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Objective: Phaleria macrocarpa fruit has been reported to be effectively used in Malaysia and neighboring countries to prevent obesity. Despite its anti-obesity potential, no research has ever predicted the compound-lipase, compound-HMG-CoA reductase interactions and in vivo investigations to further confirm its anti-obesity properties. Thus, the purpose of this study was to assess the anti-obesity and antihyperlipidemic effects of P. macrocarpa by in vitro, computational (in silico), and in vivo assays. Method: Initially, fruit was extracted through liquid CO2 and heating under reflux extraction methods to obtain liquid CO2 extracts (LCE-1 and LCE-2) and heating under reflux extract (HRE), respectively. Subsequently, all three extracts were assessed for antioxidant potentials through in vitro bioassays and FTIR analysis to identify different types of functional groups present in the existing bioactive compounds. Successively, the most active fraction (LCE-2) was subjected to GCMS analysis for the identification of lipid lowering and lipase inhibitors through molecular docking approach. Finally, anti-obesity and lipid lowering effects were further confirmed through an in vivo assay using mice. Result: LCE-2 exhibited higher DPPH (IC50 = 0.172 mg/mL) and FRAP (78.98 AAEmg/g) antioxidant activities and showed more potent peaks in FTIR chromatograms than LCE-1 and HRE. Among the identified tentative bioactive compounds viz. methyl palmitate, palmitic acid, ethyl palmitate, methyl oleate, oleic acid, cis-vaccenic acid, 3-deoxyestradiol and phenol, 2,2′-methylenebis[6-(1,1-dimethylethyl)-4-methyl- were found as an anti-obesity and lipid lowering compounds whose protein–ligand interaction was confirmed by binding affinity, amino acid residues and bonding interactions. Similarly, anti-obesity and lipid lowering findings were also found in a mice model after 6 weeks treatment at a dose of 250 mg/kg b.w. Conclusion: Based on the aforementioned in vitro, in silico and in vivo findings, it is concluded that the LCE-2 possesses lipase and HMG-CoA reductase inhibitors that can assist to develop this plant’s extract as an alternative safe lipid lowering herbal medicine in future.

Background: Bezoar (PB) is a rare, solidified form of undigested food commonly found in the gastrointestinal tract of porcupine (Hystrix brachyura). It is believed to be traditionally used to treat various diseases including different kinds of cancers in Malaysia. However, its active principles have not been found out yet. The purpose of this study was to investigate the anticancer property of PB extract as well as to identify the metabolites responsible for its anticancer effect through a widely acclaimed metabolomics approach. Methods: Initially, 25 PB extracts using various solvent ratios of methanol–water (100, 75, 50, 25, 0% v/v) were prepared in regard to metabolomics approach and subsequently the cytotoxicity of each extract was determined against (melanoma) A375 cell line. The metabolites profiling of the most potent extract was conducted using gas chromatography mass spectrometry (GC–MS) and in silico investigation was performed on Bcl-2 and cyclin/CDK1 complex protein. Results: The correlation of the bioactivity with GC–MS data produced an orthogonal partial least square (OPLS) model which pinpointed four putative active compounds namely (1) cholest-7-en-3-beta-ol,4,4-dimethyl-,acetate; (2) 4-androsten-4-ol-3,17-dione; (3) isolongifolol and (4) gallic acid. The in silico data suggested the binding score and binding mode of active metabolites with the amino acid residues of protein via hydrophobic interactions. Conclusion: This study is the first to report the identified anticancer compounds from PB extract and evaluate them using molecular docking. This further confirms and justifies its traditional usage as an alternative medicine for the treatment of cancer in Malaysia.

Objectives: Phaleria macrocarpa (Scheff.) Boerl., an evergreen tree is found in Indonesia, Malaysia and Oceania, explicitly Northern Territory of Australia and Papua New Guinea. The fruits are traditionally used to treat various ailments including diabetes, psoriasis, looseness of the bowels, skin inflammation, malignancy, kidney, liver and heart sicknesses. However, to date, no comprehensive study investigating its toxicity profile utilizing liquid CO2 extract (LCE) has been reported in ICR mice. Hence, this research was performed to investigate the both acute and sub-acute toxicities of the liquid carbon dioxide extract from ripe fruit flesh of the P. macrocarpa in mice. Methods: Acute toxicity was assessed at a single dose of 3000 mg/kg bw for 2 weeks according to the up and down method of OECD 425 guideline, while the sub-acute test was assessed by liquid carbon dioxide extract at doses of 250, 500, 1000, and 2000 mg/kg bw for 28 days. The animals’ general behaviour, food intake, body weight, organ coefficients, biochemical and histological morphology were observed and analysed. Results: After acute exposure to LCE, there was no evidence of any severe or fatal effects in the mice. An acute toxicity result exhibited that LD50 of LCE was > 3000 mg/kg bw. The findings of subacute toxicity evaluation revealed that LCE at doses of 250 and 500 mg/kg bw had no significant detrimental impact. Moreover, LCE at 1000 and 2000 mg/kg bw demonstrated toxicity to the heart, liver, kidney and lung in mice identified by histological and biochemical investigation. Conclusions: The results confirmed that the LCE dosage at 500 mg/kg bw is considered a safe dose that can provide a better therapeutic effect without eliciting any adverse side effects.