(-)-Englerin-A Has Analgesic and Anti-Inflammatory Effects Independent of TRPC4 and 5

Autor: Joao de Sousa Valente, Susan D. Brain, Khadija M. Alawi, Sabah Bharde, Ali A Zarban, Xenia Kodji, Brentton Barrett, István Nagy, Fulye Argunhan, Dibesh Thapa
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Chemistry
Multidisciplinary
Anti-Inflammatory Agents
Pharmacology
Carrageenan
TRPC4
TRPC5
chemistry.chemical_compound
Sesquiterpenes
Guaiane
0302 clinical medicine
CHANNEL
Dorsal root ganglion
Ganglia
Spinal
Edema
Biology (General)
NEURONS
Spectroscopy
Cells
Cultured
Mice
Knockout
Analgesics
Behavior
Animal
General Medicine
Cobalt
Computer Science Applications
Chemistry
medicine.anatomical_structure
Phenotype
Hyperalgesia
Physical Sciences
ROOT GANGLION-CELLS
medicine.symptom
Life Sciences & Biomedicine
Agonist
Biochemistry & Molecular Biology
ENZYME
Sensory Receptor Cells
medicine.drug_class
QH301-705.5
0699 Other Biological Sciences
Analgesic
Pain
Inflammation
Article
Catalysis
Anti-inflammatory
Inorganic Chemistry
03 medical and health sciences
In vivo
ENGLERIN
0399 Other Chemical Sciences
medicine
Animals
Physical and Theoretical Chemistry
Molecular Biology
QD1-999
TRPC Cation Channels
0604 Genetics
Science & Technology
Chemical Physics
IDENTIFICATION
POTENT
Organic Chemistry
Antagonist
Disease Models
Animal
030104 developmental biology
chemistry
(-)-Englerin A
RAT
synovitis
030217 neurology & neurosurgery
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 6380, p 6380 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 12
ISSN: 1422-0067
Popis: Recently, we found that the deletion of TRPC5 leads to increased inflammation and pain-related behaviour in two animal models of arthritis. (-)-Englerin A (EA), an extract from the East African plant Phyllanthus engleri has been identified as a TRPC4/5 agonist. Here, we studied whether or not EA has any anti-inflammatory and analgesic properties via TRPC4/5 in the carrageenan model of inflammation. We found that EA treatment in CD1 mice inhibited thermal hyperalgesia and mechanical allodynia in a dose-dependent manner. Furthermore, EA significantly reduced the volume of carrageenan-induced paw oedema and the mass of the treated paws. Additionally, in dorsal root ganglion (DRG) neurons cultured from WT 129S1/SvIm mice, EA induced a dose-dependent cobalt uptake that was surprisingly preserved in cultured DRG neurons from 129S1/SvIm TRPC5 KO mice. Likewise, EA-induced anti-inflammatory and analgesic effects were preserved in the carrageenan model in animals lacking TRPC5 expression or in mice treated with TRPC4/5 antagonist ML204.This study demonstrates that while EA activates a sub-population of DRG neurons, it induces a novel TRPC4/5-independent analgesic and anti-inflammatory effect in vivo. Future studies are needed to elucidate the molecular and cellular mechanisms underlying EA’s anti-inflammatory and analgesic effects.
Databáze: OpenAIRE
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