ReferenceID 1296

Berbamine Reduces Chloroquine-Induced Itch in Mice through Inhibition of MrgprX1

Int J Mol Sci

Chloroquine (CQ) is an antimalaria drug that has been widely used for decades. However, CQ-induced pruritus remains one of the major obstacles in CQ treatment for uncomplicated malaria. Recent studies have revealed that

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Reference Id
1296
Evidence Id
17886
Core Evidence Id
17886
Source Reference Id
2583
Herb2 Reference Id
HBREF003380
Subject Paper Key
HBIN017888_36430803
Pubmed Id
36430803
Doi
10.3390/ijms232214321
Paper Title
Berbamine Reduces Chloroquine-Induced Itch in Mice through Inhibition of MrgprX1
Paper Abstract
Chloroquine (CQ) is an antimalaria drug that has been widely used for decades. However, CQ-induced pruritus remains one of the major obstacles in CQ treatment for uncomplicated malaria. Recent studies have revealed that MrgprX1 plays an essential role in CQ-induced itch. To date, a few MrgprX1 antagonists have been discovered, but they are clinically unavailable or lack selectivity. Here, a cell-based high-throughput screening was performed to identify novel antagonists of MrgprX1, and the screening of 2543 compounds revealed two novel MrgprX1 inhibitors, berbamine and closantel. Notably, berbamine potently inhibited CQ-mediated MrgprX1 activation (IC 50 = 1.6 μM) but did not alter the activity of other pruritogenic GPCRs. In addition, berbamine suppressed the CQ-mediated phosphorylation of ERK1/2. Interestingly, CQ-induced pruritus was significantly reduced by berbamine in a dose-dependent manner, but berbamine had no effect on histamine-induced, protease-activated receptors 2-activating peptide-induced, and deoxycholic acid-induced itch in mice. These results suggest that berbamine is a novel, potent, and selective antagonist of MrgprX1 and may be a potential drug candidate for the development of therapeutic agents to treat CQ-induced pruritus.
Journal
Int J Mol Sci
Publish Year
2022
Experiment Subject
mouse
Experiment Type
Cell Experiment
Phenotype Related
Malaria; Cq-induced Pruritus
Paper Title Cn
Paper Title En
Berbamine Reduces Chloroquine-Induced Itch in Mice through Inhibition of MrgprX1
Bilingual Status
semi_complete