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Objective: To investigate the effects and mechanisms of hawthorn leaves flavonoids (HLF) on acute myocardial ischemia/reperfusion in anesthetized dogs., Methods: The acute ischemia models were prepared by ligating left anterior descending (LAD) artery for 60 min. Qualified 15 male dogs were randomly divided into 3 groups with 5 in each group: blank control (treated with normal saline 3 mL/kg) group, HLF low dosage (5 mg/kg) group and high dosage (10 mg/kg) group, with an once injection through a femoral vein 5 min before reperfusion. Epicardial electrocardiogram was adopted to measure the scope and degree of myocardial ischemia. Simultaneously, neutrophil infiltration in infarct (Inf) and remote site (RS) of myocardial tissue was measured by myeloperoxidase (MPO) activity assay. The serum interleukin-1 (IL-1) and tumor necrosis factorα (TNF-α) content were quantified by radioimmuno-assay. Furthermore, expression of G protein-coupled receptor kinase 2 (GRK2) and nuclear factor κB (NF-κB) in Inf and RS tissue were detected by Western blotting technique., Results: Ischemia and reperfusion increased the MPO activity and IL-1 and TNF-α content. HLF (10 and 5 mg/kg) could significantly decrease the degree and scope of myocardial ischemia; markedly inhibit the increase of MPO activity, and IL-1 and TNF-α content induced by myocardial ischemia/infarction. Furthermore, HLF increased GRK2 expression and inhibited NF-κB expression in Inf tissue., Conclusion: HLF could improve the situation of acute myocardial ischemia and inhibit the inflammation in anesthetized dogs, which might be due to its increasing effect on the GRK2 and NF-κB expressions.

Inflammatory response is an important mechanism in the pathogenesis of cardiovascular diseases. Cardiac fibroblasts play a crucial role in cardiac inflammation and might become a potential therapeutic target in cardiovascular diseases. Kaempferol, a flavonoid commonly existing in many edible fruits, vegetables, and Chinese herbs, is well known to possess anti-inflammatory property and thus has a therapeutic potential for the treatment of inflammatory diseases. To date, the effect of kaempferol on cardiac fibroblasts inflammation is unknown. In this study, we investigated the anti-inflammatory effect of kaempferol on lipopolysaccharide (LPS) plus ATP-induced cardiac fibroblasts and explored the underlying mechanisms. Our results showed that kaempferol at concentrations of 12.5 and 25 μg/mL significantly suppressed the release of TNF- α, IL-1β, IL-6, and IL-18 and inhibited activation of NF-κB and Akt in LPS plus ATP-induced cardiac fibroblasts. These findings suggest that kaempferol attenuates cardiac fibroblast inflammation through suppression of activation of NF-κB and Akt. [ABSTRACT FROM AUTHOR]

Abstract: Total glucosides of paeony (TGP) are active compounds extracted from the roots of Paeonia lactiflora Pall. In this study, we investigated the mechanisms of total glucosides of paeony (TGP) in the treatment of adjuvant arthritis (AA). AA in rats was established. Synoviocytes proliferation and activity of IL-1 were determined by 3-(4, 5-2dimethylthiazal-2yl) 2, 5-diphenyltetrazoliumbromide (MTT) assay. Tumor necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) were measured by radioimmunoassay. Ultrastructure of synovioctes was observed under transmission electron microscope. Phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulating kinase (ERK) and p38 kinase and expression of matrix metalloproteinases (MMPs) were detected by Western blot analysis. TGP (25, 50 and 100 mg kg−1, ig, days 14–21) inhibited secondary inflammatory reaction, bone destruction and ultrastructure change of synoviocytes in AA rats. The administration of TGP (50 and 100 mg/kg, ig, days 14–21) in AA rats significantly decreased the production of IL-1, PGE2 and TNF-α by macrophage-like synoviocytes (MLS). TGP (25 mg/kg) also decreased the production of PGE2 by MLS in AA rats. Furthermore, the increased phosphorylation of MAPKs, cell proliferation, and MMPs expression in fibroblast-like synoviocytes (FLS) stimulated by supernatants of MLS in AA rats could also be inhibited by TGP (50 and 100 mg/kg, ig, days 14–21). The results suggest that TGP possesses anti-inflammatory effects by modulating the pro-inflammatory mediators production from MLS and phosphorylation of MAPKs from FLS. [Copyright &y& Elsevier]

Abstract: The aim of this study was to investigate the expression of G proteins in fibroblast-like synoviocytes (FLSs) from rats with collagen-induced arthritis (CIA) and to determine the effect of total glucosides of paeony (TGP). CIA rats were induced with chicken type II collagen (CCII) in Freund's complete adjuvant. The rats with experimental arthritis were randomly separated into five groups and then treated with TGP (25, 50, and 100mg/kg) from days 14 to 35 after immunization. The secondary inflammatory reactions were evaluated through the polyarthritis index and histopathological changes. The level of cyclic adenosine monophosphate (cAMP) was measured by radioimmunoassay. The FLS proliferation response was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The toxin-catalyzed ADP-ribosylation of G proteins was performed through autoradiography. The results show that TGP (25, 50, and 100mg/kg) significantly decreased the arthritis scores of CIA rats and improved the histopathological changes. TGP inhibited the proliferation of FLSs and increased the level of cAMP. Moreover, the FLS proliferation and the level of Gαi expression were significantly increased, but the level of Gαs expression was decreased after stimulation with IL-1β (10ng/ml) in vitro. TGP (12.5 and 62.5μg/ml) significantly inhibited the FLS proliferation and regulated the balance between Gαi and Gαs. These results demonstrate that TGP may exert its anti-inflammatory effects through the suppression of FLS proliferation, which may be associated with its ability to regulate the balance of G proteins. Thus, TGP may have potential as a therapeutic agent for the treatment of rheumatoid arthritis. [Copyright &y& Elsevier]