High fat diet aggravates the nephrotoxicity of berberrubine by influencing on its pharmacokinetic profile

Yang, Na; Sun, Runbin; Zhao, Yuqing; He, Jun; Zhen, Le; Guo, Jiahua; Geng, Jia; Xie, Yuan; Wang, Jiankun; Feng, Suhua; Fei, Fei; Liao, Xiaoying; Zhu, Xiaoyan; Wang, Hongbo; Fu, Fenghua; Aa, Jiye; Wang, Guangji

doi:10.1016/j.etap.2016.08.003

Cited by 17 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Especially in elderly population, the proportion is as high as 66% (Naughton, 2008). Excessive accumulation in kidney for drugs always contributes to renal adverse reactions (Yang et al, 2016). Reduction in renal exposure is therefore an important strategy to prevent side effects in kidney.…”

Section: Discussionmentioning

confidence: 99%

Targeting renal OATs to develop renal protective agent from traditional Chinese medicines: Protective effect of Apigenin against Imipenem‐induced nephrotoxicity

Huo

Meng

Wang

et al. 2020

Phytotherapy Research

View full text Add to dashboard Cite

Imipenem (Imp) is a widely used broad-spectrum antibiotic. However, renal adverse effects limit its clinical application. We previously reported that organic anion transporters (OATs) facilitated the renal transport of Imp and contributed its nephrotoxicity. Natural flavonoids exhibited renal protective effect. Here, we aimed to develop potent OAT inhibitors from traditional Chinese medicines (TCMs) and to evaluate its protective effect against Imp-induced nephrotoxicity. Among 50 TCMs, Tribuli Fructus, Platycladi Cacumen, and Lycopi Herba exhibited potent inhibition on OAT1/3. After screening their main components, Apigenin strongly inhibited Imp uptake by OAT1/3-HEK293 cells with IC50 values of 1.98 ± 0.36 μM (OAT1) and 2.29 ± 0.88 μM (OAT3). Moreover, Imp exhibited OAT1/3-dependent cytotoxicity, which was alleviated by Apigenin. Furthermore, Apigenin ameliorated Imp-induced nephrotoxicity in rabbits, and reduced the renal secretion of Imp. Apigenin inhibited intracellular accumulation of Imp and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells (rPTCs). Apigenin, a flavone widely distributed in TCMs, was a potent OAT1/3 inhibitor. Through OAT inhibition, at least in part, Apigenin decreased the renal exposure of Imp and consequently protected against the nephrotoxicity of Imp. Apigenin can be used as a promising agent to reduce the renal adverse reaction of Imp in clinic.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeting renal OATs to develop renal protective agent from traditional Chinese medicines: Protective effect of Apigenin against Imipenem‐induced nephrotoxicity

Huo

Meng

Wang

et al. 2020

Phytotherapy Research

View full text Add to dashboard Cite

show abstract

“…Similarly, urine samples were collected in the metabolic cages for 12 hours after the last administration. All samples were prepared in the manner previously reported elsewhere (Yang et al, 2016).…”

Section: Methodsmentioning

confidence: 99%

Inhibitory Effects of Endogenous Linoleic Acid and Glutaric Acid on the Renal Glucuronidation of Berberrubine in Mice and on Recombinant Human UGT1A7, 1A8, and 1A9

