Efficacy of combined therapy with fish oil and phytocannabinoids in murine intestinal inflammation

Abstract

Fish oil (FO) and phytocannabinoids have received considerable attention for their intestinal anti‐inflammatory effects. We investigated whether the combination of FO with cannabigerol (CBG) and cannabidiol (CBD) or a combination of all three treatments results in a more pronounced intestinal antiinflammatory action compared to the effects achieved separately. Colitis was induced in mice by 2,4‐dinitrobenzenesulfonic acid (DNBS). CBD and CBG levels were detected and quantified by liquid chromatography coupled with time of flight mass spectrometry and ion trap mass spectrometry (LC‐MS‐IT‐TOF). Endocannabinoids and related mediators were assessed by LC‐MS. DNBS increased colon weight/colon length ratio, myeloperoxidase activity, interleukin‐1β, and intestinal permeability. CBG, but not CBD, given by oral gavage, ameliorated DNBS‐induced colonic inflammation. FO pretreatment (at the inactive dose) increased the antiinflammatory action of CBG and rendered oral CBD effective while reducing endocannabinoid levels. Furthermore, the combination of FO, CBD, and a per se inactive dose of CBG resulted in intestinal anti‐inflammatory effects. Finally, FO did not alter phytocannabinoid levels in the serum and in the colon. By highlighting the apparent additivity between phytocannabinoids and FO, our preclinical data support a novel strategy of combining these substances for the potential development of a treatment of inflammatory bowel disease.

Cannabinoids and Inflammations of the Gut-Lung-Skin Barrier

“…CBD appears to elicited analogous effects in a parallel study [71]. Using the same experimental model, Pagano et al noted similar effects when using a combination of fish oil, CBD and CBG [72]. The association of fish oil and CBD enhances their anti-inflammatory effects, which occur at lower doses (20 mg and 0.3-10 mg/kg, respectively) than the per se administration of the two substances; these findings were reported in mice with induced colitis, in which the combination of fish oil and CBD decreased the myeloperoxidase (MPO) activity, DAI score, intestinal permeability, and levels of IL-1β and IL-6 [73].…”

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

“…CBG activates TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, 5-HT 1a receptor, α2-adrenergic receptor, and PPARγ, while being a TRPM8 antagonist [210][211][212][213][214][215]. CBG has anti-inflammatory, anti-oxidative, and anti-nociceptive activities [117,209,213,216]. The anti-inflammatory property is thought to be achieved by modulating the CB2 receptor, TRP channels, and PPARγ, and by inhibiting cyclooxygenase 1 and 2 (COX-1/2) [210,211,217], while the analgesic effect of CBG is thought to be mediated through the α2-adrenergic receptor [211].…”

“…The anti-inflammatory property is thought to be achieved by modulating the CB2 receptor, TRP channels, and PPARγ, and by inhibiting cyclooxygenase 1 and 2 (COX-1/2) [210,211,217], while the analgesic effect of CBG is thought to be mediated through the α2-adrenergic receptor [211]. CBG has been shown to have potential beneficial effects in treating inflammatory bowel disease and neurological disorders, such as Huntington's disease, Parkinson's disease, and multiple sclerosis [213,215,216,218,219].…”

Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses

“…There is anecdotal human and preclinical evidence for CBG having a benefit in cases of inflammatory bowel diseases including Crohn’s and ulcerative colitis. In a mouse model of colitis, CBG was found to reduce bowel inflammation, nitric oxide production [from increased nitric oxide synthase (iNOS) expression during inflammation] and oxidative stress in intestinal cells ( Borrelli, et al, 2013 ; Pagano, et al, 2021 ). Similar to CBC, CBG (3 mg/kg and 10 mg/kg i.p.)…”