NON‐PSYCHOACTIVE CANNABINOIDS (CBD/CBG) ACT VIA CANNABINOID CB2/CB1 RECEPTORS TO REGULATE INTESTINAL MYOFIBROBLAST METABOLIC ACTIVITY AND TO INHIBIT FORSKOLIN‐MEDIATED ELEVATION OF CYCLIC‐AMP
Bibliographic record
Abstract
Intestinal fibrosis, a common complication of inflammatory bowel disease (IBD), comprises an excessive accumulation of scar tissue in the intestinal wall. Fibrosis is thought to result from an aberrant response to injury resulting in excessive extracellular matrix (ECM) deposition, which can lead to tissue stiffening and intestinal stricture formation. Activation of the cannabinoid‐receptor‐CB2 has been reported to regulate mesenchymal cell function and to dampen fibrogenic signaling. More recently, non‐psychoactive cannabinoids, Cannabdiol (CBD) and Cannabigerol (CBG), have been found to be associated with anti‐inflammatory signalling that dampens inflammation. Here, we tested the hypothesis that CBD and CBG, via cannabinoid CB1/CB2 receptors, could function as potentially negative regulators of intestinal inflammation‐associated fibrosis through modulating intestinal myofibroblast function and triggering CB2/CB2 signalling. The effects of CBD and CBG on TGF‐β induced cell metabolic activity (MTT assay) were examined using cultured myofibroblast cells isolated from mouse and human intestine. Cannabinoid‐regulated signal transduction pathways were assessed using HEK‐293 cells transfected to express human CB2 and CB2 – red‐fluorescent‐protein‐tagged receptors. We found that at 48h and 72h TGF‐β induced cell metabolic activity was attenuated by 5% and 12% compared to TGF‐β‐treatment alone by increasing concentrations of CBG (10μM). Further, CBD (500nM) was able to inhibit TGF‐β induced cell metabolic activity by 12% and 25%, compared to TGF‐β alone at 48h and 72h. In CB1/CB2‐expressing HEK cells, preliminary data showed that both CBD and CBG, acting via CB2, were able to diminish forskolin (0.5 μM)‐increased cyclic‐AMP production, without affecting changes in intracellular calcium, indicating activation of Gi. In cells co‐expressing CB1/CB2 receptors, both CBG (100 nM) and CBD (20 nM) inhibited high forskolin concentration(5–10 μM)‐stimulated cAMP production. Nontransfected HEK cells showed no responses to either CBD or CBG. We conclude that the non‐psychoactive cannabinoids, CBD/CBG can regulate non‐neuronal cells, including intestinal myofibroblasts and kidney HEK cells via both CB2 and CB1 receptors. Support or Funding Information Supported by grants from the Canadian Institutes of Health Research for MDH and Mitacs postdoctoral fellowships for VKPV
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".