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Title:	Kesan perencatan ekstrak dan sebatian daripada tumbuhan Malaysia terpilih ke atas pengagregatan pletelet dan pengoksidaan lipoprotein berketumpatan rendah (LDL) manusia.
Authors:	Fadlina Chany Saputri (P46214)
Supervisor:	Prof. Dr. Ibrahim Jantan
Keywords:	Ekstrak Lipoprotein berketumpatan rendah (LDL) Platelet Dissertations, Academic -- Malaysia
Issue Date:	12-Jul-2011
Description:	Penyaringan awal ke atas ekstrak metanol spesies Garcinia dan tumbuhan ubatan terpilih mendapati Garcinia eugeniaefolia, G. hombroniana, G. cantleyana var. cantleyana, Curcuma domestica dan C. xanthorrhiza menunjukkan aktiviti anti-oksidan terhadap lipoprotein berketumpatan rendah (LDL) dan antipengagregatan platelet manusia yang kuat. Kajian fitokimia terhadap bahagian ranting ketiga-tiga spesies Garcinia menghasilkan pemencilan lima sebatian benzofenon baru (2,6,3',5'-tetrahidroksibenzofenon, 3,4,5,3',5'-pentahidroksi benzofenon, 3,5,3',5'-tetrahidroksi-4-metoksibenzofenon, campuran 4,5,4',5'-tetrahidroksi-3-metoksibenzofenon dan 4,5,3',5'-tetrahidroksi-3-metoksibenzofenon) dan satu xanton baru (1,3,6-trihidroksi-5-metoksi-7-(3'-metil-2'-okso-but-3'-enil)-xanton), bersama dengan tujuh belas sebatian yang telah diketahui meliputi satu benzofenon (3,4,5,3'-tetrahidroksibenzofenon), lima xanton (1,7-dihidroksixanton,1,3,5-trihidroksixanton, 1,3,8-trihidroksi xanton, 2,4,7-trihidroksixanton, 1,3,5,7-tetrahidroksixanton), sembilan triterpenoid (friedelin, glutin-5-en-3β-ol, asid asetilursolik, asid ursolik, lupeol, garsihombronan B, garsihombronan D, garsihombronan E dan garsihombronan F), stigmasterol dan kuersetin. Selain itu, daripada ekstrak metanol bahagian rizom spesies Curcuma diperoleh kurkuminoid, iaitu kurkumin, demetoksikurkumin dan bisdemetoksikurkumin. Penyulingan hidro ke atas rizom spesies Curcuma pula menghasilkan minyak pati yang mengandungi ar-turmeron dan xantorizol sebagai komponen utama. Struktur kesemua sebatian telah ditentukan dengan menggunakan teknik spektroskopi. Minyak pati dan sebatian yang diperoleh telah dikaji kebolehannya dalam merencat pengagregatan platelet yang diaruhkan oleh asid arakidonik (AA), adenosina difosfat (ADP) dan kolagen menggunakan darah manusia dan pengoksidaan LDL yang dicetuskan oleh kuprum secara in vitro. Aktiviti antiplatelet ditentukan dengan menggunakan kaedah impedans elektrik. Manakala aktiviti anti-oksidan ditentukan dengan menggunakan asai TBARS. Xantorrizol menunjukkan aktiviti perencatan yang kuat terhadap pengagregatan platelet yang diaruhkan oleh AA, ADP dan kolagen dengan nilai IC50 masing-masing sebanyak 71.3, 29.4 and 90.9 μM. Antara sebatian yang dipencilkan daripada spesies Garcinia, 3,5,3',5'-tetrahidroksi-4-metoksibenzofenon sahaja yang mempamerkan aktiviti perencatan yang kuat terhadap AA, ADP dan kolagen dengan nilai IC50 masing-masing sebanyak 53.6, 125.7 and 178.6 μM. Sebatian 1,7-dihidroksixanton pula menunjukkan keberkesanan yang selektif dan kuat dalam merencat pengagregatan platelet teraruhkan ADP dengan nilai IC50 sebanyak 5.7 μM. Manakala asid asetilursolik secara selektif mampu merencat aktiviti kolagen dengan nilai IC50 sebanyak 138.8 μM. Kurkuminoid, xantorizol dan ar-turmeron menunjukkan aktiviti perencatan yang kuat ke atas pengoksidaan LDL yang dicetuskan oleh kuprum dengan julat nilai IC50 sebanyak 0.2 hingga 10.2 μM. Kebanyakan sebatian yang dipencilkan daripada spesies Garcinia menunjukkan aktiviti anti-oksidan yang tinggi. Antara kesemua sebatian yang dikaji, 1,3,5,7-tetrahidroksixanton menunjukkan aktiviti perencatan paling kuat dengan nilai IC50 sebanyak 0.5 μM berbanding probucol (0.6 μM), diikuti oleh 1,7-dihidroksixanton, 1,3,8-trihidroksixanton, 1,3,5-trihidroksixanton, 3,4,5,3',5'-pentahidroksi benzofenon dan 1,3,6-trihidroksi-5-metoksi-7-(3'-metil-2'-okso-but-3'-enil)-xanton dengan nilai IC50 masing-masing sebanyak 1.7, 1.8, 3.5, 3.6 dan 3.9 μM. Dapat disimpulkan bahawa kurkuminoid, xantorizol dan ar-turmeron berperanan dalam menentukan aktiviti antiplatelet dan antipengoksidaan LDL daripada spesies Curcuma. 