peoniflorin and Fibrosis

Baojin Chenfei formula (BCF), a Chinese herbal formula, has significant effects on improving the clinical symptoms of patients with silicosis. However, its active compounds and the underlying mechanisms have not yet fully been elucidated.. This study aimed to explore the underlying mechanisms of BCF in treating silicosis.. The rat model of silicosis was developed via a single intratracheal instillation of SiO. BCF significantly alleviated SiO. Active compounds of BCF, such as glycyrrhetic acid and paeoniflorin, could suppress inflammatory response by the MAPK pathway and suppress fibroblast activation by the EGFR-PI3K-AKT pathway. These might be the mechanisms of BCF in treating silicosis.

Topics: Animals; Drugs, Chinese Herbal; ErbB Receptors; Fibrosis; Glycyrrhetinic Acid; Inflammation; Molecular Docking Simulation; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Silicon Dioxide; Silicosis

Paeoniforin (Pae) is a monoterpenoid glycoside compound and has many biological activities, such as immunosuppression, anti-inflammation and anti-cell proliferation. However, the effects and mechanisms of Pae on chronic heart failure (CHF) remain unclear. This study was conducted to assess the effects and mechanisms of Pae on myocardial fbrosis in isoprenaline (Iso)-induced CHF rats. Pae (20 mg/kg) was intragastrically administrated to CHF rats for 6 weeks. Cardiac structure and function were assessed. The protein and mRNA levels of transforming growth factor β1 (TGF-β1) and p38 were detected. Compared to Iso group, Pae could alleviate myocardial fibrosis and improve cardiac function in CHF rats. The levels of collagen volume fraction (13.75%±3.77% vs. 30.97%±4.22%, P<0.001) and perivascular collagen volume area (14.32%±2.50% vs. 28.31%±3.16%, P<0.001) were signifcantly reduced in Pae group as compared with those in Iso group. The expression of TGF-β1 protein (0.30±0.07 vs. 0.66±0.07, P<0.05) and mRNA (3.51±0.44 vs. 7.58±0.58, P<0.05) decreased signifcantly in Pae group as compared with that in Iso group. The expression of p38 protein (0.36±0.12 vs. 0.81±0.38, P<0.05) and mRNA (3.84±0.05 vs. 4.40±0.17, P<0.05) also decreased markedly in Pae group as compared with that in Iso group. Pae could attenuate myocardial fbrosis and improve cardiac function in CHF rats by down-regulating the p38 MAPK signaling pathway.

Topics: Animals; Cardiomyopathies; Disease Models, Animal; Down-Regulation; Fibrosis; Gene Expression Regulation; Glucosides; Heart Function Tests; Isoproterenol; Male; MAP Kinase Signaling System; Monoterpenes; Rats; Transforming Growth Factor beta1

Cardiac remodeling is a key determinant in the clinical course and outcome of heart failure and characterized by cardiac hypertrophy, fibrosis, cardiomyocyte apoptosis and inflammation. The anti-inflammatory, anti-apoptotic and anti-fibrotic effects of paeoniflorin have been identified in various types of tissue and cells. However, the role of paeoniflorin in cardiac remodeling remains unclear. We performed aortic banding (AB) in mice to induce a cardiac remodeling model in response to pressure overload. Paeoniflorin (20 mg/kg) was administered by daily intraperitoneal (i.p.) injection. Paeoniflorin treatment promoted the survival rate and improved cardiac function of mice at 8 weeks post surgery. AB-induced cardiac hypertrophy, as assessed by heart weight, gross heart, HE and WGA staining, cross-sectional area of cardiomyocyte and mRNA expresssion of hypertrophic makers, was attenuated by paeoniflorin. Paeoniflorin also inhibited collagen deposition, expression of TGFβ, CTGF, collagen Iα and collagen IIIα, and phosphorylation of Smad2 and Smad3 in the heart exposed to pressure overload. Cardiomyocyte apoptosis and induction of Bax and cleaved caspase3 in response to AB were suppressed by paeoniflorin. Furthermore, paeoniflorin decreased the quantity of CD68+ cells, protein levels of TNF-α and IL-1β, and phosphorylation of IκBα and NFκB-p65 in the heart after AB. In conclusion, paeoniflorin attenuated cardiac hypertrophy, fibrosis, apoptosis and inflammation, and improved left ventricular function in pressure overloaded mice. The cardioprotective effect of paeoniflorin is associated with the inhibition of TGFβ/Smads and NF-κB pathways.

Topics: Animals; Apoptosis; Benzoates; Biomarkers; Bridged-Ring Compounds; Cardiomegaly; Fibrosis; Glucosides; Heart; Inflammation; Male; Mice; Mice, Inbred C57BL; Monoterpenes; Myocytes, Cardiac; NF-kappa B; Signal Transduction; Smad Proteins; Transforming Growth Factor beta; Ventricular Function, Left; Ventricular Remodeling

Paeoniflorin (PF), the major active constituent of Paeonia lactiflora Pallas, has previously been reported to alleviate hepatic fibrosis. Whether and how it affects renal fibrosis was evaluated in the present study. The experimental renal fibrosis was induced by unilateral ureteral obstruction (UUO) operation in mice, and PF was orally administered for consecutive 7 days. Renal interstitial destruction and fibrosis degree were evaluated by histopathological examination and hydroxyproline assay. It was shown that PF treatment markedly ameliorated renal interstitial fibrotic lesions, attenuated synthesis of collagen and plasminogen activator inhibitor-1 (PAI-1), an important inhibitor of extracellular matrix degrading enzymes, in UUO mice. PF also suppressed epithelial-mesenchymal transition (EMT) by down-regulating TGF-β1 expression and maintaining BMP-7 mRNA expression, and inhibited Smad2/3 activation in fibrotic kidneys induced by UUO. These observations suggest that PF can effectively prevent renal interstitial fibrosis, and the underlying mechanisms are, at least in part, through blocking EMT via BMP-7 recovery and TGF-β/Smad signaling inhibition.

Topics: Animals; Benzoates; Bone Morphogenetic Protein 7; Bridged-Ring Compounds; Collagen; Down-Regulation; Epithelial-Mesenchymal Transition; Fibrosis; Gene Expression Regulation; Glucosides; Kidney Diseases; Male; Mice; Mice, Inbred ICR; Monoterpenes; Paeonia; Phosphorylation; Plasminogen Activator Inhibitor 1; Smad2 Protein; Transforming Growth Factor beta1; Ureteral Obstruction