A New Gold(III) Complex, TGS 703, Shows Potent Anti-Inflammatory Activity in Colitis via the Enzymatic and Non-Enzymatic Antioxidant System-An In Vitro, In Silico, and In Vivo Study

• Published in: International journal of molecular sciences Vol. 24; no. 8; p. 7025
• Main Authors: Włodarczyk, Jakub, Krajewska, Julia, Szeleszczuk, Łukasz, Szałwińska, Patrycja, Gurba, Agata, Lipiec, Szymon, Taciak, Przemysław, Szczepaniak, Remigiusz, Mlynarczuk-Bialy, Izabela, Fichna, Jakub
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-04-2023; MDPI
• Subjects: Analysis; Animals; anti-inflammatory; Anti-Inflammatory Agents - adverse effects; Anti-inflammatory drugs; Antioxidants; Antioxidants - therapeutic use; Colitis - chemically induced; Colitis - drug therapy; Colitis - pathology; Dextran Sulfate - adverse effects; Diet therapy; Disease Models, Animal; Enzymes; gold; Gold - pharmacology; Gold - therapeutic use; Inflammation; Inflammation - drug therapy; inflammatory bowel disease; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - pathology; Mice; Ulcerative colitis; Poland; gold; anti-inflammatory; inflammatory bowel disease
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24087025

Inflammatory bowel diseases (IBD) and their main representatives, Crohn's disease and ulcerative colitis, are worldwide health-care problems with constantly increasing frequency and still not fully understood pathogenesis. IBD treatment involves drugs such as corticosteroids, derivatives of 5-aminosalicylic acid, thiopurines, and others, with the goal to achieve and maintain remission of the disease. Nowadays, as our knowledge about IBD is continually growing, more specific and effective therapies at the molecular level are wanted. In our study, we tested novel gold complexes and their potential effect on inflammation and IBD in vitro, in silico, and in vivo. A series of new gold(III) complexes (TGS 404, 512, 701, 702, and 703) were designed and screened in the in vitro inflammation studies. In silico modeling was used to study the gold complexes' structure vs. their activity and stability. Dextran sulphate sodium (DSS)-induced mouse model of colitis was employed to characterize the anti-inflammatory activity in vivo. Lipopolysaccharide (LPS)-stimulated RAW264.7 cell experiments proved the anti-inflammatory potential of all tested complexes. Selected on the bases of in vitro and in silico analyses, TGS 703 significantly alleviated inflammation in the DSS-induced mouse model of colitis, which was confirmed by a statistically significant decrease in the macro- and microscopic score of inflammation. The mechanism of action of TGS 703 was linked to the enzymatic and non-enzymatic antioxidant systems. TGS 703 and other gold(III) complexes present anti-inflammatory potential and may be applied therapeutically in the treatment of IBD.