Forhidrol, a bioactive fraction of Phaleria macrocarpa (Scheff.) Boerl., increases reverse cholesterol transport pathway by down-regulation of cholesteryl ester transfer protein activity


Submitted: June 23, 2017
Accepted: February 4, 2018
Published: May 11, 2018
Abstract Views: 1103
PDF: 509
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Authors

  • Guntur Berlian Section of Molecular Pharmacology, Department of Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, PT Dexa Medica, Cikarang, Indonesia.
  • Olivia M. Tandrasasmita Section of Molecular Pharmacology, Department of Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, PT Dexa Medica, Cikarang, Indonesia.
  • Dwi A.S. Suciptan Section of Molecular Pharmacology, Department of Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, PT Dexa Medica, Cikarang, Indonesia.
  • Raymond R. Tjandrawinata Section of Molecular Pharmacology, Department of Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, PT Dexa Medica, Cikarang, Indonesia.
Phaleria macrocarpa (Scheff.) Boerl. is one of the most popular medicinal plants in Indonesia. This plant has traditionally been used to lower cholesterol and control hypertension. This study was performed to examine the effect of Forhidrol, a bioactive fraction of P. macrocarpa (Scheff.) Boerl., to increase reverse cholesterol transport through the down-regulation of cholesteryl ester transfer protein (CETP) activity in hepatocellular carcinoma cell lines. Measurement of target genes including liver X receptor (LXR), sterol regulatory element-binding protein 1 (SREBP1), scavenger receptor class B type 1, low-density lipoprotein (LDL) receptor, apolipoprotein B, CYP11B1, CYP11B2, peroxisome proliferatoractivated receptor α (PPARα), peroxisome proliferator-activated receptor δ (PPARδ) and peroxisome proliferator-activated receptor γ (PPARγ) were done using realtime polymerase chain reaction assay. Secreted CETP and apolipoprotein A-1 were analyzed using western blot. CETP activity in vitro was measured using CETP inhibitor drug screening kit and triglyceride synthesis was measured using enzyme-linked immunosorbent assay. Forhidrol was found to significantly down-regulate CETP mRNA expression, as well as total CETP and cholesteryl esters transfer activity (P<0.05). It specifically reduced transcriptional level of regulatory genes of CETP promoter including SREBP-1 and LXR. Forhidrol also significantly increased PPARδ and PPARα expression (P<0.05) and slightly repressed triglycerides synthesis. In vivo study showed elevated high-density lipoprotein (HDL) levels in rabbits after 4-week treatment of Forhidrol at a dose of 37.5 mg/1.5 kg body weight compared to placebo. Conversely, LDL, triglyceride and CETP activity were decreased. Forhidrol increased HDL levels by reducing CETP-dependent transfer of cholesterol from HDL to LDL particles. Looking at possible side effects, Forhidrol apparently acted as a safe agent without negative effect towards blood pressure. These findings suggested that Forhidrol may be further developed as a potential anti-atherogenic drug.

Supporting Agencies

the authors received financial supports from PT Dexa Medica to conduct this study (Grant No. 070/MPC/DLBS/2015).

Berlian, G., Tandrasasmita, O. M., Suciptan, D. A., & Tjandrawinata, R. R. (2018). Forhidrol, a bioactive fraction of Phaleria macrocarpa (Scheff.) Boerl., increases reverse cholesterol transport pathway by down-regulation of cholesteryl ester transfer protein activity. Journal of Biological Research - Bollettino Della Società Italiana Di Biologia Sperimentale, 91(1). https://doi.org/10.4081/jbr.2018.6863

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