Anas Subarnas

Identification of compounds in the essential oil of nutmeg seeds (Myristica fragrans Houtt.) that inhibit locomotor activity in mice.

The present study was designed to evaluate the inhibitory effect of nutmeg (Myristica fragrans Houtt.) seed essential oil on the locomotor activity of mice in a wheel cage. Active compounds in the essential oil were identified by off-line solid phase extraction (SPE-C18) and GC/MS analysis. The essential oil was administered by inhalation at doses of 0.1, 0.3, and 0.5 mL/cage. The results showed that inhalation of nutmeg seed essential oil at a dose of 0.5 mL/cage decreased locomotion by 68.62%; and inhalation of 0.1 and 0.3 mL/cage inhibited locomotion by 62.81% and 65.33%, respectively. Generally, larger doses and longer administrations of nutmeg seed essential oil exhibited greater locomotor inhibition. Subsequently, the plasma concentrations of essential oil compounds were measured. The most concentrated compound in the plasma was myristicin. Half an hour after the addition of 1 mL/cage of nutmeg seed oil, the plasma concentration of myristicin was 3.7 μg/mL; one and two hours after the addition, the blood levels of myristicin were 5.2 μg/mL and 7.1 μg/mL, respectively. Other essential oil compounds identified in plasma were safrole (two-hour inhalation: 1.28 μg/mL), 4-terpineol (half-hour inhalation: 1.49 μg/mL, one-hour inhalation: 2.95 μg/mL, two-hour inhalation: 6.28 μg/mL) and fatty esters. The concentrations of the essential oil compounds in the blood plasma were relatively low (μg/mL or ppm). In conclusion, the volatile compounds of nutmeg seed essential oil identified in the blood plasma may correlate with the locomotor-inhibiting properties of the oil when administered by inhalation.

Analysis of Indonesian Spice Essential Oil Compounds That Inhibit Locomotor Activity in Mice

Some fragrance components of spices used for cooking are known to have an effect on human behavior. The aim of this investigation was to examine the effect of the essential oils of basil (Ocimum formacitratum L.) leaves, lemongrass (Cymbopogon citrates L.) herbs, ki lemo (Litsea cubeba L.) bark, and laja gowah (Alpinia malaccencis Roxb.) rhizomes on locomotor activity in mice and identify the active component(s) that might be responsible for the activity. The effect of the essential oils was studied by a wheel cage method and the active compounds of the essential oils were identified by GC/MS analysis. The essential oils were administered by inhalation at doses of 0.1, 0.3, and 0.5 mL/cage. The results showed that the four essential oils had inhibitory effects on locomotor activity in mice. Inhalation of the essential oils of basil leaves, lemongrass herbs, ki lemo bark, and laja gowah rhizomes showed the highest inhibitory activity at doses of 0.5 (57.64%), 0.1 (55.72%), 0.5 (60.75%), and 0.1 mL/cage (47.09%), respectively. The major volatile compounds 1,8-cineole, α-terpineol, 4-terpineol, citronelol, citronelal, and methyl cinnamate were identified in blood plasma of mice after inhalation of the four oils. These compounds had a significant inhibitory effect on locomotion after inhalation. The volatile compounds of essential oils identified in the blood plasma may correlate with the locomotor-inhibiting properties of the oil when administered by inhalation.

Potential Activity of Fevicordin-A from Phaleria macrocarpa (Scheff) Boerl. Seeds as Estrogen Receptor Antagonist Based on Cytotoxicity and Molecular Modelling Studies

Fevicordin-A (FevA) isolated from Phaleria macrocarpa (Scheff) Boerl. seeds was evaluated for its potential anticancer activity by in vitro and in silico approaches. Cytotoxicity studies indicated that FevA was selective against cell lines of human breast adenocarcinoma (MCF-7) with an IC50 value of 6.4 μM. At 11.2 μM, FevA resulted in 76.8% cell death of T-47D human breast cancer cell lines. Critical pharmacophore features amongst human Estrogen Receptor-α (hERα) antagonists were conserved in FevA with regard to a hypothesis that they could make notable contributions to its pharmacological activity. The binding stability as well as the dynamic behavior of FevA towards the hERα receptor in agonist and antagonist binding sites were probed using molecular dynamics (MD) simulation approach. Analysis of MD simulation suggested that the tail of FevA was accountable for the repulsion of the C-terminal of Helix-11 (H11) in both agonist and antagonist receptor forms. The flexibility of loop-534 indicated the ability to disrupt the hydrogen bond zipper network between H3 and H11 in hERα. In addition, MM/GBSA calculation from the molecular dynamic simulations also revealed a stronger binding affinity of FevA in antagonistic action as compared to that of agonistic action. Collectively, both the experimental and computational results indicated that FevA has potential as a candidate for an anticancer agent, which is worth promoting for further preclinical evaluation.

Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha

Tamoxifen is the most frequently used anti-estrogen adjuvant treatment for estrogen receptor-positive breast cancer. However, it is associated with an increased risk of several serious side–effects, such as uterine cancer, stroke, and pulmonary embolism. The 2′,4′-dihydroxy-6-methoxy-3,5-dimethylchalcone (ChalcEA) from plant leaves of Eugenia aquea, has been found to inhibit the proliferation of MCF-7 human breast cancer cells in a dose-dependent manner, with an IC50 of 74.5 μg/mL (250 μM). The aim of this work was to study the molecular interactions of new ChalcEA derivatives formed with the Estrogen Receptor α (ERα) using computer aided drug design approaches. Molecular docking using Autodock 4.2 was employed to explore the modes of binding of ChalcEA derivatives with ERα. The 3D structure-based pharmacophore model was derived using LigandScout 4.1 Advanced to investigate the important chemical interactions of the ERα-tamoxifen complex structure. The binding energy and the tamoxifen-pharmacophore fit score of the best ChalcEA derivative (HNS10) were −12.33 kcal/mol and 67.07 kcal/mol, respectively. The HNS10 interacted with Leu346, Thr347, Leu349, Ala350, Glu353, Leu387, Met388, Leu391, Arg394, Met421, and Leu525. These results suggest that the new ChalcEA derivatives could serve as the lead compound for potent ERα inhibitor in the fight against breast cancer.

Catechin isolated from Garcinia celebica leaves inhibit Plasmodium falciparum growth through the induction of oxidative stress

Background: Resistance of antimalarial drugs to Plasmodium falciparum has become a major concern in malaria eradication. Although it is also affected by several socioeconomic factors, a new antiplasmodial agent is needed for a global malaria control program. Objective: In this study, we attempted to uncover the antiplasmodial properties of Garcinia celebica, an Indonesian medicinal plant, along with the responsible compound and its possible mechanism. Materials and Methods: The G. celebica leaves were ethanol extracted and fractionated based on their polarity using n-hexane, ethyl acetate, and water. The antiplasmodial activity was tested in vitro against chloroquine-resistant P. falciparum at 100 μg/ml for 72 h. The active compound of the most active ethyl acetate fraction was subsequently isolated using column chromatography and identified by nuclear magnetic resonance. Results: The IC50of (+)-catechin, the characterized compound, against P. falciparum was 198 μM in 24 h and experiment. The isolated catechin inhibited P. falciparum growth in both trophozoite and schizont stages. An additional experiment also suggests that the antiplasmodial property of catechin occurs through the induction of the oxidative stress to P. falciparum. Conclusion: This result shows that the potential of catechin and its antimalarial properties should be explored further. Abbreviations used: RBC: Red Blood Cells; IC50: Inhibition Concentrattino 50; MeOH: Methanol; RPMI: Roswell Park Memorial Institute; EI: Electron Ionization.

AKTIVITAS ANTIOKSIDAN EKSTRAK dan FRAKSI KULIT BATANG TRENGGULI (Cassia fistula L) DENGAN METODE DPPH

Kulit batang trengguli (Cassia fistula L) mengandung senyawa yang bersifat antioksidan yang dapat ditentukan dengan metode peredaman radikal bebas 1,1-Difenil-2- Pikrilhidrazil (DPPH). Penelitian ini dilakukan untuk mengetahui adanya peredaman radikal bebas DPPH oleh ekstrak etanol kulit batang trengguli (EEKBT), fraksi Etil asetat (FEAKBT), fraksi n-Heksan (FnHKBT), fraksi air (FAKBT) dan vitamin C sebagai pembanding. Identifikasi golongan senyawa dilakukan dengan penapisan fitokimia. Fraksinasi dilakukan dengan metode ekstraksi cair-cair dengan tingkat kepolaran yang berbeda. Aktivitas antioksidan dilakukan dengan peredaman warna radikal bebas DPPH menggunakan spektrofotometri UVVis. Penelitian menunjukkan bahwa Fraksi etil asetat memiliki aktivitas antioksidan paling baik dengan nilai IC50 3,980 μg/ml dibandingkan vitamin C 4,716 μg/ml. Sedangkan nilai IC50 ekstrak etanaol, fraksi n-heksan, fraksi air adalah 10,613 μg/ml, 38,904 μg/ml dan 7,636 μg/ml terhadap peredaman warna DPPH. Kata kunci : Antioksidan, Cassia fistula, Fraksinasi, metode DPPH