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1.
Int J Mol Sci ; 25(12)2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38928387

ABSTRACT

Cannabinoids and their receptors play a significant role in the regulation of gastrointestinal (GIT) peristalsis and intestinal barrier permeability. This review critically evaluates current knowledge about the mechanisms of action and biological effects of endocannabinoids and phytocannabinoids on GIT functions and the potential therapeutic applications of these compounds. The results of ex vivo and in vivo preclinical data indicate that cannabinoids can both inhibit and stimulate gut peristalsis, depending on various factors. Endocannabinoids affect peristalsis in a cannabinoid (CB) receptor-specific manner; however, there is also an important interaction between them and the transient receptor potential cation channel subfamily V member 1 (TRPV1) system. Phytocannabinoids such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) impact gut motility mainly through the CB1 receptor. They were also found to improve intestinal barrier integrity, mainly through CB1 receptor stimulation but also via protein kinase A (PKA), mitogen-associated protein kinase (MAPK), and adenylyl cyclase signaling pathways, as well as by influencing the expression of tight junction (TJ) proteins. The anti-inflammatory effects of cannabinoids in GIT disorders are postulated to occur by the lowering of inflammatory factors such as myeloperoxidase (MPO) activity and regulation of cytokine levels. In conclusion, there is a prospect of utilizing cannabinoids as components of therapy for GIT disorders.


Subject(s)
Cannabinoids , Gastrointestinal Diseases , Gastrointestinal Motility , Permeability , Humans , Cannabinoids/pharmacology , Cannabinoids/therapeutic use , Gastrointestinal Motility/drug effects , Animals , Gastrointestinal Diseases/drug therapy , Gastrointestinal Diseases/metabolism , Permeability/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Endocannabinoids/metabolism
2.
Pharmaceuticals (Basel) ; 17(5)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38794127

ABSTRACT

Phytosterols are a large group of substances belonging to sterols-compounds naturally occurring in the tissues of plants, animals, and humans. The most well-known animal sterol is cholesterol. Among phytosterols, the most significant compounds are ß-sitosterol, stigmasterol, and campesterol. At present, they are mainly employed in functional food products designed to counteract cardiovascular disorders by lowering levels of 'bad' cholesterol, which stands as their most extensively studied purpose. It is currently understood that phytosterols may also alleviate conditions associated with the gastrointestinal system. Their beneficial pharmacological properties in relation to gastrointestinal tract include anti-inflammatory and hepatoprotective activity. Also, the anti-cancer properties as well as the impact on the gut microbiome could be a very interesting area of research, which might potentially lead to the discovery of their new application. This article provides consolidated knowledge on a new potential use of phytosterols, namely the treatment or prevention of gastrointestinal diseases. The cited studies indicate high therapeutic efficacy in conditions such as peptic ulcer disease, IBD or liver failure caused by hepatotoxic xenobiotics, however, these are mainly in vitro or in vivo studies. Nevertheless, studies to date indicate their therapeutic potential as adjunctive treatments to conventional therapies, which often exhibit unsatisfactory efficacy or serious side effects. Unfortunately, at this point there is a lack of significant clinical study data to use phytosterols in clinical practice in this area.

3.
Plants (Basel) ; 11(7)2022 Apr 04.
Article in English | MEDLINE | ID: mdl-35406959

ABSTRACT

Lipoxygenases (LOXs), naturally occurring enzymes, are widely distributed in plants and animals. LOXs can be non-sulfur iron, non-heme iron, or manganese-containing dioxygenase redox enzymes. LOXs catalyze the oxidation of polyunsaturated fatty acids into fatty acid hydroperoxides. Linolenic acid, a precursor in the jasmonic acid (JA) biosynthesis, is converted to 12-oxo-phytodienoic acid through oxygenation with LOX, allene oxide synthase, and allene oxide cyclase. Moreover, JA participates in seed germination, fruit ripening, senescence, and many other physio-biochemical processes. LOXs also play crucial roles in defense responses against biotic stress, i.e., insects, pests, pathogenic attacks, and abiotic stress, such as wounding, UV-rays, extreme temperature, oxidative stress, and drought.

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