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ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi capsule (FTZ) is a patented preparation of Chinese herbal medicine that has been used to treat hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and other glucolipid metabolic diseases (GLMDs) in the clinic for almost 10 years. However, how FTZ reduces albuminuria and attenuates diabetic kidney disease (DKD) progression is unknown. AIM OF THE STUDY: To clarify the effects of FTZ on DKD mice model and to explore the underlying mechanisms. MATERIALS AND METHODS: We used streptozotocin (STZ) (40 mg/kg/d, i.p. for 5 days, consecutively) combined with a high-fat diet (HFD) to induce a DKD mouse model, followed by FTZ (1, 2 g/kg/d, i.g.) treatment for 12 weeks. Losartan (30 mg/kg/d, i.g.) was used as a positive control. Measurements of 24 h proteinuria, serum creatinine (SCr), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels and expression levels of fibronectin (FN), collagen IV, inflammatory cytokines, inflammatory cells, interleukin-17A (IL-17A) and the nuclear transcription factor-κB (NF-κB) signaling pathway in the kidney were examined. RESULTS: FTZ effectively decreased 24 h proteinuria, Scr, FBG, TC, TG, and LDL-C levels, inhibited mesangial cell expansion, reduced FN and collagen IV accumulation, and F4/80+ macrophage cell infiltration and Ly-6G+ neutrophil infiltration in glomerulus and tubulointerstitium. Furthermore, IL-17A production and the NF-κB signaling pathway were also downregulated after the administration of FTZ. CONCLUSION: FTZ might attenuate DKD progression, and inhibited kidney inflammation and fibrosis by inhibiting the expression of RORγT and IL-17A in vivo, offering novel insights for the clinical application of FTZ.
Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Animais , LDL-Colesterol , Colágeno , Diabetes Mellitus/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Inflamação/tratamento farmacológico , Interleucina-17 , Rim , Masculino , Medicina Tradicional Chinesa , Camundongos , NF-kappa B , Proteinúria/tratamento farmacológicoRESUMO
A high-throughput method was developed and applied to screen for the active antihepatic steatosis components within Coptidis Rhizoma Alkaloids Extract (CAE). This method was a combination of two previously described assays: HepG2 cell extraction with HPLC analysis and a free fatty acid-induced (FFA) hepatic steatosis HepG2 cell assay. Two alkaloids within CAE, berberine and coptisine, were identified by HepG2 cell extraction with HPLC analysis as high affinity components for HepG2. These alkaloids were also determined to be active and potent compounds capable of lowering triglyceride (TG) accumulation in the FFA-induced hepatic steatosis HepG2 cell assay. This remarkable inhibition of TG accumulation (P < 0.01) by berberine and coptisine occurred at concentrations of 0.2 µ g/mL and 5.0 µ g/mL, respectively. At these concentrations, the effect seen was similar to that of a CAE at 100.0 µ g/mL. Another five alkaloids within CAE, palmatine, epiberberine, jateorhizine, columbamine, and magnoline, were found to have a lower affinity for cellular components from HepG2 cells and a lower inhibition of TG accumulation. The finding of two potent and active compounds within CAE indicates that the screening method we developed is a feasible, rapid, and useful tool for studying traditional Chinese medicines (TCMs) in treating hepatic steatosis.
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Traditional Chinese medicine (TCM) has been increasingly used for the treatment of dyslipidemia and cardiovascular disease. Recently, much progress has been made in studies on the mechanisms of action of the lipid-regulating effect of TCM in animal experiments. Current researches showed that the lipid-regulating effect of TCM may be related to the following actions: (1) inhibiting intestinal absorption of lipids; (2) reducing the biosynthesis of endogenous lipids; (3) increasing the catabolism of lipid, sterol substances in live system; (4) increasing the secretion of sterol substances in live system; (5) regulating transcription factors related to lipid metabolism. This paper provides an overview of the recent advances and discusses their implications in future development of lipid-lowering drugs from TCM.
