compared with the control group, the T max was increased from 0.75 ± 0.29 to 3.00 ± 0.00 h (p < 0.05), and the MRT (0-24) was increased from 4.90 ± 0.51 to 6.57 ± 0.66 h (p < 0.05), but the clearance was obviously decreased from 4.10 ± 0.72 to 2.42 ± 0.70 L/h/kg (p < 0.05) in experimental group. Although the C max and t 1/2 of tofacitinib were increased, there were no significant differences (p > 0.05). Conclusions: This research demonstrated a drug-drug interaction between naringenin and tofacitinib possibly when preadministered with naringenin; thus, we should pay attention to this possibility in the clinic.

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Effects of diosmetin on nine cytochrome P450 isoforms, UGTs and three drug transporters in vitro

Cited by 21 publications

References 21 publications

Comparison of the Hepatoprotective Effects of Four Endemic Cirsium Species Extracts from Taiwan on CCl4-Induced Acute Liver Damage in C57BL/6 Mice

Comparison of the Hepatoprotective Effects of Four Endemic Cirsium Species Extracts from Taiwan on CCl4-Induced Acute Liver Damage in C57BL/6 Mice

Effects of Shaoyao-Gancao-Fuzi Decoction on the Pharmacokinetics of CYP3A4-Mediated Tofacitinib in Rats

Effects of naringenin on the pharmacokinetics of tofacitinib in rats

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