Most conventional UC therapies rely primarily on downregulating aberrant immune responses
and inflammatory cascades. Mesalamine and corticosteroids are the mainstays in management
of UC. However, 20% to 32% of UC patients do not respond to steroid.4 Some antibiotics
offer protection against experimental and clinical colitis.
Mesalazine (also known as mesalamine or 5- amino salicylic acid, 5-ASA) has a
well-established role in UC management. It is the first line therapy for mild to moderate
UC and it is considered the cornerstone in the management of UC. The mechanism of action
of mesalazine is diverse. It acts locally on colonic mucosa and reduce inflammation by
several anti-inflammatory processes. It has a potent antioxidant and free-radical
scavenger properties.
Nitrosative stress caused by inducible nitric oxide synthase (iNOS)-derived nitric oxide
(NO) production and matrix metalloproteinases (MMPs) have been shown to play an important
role in the pathogenesis of UC. As in human UC, expression of MMPs and iNOS are also
implicated in the pathogenesis of experimental colitis, Therefore, it is important to
develop and evaluate agents that have low-severity adverse effects that can treat UC by
blocking inflammatory responses involved in nitrosative stress and/or MMP activation.
Minocycline, a semisynthetic tetracycline, is a safe, widely used and inexpensive
antibiotic with a broad spectrum.
Several recent studies have demonstrated that, in addition to its antimicrobial effects,
minocycline exerts anti-inflammatory, antiangiogenic, and antiapoptotic effects. These
biological effects of minocycline have been shown to have a therapeutic or preventive
effect in neurodegenerative disease, neural ischemic damage, ischemic renal injury,
rheumatoid arthritis, acne vulgaris, pyoderma gangrenosum, and periodontitis. The
mechanisms by which minocycline alleviates these illnesses involve suppressing expression
and/or activity of iNOS, MMPs, TNF-α and caspases, and blocking cytochrome-c release.
Several animal models of intestinal inflammation have been established, although some
only partially resemble human UC.
Also, minocycline improved the colonic oxidative status and decreased the expression of
different chemotactic mediators like expressions of the chemokine's monocyte chemotactic
protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) as well as
of the intercellular adhesion molecule-1 (ICAM-1) in the inflamed tissue. However, the in
vitro experiments performed revealed that minocycline reduced the release of the
chemokine IL-8 by the intestinal epithelial cells Caco-2.
The immunological activity of minocycline was reinforced by its remarkable effect in
restoring a balanced intestinal microbiota. the preclinical study shows that the counts
of lactobacilli and bifidobacteria, which were downregulated in colitic rats from control
group when compared with healthy rats, only appeared increased after treatment with
minocycline.