Elin Yulinah Sukandar

Toxicity studies of a bioactive protein with antithrombotic-thrombolytic activity, DLBS1033.

Abstract DLBS1033 is a bioactive protein extract containing Lumbricus rubellus and has been known to have antithrombotic/thrombolytic activity. The present study was aimed to assess the safety aspect of DLBS1033 in a preclinical setting, which included observation on toxic signs after acute and repeated administrations, and the drug’s effect on prenatal development and drug interaction. In acute toxicity study, a high dose level (16.2 g/kg) of DLBS1033 was well tolerated. In subchronic toxicity study, after the doses of 270, 540 and 1080 mg/kg of DLBS1033 per day, no mortality was observed and other parameters were all observed to be normal. In prenatal developmental toxicity, no observed adverse effect level (NOAEL) of DLBS1033 was observed at a moderate dose (540 mg/kg). Coadministration of DLBS1033 with clopidogrel or aspirin did not cause gastric lesions, except when all three drugs were coadministrated. Taken together, results of the present study suggested that DLBS1033 is safe for long-term administration, with a caution at a high dose used during pregnancy, and can be used in combination with one of the antiplatelet drugs.

Combination Effect of Antituberculosis Drugs and Ethanolic Extract of Selected Medicinal Plants against Multi-Drug Resistant Mycobacterium tuberculosis Isolates

Adverse drug reaction and resistance to antituberculosis drugs remain the causes of tuberculosis therapeutic failure. This research aimed to find the combination effect of standard antituberculosis drugs with Hibiscus sabdariffa L., Kaempferia galanga L., and Piper crocatum N.E. Br against multi-drug resistant (MDR) Mycobacterium tuberculosis isolates. Two MDR strains (i.e., isoniazid/ethambutol resistant and rifampicin/streptomycin resistant) of M. tuberculosis were inoculated in Löwenstein–Jensen medium containing a combination of standard antituberculosis drugs and ethanolic extracts of H. sabdariffa calyces, K. galanga rhizomes, and P. crocatum leaves using various concentration combinations of drug and extract. The colony numbers were observed for 8 weeks. The effect of the combination was analyzed using the proportion method which was calculated by the mean percentage of inhibition reduction in a number of colonies on drug–extract containing medium compared to extract-free control medium. The results showed that all three plant extracts achieved good combination effects with rifampicin against the rifampicin/streptomycin resistant strain. Antagonistic effects were, however, observed with streptomycin, ethambutol and isoniazid, therefore calling for caution when using these plants in combination with antituberculosis treatment.

Antihyperuricemic Effect of Ethanol Extract of Snake Fruit (Salacca edulis Reinw.) var. Bongkok on Wistar Male Rat

The aim of the study was to investigate antihyperuricemic effect of snake fruit (Salacca edulis Reinw.) var. Bongkok Wistar male rates. Antihyperuricemic investigation on Wistar male rats showed that administration of ethanol extract at doses of 200 mg/kg bw decreased serum uric acid level significantly compared to control group at hour 6 and 7 (P < 0.05) after inducing with potassium oxonate intraperitoneally simultaneously with uric acid orally. Whereas, administration of ethanol extract at doses of 100 mg/kg bw did not decrease serum uric acid level significantly different compared to control group at hour 6 and 7 (P < 0.05). Determination of uric acid level in urine, administration of ethanol extract at a dose of 200 mg/kg bw, or probenecid as a standard drug, at a dose of 45 mg/kg bw increased excretion of urine uric acid level significantly different compared to control group in day of 7 (P < 0.05) after inducing with potassium oxonate intraperitoneally simultaneously with uric acid orally. However, increase of uric acid excretion by ethanol extract was lower compared to that of probenecid at a dose of 45 mg/kg bw. Mechanism of action of the ethanol extract as an antihyperuricemia has been proposed by inhibition of xanthine oxidase and finally decreased the synthesis of uric acid and increased the excretion of urine uric acid level.

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.

Angiotensin Converting Enzyme Inhibitor Activity of Ethanol Extract of Sonchus Arvensis (Linn.) Leaves

Objective: This research was to know the activity of Ethanol extract of Sonchus arvensis (Linn.) leaves in inhibiting the angiotensin converting enzyme (ACE) activity. ACE is an enzyme that functions to convert the Angiotensin I into Angiotensin II. The Angiotensin II has a role in the process of hypertension, it has a strong vasoconstriction effect inducting the hypertension. Methods: The ethanol extract of Sonchus arvensis (Linn.) was made through the maceration method with ethanol 96% as solvent. The inhibition extract activity of ACE activity was evaluated using N-hippuryl-L-histidyl-L-leucine (HHL) as a substrate and will be cleaved by ACE. The inhibitory activity of ethanol extract of Sonchus arvensis (Linn.) leaves towards ACE was calculated based on the number of hypural acid was created and calculated based on the absorbance value at 228 nm wavelength measured using spectrophotometer UV. The results: The ethanol extract of Sonchus arvensis (Linn.) has inhibition activity ACE at IC50 46.71 μg/ml and IC50 from captopril as a reference drug in 1,26 μg/ml. Therefore, it can be said that the inhibitory activity of Ethanol extract was lower that captopril. Conclusion: Sonchus arvensis (Linn.) is potentially used as the ACE inhibitor and is potential to be developed as antihypertension.

The effect of aqueous extract of Kalanchoe Folium on methylprednisolone pharmacokinetic profile

Aqueous extract of Kalanchoe pinnata leaves had immunosupressant effect on lupus nephritis model. When it combined with methylprednisolone, there is a risk of interaction. In this study rats divided into two groups, a group that received methylprednisolone (MP) (0.72 mg/kgBW) and a group that received MP in combination with extract (0.36 mg/kg BW MP and 140 mg/kg BW extract). These treatment were given everyday for 4 weeks. Methylprednisolone concentration in rats serum was measured using HPLC with extraction method according to Lawson method (1985). The column used was Inertsil C-18 using mobile phase KH2PO4 : metanol (15:85) buffer, flow rate 0.6 mL/minutes, UV detector (λ = 230 nm) and pressure 1319 psi. The result showed that there was an interaction occurred. The combination of MP and aqueous extract of K. pinnata leaves showed interaction which causing methylprednisolone level comparable with methylprednisolone level in MP group. Mean of decreasing MP level in serum was 0.285 ppm. It means that aque...