Cynaroside (CYN) is the predominant derivative of luteolin in aerial parts of Bidens tripartita which has been used in folk medicine as a diaphoretic, diuretic, antiseptic and anti-inflammatory agent. In our study, alginate (ALG), which is an anionic polymer with bioadhesive properties, was used as a CYN carrier, and multiple hydrogel formulations were created. Additionally, the present study evaluated the in vivo anti-inflammatory and anti-allergic activities of all preparations.Novel gel formulations as topical carriers for CYN obtained from B. tripartita were developed and characterized. The bioadhesive properties of the designed preparations were also evaluated in an ex vivo model using the skin of hairless mice. In vitro CYN release from all formulations was examined and analysed by HPLC. Histopathological evaluation of mouse skin sections stained with H&E after carrageenan and oxazolone administration was also carried out. In addition, the influence of CYN on cell proliferation was examined by the PCNA staining method.The results showed that 10 % CYN inhibited the release of anti-inflammatory mediators, and both tested concentrations, which included 5 % and 10 % (2 mg and 20 mg CYN per site, respectively), reduced oxazolone-induced ear swelling. Histopathological examination of the samples revealed a marked reduction in paw skin and ear tissue inflammation and in inflammatory infiltrates. The influence of CYN on cell proliferation was examined by the PCNA staining method, and the staining and distribution of PCNA-immunoreactive (PCNA-IR) cells were observed. After the application of the 5 % and 10 % hydrogels, the investigated samples showed decreased nuclear immunoreactivity to PCNA, which was similar to that of the control. Moreover, after application of the placebo formulation, fewer PCNA-IR cells were also observed.The obtained data suggest that the topical application of CYN significantly reduces the number of T cells, mast cells and histiocytes in mouse skin with inflammation or atopic dermatitis.