Yang¹,

Li²,

Yan³

et al. 2018

Mol Pharmacol

Self Cite

View full text Add to dashboard Cite

Berberrubine (BRB) has a strong lipid-lowering effect and can be extensively metabolized into berberrubine-9---d-glucuronide (BRBG) in vivo. Recently, pharmacokinetics studies showed that the production of BRBG was significantly decreased in the urine of mice fed with a high-fat diet (HFD), indicating a decreased glucuronidation capacity. Based on the UDP-glucuronosyltransferase (UGT) isoform identification, hepatic and renal microsomal incubation, glucuronidation was examined to suggest the metabolism of BRB in liver and kidneys. The results showed that the renal UGT activity for metabolizing BRB markedly decreased, which may be highly related to the decreased expression and activity of renal Ugt1a7c. Surprisingly, in vitro studies revealed neither BRB nor BRBG inhibited the renal UGT activity. By employing an integrated strategy of metabolomics and pharmacokinetics, we identified and confirmed for the first time the inhibitory effect of some potential endogenous molecules on the renal glucuronidation of C57BL/6J mice, such as glutaric acid (GA) and linoleic acid (LA). By employing recombinant human UGTs, we found that GA and LA efficiently affect the activity of recombinant human UGT1A7, 1A9, and 1A8 at their normal or abnormal physiologic levels in vivo. GA (2 mM) markedly inhibited the activity of UGT1A7 by 89.4% and UGT1A9 by 32.8%. The inhibition rates reached 99.3% for UGT1A9, 48.3% for UGT1A7, and 46.8% for UGT1A8 with LA at 200 M. It has been suggested that the endogenous molecules have the potential to affect the efficiency of glucuronidation, which might be a key factor contributing to individual differences in drug metabolism.

show abstract

“…Studies have shown that berberrubine, a metabolite of berberine, is produced in RCRW [9]. Berberrubine possesses hypoglycemic [10], anti-tumor, and anti-inflammatory properties [11]. Studies have shown that RCRW improved insulin resistance in 3T3-L1 adipocytes, and enhanced the ability of adipocytes to take up glucose and use it to improve insulin resistance at the cellular level in vitro [12].…”

Section: Introductionmentioning

confidence: 99%

Fingerprint and multi-component quantitative analyses for quality evaluation of Rhizoma coptidis steamed with rice wine

Wang¹,

Zeng²,

Lou³

et al. 2021

Trop. J. Pharm Res

View full text Add to dashboard Cite

Purpose: To establish a method for the simultaneous determination of multi-components of Rhizoma coptidis steamed with rice wine (RCRW), and to provide a reference for assessing its standard of quality. Method: Chromatographic separation was performed on a high performance liquid chromatography (HPLC) system to determine the characteristic fingerprint of RCRW. The mobile phase consisted of acetonitrile (A) and 0.1 % trifluoroacetic acid (B), with gradients of B as follows: 15 - 20 % from 0 – 30 min; 20 - 25 % from 30 - 50 min; 25 - 35 % for 50 - 60 min, and 35 % for 60 - 70 min. Results: In the multiple reaction monitoring mode, eight components of RCRW were isolated by HPLCphoto-diode array (PDA) method. A fingerprint of the RCRW was established and 8 peaks were calibrated. The method was further validated in terms of linearity (R2 > 0.9993), precision (relative standard deviation, RSD < 1.51 %); repeatability (RSD < 2.98 %) and stability (RSD < 1.93 %). Mean recovery rate ranged from 96.2 to 103.8 %, while RSD values ranged from 0.92 to 2.88 %. Conclusion: These results show that HPLC-PDA method is accurate and feasible, and that they provide a reference for further comprehensive and effective quality control of RCRW.

show abstract

High fat diet aggravates the nephrotoxicity of berberrubine by influencing on its pharmacokinetic profile

Cited by 17 publications

References 31 publications

Targeting renal OATs to develop renal protective agent from traditional Chinese medicines: Protective effect of Apigenin against Imipenem‐induced nephrotoxicity

Targeting renal OATs to develop renal protective agent from traditional Chinese medicines: Protective effect of Apigenin against Imipenem‐induced nephrotoxicity

Inhibitory Effects of Endogenous Linoleic Acid and Glutaric Acid on the Renal Glucuronidation of Berberrubine in Mice and on Recombinant Human UGT1A7, 1A8, and 1A9

Fingerprint and multi-component quantitative analyses for quality evaluation of Rhizoma coptidis steamed with rice wine

Contact Info

Product

Resources

About