Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB2 receptor agonist ABK5

Tang, Yaliang; Wolk, Barbara; Britch, Stevie C; Craft, Rebecca M.; Kendall, Debra A.

doi:10.1016/j.jphs.2020.12.006

Cited by 8 publications

(3 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since selective activation of CB 2 does not cause psychoactive effects [ 8 , 11 ], CB 2 subtype selective agonists are good drug candidates for reducing neuroinflammation and associated pain. We have previously reported that a CB 2 subtype selective agonist ABK5, which has a distinct structure from known cannabinoid receptor agonists, inhibits inflammation in human T cells [ 28 ]. ABK5-1 is an ABK5 analog which is also a subtype selective CB 2 agonist with marginally stronger anti-inflammatory effects than the lead compound.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we have reported that a CB 2 subtype-selective agonist, ABK5, which is a compound with a distinct structure from the known CB 2 , agonists, has anti-inflammatory effects in T-cells. ABK5 inhibited IL-2 and TNF-α production and chemotaxis induced by CXCL12 [ 27 , 28 ]. To optimize ABK5 for better efficacy, we introduced several analogs of ABK5, and found ABK5-1 ( Figure 1 ) had a good binding affinity to CB 2 (K i =28 nM) without CB 1 binding.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of a CB2 Subtype Selective Agonist ABK5-1 on Cytokine Production in Microglia

Tang

Wolk

Kendall

2021

Journal of Cellular Signaling

View full text Add to dashboard Cite

Background and objectives: Neuroinflammation is closely associated with various diseases including neuropathic pain. Microglia are immune cells in the central nervous system which are the main players of immunity and inflammation. Since microglia are activated by nerve injury, and they produce proinflammatory mediators to cause neuropathic pain, targeting activated microglia is considered to be a strategy for treating neuropathic pain. Activation of the cannabinoid CB 2 receptor is known to have anti-inflammatory effects in microglia. ABK5-1 is a CB 2 subtype selective agonist which inhibits IL-1β and IL-6 production in the microglia cell line BV-2. The purpose of the current study is to further analyze anti-inflammatory effects of ABK5 in terms of different cytokines and the possible pathway involved in the effect in the BV-2 cell line.Methods: A cytokine array was performed to screen the effect of ABK5-1 on forty inflammatory mediators in BV-2 cells. Changes of the inflammatory mediators was further supported by mRNA analysis, and a possible signaling molecule that involved the observation was evaluated by western blot.Results: Stimulating BV-2 cells by lipopolysaccharide increased expression of eleven inflammatory mediators, and ABK5-1 treatment resulted in more than a 50% decrease of sICAM1, IL-6, and RANTES. Real-time PCR results showed a decrease of G-CSF, ICAM1, MCP-1, MIP-1α, and MIP-1β mRNA levels. Western blot analysis showed that ABK5-1 inhibited LPS-induced ERK phosphorylation, which can be a mechanism of ABK5-1-mediated anti-inflammatory effect. Conclusions:Our current results support the possibility that ABK5-1 is an anti-inflammatory drug for microglia.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of a CB2 Subtype Selective Agonist ABK5-1 on Cytokine Production in Microglia

Tang

Wolk

Kendall

2021

Journal of Cellular Signaling

View full text Add to dashboard Cite

show abstract

“…CB 2 is largely expressed in immune cells, and CB 2 agonists have no analgesic effect [ 122 ]. Therefore, inhibition of inflammation by CB 2 agonists is believed to contribute to the relief of associated pain [ 123 ]. Nevertheless, nerve injury enhances CB 2 expression in DRG, and CB 2 agonists reduce neuropathic pain [ 115 ].…”

Section: Role Of Post-translational Modification Of Dna-associated Hi...mentioning

confidence: 99%

Molecular Insights into Epigenetics and Cannabinoid Receptors

Basavarajappa

Subbanna²

2022

Biomolecules

View full text Add to dashboard Cite

The actions of cannabis are mediated by G protein-coupled receptors that are part of an endogenous cannabinoid system (ECS). ECS consists of the naturally occurring ligands N-arachidonylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB1 and CB2 cannabinoid receptors. Epigenetics are heritable changes that affect gene expression without changing the DNA sequence, transducing external stimuli in stable alterations of the DNA or chromatin structure. Cannabinoid receptors are crucial candidates for exploring their functions through epigenetic approaches due to their significant roles in health and diseases. Epigenetic changes usually promote alterations in the expression of genes and proteins that can be evaluated by various transcriptomic and proteomic analyses. Despite the exponential growth of new evidence on the critical functions of cannabinoid receptors, much is still unknown regarding the contribution of various genetic and epigenetic factors that regulate cannabinoid receptor gene expression. Recent studies have identified several immediate and long-lasting epigenetic changes, such as DNA methylation, DNA-associated histone proteins, and RNA regulatory networks, in cannabinoid receptor function. Thus, they can offer solutions to many cellular, molecular, and behavioral impairments found after modulation of cannabinoid receptor activities. In this review, we discuss the significant research advances in different epigenetic factors contributing to the regulation of cannabinoid receptors and their functions under both physiological and pathological conditions. Increasing our understanding of the epigenetics of cannabinoid receptors will significantly advance our knowledge and could lead to the identification of novel therapeutic targets and innovative treatment strategies for diseases associated with altered cannabinoid receptor functions.

show abstract