The anti inflammatory action has been attributed to

The anti-inflammatory action has been attributed to polyphenolic components such as tannins [8] and procyanidins [17] from a variety of natural products. Based on the linkage between the successive monomeric units, procyanidins are classified as Types A, B or C procyanidine polyphenols. Type-A procyanidine polyphenols (TAPP) from cinnamon bark has been reported to exhibit activities against microorganisms [18], suggesting a potential role of TAPP in regulating immune function with unknown mechanism. Further, TAPP has been shown anti-inflammatory effects in cell culture studies in vitro[16]. Recently, we have demonstrated ameliorative effects of TAPP from cinnamon bark in animal model of allergic ap-1 [19]. However, TAPP has not yet been evaluated in vivo using animal models of rheumatoid arthritis (RA). The objective of present work is to evaluate efficacy and safety of TAPP isolated from C. zeylanicum in animal model of acute inflammation and RA in rats.
Materials and methods
Results
Discussion The cinnamon bark polyphenol extract is water-soluble and can be standardized to type-A proanthocyanidins [33]. In the present study, we are reporting anti-inflammatory and anti-arthritic potential of type-A proanthocyanidins from cinnamon bark, TAPP, in animal models. The recognition of different mediators for different phases of CPE has important implications for interpreting the anti-inflammatory effect of the drugs. The development of such edema in the rat paw is a biphasic event. The initial phase of the edema has been attributed to the release of histamine and serotonin which is then maintained during the plateau phase because of kinin-like substances [34]. Further, involvement of histamine and serotonin with other mediators in the pathogenesis of rheumatoid arthritis was also reported by many researchers [35–37]. Effectiveness of the test compounds in the 1st hour after carrageenan injection is indicative of their antihistaminic and/or anti-serotonin action. The 2nd accelerating phase of carrageenan edema is attributed to release of prostaglandins [38]. Our test compound, TAPP was not effective in the 1st hour of treatment but was found effective in the 2nd phase at 8mg/kg and higher dose (observed at 3h) thus suggesting prostaglandins inhibition effect of TAPP (Table 1). However, possibility of other mechanism such as inhibition of leukocyte emigration by TAPP cannot be ruled out. The ability of anti-inflammatory test compounds to offer benefits in clinical management of rheumatic diseases and so modification of arthritic syndromes in laboratory animals is an important criterion in anti-inflammatory screening procedure. In 1963, AIA in rats was used as primary animal model for RA using intradermal administration of Freund adjuvant in oil emulsion [39]. AIA is a rather aggressive and monophasic form of arthritis. Usually, the AIA is severe and finally leads to complete ankylosis and permanent joint deformations similar to progressive symptoms of RA patients. AIA has been used extensively as an experimental model for studying immune-inflammatory processes of arthritic diseases in humans, in particular RA, as well as for screening and testing novel anti-arthritic agents [40]. Therefore, we tested TAPP against established polyarthritis model of AIA rats using therapeutic schedule of treatment [25,41]. We induced AIA in rats, allowed it to develop for 12d and evaluated effects of TAPP on day-21 of the study. The progression of arthritis was confirmed in our study by scoring total arthritis lesions. The diseases progressed till day-12 and then became quiescent. TAPP halted the progression which was evident by significant decrease shown in the total arthritic score (Table 3). The inflammation associated with AIA is mainly dependent on prostaglandin E2 (PGE2) generated by cyclooxygenases (COXs) [40,42]. Besides, the role of cytokines like TNF-α and IL-1 has also been implicated in this model [43]. TAPP treatment to AIA rats reduced ankle diameters of arthritic paw. Therefore, the anti-inflammatory action of TAPP may be mediated by prostaglandin and/or cytokine inhibition. These results are also in line with reports that anti-inflammatory action of cinnamon bark has been attributed to polyphenolic component such as tannins [8] and procyanidines [17]. The inhibition of lipid peroxidation, capillary permeability and fragility, and enzymes such as phospholipase A2, cyclooxygenase, and lipoxygenase were reported as alleged mechanism for cinnamon tannins and polyphenols [8,17].