Fenugreek (Trigonella foenum graecum L) is a plant traditionally used for the treatment of diabetes. It contains an unusual amino acid, 4-hydroxyisoleucine, demonstrated to have insulinotropic and antidiabetic properties in animal models. Here we examine the effect of 4-hydroxyisoleucine on liver function and blood glucose in two rat models of insulin resistance, fructose-fed rats and streptozotocin-induced diabetes type 2. In fructose-fed rats, levels of glucose and liver damage marker aspartate transaminase were markedly (84% and 93%, respectively) and significantly elevated compared with controls (p < < < < < 0.001 for both). Alanine transaminase was elevated slightly (18%), and all markers were restored to near control values after treatment with 4-hydroxyisoleucine at 50 mg/kg per day for 8 weeks, the effect being significant (p < < < < < 0.01) for all markers. This prolonged exposure to 4-hydroxyisoleucine was well tolerated in control animals and did not alter levels of glucose or liver damage markers significantly. In diabetic rats, treatment with 4-hydroxyisoleucine did not affect glucose or liver damage markers, but did improve HDL-cholesterol levels (31% increase, p < < < < < 0.05). These findings indicate 4-hydroxyisoleucine as a useful and well-tolerated treatment for insulin resistance, both directly as a hypoglycaemic and also as a protective agent for the liver.

Objective and Aim. Atorvastatin inhibits cholesterol synthesis which is critically important in the formation of the viral envelope and secretion. The efficacy and safety of giving atorvastatin (40 mg/day) as an adjunct to tenofovir in the treatment of hepatitis B (HBV) were assessed. Method. In this single-blind clinical trial, 40 patients with active chronic hepatitis B were randomly allocated to treatment or control groups. The treatment group received the standard treatment for chronic HBV (300 mg tenofovir twice a day) along with 40 mg/day atorvastatin for 12 months, while the control group received a placebo once daily in addition to the standard tenofovir regimen. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and HBV DNA copy numbers were measured at the beginning of the treatment and 1, 3, 6, 9, 12 months later. Results. One month after starting the treatment, the HBV copy number in the atorvastatin + tenofovir-treated group was significantly lower, by 200×, compared with the control group. After three months of the treatment, there was no detectable HBV DNA in 50% of the atorvastatin + tenofovir-treated group compared with 30% in the control group. The half-life of plasma viral load was 2.03 and 3.32 months in the atorvastatin + tenofovir-treated and control groups, respectively. No adverse events due to taking atorvastatin were observed. Conclusions. The combination of atorvastatin with tenofovir increased antiviral activity and led to a faster recovery from viral infection. Therefore, this modality can be recommended as a safe combination therapy for chronic hepatitis B patients.

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Introduction. There are a few evidences about targeting isoprenoids biosynthesis pathway in bacteria for finding new antibiotics. This study was conducted to assess antibacterial effects of vanadyl sulfate (VS), one of the mevalonate kinase inhibitors to find a new target for killing bacteria. Materials and Methods. Antibacterial effect of VS alone and in combination with glycine or EDTA was assessed on Escherichia coli and Pseudomonas aeruginosa as Gram-negative and Staphylococcus aureus and Enterococcus faecalis as Gram-positive bacteria using serial dilution method and minimum inhibitory concentrations (MICs) identified. Result. MICs for S. aureus and E. coli were 4 and 8 mg/mL, respectively. VS could not affect the growth of two other bacteria. However, VS in combination with glycine not only inhibited the growth of E. faecalis and P. aeruginosa, but also reduced MICs for VS-sensitive bacteria (S. aureus and E. coli). EDTA could reduce MIC for E. coli and P. aeruginosa. Conclusion. VS could inhibit the growth of S. aurous and E. coli, and adding glycine or EDTA improved VS antibacterial activity presumably via instability of the cell wall and enhanced transport of VS through bacterial cell wall. Inhibition of the isoprenoid pathway might provide new tools to overcome bacterial resistance.