RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Rhododendron molle G. Don (Ericaceae) (RM) is a natural medicinal plant. Its root extracts have been applied in clinic and proved to be effective in chronic glomerulonephritis and rheumatoid arthritis in China. Surprising, little is understood about the key compound of RM and the exact mechanisms underlying its treatment on kidney diseases. In this study, we will explore whether rhodojaponin II (R-II), as the important compound of RM, also exerts the major effect. MATERIALS AND METHODS: Mouse model of focal segmental glomerulosclerosis was induced by single dose of adriamycin injection. Induced adriamycin nephropathy (ADRN) mice were treated individually with RM root extract (5â¯mg/kg, nâ¯=â¯5), RM root extract (60â¯mg/kg, nâ¯=â¯5), R-II (0.04â¯mg/kg, nâ¯=â¯6) or captopril (30â¯mg/kg, nâ¯=â¯5) for five weeks. Podocyte marker (nephrin and podocin) expressions were examined by immunohistochemical staining and Western Blot analysis. Fibronectin level was evaluated by immunohistochemical staining and Western Blot analysis. Interstitial infiltrated inflammatory cells (CD4+ T cells, CD8+ T cells, and CD68+ macrophages) were examined with immunohistochemical staining. The expressions of NF-ĸB p-p65 and TGF-ß1/Smad pathway associated key proteins, such as TGF-ß1, Smad3, phosphorylated-Smad3 (p-Smad3), and Smad7, were analyzed respectively by Western Blot analysis. RESULTS: RM root extract (5â¯mg/kg) and its important compound R-II (0.04â¯mg/kg) significantly ameliorated proteinuria, podocyte injury, and glomerulosclerosis, meanwhile, they hampered interstitial fibrosis in mice with ADRN. R-II significantly reduced NF-ĸB p65 phosphorylation, interstitial infiltrated CD4+ T cells, CD8+ T cells, and CD68+ macrophages, at the same time, down-regulated TGF-ß1 and p-Smad3 protein expressions in mice with ADRN. CONCLUSION: RM root extract, R-II, could effectively ameliorate proteinuria and kidney injury in ADRN, related to its anti-inflammatory effects, as well as suppression of TGF-ß1/Smad signaling pathway.
Assuntos
Anti-Inflamatórios , Diterpenos , Glomerulosclerose Segmentar e Focal , Extratos Vegetais , Proteinúria , Rhododendron , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Doxorrubicina , Glomerulosclerose Segmentar e Focal/induzido quimicamente , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/metabolismo , Glomerulosclerose Segmentar e Focal/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos Endogâmicos BALB C , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Proteinúria/induzido quimicamente , Proteinúria/tratamento farmacológico , Proteinúria/metabolismo , Proteinúria/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
AIM: To explore the anti-fibrotic effect of a traditional Chinese medicine, compound rhodiola sachalinensis A Bor on CCl(4)-induced liver fibrosis in rats and its probable molecular mechanisms. METHODS: Ninety healthy male SD rats were randomly divided into three groups: normal group (n=10), treatment group of compound rhodiola sachalinensis A Bor (n=40) and CCl(4)-induced model group (n=40). The liver fibrosis was induced by CCl(4) subcutaneous injection. Treatment group was administered with compound rhodiola sachalinensis A Bor (0.5 g/kg) once a day at the same time. Then the activities of several serum fibrosis-associated enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), N-acetyl-beta-D-glucosaminidase (beta-NAG) and the levels of serum procollagen III (PCIII), collagen IV (CIV), hyaluronic acid (HA) were assayed. The histopathological changes were observed with HE, VG and Masson stain. The expression of TGF-beta1 mRNA, alpha1 (I) mRNA and Na(+)/Ca(2+) exchanger (NCX) mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR) in situ. RESULTS: Compound rhodiola sachalinensis A Bor significantly reduced serum activities of ALT, AST, beta-NAG and decreased the levels of PCIII, CIV, HA, improved the liver histopathological changes, inhibited the expression of TGF-beta1 mRNA, alpha (I) mRNA and Na(+)/Ca(2+) exchanger mRNA in rats. CONCLUSION: Compound rhodiola sachalinensis A Bor can intervene in CCl(4)-induced liver fibrosis in rats, in which potential mechanisms may be decreasing the production of TGF-beta1, reducing the production of collagen, preventing the activation of hepatic stellate cell (HSC) and inhibiting the expression of TGF-beta1 mRNA, alpha1(I) mRNA and Na(+)/Ca(2+) exchanger mRNA.