Forhidrol, a bioactive fraction of Phaleria macrocarpa (Scheff.) Boerl., increases reverse cholesterol transport pathway by down-regulation of cholesteryl ester transfer protein activity
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...
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| Format: | Article |
| Language: | English |
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PAGEPress Publications
2018-05-01
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| Series: | Journal of Biological Research |
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| Online Access: | https://www.pagepressjournals.org/index.php/jbr/article/view/6863 |
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| author | Guntur Berlian Olivia M. Tandrasasmita Dwi A.S. Suciptan Raymond R. Tjandrawinata |
| author_facet | Guntur Berlian Olivia M. Tandrasasmita Dwi A.S. Suciptan Raymond R. Tjandrawinata |
| author_sort | Guntur Berlian |
| collection | DOAJ |
| description | 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. |
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| id | doaj.art-496f4e643c7b4e768487c87b9d70af28 |
| institution | Directory Open Access Journal |
| issn | 1826-8838 2284-0230 |
| language | English |
| last_indexed | 2024-12-14T11:32:28Z |
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| spelling | doaj.art-496f4e643c7b4e768487c87b9d70af282022-12-21T23:03:12ZengPAGEPress PublicationsJournal of Biological Research1826-88382284-02302018-05-0191110.4081/jbr.2018.68635709Forhidrol, a bioactive fraction of Phaleria macrocarpa (Scheff.) Boerl., increases reverse cholesterol transport pathway by down-regulation of cholesteryl ester transfer protein activityGuntur Berlian0Olivia M. Tandrasasmita1Dwi A.S. Suciptan2Raymond R. Tjandrawinata3Section of Molecular Pharmacology, Department of Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, PT Dexa Medica, CikarangSection of Molecular Pharmacology, Department of Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, PT Dexa Medica, CikarangSection of Molecular Pharmacology, Department of Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, PT Dexa Medica, CikarangSection of Molecular Pharmacology, Department of Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, PT Dexa Medica, CikarangPhaleria 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.https://www.pagepressjournals.org/index.php/jbr/article/view/6863Phaleria macrocarpa (Scheff.) Boerl.cholesteryl ester transfer protein inhibitorAtherosclerosis. |
| spellingShingle | Guntur Berlian Olivia M. Tandrasasmita Dwi A.S. Suciptan Raymond R. Tjandrawinata 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 Phaleria macrocarpa (Scheff.) Boerl. cholesteryl ester transfer protein inhibitor Atherosclerosis. |
| title | Forhidrol, a bioactive fraction of Phaleria macrocarpa (Scheff.) Boerl., increases reverse cholesterol transport pathway by down-regulation of cholesteryl ester transfer protein activity |
| title_full | Forhidrol, a bioactive fraction of Phaleria macrocarpa (Scheff.) Boerl., increases reverse cholesterol transport pathway by down-regulation of cholesteryl ester transfer protein activity |
| title_fullStr | Forhidrol, a bioactive fraction of Phaleria macrocarpa (Scheff.) Boerl., increases reverse cholesterol transport pathway by down-regulation of cholesteryl ester transfer protein activity |
| title_full_unstemmed | Forhidrol, a bioactive fraction of Phaleria macrocarpa (Scheff.) Boerl., increases reverse cholesterol transport pathway by down-regulation of cholesteryl ester transfer protein activity |
| title_short | Forhidrol, a bioactive fraction of Phaleria macrocarpa (Scheff.) Boerl., increases reverse cholesterol transport pathway by down-regulation of cholesteryl ester transfer protein activity |
| title_sort | forhidrol a bioactive fraction of phaleria macrocarpa scheff boerl increases reverse cholesterol transport pathway by down regulation of cholesteryl ester transfer protein activity |
| topic | Phaleria macrocarpa (Scheff.) Boerl. cholesteryl ester transfer protein inhibitor Atherosclerosis. |
| url | https://www.pagepressjournals.org/index.php/jbr/article/view/6863 |
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