introduction

Inflammation is a universal response of an organism to predominantly local tissue alterations of diverse nature.
According to the canons of general pathology, inflammation is a typical complex (local and systemic) general
pathological process which forms the basis of disease pathogenesis with a variety of inflammatory focus localizations and
symptomatology [1].
The factors that can stimulate inflammation include microorganisms, physical agents, chemicals, inappropriate
immunological responses, and tissue death. Infectious agents such as viruses and bacteria are some of the most common
stimuli of inflammation. Viruses give rise to inflammation by entering and destroying cells of the body; bacteria release
substances called endotoxins that can initiate inflammation. Physical trauma, burns, radiation injury, and frostbite can
damage tissues and also bring about inflammation, as can corrosive chemicals such as acids, alkalis, and oxidizing agents.
As mentioned above, malfunctioning immunological responses can incite an inappropriate and damaging inflammatory
response. Inflammation can also result when tissues die from a lack of oxygen or nutrients, a situation that often is caused
by loss of blood flow to the area [2].
Classical inflammation is characterized by a stereotypic complex of vascular changes, which lead to edema followed by
migration of leukocytes to the damaged area and formation of an inflammatory focus. The presence of a focus of
inflammation is a key attribute of different variants of classical inflammation and its distinguishing feature from non-
classical variants of inflammation. The primary function of the inflammatory focus is to isolate the damage factor, then
eliminate it and subsequently regenerate or repair (sclerosis) the injured tissue. The most evident phenomena of
inflammation—redness, swelling, fever, pain, dysfunction [1] .
Carrageenan is a generic name for a family of gel-forming and viscosifying polysaccharides, which are obtained by
extraction from certain species of red alga Chondrus crispus, Carrageenan is derived from a number of seaweeds of the
class Rhodophyceae. This seaweed is common in the Atlantic Ocean near Britain, Europe and North America [3].
Carrageenan is the general name of a group of high-molecular-weight hydrophilic sulphated polysaccharides formed by
alternate units of d-galactose and 3,6-anhydro-galactose (3,6-AG) joined by alternating α-1,3 and β-1,4-glycosidic bonds.
It contains between 15% and 40% of ester-sulphate, meaning it is an anionic polysaccharide. Carrageenan can be
classified into six basic forms depending on their sulphate content, source of extraction, and solubility: kappa (κ-), iota (ɩ-
), lambda (λ-), mu (μ-), nu (ν-), beta (β-), and Theta (θ-) carrageenan. The most important types of CG applied in the
pharmaceutical and commercial field are kappa-carrageenan (kappa-CG), iota-carrageenan (iota-CG), and lambda-
carrageenan (lambda-CG). These are generally obtained separately or as a well-defined mixture, since most seaweeds
contain hybrid [4].

A previous studies was done for carrageenan-induced paw edema in rats, Paw swelling is one of the major factors in
assessing the degree of inflammation and efficacy of the tested drugs As expected, hindpaw carrageenan injection results
in oedema and an increase in neutrophil infiltration as determined by MPO activity [5], The results showed that
intraplantar injection of carrageenan led to time-dependent development of peripheral inflammation, which resulted in a
significant increase in the levels of tumor necrosis factor α (TNF-α) and NF-κB (nuclear factor kappa-light-chain-
enhancer of activated B cells) and interleukin 1 (IL-1) β, nitric oxide (NO) and prostaglandin E 2 (PGE2) and also iNOS
and COX-2 protein expression in inflamed paw[6].
Although studies on pathophysiology of inflammation have revealed significant progress, managing inflammation is still a
major health issue, Vildagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that is being evaluated in the treatment of
patients with type 2 diabetes mellitus. It improves glycemic control by inhibiting DPP-4 from inactivating the incretin
hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, prolonging incretin activity in
response to ingestion of nutrients. This allows for increased insulin sensitivity, decreased glucagon secretion and
improved β-cell function in a glucose-dependent manner [7], there some study suggest that the benefits of vildagliptin
extend far beyond glycemic control. Significant improvement of reduction of inflammation [8] but not verified.
Therefore, the goal of the present study was to assess the role of vildagliptin in induction-induced inflammation and
explore the underlying mechanisms.
Reference
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[2] Britannica, The Editors of Encyclopaedia. "inflammation". Encyclopedia Britannica, 3 Feb. 2023,
https://www.britannica.com/science/inflammation.
[3] Necas J, Bartosikova L. Carrageenan: a review. Vet Med-Czech. 2013;58(4):187-205. doi: 10.17221/6758-
VETMED.
[4] Pacheco-Quito, E.-M.; Ruiz-Caro, R.; Veiga, M.-D. Carrageenan: Drug Delivery Systems and Other
Biomedical Applications. Mar. Drugs 2020, 18, 583. https://doi.org/10.3390/md18110583
[5] Bhatia, M., Sidhapuriwala, J., Moochhala, S.M. and Moore, P.K. (2005), Hydrogen sulphide is a mediator of
carrageenan-induced hindpaw oedema in the rat. British Journal of Pharmacology, 145: 141-144.
https://doi.org/10.1038/sj.bjp.0706186
[6] Mansouri MT, Hemmati AA, Naghizadeh B, Mard SA, Rezaie A, Ghorbanzadeh B. A study of the
mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats.
Indian J Pharmacol. 2015 May-Jun;47(3):292-8. doi: 10.4103/0253-7613.157127. PMID: 26069367; PMCID:
PMC4450555.
[7] Henness, S., Keam, S.J. Vildagliptin. Drugs 66, 1989–2001 (2006). https://doi.org/10.2165/00003495-
200666150-00007
[8] Wiciński, M.; Górski, K.; Wódkiewicz, E.; Walczak, M.; Nowaczewska, M.; Malinowski, B. Vasculoprotective
Effects of Vildagliptin. Focus on Atherogenesis. Int. J. Mol. Sci. 2020, 21, 2275.
https://doi.org/10.3390/ijms21072275