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Zuotai is a drug containing mercury considered to be the king of Tibetan medicine. The biosafety of Zuotai led people's attention and so far little is known about the toxicity of Zuotai to mast cells. RBL-2H3 cells which used as an alternative model of mast cells were treated with Zuotai, β-HgS and positive drug Compound 48/80 respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the toxicity of drugs to RBL-2H3 cells. The degranulation of RBL-2H3 cells was studied from β-hexosaminidase, histamine, interleukin (IL)-4 and tumor necrosis factor-α (TNF-α). The result showed that Zuotai can affect the cytotoxicity and degranulation of RBL-2H3 cells and the results can provide reference for the toxicity evaluations of Tibetan medicine Zuotai.

Abstract Ethnopharmacological relevance Zuotai (gTso thal) has a long history in the treatment of cardiovascular disease, liver and bile diseases, spleen and stomach diseases as a precious adjuvant in Tibetan medicine. However, Zuotai is a mercury preparation that contains 54.5% HgS. Its application has always been controversial. Aim of the study To evaluate the toxicological effects of Zuotai in hepatocytes and in zebrafish. Materials and methods MTT was used to determine the survival rate of hepatocytes; Hoechst and TUNEL staining were used to detect the apoptosis cells; Western blot and RT-qPCR assay were used to determine the expression levels of the protein and mRNA; Liver morphology observation and H&E staining were used to evaluate the hepatotoxicity of Zuotai in Zebfrafish. Results The survival rate of L-02 cells, HepG2 cells and RBL-2A cells reduced by Zuotai (10−4–0.1 mg/mL) in a dose and time-dependent manner. Zuotai (0.1 mg/mL) induced HepG2 cells shrinkage, condensation and fragmentation and increased the number of apoptosis cells. The protein expression levels of cleaved Caspase-3 and Bax were increased and the expression levels of Bcl-2 were reduced after HepG2 cells exposed to Zuotai (10−4–0.1 mg/mL) for 24 h. In addition, Zuotai (0.2 mg/mL) induced the darker liver color of the larval zebrafish and changed the liver morphologic of adult zebrafish. Zuotai (0.2 mg/mL) also increased the mRNA levels of CYP1A1, CYP1B1 and MT-1 in the liver of adult zebrafish. However, no significantly hepatotoxicity was observed after hepatocytes and zebrafish exposed to HgS at the same dose. Conclusions Results showed that Zuotai induced hepatotoxicity effectively under a certain dose but its hepatotoxicity likely occurs via other mechanisms that did not depend on HgS. Graphical abstract Zuotai, a clinical adjuvant in Tibetan medicine, contains 54.5% HgS, which can induce apoptosis of liver cells and liver injury in zebrafish. However, HgS, the principal component of Zuotai did not exhibit hepatotoxicity at the same dose. fx1 [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with a broad spectrum of liver injury. Oxidant stress is believed to be the pathogenesis of NAFLD as the "second hit". Hydrogen peroxide is widely used as an oxidant reagent to induce the oxidant injury of cells and larval zebrafish. Recently, cichoric acid is being studied extensively for its obesity attenuating, hepatic steatosis reduction and anti-oxidant effects. In this study, to identify whether CRA could protect the H2O2 induced oxidant injury via anti-oxidant impact by using L02 and HepG2 hepatocytes as in vitro and larval zebrafish as in vivo injury models, and evaluated the protective and anti-oxidant effects of CRA by pretreated it on both in vitro and in vivo models. CRA was found to reduce the production of ROS and MDA, activate the anti-oxidant enzymes SOD and GSH-px, and pathways Keap1-Nrf2 and HO-1. These results demonstrated that CRA might protect the liver injury by its anti-oxidant effect, which could be a potential therapeutic agent of NAFLD.

Abstract Ethnopharmacological relevance Tibetan medicine has been practiced for 3800 years. Anzhijinhua San (AZJHS), which is a traditional Tibetan medicine, has been effective in the treatment of indigestion, anorexia and cold diarrhea. However, the effects of AZJHS on allergic diarrhea have not been reported. Aim of the study The aim of the present study was to elucidate the effect of AZJHS on experimental ovalbumin-induced diarrhea and elucidate its possible mechanism. Materials and methods Female BALB/c mice were sensitized by intraperitoneal injection with 50 μg ovalbumin (OVA) and 1 mg alum in saline twice during a 2-week period. From day 28, mice were orally challenged with OVA (50 mg) every other day for a total of ten times. AZJHS (46.8 and 468.0 mg/kg) was orally administered every other day from day 0–46. Food allergy symptoms were evaluated. OVA- specific IgE, 5-HT and its metabolites in serum were determined. Immunohistochemical and histopathology were performed in gastrointestinal tract tissues. 5-HT-related gene expression was assayed in the colon. Results Severe symptoms of allergic diarrhea were observed in the model group (diarrhea, anaphylactic response, and rectal temperature). AZJHS (46.8 and 468.0 mg/kg) significantly reduced mouse diarrhea and significantly prevented the increases in OVA-specific IgE levels (P < 0.05), which challenge with OVA. AZJHS (46.8 and 468.0 mg/kg) significantly prevented the increases in 5-HT-positive cells. The nuclei of EC cells in the AZJHS (46.8 and 468.0 mg/kg) group increased in size and the secretory granules were fewer in number compared with those in the model group. AZJHS (46.8 and 468.0 mg/kg) significantly increased the relative fold changes of 5-HTP and 5-HT compared with the model group. The mRNA expression of the serotonin transporter (Sert) and serotonin receptor 3A (Htr3a) was significantly decreased after the 10th challenge with OVA, and AZJHS (46.8 and 468.0 mg/kg) significantly increased these levels. Conclusions We demonstrated that the administration of AZJHS attenuated OVA-induced diarrhea by regulating the serotonin pathway. These results indicated that AZJHS may be a potential candidate as an anti-allergic diarrhea agent. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]