Cannabidiol Improves Antioxidant Capacity and Reduces Inflammation in the Lungs of Rats with Monocrotaline-Induced Pulmonary Hypertension

Abstract

Cannabidiol (CBD) is a plant-derived compound with antioxidant and anti-inflammatory properties. Pulmonary hypertension (PH) is still an incurable disease. CBD has been suggested to ameliorate monocrotaline (MCT)-induced PH, including reduction in right ventricular systolic pressure (RVSP), a vasorelaxant effect on pulmonary arteries and a decrease in the white blood cell count. The aim of our study was to investigate the effect of chronic administration of CBD (10 mg/kg daily for 21 days) on the parameters of oxidative stress and inflammation in the lungs of rats with MCT-induced PH. In MCT-induced PH, we found a decrease in total antioxidant capacity (TAC) and glutathione level (GSH), an increase in inflammatory parameters, e.g., tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), nuclear factor kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and cluster of differentiation 68 (CD68), and the overexpression of cannabinoid receptors type 1 and 2 (CB1-Rs, CB2-Rs). Administration of CBD increased TAC and GSH concentrations, glutathione reductase (GSR) activity, and decreased CB1-Rs expression and levels of inflammatory mediators such as TNF-α, IL -1β, NF-κB, MCP-1 and CD68. In conclusion, CBD has antioxidant and anti-inflammatory effects in MCT-induced PH. CBD may act as an adjuvant therapy for PH, but further detailed preclinical and clinical studies are recommended to confirm our promising results.

Effects of Cannabidiol on Innate Immunity: Experimental Evidence and Clinical Relevance

“…Interestingly, the effects of CBD are quite different in different cell subpopulations involved in innate immunity. For example, CBD exerts a prevalent inhibitory effect on astrocytes [ 92 , 93 , 105 ] and PMN [ 26 , 36 , 94 , 153 , 155 , 156 , 157 , 158 , 159 , 160 , 164 ], whereas, in microglia, oligodendrocytes, monocytes/macrophages, and mast cells, results are contradictory, with some authors reporting anti-inflammatory effects for CBD [ 90 , 90 , 99 , 101 , 102 , 103 , 104 , 105 , 106 , 110 , 111 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 124 , 125 , 126 , 127 , 129 ] and other authors reporting proinflammatory effects [ 89 , 107 , 108 , 110 , 111 , 120 , 122 , 123 , 124 , 125 , 129 ]. Lastly, to the best of our knowledge, no studies have reported CBD’s effects on dendritic cells, NK cells, eosinophils, and basophils.…”

“…Chemotaxis and tissue infiltration are fundamental processes in the inflammatory cascade; for this reason, CBD’s effects on these processes were studied by several authors. The reported results showed that CBD not only inhibits macrophages chemotaxis, as shown by Sacerdote in an in vitro model [ 88 ], but also tissue infiltration, as shown in different animal models of inflammatory diseases, such as liver inflammation [ 81 ], multiple sclerosis [ 87 ], pulmonary hypertension [ 92 ], and colitis [ 83 ].…”

8,9-Dihydrocannabidiol, an Alternative of Cannabidiol, Its Preparation, Antibacterial and Antioxidant Ability

“…The antioxidant activity of CBD [ 32 ] as well as its combined regimens with other antioxidants [ 33 ] have drawn much attention recently The antioxidant and anti-inflammatory effects of CBD in monocrotaline-induced pulmonary hypertension have been reported [ 34 ]. CBD was found to be more effective than vitamin C and E as a neuroprotective antioxidant [ 35 ] Herein, H 2 CBD and Compound 4 presented similar antioxidant activity as VC, but exhibited a much higher thermostability of antioxidant activity than VC.…”

The two synthetic cannabinoid compounds 4′‐F‐CBD and HU‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes

“…The naturally occurring cannabinoid CBD has been reported to possess robust anti‐inflammatory properties (Dos‐Santos‐Pereira et al, 2020; Henshaw et al, 2021) that are illustrated for instance in animal models of pulmonary hypertension (Krzyzewska et al, 2022), rheumatoid arthritis (Lowin et al, 2020), interstitial cystitis/bladder pain (Kuret et al, 2023) and brain degeneration (Dos Santos Pereira et al, 2020; Dos‐Santos‐Pereira et al, 2016; Meyer et al, 2022). Here, we wished to evaluate the anti‐inflammatory potential of two synthetic structural analogs of CBD, 4′‐F‐CBD (Breuer et al, 2016; Li et al, 2020) and HU‐910 (Horvath et al, 2012) using brain glial cells in culture.…”