3,5,3',5'-Tetrahidroksi-4-metoksibenzofenon, 1,7-dihidroksixanton dan 1,3,5,7-tetrahidroksixanton pula berpotensi untuk dibangunkan sebagai agen pelindung kardiovaskular.,Preliminary screening on the methanol extracts of several Garcinia species and selected medicinal plants have indicated that Garcinia eugeniaefolia, G. hombroniana, G. cantleyana var. cantleyana, Curcuma domestica and C. xanthorrhiza showed strong human low-density lipoprotein (LDL) antioxidant and antiplatelet aggregation activities. Phytochemical investigation of the twigs of the three Garcinia species resulted in the isolation of five new benzophenones (2,6,3',5'-tetrahydroxybenzophenone, 3,4,5,3',5'-pentahydroxybenzophenone, 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone, mixture of 4,5,4',5'-tetrahydroxy-3-methoxybenzophenone and 4,5,3',5'-tetrahydroxy-3-methoxybenzophenone) and one new xanthone (1,3,6-trihydroxy-5-methoxy-7-(3'-methyl-2'-oxo-but-3'-enyl)-xanthone), with seventeen known compounds including one benzophenone (3,4,5,3'-tetrahydroxybenzophenone), five xanthones (1,7-dihydroxyxanthone, 1,3,5-trihydroxyxanthone, 1,3,8-trihydroxyxanthone, 2,4,7-trihydroxyxanthone, 1,3,5,7-tetrahydroxyxanthone), nine triterpenoids (friedelin, glutin-5-en-3β-ol, acetylursolic acid, ursolic acid, lupeol, garcihombronane B, garcihombronane D, garcihombronane E and garcihombronane F), stigmasterol and quercetin. While the methanol extracts of the rhizomes of Curcuma species yielded curcuminoids, i.e. curcumin, demethoxycurcumin and bisdemethoxycurcumin. Hydrodistillation of the rhizomes yielded essential oils which contained ar-turmerone and xanthorrhizol as the major components. The structures of the compounds were elucidated by spectroscopic methods. The compounds and the essential oils were investigated for their ability to inhibit arachidonic acid (AA)-, adenosine diphosphate (ADP)-, and collagen-induced platelet aggregation in human whole blood and copper-mediated low-density lipoprotein (LDL) oxidation in vitro. The antiplatelet activity was examined using an electrical impedance method. The antioxidant activity of the compounds was examined using thiobarbituric acid reactive substances (TBARS) assay with human LDL as the oxidation substrate. Xanthorrhizol showed strong inhibitory activity against platelet aggregation induced by AA, ADP and collagen with IC50 values of 71.3, 29.4 and 90.9 μM, respectively. Among the compounds from Garcinia species, only 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone exhibited strong inhibitory activity against platelet aggregation induced by AA, ADP and collagen with IC50 values of 53.6, 125.7 and 178.6 μM, respectively. Compound 1,7-dihydroxyxanthone showed selective and strongest inhibition on platelet aggregation induced by ADP with IC50 value of 5.7 μM, while acetylursolic acid selectively inhibited the collagen-induced platelet aggregation with IC50 value of 138.8 μM. Curcuminoids, xanthorrhizol and ar-turmerone exhibited strong inhibitory activity on oxidation of LDL with IC50 values ranging from 0.2 to 10.2 μM. Most of the compounds isolated from Garcinia species showed high antioxidant activity. Among them, 1,3,5,7-tetrahydroxyxanthone showed the strongest inhibitory activity with IC50 value of 0.5 μM, comparable to that of probucol (0.6 μM) followed by 1,7-dihydroxyxanthone, 1,3,8-trihydroxyxanthone, 1,3,5-trihydroxyxanthone, 3,4,5,3',5'-pentahydroxy benzophenone and 1,3,6-trihydroxy-5-methoxy-7-(3'-methyl-2'-oxo-but-3'-enyl)-xanthone with IC50 values of 1.7, 1.8, 3.5, 3.6 and 3.9 μM, respectively. In conclusion, the curcuminoids, xanthorrhizol and ar-turmerone were responsible for the high LDL antioxidant and antiplatelet activities of the Curcuma species. 3,5,3',5'-Tetrahydroxy-4-methoxybenzophenone, 1,7-dihydroxyxanthone and 1,3,5,7-tetrahydroxyxanthone have potential to be developed into cardiovascular protective agents.,Ph.D
Pages:	437
Call Number:	QV766 .F145k 2012 9
Publisher:	UKM, Kuala Lumpur
Appears in Collections:	Faculty of Pharmacy / Fakulti Farmasi

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