Cannabidiol as a Promising Therapeutic Option in IC/BPS: In Vitro Evaluation of Its Protective Effects against Inflammation and Oxidative Stress.
Tadeja KuretMateja Erdani KreftRok RomihPeter VeraničPublished in: International journal of molecular sciences (2023)
Several animal studies have described the potential effect of cannabidiol (CBD) in alleviating the symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic inflammatory disease of the urinary bladder. However, the effects of CBD, its mechanism of action, and modulation of downstream signaling pathways in urothelial cells, the main effector cells in IC/BPS, have not been fully elucidated yet. Here, we investigated the effect of CBD against inflammation and oxidative stress in an in vitro model of IC/BPS comprised of TNFα-stimulated human urothelial cells SV-HUC1. Our results show that CBD treatment of urothelial cells significantly decreased TNFα-upregulated mRNA and protein expression of IL1α, IL8, CXCL1, and CXCL10, as well as attenuated NFκB phosphorylation. In addition, CBD treatment also diminished TNFα-driven cellular reactive oxygen species generation (ROS), by increasing the expression of the redox-sensitive transcription factor Nrf2, the antioxidant enzymes superoxide dismutase 1 and 2, and hem oxygenase 1. CBD-mediated effects in urothelial cells may occur by the activation of the PPARγ receptor since inhibition of PPARγ resulted in significantly diminished anti-inflammatory and antioxidant effects of CBD. Our observations provide new insights into the therapeutic potential of CBD through modulation of PPARγ/Nrf2/NFκB signaling pathways, which could be further exploited in the treatment of IC/BPS.
Keyphrases
- oxidative stress
- induced apoptosis
- signaling pathway
- cell cycle arrest
- dna damage
- rheumatoid arthritis
- endoplasmic reticulum stress
- pi k akt
- transcription factor
- anti inflammatory
- cell death
- reactive oxygen species
- high grade
- risk assessment
- metabolic syndrome
- climate change
- poor prognosis
- insulin resistance
- adipose tissue
- inflammatory response
- immune response
- dendritic cells
- high resolution
- atomic force microscopy
- human health
- heat shock