Functional Selectivity of Coumarin Derivates Acting Via GPR55 in Neuroinflammation

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Jan 21

PMID 35055142

Authors

Matthias Apweiler

Jana Streyczek

Soraya Wilke Saliba

Juan Antonio Collado

Thomas Hurrle

Simone Grassle

Eduardo Munoz

Claus Normann

Sabine Hellwig

Stefan Brase

Bernd L Fiebich

Affiliations

Soon will be listed here.

Abstract

Anti-neuroinflammatory treatment has gained importance in the search for pharmacological treatments of different neurological and psychiatric diseases, such as depression, schizophrenia, Parkinson's disease, and Alzheimer's disease. Clinical studies demonstrate a reduction of the mentioned diseases' symptoms after the administration of anti-inflammatory drugs. Novel coumarin derivates have been shown to elicit anti-neuroinflammatory effects via G-protein coupled receptor GPR55, with possibly reduced side-effects compared to the known anti-inflammatory drugs. In this study, we, therefore, evaluated the anti-inflammatory capacities of the two novel coumarin-based compounds, KIT C and KIT H, in human neuroblastoma cells and primary murine microglia. Both compounds reduced PGE-concentrations likely via the inhibition of COX-2 synthesis in SK-N-SH cells but only KIT C decreased PGE-levels in primary microglia. The examination of other pro- and anti-inflammatory parameters showed varying effects of both compounds. Therefore, the differences in the effects of KIT C and KIT H might be explained by functional selectivity as well as tissue- or cell-dependent expression and signal pathways coupled to GPR55. Understanding the role of chemical residues in functional selectivity and specific cell- and tissue-targeting might open new therapeutic options in pharmacological drug development and might improve the treatment of the mentioned diseases by intervening in an early step of their pathogenesis.

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References

Kenakin T, Christopoulos A . Signalling bias in new drug discovery: detection, quantification and therapeutic impact. Nat Rev Drug Discov. 2013; 12(3):205-16. DOI: 10.1038/nrd3954. View

Norregaard R, Kwon T, Frokiaer J . Physiology and pathophysiology of cyclooxygenase-2 and prostaglandin E2 in the kidney. Kidney Res Clin Pract. 2016; 34(4):194-200. PMC: 4688592. DOI: 10.1016/j.krcp.2015.10.004. View

Olajide O, Velagapudi R, Okorji U, Sarker S, Fiebich B . Picralima nitida seeds suppress PGE2 production by interfering with multiple signalling pathways in IL-1β-stimulated SK-N-SH neuronal cells. J Ethnopharmacol. 2014; 152(2):377-83. DOI: 10.1016/j.jep.2014.01.027. View

Wrobel A, Serefko A, Szopa A, Ulrich D, Poleszak E, Rechberger T . O-1602, an Agonist of Atypical Cannabinoid Receptors GPR55, Reverses the Symptoms of Depression and Detrusor Overactivity in Rats Subjected to Corticosterone Treatment. Front Pharmacol. 2020; 11:1002. PMC: 7360849. DOI: 10.3389/fphar.2020.01002. View

Pan T, Zhou D, Shi Z, Qiu Y, Zhou G, Liu J . Centromere protein U (CENPU) enhances angiogenesis in triple-negative breast cancer by inhibiting ubiquitin-proteasomal degradation of COX-2. Cancer Lett. 2019; 482:102-111. DOI: 10.1016/j.canlet.2019.11.003. View

Craft J, Watterson D, Van Eldik L . Neuroinflammation: a potential therapeutic target. Expert Opin Ther Targets. 2005; 9(5):887-900. DOI: 10.1517/14728222.9.5.887. View

Kang S, Lee A, Park S, Liu K, Im D . O-1602 Promotes Hepatic Steatosis through GPR55 and PI3 Kinase/Akt/SREBP-1c Signaling in Mice. Int J Mol Sci. 2021; 22(6). PMC: 8003045. DOI: 10.3390/ijms22063091. View

Rempel V, Volz N, Glaser F, Nieger M, Brase S, Muller C . Antagonists for the orphan G-protein-coupled receptor GPR55 based on a coumarin scaffold. J Med Chem. 2013; 56(11):4798-810. DOI: 10.1021/jm4005175. View

Lipina C, Walsh S, Mitchell S, Speakman J, Wainwright C, Hundal H . GPR55 deficiency is associated with increased adiposity and impaired insulin signaling in peripheral metabolic tissues. FASEB J. 2018; 33(1):1299-1312. PMC: 6355063. DOI: 10.1096/fj.201800171R. View

10.

Sawzdargo M, Nguyen T, Lee D, Lynch K, Cheng R, Heng H . Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain. Brain Res Mol Brain Res. 1999; 64(2):193-8. DOI: 10.1016/s0169-328x(98)00277-0. View

11.

Hill J, Zuluaga-Ramirez V, Gajghate S, Winfield M, Sriram U, Rom S . Activation of GPR55 induces neuroprotection of hippocampal neurogenesis and immune responses of neural stem cells following chronic, systemic inflammation. Brain Behav Immun. 2018; 76:165-181. PMC: 6398994. DOI: 10.1016/j.bbi.2018.11.017. View

12.

Saliba S, Jauch H, Gargouri B, Keil A, Hurrle T, Volz N . Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells. J Neuroinflammation. 2018; 15(1):322. PMC: 6240959. DOI: 10.1186/s12974-018-1362-7. View

13.

Choi G, Han H . Glucocorticoid impairs mitochondrial quality control in neurons. Neurobiol Dis. 2021; 152:105301. DOI: 10.1016/j.nbd.2021.105301. View

14.

Esposito E, Di Matteo V, Benigno A, Pierucci M, Crescimanno G, Di Giovanni G . Non-steroidal anti-inflammatory drugs in Parkinson's disease. Exp Neurol. 2007; 205(2):295-312. DOI: 10.1016/j.expneurol.2007.02.008. View

15.

Rivers-Auty J, Mather A, Peters R, Lawrence C, Brough D . Anti-inflammatories in Alzheimer's disease-potential therapy or spurious correlate?. Brain Commun. 2020; 2(2):fcaa109. PMC: 7585697. DOI: 10.1093/braincomms/fcaa109. View

16.

Celorrio M, Rojo-Bustamante E, Fernandez-Suarez D, Saez E, de Mendoza A, Muller C . GPR55: A therapeutic target for Parkinson's disease?. Neuropharmacology. 2017; 125:319-332. DOI: 10.1016/j.neuropharm.2017.08.017. View

17.

Kohler-Forsberg O, N Lydholm C, Hjorthoj C, Nordentoft M, Mors O, Benros M . Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials. Acta Psychiatr Scand. 2019; 139(5):404-419. DOI: 10.1111/acps.13016. View

18.

Whyte L, Ryberg E, Sims N, Ridge S, Mackie K, Greasley P . The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc Natl Acad Sci U S A. 2009; 106(38):16511-6. PMC: 2737440. DOI: 10.1073/pnas.0902743106. View

19.

Shore D, Reggio P . The therapeutic potential of orphan GPCRs, GPR35 and GPR55. Front Pharmacol. 2015; 6:69. PMC: 4397721. DOI: 10.3389/fphar.2015.00069. View

20.

Candelario-Jalil E, Akundi R, Bhatia H, Lieb K, Appel K, Munoz E . Ascorbic acid enhances the inhibitory effect of aspirin on neuronal cyclooxygenase-2-mediated prostaglandin E2 production. J Neuroimmunol. 2006; 174(1-2):39-51. DOI: 10.1016/j.jneuroim.2006.01.003. View