| Title |
Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency
|
|---|---|
| Published in |
Drug Design, Development and Therapy, October 2015
|
| DOI | 10.2147/dddt.s91561 |
| Pubmed ID | |
| Authors |
Meng Yan, Kaiping Zhang, Yanhui Shi, Lifang Feng, Lin Lv, Baoxin Li |
| Abstract |
Berberine (BBR), an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG) potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293) cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652) and phenylalanine (Phe656) in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. |
Mendeley readers
The data shown below were compiled from readership statistics for 7 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Mexico | 1 | 14% |
| Unknown | 6 | 86% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 2 | 29% |
| Professor | 1 | 14% |
| Student > Doctoral Student | 1 | 14% |
| Student > Master | 1 | 14% |
| Unknown | 2 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 4 | 57% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 14% |
| Unknown | 2 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 October 2015.
All research outputs
#22,756,649
of 25,371,288 outputs
Outputs from Drug Design, Development and Therapy
#1,754
of 2,268 outputs
Outputs of similar age
#245,761
of 286,873 outputs
Outputs of similar age from Drug Design, Development and Therapy
#86
of 110 outputs
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