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Introduction: betel nut extract (Areca catechu L.), purwoceng (Pimpinella pruatjan) and ginseng (Panax ginseng) are known to have aphrodisiac effect. The aim of this research is to know the comparison of injected PLGA polymer nanoparticle substance as nanoparticle carrier of extract combination with the betel nut extract (Areca catechu L.), purwoceng (Pimpinella pruatjan) and ginseng (Panax ginseng) in which sub acutely causing the toxic effect on liver and kidney organ to the changes in blood biochemistry seen from SGPT, SGOT, Kreatinin and blood urea levels. Method: This research uses True experimental Design with pre-post-test only control group design. The production of betel nut extract combination substance (Areca catechu L.), purwoceng (Pimpinella pruatjan) and ginseng (Panax ginseng). The production of purwoceng and ginseng mixed nanoparticles substances with biodegradable polylactic-co-glycolic-acid (PLGA) and polyvinyl alcohol (PVA) polymers. Phytochemical tests of herbal extracts. The test animals in this study were male wistar rats aged 2-3 months which were injected with 3 dose levels of 1000 mg / kgBB, 500 mg / KgBB and 50 mg / KgBB orally for 28 days. On days 0 and 29 the blood of those animals were taken for measurement of SGPT, SGOT, Kreatinin and urea levels. The biochemical content obtained was then analyzed using One-way ANOVA and paired-T test. Result: The Betel nut Extract (Areca catechu L.), purwoceng (Pimpinella pruatjan) and ginseng (Panax ginseng) from result of phytochemical test containing flavonoid group compound. Results from the preparation of Nanoparticles on the optimum formula with% EE 90.703%; PSA 444.4 nm; PDI 0.310 and Zeta Potential -0.4 mV. The morphology of the nanoparticles is spherical. The blood biochemistry analysis measurement in the form of SGPT, SGOT, Kreatinin and urea obtained ANOVA value of 95% 0,267; 0,134; 0.586; 0,71 value p> 0.05 showed the giving of extract and nanoparticle still safe or still in normal limit and sig test value P Paired between 2 variables test of biochemical content p> 0.05 (95%) mean there is no difference between treatment before and after. Conclusions: The provision of either nanoparticle or betel nut extracts from the combination of betel nut, purwoceng and ginseng did not give toxic effect on liver and kidney organ to the changes in liver and kidney biochemistry seen from SGPT, SGOT, Kreatinin and urea levels. There was an absence of genetic kinship relation between the dosage of nanopartikel substance extract and the extract from a combination of betel nut, purwoceng and ginseng with sub acute toxicity effect on liver and kidney organ.