Purpose: Substantial evidence indicates that obesity induces neuronal damage due to fat accumulation in the body especially in the brain and heart. The common anti-obesity product in the market is orlistat which act as lipase inhibitor through bond covalently to the active site on lipases. As the essential manifestation of lipase inhibitor was obvious ungainliness of neuronal imperativeness homeostasis inciting heftiness change after long time of treatment. Therefore the purpose of the study was to develop and characterize solid self-nanoemulsifying drug delivery system (SNEDDS) of natural Ginsenosides (Ginseng extract) to improve its oral bioavailability and brain targeting then evaluate its anti-obesity efficiency as a natural product to be an alternative to orlistat to avoid its neural side effect.
Methods: Solubility of ginsenosides in various oils, surfactants, and co-surfactants were studied to identify the components of SNEDDS; pseudo-ternary phase diagrams were plotted to identify the efficient self-emulsifying regions. Ginsenosides-loaded SNEDDS were prepared using isopropyl myristate or caproyl as oil; Tween 80 as surfactant; and Transcutol as cosurfactant. The formulations that passed thermostability evaluation test were assessed for particle size analysis, morphological characterization, refractive index, zeta potential, viscosity, electroconductivity, drug release profile, ex vivo permeability as well as Brain targeting. the anti-obesity efficiency of the optimized Ginsenosides SNEDDS compared with orlistat were performed using high food diet (HFD) rat model. In this study, thirty six male rats were used and divided randomly into six groups 6 rats for each. Each group treated as follows: Control feed basal diet (gp1), another five groups feed with high fat diet and treated with distilled water (gp2), orlistat (gp3), Ginsenosides standard solution (gp4), Ginsenosides SNE1 (gp5), and Ginsenosides SNE2 (gp6). Different neurotransmitters, such as Serotonin (5HT) and its metabolite (5HIAA), Dopamine (DP) & its metabolite (DOPAC), Nor-epinephrine (NE) in brain tissues were measured. Thyroxine 4 (T 4) and lipid profile, including (TC, TG, LDL, HDL and VLDL) were also measured
Results: Results revealed that two optimized formulae have the ability to form a good and stable nanoemulsion when diluted with water; the mean droplet size of all formulae was at the nanometric range with optimum polydispersity index values. All formulae showed negative zeta potential, One hundred percent of Ginsenosides was released from most formulae within 30 min. the results demonstrated that the ginsenosides SNE formulation could improve the neuronal dysfunction, decrease oxidative-nitrositve stress markers, recover brain balance energy, and decrease lipid profile and thyroid metabolic function in comparison with the high fat diet group. This effect could be attributed to the ability of SNE loaded ginsenosides to decrease serotonin level and to increase dopamine and thyroxine levels in comparison to their levels in FHD group and orlistat group. Also, it could maintain the lipase level as a control group in comparison to orlistat that decrease the lipase activity to 50%. This decrease in lipase activity is the responsible factor for the GIT disturbing side effect of orlistat.
Conclusion: In conclusion natural Ginsenosides based nanotechnology approaches as SNEDDS showed best choice treatment than conventional extract as it increases its efficiency and than orlistat as it avoids neuronal metabolic and energy dysfunction of orlistat. It can be concluded that SNEDDS of Ginsenosides may ameliorate metabolic syndromes and maintain homeostatic balance.