Asperulosidic Acid Ameliorates Renal Interstitial Fibrosis via Removing Indoxyl Sulfate by Up-Regulating Organic Anion Transporters in a Unilateral Ureteral Obstruction Mice Model
机构：[1]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China[2]NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China[3]Changsha Research and Development Center on Obstetric and Gynecologic Traditional Chinese Medicine Preparation, Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410008, China [4]School of Pharmaceutical Science, University of South China, Hengyang 421001, China
Asperulosidic acid is a bioactive iridoid isolated from Hedyotis diffusa Willd. with anti-inflammatory and renal protective effects. However, its mechanism on renal interstitial fibrosis has not been elucidated yet. The present study aims to explore whether asperulosidic acid could retard renal fibrosis by reducing the circulating indoxyl sulfate (IS), which is a uremic toxin and accelerates chronic kidney disease progression by inducing renal fibrosis. In this paper, a unilateral ureteral obstruction (UUO) model of Balb/C mice was established. After the mice were orally administered with asperulosidic acid (14 and 28 mg/kg) for two weeks, blood, liver and kidney were collected for biochemical, histological, qPCR and Western blot analyses. Asperulosidic acid administration markedly reduced the serum IS level and significantly alleviated the histological changes in glomerular sclerosis and renal interstitial fibrosis. It is noteworthy that the mRNA and protein levels of the organic anion transporter 1 (OAT1), OAT3 and hepatocyte nuclear factor 1α (HNF1α) in the kidney were significantly increased, while the mRNA expressions of cytochrome P450 2e1 (Cyp2e1) and sulfotransferase 1a1 (Sult1a1) in the liver were not altered after asperulosidic acid administration. These results reveal that asperulosidic acid could accelerate the renal excretion of IS by up-regulating OATs via HNF1α in UUO mice, thereby alleviating renal fibrosis, but did not significantly affect its production in the liver, which might provide important information for the development of asperulosidic acid.
基金：
This research was funded by the Guangdong Basic and Applied Basic Research Foundation,
grant numbers 2021A1515011604 and 2023A1515011814.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|2 区化学
小类|3 区化学：综合3 区生化与分子生物学
最新[2025]版：
大类|3 区化学
小类|3 区生化与分子生物学3 区化学：综合
第一作者：
第一作者机构：[1]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China
通讯作者：
通讯机构：[3]Changsha Research and Development Center on Obstetric and Gynecologic Traditional Chinese Medicine Preparation, Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410008, China [4]School of Pharmaceutical Science, University of South China, Hengyang 421001, China
推荐引用方式(GB/T 7714)：
Wang Jing,Shi Birui,Pan Yueqing,et al.Asperulosidic Acid Ameliorates Renal Interstitial Fibrosis via Removing Indoxyl Sulfate by Up-Regulating Organic Anion Transporters in a Unilateral Ureteral Obstruction Mice Model[J].Molecules (Basel, Switzerland).2023,28(23):doi:10.3390/molecules28237690.
APA：
Wang Jing,Shi Birui,Pan Yueqing,Yang Zhuan,Zou Wei&Liu Menghua.(2023).Asperulosidic Acid Ameliorates Renal Interstitial Fibrosis via Removing Indoxyl Sulfate by Up-Regulating Organic Anion Transporters in a Unilateral Ureteral Obstruction Mice Model.Molecules (Basel, Switzerland),28,(23)
MLA：
Wang Jing,et al."Asperulosidic Acid Ameliorates Renal Interstitial Fibrosis via Removing Indoxyl Sulfate by Up-Regulating Organic Anion Transporters in a Unilateral Ureteral Obstruction Mice Model".Molecules (Basel, Switzerland) 28..23(2023)
化学