Anti-Neuraminidase Bioactives from Manggis Hutan (Garcinia celebica L.) Leaves: Partial Purification and Molecular Characterization.

The neuraminidase enzyme (NA) from the influenza virus is responsible for the proliferation and infections of the virus progeny, prompting several efforts to discover and optimize effective neuraminidase inhibitors. The main aim of this study is to discover a new potential neuraminidase inhibitor that comes from Garcinia celebica leaves (GCL). The bioassay-guided isolation method was performed to obtain lead compounds. The binding interaction of the isolated compounds was predicted by using molecular docking studies. Friedeline (GC1, logP > 5.0), two lanastone derivatives (methyl-3α,23-dihydroxy-17,14-friedolanstan-8,14,24-trien-26-oat (GC2) and 24E-3a,9,23-trihydroxy-17,14-friedolanostan-14,24-dien-26-oate (GC3) with LogP > 5.0) and catechin (GC4, LogP = 1.4) were identified. The inhibitory potency of these four compounds on NA from C. perfringens and H1N1 was found to be as follows: GC4 > GC2 > GC3 > GC1. All compounds exhibited higher inhibitory activity towards C. perfringens NA compared to H1N1 NA. From the molecular docking results, GC4 favorably docked and interacted with Arg118, Arg371, Arg292, Glu276 and Trp178 residues, whilst GC2 interacted with Arg118, Arg371, Arg292, Ile222, Arg224 and Ser246. GC3 interacted with Tyr406 only. GC4 had potent NA inhibition with free energy of binding of -12 kcal/mol. In the enzyme inhibition study, GC4 showed the highest activity with an IC50 of 60.3 µM and 91.0 µM for C. perfringens NA and H1N1 NA-respectively.

ANTIBACTERIAL PROPERTIES OF SELECTED PLANTS CONSUMED BY PRIMATES AGAINST ESCHERICHIA COLI AND BACILLUS SUBTILIS.

Bacterial antimicrobial resistance is a major health problem worldwide. Plants consumed by non-human primates are potentially safe for humans. In this study, we examined the potential antibacterial properties of plants consumed by non-human primates in Indonesia. We studied the antibacterial properties of the leaf extracts of 34 primate-consumed plants against Escherichia coli and Bacillus subtilis in vitro. The plants were collected from the Pangandaran Conservation Area, West Java Province, Indonesia. The leaves were dried and then powdered by crushing and the potential active ingredients were extracted with 95% ethanol at room temperature for 24 hours. The obtained solvent was then dried at 50ºC under reduced pressure. The antibacterial properties of each product were then tested to determine the minimum inhibitory and minimum bactericidal concentrations using the broth microdilution technique and a disc diffusion test was also performed. The results show Kleinhovia hospita, Dillenia excelsa and Garcinia celebica had the best antibacterial properties against Escherichia coli and Ficus benjamina, Ficus altissima, and Elaeocarpus glaber had the best antibacterial properties against Bacillus subtilis. Some of the studied leaf extracts in our study have the potential to be developed into antibacterial medications and need to be studied further.

Genetic and Functional Analyses of Archaeal ATP-Dependent RNA Ligase in C/D Box sRNA Circularization and Ribosomal RNA Processing.

RNA ligases play important roles in repairing and circularizing RNAs post-transcriptionally. In this study, we generated an allelic knockout of ATP-dependent RNA ligase (Rnl) in the hyperthermophilic archaeon Thermococcus kodakarensis to identify its biological targets. A comparative analysis of circular RNA reveals that the Rnl-knockout strain represses circularization of C/D box sRNAs without affecting the circularization of tRNA and rRNA processing intermediates. Recombinant archaeal Rnl could circularize C/D box sRNAs with a mutation in the conserved C/D box sequence element but not when the terminal stem structures were disrupted, suggesting that proximity of the two ends could be critical for intramolecular ligation. Furthermore, T. kodakarensis accumulates aberrant RNA fragments derived from ribosomal RNA in the absence of Rnl. These results suggest that Rnl is responsible for C/D box sRNA circularization and may also play a role in ribosomal RNA processing.

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 IC50 of (+)-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. SUMMARY: Garcinia celebica leaf extract and fractions inhibit Plasmodium falciparum growthCatechin, the active compound of Garcinia celebica leaf extract, inhibits Plasmodium falciparum growth in a time- and dose-dependent manner Abbreviations used: RBC: Red Blood Cells; IC50: Inhibition Concentrattino 50; MeOH: Methanol; RPMI: Roswell Park Memorial Institute; EI: Electron Ionization.