A 13-week subchronic toxicity study of an Eriobotrya japonica leaf extract in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Eriobotrya japonica leaf is widely used in traditional medicine, and exhibits various beneficial effects such as anti-inflammatory, antiviral, antioxidant, and antitumor activities. However, limited data are available on the potential adverse effects of E. japonica. AIM OF THE STUDY: This study investigated the potential subchronic toxicity of an E. japonica leaf extract (EJE) through a 13-week repeated oral dose experiment in Sprague-Dawley rats. MATERIALS AND METHODS: Forty male and 40 female rats were randomly assigned to four experimental groups: three treatment groups receiving 250, 500, and 1000 mg/kg/day of EJE and a vehicle control group receiving sterile distilled water for 13 weeks. RESULTS: Repeated oral administration of EJE for 13 weeks did not cause any treatment-related adverse effects with respect to clinical symptoms, body weight, food and water consumption, urinalysis, ophthalmology, necropsy findings, hematology, serum biochemistry, organ weight, and histopathological examination at any dose tested. Although some changes were observed in clinical symptoms, organ weight, hematology, and histopathology, these findings did not show a dose-response relationship and were within normal historical ranges for control rats. CONCLUSION: Under the present experimental conditions, the no-observed-adverse-effect level of EJE was > 1000 mg/kg/day in both sexes and no target organs were identified. The results suggest that the EJE is a safe traditional medicine for clinical applications at proper dose.

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study.

BACKGROUND: Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. METHODS: A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. RESULTS: Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels. CONCLUSION: The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01634256

Design and synthesis of novel antidiabetic agents.

The synthesis and structure-activity relationships of a novel series of substituted quercetins that activates peroxisome proliferator-activated receptor gamma (PPARgamma) are reported. The PPARgamma agonistic activity of the most potent compound in this series is comparable to that of the thiazolidinedione-based antidiabetic drugs currently in clinical use.