Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE:Aristolochic acid nephropathy (AAN) is a kidney disease caused by the administration of plants containing aristolochic acids (AAs). Aristolochic acid I (AAI) is the main toxic component in AAs. Organic anion transporters (OATs) 1 and 3 mediate the renal uptake of AAI, which is related to AAN. In our previous study, we found that anthraquinones derived from the herbal medicine Rheum palmatum L. (RP) inhibited both OAT1 and OAT3, with rhein exhibiting the greatest potency among the components. AIM OF THE STUDY:This study aimed to investigate the effects of rhein and RP extract on the pharmacokinetics and tissue distribution of AAI and its demethylated metabolite (8-hydroxy-aristolochic acid I [AAIa]) in rats. MATERIALS AND METHODS:Rhein and RP extract were used as OAT inhibitors, and AAI was used as the toxic substrate. The pharmacokinetics and tissue distribution of AAI and AAIa in rats following the intravenous injection of AAI (10 mg/kg) in the presence and absence of rhein (100 mg/kg) or RP extract (5 g crude drug/kg) were investigated. RESULTS:Co-administration with rhein increased AUC0-∞ of AAI and AAIa by 39 and 44%, respectively. However, the renal level of AAI was decreased to 50, 42, and 58% of those in rats treated with AAI alone at 5, 10, and 20 min after treatment, respectively, and the renal level of AAIa was decreased to 58, 57, and 61% of the level in rats treated with AAI alone, respectively, at these time points. In the RP extract co-administration group, AAI and AAIa plasma exposure was not significantly increased, but renal accumulation of AAI was decreased to 63, 58, and 68% of that in rats treated with AAI alone at 5, 10, and 20 min after treatment, respectively. In addition, renal accumulation of AAIa was decreased to 74, 70, and 70% of that in rats treated with AAI alone at 5, 10, and 20 min after treatment, respectively. CONCLUSIONS:This study indicated that co-administration with rhein significantly increased the plasma exposure of AAI and AAIa while decreased their renal accumulation in rats. RP extract reduced the renal accumulation of AAI and AAIa, but have no significant effect on their plasma exposure levels in rats.
journal_name
J Ethnopharmacoljournal_title
Journal of ethnopharmacologyauthors
Ma L,Shen Z,Hu H,Zhou H,Yu L,Jiang H,Zeng Sdoi
10.1016/j.jep.2020.113537subject
Has Abstractpub_date
2021-03-01 00:00:00pages
113537eissn
0378-8741issn
1872-7573pii
S0378-8741(20)33425-5journal_volume
267pub_type
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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abstract::An ethnobotanical study was carried out in six villages in the Bunda district, Mara Region, Tanzania, where the use of plants still has a special meaning to the society, in the treatment of various diseases. Information was obtained from the traditional healers and other experienced persons, having some knowledge on m...
journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章
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更新日期:2020-05-23 00:00:00
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章
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更新日期:2005-01-04 00:00:00
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journal_title:Journal of ethnopharmacology
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更新日期:2012-06-01 00:00:00
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journal_title:Journal of ethnopharmacology
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更新日期:2016-09-15 00:00:00
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章
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更新日期:2011-06-22 00:00:00
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章,评审
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更新日期:2005-08-22 00:00:00
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章
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更新日期:2014-05-14 00:00:00
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章,评审
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更新日期:2020-04-06 00:00:00