Abstract:Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE) has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ)/kg. TQRFNE and distilled water (DW) as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW) group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.

Despite the pharmacological properties of thymoquinone (TQ), its administrationin vivoremains problematic partly due to its poor water solubility, leading to low absorptivity and bioavailability. Hence, the objective of this study is to prepare, characterize, and evaluate the stability of TQ nanoemulsion (TQNE). Conventional emulsion from TQ (TQCE) and empty nano- and conventional emulsions from Triolein (TRNE and TRCE) are also produced for comparison purposes. The oil-in-water nanoemulsions of TQ and Triolein were produced by high-pressure homogenization. Emulsions were characterized physically by droplet size, polydispersity index, zeta potential, and refractive index. The changes of these parameters in TQNE samples stored for 6 months at 4 and 25°C were not statistically significant (P<0.05). In addition, the initial particle sizes of TQNE and TRNE were 119.6 and 119.5 nm, respectively. Stability studies were also performed for the period of 6 months. At the end of the experiment, the percent of remaining TQ in TQNE at 4, 25, and 40°C was 90.6, 89.1, and 87.4 % respectively. Slower degradation of TQ indicated the chemical stability of TQ in TQNE samples. These results indicated that TQNE is stable over a period of 6 months.

Dysregulated metabolism is implicated in obesity and other disease conditions like type 2 diabetes mellitus and cardiovascular diseases, which are linked to abnormalities of peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ has been the focus of much research aimed at managing these diseases. Also, germinated brown rice (GBR) is known to possess antidiabetic, antiobesity and hypocholesterolemic effects. We hypothesized that GBR bioactive compounds may mediate some of the improvements in metabolic indices through PPARγ modulation. Cultured HEP-G2 cells were treated with 50 ppm and 100 ppm of extracts from GBR (GABA, ASG and oryzanol) after determination of cell viabilities using MTT assays. Results showed that all extracts upregulated the expression of the PPARγ. However, combination of all three extracts showed downregulation of the gene, suggesting that, in combination, the effects of these bioactives differ from their individual effects likely mediated through competitive inhibition of the gene. Upregulation of the gene may have therapeutic potential in diabetes mellitus and cardiovascular diseases, while its downregulation likely contributes to GBR’s antiobesity effects. These potentials are worth studying further.

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