Alisma Shugan Decoction (ASD) Ameliorates Hepatotoxicity and Associated Liver Dysfunction by Inhibiting Oxidative Stress and p65/Nrf2/JunD Signaling Dysregulation In Vivo.

BACKGROUND Liver fibrosis, defined as the aberrant accumulation of extracellular matrix (ECM) proteins such as collagen in the liver, is a common feature of chronic liver disease, and often culminates in portal hypertension, liver cirrhosis, and hepatic failure. Though therapeutically manageable, fibrosis is not always successfully treated by conventional antifibrotic agents. While the traditional Chinese medicine (TCM) Alisma Shugan Decoction (ASD) has several health benefits, including anti-inflammation, anti-oxidation, and limitation of cardiovascular and respiratory disorders, it remains unclear if it has any hepato-protective potential. MATERIAL AND METHODS The present study examined the therapeutic effect of ASD in thioacetamide (TAA)-induced liver injury and fibrosis rat models. RESULTS We demonstrated that 50 mg/kg ASD significantly reversed TAA-induced elevation of alanine or aspartate transaminase levels, elicited no dyscrasia, and conferred a 40% (p<0.01) or 20% (p<0.05) survival advantage, compared to rats treated with TAA or TAA+ASD, respectively. Treatment with ASD reversed TAA-induced liver injury and fibrogenesis via repression of alpha-SMA protein and reduction of the collagen area and fibrosis score. Concurrently, ASD markedly suppressed the mRNA expression of fibrogenic procollagen, ICAM-1, MMP2, MMP9, and MMP13, and production of TIMP-1, ICAM-1, CXCL7, or CD62L cytokine in rat liver injury models. Interestingly, ASD-elicited reduction of liver injury and fibrogenesis was mediated by dysregulated p65/NrF-2/JunD signaling, with a resultant 3.18-fold (p<0.05) increase in GSH/GSSH ratio, and a 3.61-fold (p<0.01) or 1.51-fold (p<0.01) reduction in the 4-hydroxynonenal and malondialdehyde (MDA) levels, respectively, indicating reduced oxidative stress in the ASD-treated rats, and suggesting an hepato-protective role for ASD. CONCLUSIONS In conclusion, the present study provides supplementary evidence of the therapeutic benefit of ASD as an efficient treatment option in cases of liver injury and fibrosis. Further large-cohort validation of these findings is warranted.

Simultaneous removal of nitrogen and phosphorus by cetylpyridinium bromide modified zeolite.

In this study, surfactant modified zeolite-clinoptilolite (SMZ) by CPB (cetylpyridinium bromide) was used for simultaneous removal of ammonium, nitrate and phosphate in synthetic wastewater, and the sorption properties of SMZ were determined and compared with natural zeolite. Results showed that natural clinoptilolite had good affinity for ammonium (8.940 mg/g), but not for nitrate (0.427 mg/g) and phosphate (0.801 mg/g). With the increase of surfactant loading from 5 g/L to 40 g/L, the sorption capacity for nitrate increased from 0.462 mg/g to 4.661 mg/g. when the surfactant loading is 40 g/L, the SMZ has a phosphate adsorption capacity of 2.119 mg/g. The SMZ had a significant enhancement on nitrate and phosphate sorption, could simultaneously remove ammonium, nitrate and phosphate at specific conditions, with removal efficiency up to 85.2%, 83.1% and 56.7%, respectively. Orthogonal experiments showed that ammonium concentration was the most important factor for ammonium sorption on SMZ. Surfactant loading was the major factor for nitrate and phosphate sorption. With the increase of surfactant loading from 5 g/L to 40 g/L, the sorption capacity for nitrate increased from 0.462 mg/g to 4.661 mg/g. When the surfactant loading is 40 g/L, the SMZ has the best phosphate adsorption capacity 2.119 mg/g. Samples were characterized by X-ray diffraction (XRD) and Brunauer-Emmett-Teller (BET). Semi-empirical quantum mechanics molecular simulation indicated that electrostatic attraction existed between CPB and dihydrogen phosphate ion. Results indicate that SMZs might have great potential of removing cations and anions simultaneously in the aquatic environment, which is good for eutrophication control and nutrients removal.

Simultaneous removal of ammonium and nitrate by HDTMA-modified zeolite.

In this study, surfactant (hexadecyltrimethylammonium, HDTMA) modified zeolite (clinoptilolite) (SMZ) was used for simultaneous removal of ammonium and nitrate in wastewater, and the sorption properties of SMZ were determined. Results showed that natural clinoptilolite had good affinity for ammonium, but low sorption ability for nitrate, and the ammonium sorption process was well described by the pseudo-second order kinetic model. The SMZ had a significant enhancement on nitrate sorption and could simultaneously remove ammonium and nitrate at specific conditions, with removal efficiency up to 93.6% and 81.8%, respectively. The sorption process fitted well with the Langmuir isotherm. Orthogonal experiments showed that ammonium concentration was the most important factor for ammonium sorption on SMZ. However, surfactant loading was the major factor for nitrate sorption. Meanwhile, phosphate did not interfere with nitrate removal. Semi-empirical quantum mechanics molecular simulation indicated that electrostatic attraction existed between HDTMA and nitrate. Results of this study demonstrated that SMZs may have great potential for removing cations and anions simultaneously in the aquatic environment.

Alisma Shugan Decoction attenuates hepatic fibrosis and endoplasmic reticulum stress in mice with carbon tetrachloride-induced fibrosis.

Background: Over the years, Alisma Shugan Decoction (ASD), because of its potent anti-inflammation activity, has been used in traditional Chinese medicine (TCM) for treatment of many inflammation-associated disorders including those of the heart, blood vessel and brain. Methods: Herein, we examined the probable therapeutic effect of ASD in carbon tetrachloride (CCl4)-induced liver injury and fibrosis mice models. Results: Our results demonstrate that ASD dose-dependently reduced the fibrosis-related increased collagen deposition secondary to liver tissue exposure to CCl4. Data from our biochemical analyses showed significantly less liver damage biomarkers including ALT, AST and hydroxyproline in the ASD-treated samples, suggesting hepato-protective effect of ASD. Furthermore, we demonstrated that treatment with ASD significantly reversed CCl4-induced elevation of TNF-α, IL-6, IL-1ß and MP-1. Interestingly, NF-κB signalling, a principal regulator of inflammation was markedly suppressed by ASD treatment. In addition, treatment with ASD deregulated stress signalling pathways by suppressing the expression of markers of unfolded protein response, such as ATF6, IRE and GRP78. Conclusion: In conclusion, the present study provides preclinical evidence for the use of ASD as an efficacious therapeutic option in cases of chemical-induced liver damage and/or fibrosis. Further large-cohort validation of these findings is warranted.