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

Section of Vascular Biology and Inflammation, BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King’s College London, Franklin-Wilkins Building, London SE1 9NH, UK
Department of Pharmacological Sciences, Faculty of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
Nociception Group, Section of Anaesthetic, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
Author to whom correspondence should be addressed.
Academic Editor: Zsuzsanna Helyes
Int. J. Mol. Sci. 2021, 22(12), 6380;
Received: 16 May 2021 / Revised: 10 June 2021 / Accepted: 11 June 2021 / Published: 15 June 2021
(This article belongs to the Special Issue Molecular Links between Sensory Nerves, Inflammation, and Pain)
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. View Full-Text
Keywords: (-)-Englerin A; TRPC5; TRPC4; carrageenan; inflammation; synovitis (-)-Englerin A; TRPC5; TRPC4; carrageenan; inflammation; synovitis
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MDPI and ACS Style

de Sousa Valente, J.; Alawi, K.M.; Bharde, S.; Zarban, A.A.; Kodji, X.; Thapa, D.; Argunhan, F.; Barrett, B.; Nagy, I.; Brain, S.D. (-)-Englerin-A Has Analgesic and Anti-Inflammatory Effects Independent of TRPC4 and 5. Int. J. Mol. Sci. 2021, 22, 6380.

AMA Style

de Sousa Valente J, Alawi KM, Bharde S, Zarban AA, Kodji X, Thapa D, Argunhan F, Barrett B, Nagy I, Brain SD. (-)-Englerin-A Has Analgesic and Anti-Inflammatory Effects Independent of TRPC4 and 5. International Journal of Molecular Sciences. 2021; 22(12):6380.

Chicago/Turabian Style

de Sousa Valente, João, Khadija M Alawi, Sabah Bharde, Ali A. Zarban, Xenia Kodji, Dibesh Thapa, Fulye Argunhan, Brentton Barrett, Istvan Nagy, and Susan D. Brain. 2021. "(-)-Englerin-A Has Analgesic and Anti-Inflammatory Effects Independent of TRPC4 and 5" International Journal of Molecular Sciences 22, no. 12: 6380.

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