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Ethnopharmacological relevance: This study examined the protective effects of total saponins from Ornithogalum saundersiae (Liliaceae) on d-galactosamine (d-GalN) and lipopolysaccharide (LPS) – induced fulminant hepatic failure. Materials and methods: Total saponins of Ornithogalum saundersiae (Liliaceae) (OC) were prepared with ethyl alcohol extract from bulbs of the plant. Mice were given an intraperitoneal injection of d-GalN (700mg/kg)/LPS (10μg/kg). OC (100mg/kg, 200mg/kg and 300mg/kg) was administered orally for 3 days continuously, and at the last day at 1h before the d-GalN/LPS injection. Mice were sacrificed at 8h after the d-GalN/LPS injection. The liver injury was assessed biochemically, investigating aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), glutathione (GSH) activities, and the expressions of caspase-3 and hypoxia inducible factor-1α (HIF-1α) as well. Tumor necrosis factor (TNF-α) content was measured after d-GalN/LPS induced 1h by ELISA assay. The survival rates after application of OC in 24h also were observed. Results: d-GalN/LPS increased the serum aminotransferase levels and lipid peroxidation, while decreased the reduced glutathione level. The pretreatment with OC attenuated these changes in a dose-dependent manner. Elevation of TNF-α level and activation of caspase-3, HIF-1α were observed in the d-GalN/LPS group, which was attenuated by OC. The survival rate of the OC groups was significantly higher than that of the d-GalN/LPS group. Conclusions: Protection afforded by OC against d-GalN/LPS-induced fulminant hepatic failure is the result of reduced oxidative stress, inhibited expression of caspase-3, HIF-1α, and anti-apoptotic activity. [Copyright &y& Elsevier]

Ethnopharmacological relevance Xie-Zhuo-Chu-Bi-Fang (XZCBF) is an empirical formula that was developed based on the principles of traditional Chinese medicine, for the therapeutic purpose of treating hyperuricemia. XZCBF has been clinically utilized in the Department of Traditional Chinese Medicine at General Hospital of Guangzhou Military Command of PLA for many years and has exhibited favorable efficacy. The aim of the study is to evaluate the effects of XZCBF on the expression of uric acid transporter 1 (URAT1) and miR-34a in hyperuricemic mice and to determine, the correlation between the two expression levels. Materials and methods A hyperuricemic animal model was created by administering adenine and allantoxanic acid potassium salt to mice. The blood uric acid levels were measured in these model mice after treatment with XZCBF for 15 days. The potential targets of miR-34a were screened. The expression levels of miR-34a and URAT1 in the renal tissues collected from the model mice were determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and their correlation was further established by immunohistochemistry and in situ hybridization. Results The uric acid levels in the model mice were significantly higher than those in the blank controls ( P <0.05). These levels were significantly lower in the three groups receiving different doses of XZCBF ( P <0.05), which was, in agreement with the downregulation of URAT1 and the upregulation of miR-34a in each group. The mRNA expression level of URAT1 was positively correlated with the concentration of uric acid but, negatively correlated with the expression level of miR-34a. Conclusions The ability of XZCBF to facilitate the excretion of uric acid and to lower its level in the model group was mediated by the upregulation of miR-34a and the inhibition of URAT1 mRNA expression, which suggests that XZCBF could be an option for the treatment of hyperuricemia in mice. [ABSTRACT FROM AUTHOR]