The objective of this study is to investigate the participation of inflammatory and oxidative stress mediators and the effects on the expression of matrix metalloproteinase (MMP)-2, MMP-9, and receptor activator of NF-κB ligand (RANKL)/receptor activator of NF-κB (RANK)/osteoprotegerin (OPG) pathway in the response to treatment with olmesartan, an angiotensin II type 1 receptor blocker. Male Wistar albino rats were randomly divided into five groups of ten rats each: (1) non-ligature with water, (2) ligature with water, (3) ligature with 1 mg/kg olmesartan, (4) ligature with 6 mg/kg olmesartan, and (5) ligature with 10 mg/kg olmesartan. All groups were treated with olmesartan or the vehicle by gavage daily for 10 days. Following the treatment course, the periodontal tissue of the animals was analyzed by histopathology and immunohistochemistry to determine the expression of cyclooxygenase-2 (COX-2), MMP-2, MMP-9, and members of the RANKL/RANK/OPG pathway and by ELISA and spectroscopic assay to determine the levels of interleukin (IL)-1β, IL-10, tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), malonaldehyde (MDA), and glutathione. The concentrations of MPO and MDA were reduced in the group that received 6 mg/kg olmesartan (p < 0.05). In addition, the group that was treated with 6 mg/kg olmesartan showed a decreased level of IL-1β (p < 0.05), and all doses of olmesartan resulted in decreased levels of TNF-α. Furthermore, treatment with 6 mg/kg olmesartan led to downregulation of the expression of COX-2, MMP-2, MMP-9, RANKL, and RANK and to upregulation of the expression of OPG. These findings suggest that 6 mg/kg olmesartan reduces the inflammatory process and bone loss by downregulating MMPs and RANKL in osteoblasts and by upregulating OPG.

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Abstract:The bark of A. occidentale L. is rich in tannins. Studies have described various biological activities of the plant, including antimicrobial, antioxidant, antiulcerogenic and antiinflammatory actions. The objective of this study was to assess the activity of the ethyl acetate phase (EtOAc) of A. occidentale on acute inflammation and to identify and quantify its phenolic compounds by HPLC. The method was validated and shown to be linear, precise and accurate for catechin, epicatechin, epigallocatechin and gallic acid. Swiss albino mice (Mus musculus) were treated with saline, Carrageenan (2.5%), Indomethacin (10 mg/kg), Bradykinin (6 nmol) and Prostaglandine E2 (5 µg) at different concentrations of EtOAc -A. occidentale (12.5; 25; 50; and 100 mg/kg/weight p.o.) for the paw edema test. Challenge was performed with carrageenan (500 µg/mL i.p.) for the doses 50 and 100 mg/kg of EtOAc. Levels of cytokines IL-1, TNF-α, IL-6 and IL-10 were also measured. All EtOAc -A. occidentale concentrations reduced the edema. At 50 and 100 mg/kg, an anti-inflammatory response of the EtOAc was observed. Carrageenan stimulus produced a neutrophil count of 28.6% while 50 and 100 mg/kg of the phase reduced this to 14.5% and 9.1%, respectively. The EtOAc extract reduced levels of IL-1 and TNF-α. These results suggest that the EtOAc plays a modulatory role in the inflammatory response. The chromatographic method can be used for the analysis of the phenolic compounds of the EtOAc phase.

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