Experimental cannabinoid 2 receptor activation by phyto-derived and synthetic cannabinoid ligands in LPS-Induced interstitial cystitis in mice

Geraint Berger, Nipun Arora, Ian Burkovskiy, Yanfang Xia, Anu Chinnadurai, Robert Westhofen, Georg Hagn, Ashley Cox, Melanie Kelly, Juan Zhou, Christian Lehmann

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Interstitial cystitis (IC) is a chronic bladder disorder with unclear etiology. The endocannabinoid system has been identified as a key regulator of immune function, with experimental evidence for the involvement of cannabinoid receptors in bladder inflammation. This study used intravital microscopy (IVM) and behavioral testing in lipopolysaccharide-induced IC, to investigate the anti-inflammatory analgesic effects of a natural dietary sesquiterpenoid, beta-caryophyllene (BCP), which is present in cannabis among other plants, and has reported agonist actions at the cannabinoid 2 receptor (CB2R). BCP's anti-inflammatory actions were compared to the synthetic CB2R-selective cannabinoid, HU308, and to an FDA-approved clinical treatment (dimethyl sulfoxide: DMSO). IVM data revealed that intravesical instillation of BCP and/or HU308 significantly reduces the number of adhering leukocytes in submucosal bladder venules and improves bladder capillary perfusion. The effects of BCP were found to be comparable to that of the selective CB2R synthetic cannabinoid, HU308, and superior to intravesical DMSO treatment. Oral treatment with BCP was also able to reduce bladder inflammation and significantly reduced mechanical allodynia in experimental IC. Based on our findings, we believe that CB2R activation may represent a viable therapeutic target for IC, and that drugs that activate CB2R, such as the generally regarded as safe (GRAS) dietary sesquiterpenoid, BCP, may serve as an adjunct and/or alternative treatment option for alleviating symptoms of inflammation and pain in the management of IC.

Original languageEnglish
Article number4239
JournalMolecules
Volume24
Issue number23
DOIs
Publication statusPublished - Nov 21 2019

Bibliographical note

Funding Information:
Funding: This research was funded in part by MITACS Canada and Innovacorp (NS, Canada).

Publisher Copyright:
© 2019 by the authors.

ASJC Scopus Subject Areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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