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OBJECTIVE: The present study was designed to observe the effects and the possible mechanisms of Fufang Zhenzhu Tiaozhi Prescription (, FZT), a Chinese herbal preparation, on atherosclerosis in apolipoprotein E deficient (ApoE-/-) mice. METHODS: ApoE-/- mice were randomized to groups orally administrated without or with FZT (4.5 and 9 g crude drug/kg body weight, respectively). Atherosclerotic plaques, lipids profifiles in serum, aortic cholesterol content, serum indices of oxidative stress were measured, and mRNA expressions of scavenger receptors CD36 and scavenger receptor-A (SR-A) in aorta were analyzed. RESULTS: FZT dose-dependently suppressed the atherosclerotic plaques and reduced the cholesterol contents in aorta (P<0.05, P<0.01). In addition, FZT decreased the levels of total cholesterol and triglyceride in serum (P<0.05, P<0.01), inhibited the production of oxidized low density lipoprotein and malonaldehyde, and increased the superoxide dismutase activity in serum (P<0.05 or P<0.01). Furthermore, FZT down-regulated the mRNA expressions of CD36 and SR-A in the aorta (P<0.05, P<0.01). CONCLUSIONS: FZT reduced the atherosclerotic formation in ApoE-/- mice. The mechanisms might be related to the decrease of serum lipid level, the improvement of oxidative stress and the down-regulated expressions of scavenger receptors CD36 and SR-A, consequently reducing the foam cell formation, the hallmark of early atherosclerosis.
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OBJECTIVE: To investigate the effects of flavonoids from the leaves of Diospyros kaki L (FLDK) on the adhesion between the lymphocyte and the neurone. METHODS: Centrifugal assay for fluorescence-bsaed cell adhesion was used to assay the adhesion between the lymphocyte and the dorsal root ganglion (DRG). RESULTS: The adhesion was significantly suppressed in the presence of FLDK dose-dependently at 5, 25 microg/mL concentration. FLDK was also effective to inhibit the adhesion under the challenge of ICAM-1 by 28.5% and 50.1%, respectively. Furthermore, FLDK enforced the inhibition of anti-NCAM antibody on the lymphocyte adhesion to DRG cells. CONCLUSION: FLDK might contribute to the prevention and treatment of the inflammation injury under neuron insult such as ischemia/reperfusion, neurotrauma and other neurodegenerative disease by inhibiting the adhesion between lymphocytes and neurons.
Assuntos
Adesão Celular/efeitos dos fármacos , Diospyros/química , Flavonoides/farmacologia , Gânglios Espinais/citologia , Linfócitos/citologia , Substâncias Protetoras/farmacologia , Animais , Relação Dose-Resposta a Droga , Flavonoides/administração & dosagem , Flavonoides/isolamento & purificação , Gânglios Espinais/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Masculino , Moléculas de Adesão de Célula Nervosa/efeitos dos fármacos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Folhas de Planta/química , Plantas Medicinais/química , Substâncias Protetoras/administração & dosagem , Ratos , Ratos WistarRESUMO
OBJECTIVE: To observe the effects of flavone from leaves of Diospyros kaki on expression of apoptosis signal-regulating kinase 1 (ASK1) and rat vascular smooth muscle cells (VSMCs) proliferation by tumor necrosis factor alpha in vitro. METHODS: Rat aortic VSMCs were cultured in vitro and treated with tumor necrosis factor alpha (TNF-alpha) and flavone from leaves of Diospyros kaki, respectively, and were observed in comparison with the control group. The ratio of cell proliferation was determined by non-radioactive MTS/PES as-say. The expression of ASK1 protein was evaluated by the immunoblotting technique using anti-ASKL antibody. RESULTS: The ratio of cell proliferation was 0.817 +/- 0.074 in the control group, and was 1.865 +/- 0.093 in TNF-alpha20 ng/ml group. It was shown that TNF-alpha significantly induced rat VSMCs proliferation (P < 0.05). The ratio of cell proliferatioh was 0.905 +/- 0.044 in flavone from leaves of Diospyros kaki group corresponding to concentration of 50 microg/ml. It was shown that flavone from leaves of Diospyros kaki alone had no effect on rat VSMCs proliferation (p > 0.05). With TNF-alpha stimulation, flavone from leaves of Diospyros kaki significantly inhibited rat expression of ASK1 protein enhanced by TNF-alpha was significantly inhibited rat-VSMNCs proliferation (1.247 +/- 0.061 vs. 1.865 +/- 0.093, p < 0.05). The expression of ASK1 protein enhanced by TNF-alpha was significantly inhibited by flavone from leaves of Diospyros kaki in VSMCs. CONCLUSION: Flavone from leaves of Diospyros kaki can significantly inhibit expression of ASK1 protein stimulated by TNF-alpha of rat VSMcs in vitro.