{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:04:57Z","timestamp":1760234697681,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["ARUK21524"],"award-info":[{"award-number":["ARUK21524"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s anti-inflammatory and analgesic effects.<\/jats:p>","DOI":"10.3390\/ijms22126380","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T11:00:33Z","timestamp":1623754833000},"page":"6380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["(-)-Englerin-A Has Analgesic and Anti-Inflammatory Effects Independent of TRPC4 and 5"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1888-6324","authenticated-orcid":false,"given":"Jo\u00e3o","family":"de Sousa Valente","sequence":"first","affiliation":[{"name":"Section of Vascular Biology and Inflammation, BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King\u2019s College London, Franklin-Wilkins Building, London SE1 9NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khadija M","family":"Alawi","sequence":"additional","affiliation":[{"name":"Section of Vascular Biology and Inflammation, BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King\u2019s College London, Franklin-Wilkins Building, London SE1 9NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabah","family":"Bharde","sequence":"additional","affiliation":[{"name":"Section of Vascular Biology and Inflammation, BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King\u2019s College London, Franklin-Wilkins Building, London SE1 9NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali A.","family":"Zarban","sequence":"additional","affiliation":[{"name":"Section of Vascular Biology and Inflammation, BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King\u2019s College London, Franklin-Wilkins Building, London SE1 9NH, UK"},{"name":"Department of Pharmacological Sciences, Faculty of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xenia","family":"Kodji","sequence":"additional","affiliation":[{"name":"Section of Vascular Biology and Inflammation, BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King\u2019s College London, Franklin-Wilkins Building, London SE1 9NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7435-5483","authenticated-orcid":false,"given":"Dibesh","family":"Thapa","sequence":"additional","affiliation":[{"name":"Section of Vascular Biology and Inflammation, BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King\u2019s College London, Franklin-Wilkins Building, London SE1 9NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7616-2151","authenticated-orcid":false,"given":"Fulye","family":"Argunhan","sequence":"additional","affiliation":[{"name":"Section of Vascular Biology and Inflammation, BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King\u2019s College London, Franklin-Wilkins Building, London SE1 9NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brentton","family":"Barrett","sequence":"additional","affiliation":[{"name":"Section of Vascular Biology and Inflammation, BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King\u2019s College London, Franklin-Wilkins Building, London SE1 9NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3475-6108","authenticated-orcid":false,"given":"Istvan","family":"Nagy","sequence":"additional","affiliation":[{"name":"Nociception Group, Section of Anaesthetic, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9684-8342","authenticated-orcid":false,"given":"Susan D.","family":"Brain","sequence":"additional","affiliation":[{"name":"Section of Vascular Biology and Inflammation, BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King\u2019s College London, Franklin-Wilkins Building, London SE1 9NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7589","DOI":"10.1021\/acs.jmedchem.8b01954","article-title":"Review of Transient Receptor Potential Canonical (TRPC5) Channel Modulators and Diseases","volume":"62","author":"Sharma","year":"2019","journal-title":"J. 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