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

Guntur Berlian, Olivia M. Tandrasasmita, Dwi AS. Suciptan, Raymond R. Tjandrawinata
  • 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 AS. 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 | raymond@dexa-medica.com

Abstract

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 (HepG2). Measurement of target genes including LXR, SREBP1, SRB1, LDL-R, ApoB, CYP11B1, CYP11B2, PPARα, PPARδ and PPARγ were done using realtime PCR assay. Secreted CETP and ApoA-I were analyzed using western blot. CETP activity in vitro was measured using CETP inhibitor drug screening kit and triglyceride synthesis was measured using ELISA. Forhidrol was found to significantly down-regulate CETP mRNA expression, as well as total CETP and CE 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 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.

Keywords

Phaleria macrocarpa (Scheff.) Boerl.; CETP inhibitor; Atherosclerosis.

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Submitted: 2017-06-23 11:48:36
Published: 2018-05-11 15:16:51
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Copyright (c) 2018 Guntur Berlian, Olivia M. Tandrasasmita, Dwi AS. Suciptan, Raymond R. Tjandrawinata

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