Neng Fisheri Kurniati

In Vitro Study on Antihypertensive and Antihypercholesterolemic Effects of a Curcumin Nanoemulsion

Atherosclerosis and hypertension can potentially progess into dangerous cardiovascular diseases such as myocardial infarction and stroke. Statins are widely used to lower cholesterol levels while antihypertensive agents such as captopril are widely prescribed to treat high blood pressure. Curcumin, a phenolic compound isolated from Curcuma domestica, has been proven effective for a broad spectrum of diseases, including hypertension and hypercholesterolemia. Therefore, curcumin is quite promising as an alternative therapeutic compound. Our previous studies have proven a significant increase in physical properties, bioavailability, and stability of curcumin when encapsulated in a nanoemulsion. The purpose of this study was to assess the ability of the nanoemulsion in enhancing curcumin activity as a antihypertensive and antihypercholesterolemic agent. The formulation and preparation method of the curcumin nanoemulsion have been developed in our previous study. Physical characterization was performed, including measurement of droplet size, polidispersity index, zeta potential, entrapment efficiency, and loading capacity. Antihypertensive activity of curcumin was evaluated by determining Angiotensin Converting Enzyme (ACE) inhibition in vitro. A substrate for ACE, hippuryl-L-histidyl-L-leucine was allowed to react with ACE, resulting in hippuric acid formation as the product. The degree of ACE inhibition by curcumin was represented by the amount of hippuric acid formed. Antihypercholesterolemic activity of curcumin was studied using the HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance which represents the oxidation of NADPH by the catalytic subunit of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) in the presence of the substrate HMG-CoA. Curcumin is known to have no significant difference in inhibiting ACE compared to Captopril, but when it was incorporated in the self-nanoemulsifying carrier, it slightly increased the inhibitory effect on ACE. In contrast, the effect of curcumin in reducing cholesterol based on the HMGR assay was more pronounced. Curcumin encapsulated in a nanoemulsion showed significant cholesterol-lowering activity compared to a standard drug, pravastatin. Therefore, we conclude that curcumin does not show ACE inhibitory effects, but has potential use as an alternative therapeutic compound to treat hyperlipidaemia. Curcumin encapsulated in a nanoemulsion increased not only the HMGR inhibition, but also ACE inhibition of curcumin. These effects are suggested to be the result of improved solubility in the nanoemulsion system.

Alpha Mangostin and Xanthone from Mangosteen (Garcinia mangostana L.) Role on Insulin Tolerance and PPAR-? in Preclinical Model Diabetes Mellitus

Objective : This research elaborated role of alpha mangostin and xanthone on insulin resistance and peroxisome proliferator–activated receptor (PPAR)-? by measuring blood glucose level and PPAR- ? expression on adipocyte cell culture. Methods : Insulin tolerance test were conducted using male wistar rat divided into 9 groups, which were normal, control (D-Glucose induced only), glibenclamide, various doses of a-mangostin and xanthone (5, 10, 20 mg/kgbw). All group induced by D-glucose 3 g/kg orally 30 minutes later. Blood glucose levels changes were observed at 90 th and 150 th minute. While other study observed PPAR-? expression on adipocyte cell culture that treated with a-mangostin/xanthone/pioglitazone in various concentration. Results : KITT in all treatment groups were significantly different (p<0.05) when compared to the positive control group, except xanthone 5 mg/kgbw. This suggests that a-mangostin 5, 10 and 20 mg/kgbw, xanthone 10 and 20 mg/kgbw, as well as metformin, have the effect of lowering insulin resistance in white rats given a 10-day fatty emulsion. Almost similar with thiazolinedione, alpha mangostin and xanthone increase PPAR-g expression in adipocyte when the concentration bigger. But xanthone effect not as good as ?-mangostin or thiazolinedione effect. Conclusion : Alpha mangostin and xanthone are two substances that showed potential effect to improve insulin tolerance by increasing PPAR-g in adipocyte.