1. Selective Activation of Nociceptor TRPV1 Channel and Reversal of Inflammatory Pain in Mice by a Novel Coumarin Derivative Muralatin L from Murraya alata.
- Author
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Wei NN, Lv HN, Wu Y, Yang SL, Sun XY, Lai R, Jiang Y, and Wang K
- Subjects
- Amino Acid Sequence, Animals, Binding Sites, Calcium metabolism, Capsaicin pharmacology, Capsaicin therapeutic use, Coumarins chemistry, Coumarins pharmacology, Ganglia, Spinal pathology, HEK293 Cells, Humans, Inflammation complications, Ion Channel Gating drug effects, Magnetic Resonance Spectroscopy, Mice, Inbred C57BL, Mice, Knockout, Models, Molecular, Molecular Sequence Data, Neurons drug effects, Neurons metabolism, Pain complications, Rats, TRPV Cation Channels agonists, TRPV Cation Channels chemistry, Coumarins therapeutic use, Inflammation drug therapy, Murraya chemistry, Nociceptors metabolism, Pain drug therapy, TRPV Cation Channels metabolism
- Abstract
Coumarin and its derivatives are fragrant natural compounds isolated from the genus Murraya that are flowering plants widely distributed in East Asia, Australia, and the Pacific Islands. Murraya plants have been widely used as medicinal herbs for relief of pain, such as headache, rheumatic pain, toothache, and snake bites. However, little is known about their analgesic components and the molecular mechanism underlying pain relief. Here, we report the bioassay-guided fractionation and identification of a novel coumarin derivative, named muralatin L, that can specifically activate the nociceptor transient receptor potential vanilloid 1 (TRPV1) channel and reverse the inflammatory pain in mice through channel desensitization. Muralatin L was identified from the active extract of Murraya alata against TRPV1 transiently expressed in HEK-293T cells in fluorescent calcium FlexStation assay. Activation of TRPV1 current by muralatin L and its selectivity were further confirmed by whole-cell patch clamp recordings of TRPV1-expressing HEK-293T cells and dorsal root ganglion neurons isolated from mice. Furthermore, muralatin L could reverse inflammatory pain induced by formalin and acetic acid in mice but not in TRPV1 knock-out mice. Taken together, our findings show that muralatin L specifically activates TRPV1 and reverses inflammatory pain, thus highlighting the potential of coumarin derivatives from Murraya plants for pharmaceutical and medicinal applications such as pain therapy., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2016
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