恆春福木莖部及山竹果肉之化學成分及生物活性之研究

Studies on the Chemical Constituents and Bioactivities of Stem of Garcinia multiflora and Fruit Pulp of Garcinia mangostana

鄭霖陽(Lin-Yang Cheng)

指導教授 ： 鍾美英

共同指導教授 ： 陳日榮(Jih-Jung Chen)

高雄醫學大學/藥學院/藥學系博士班/博士(2019年)

摘要

恆春福木與山竹，同為福木屬(金絲桃科)植物，為灌木，分佈於中國南部及台灣。本實驗室針對台灣產植物及市售水果進行抗發炎活性及抗血小板凝集篩選，其中恆春福木莖部及山竹果肉為活性植物。自恆春福木莖部分離得到三個新acylphloroglucinols: garcimultiflorone K (1), 13,14-didehydroxyisoxanthochymol (2), 13,14-didehydroxy- garcicowin C (3); 以及九個已知化合物，分別為garcinol (6), garcimultiflorone A (7), garcimultiflorone B (8), sampsonione B (9), 3-hydroxy-5-methoxybiphenyl (10), 1,24-tetracosanediol diferulate (11), friedelan-3-one (12), -sitostenone (13) 及stigmasta-4,22-dien-3-one (14) 。自山竹果肉部分離得到兩個新xanthones: 5-O-prenylmorusignin J (4), 6-O-prenylcalabaxanthone (5); 以及十八個已知化合物，分別為ananixanthone (15), morusignin J (16), calabaxanthone (17), xanthochymon B (18), 9-hydroxycalabaxanthone (19), thwaitesixanthone (20), brasilixanthone B (21), dulcisxanthone D (22), -mangostin (23), -mangostin (24), calocalabaxanthone (25), 1,7-dihydroxy-2-isoprenyl-3- methoxyxanthone (26), 1,3-dihydroxy-2-isoprenyl-7-methoxyxanthone (27), 1,5-dihydroxy-2-isoprenyl-3-methoxyxanthone (28), mangostenone A (29), cowaxanthone D (30), -sitosterol (31)及stigmasterol (32)。上述化合物之結構，經由各種圖譜分析(包括1D NMR, 2D NMR, MS, CD及X-ray)及文獻數據比對予以確認。分離得到的化合物中，13,14-didehydoxyisoxanthochymol (2)及sampsonione B (9)於30 M濃度下對於lipopolysachharide(LPS)誘導巨噬細胞NF-B活化具有抑制效果，其relative luciferace activity值(抑制%)分別為0.75 ± 0.03 (24 ± 4 %)及 0.12 ± 0.03 (88 ± 4 %)。5-O-Prenylmorusignin J (4), morusignin J (16), xanthochymon B (18), -mangostin (24), calocalabaxanthone (25), mangostenone A (29)及cowaxanthone D (30)對於fMLP誘導人類嗜中性白血球產生超氧陰離子(superoxide anion)，具有良好的抑制活性，其IC50值介於為0.66 − 39.00 M。另外，9-hydroxycalabaxanthone (19), -mangostin (24)及1,3-dihydroxy-2-isoprenyl-7-methoxyxanthone (27)對於U46619 (prostaglandin PGH2之合成類似物)所誘導之血小板凝集，亦具有不錯的抑制效果，其IC50值分別為33.77 ± 2.38, 29.99 ± 0.21及31.50 ± 0.10 M。此外，garcimultiflorone K (1)對於通過微小血管形成具抑制作用而表現出具有抗血管新生活性，其IC50值為14.3 ± 1.4 M。

關鍵字

恆春福木 ； 山竹 ； 金絲桃科 ； 生物活性

並列摘要

Garcinia multiflora and Garcinia mangostana are Plants of Garcinia (Guttiferae). The plants are shrubs and distributed in South China and Taiwan. In our studies on the anti-inflammatory constituents of Formosan plants and fruits, many species have been screened for in vitro anti-inflammatory and anti-platelet aggregative activity, and G. multiflora and G. mangostana have been found to be the active species. Three new acylphloroglucinols, garcimultiflorone K (1), 13,14-didehydroxy- isoxanthochymol (2), 13,14-didehydroxygarcicowin C (3), and 9 known compounds: garcinol (6), garcimultiflorone A (7), garcimultiflorone B (8), sampsonione B (9), 3-hydroxy-5-methoxybiphenyl (10), 1,24-tetra- cosanediol diferulate (11), friedelan-3-one (12), -sitostenone (13), and stigmasta-4,22-dien-3-one (14), have been isolated and identified from the stem of G. multiflora. From fruit pulp of G. mangostana, we have isolated two new xanthones, 5-O-prenylmorusignin J (4), 6-O-prenylcalabaxanthone (5), together with 18 known compounds: ananixanthone (15), morusignin J (16), calabaxanthone (17), xanthochymon B (18), 9-hydroxycalabaxanthone (19), thwaitesixanthone (20), brasilixanthone B (21), dulcisxanthone D (22), -mangostin (23), -mangostin (24), calocalabaxanthone (25), 1,7-dihydroxy-2-isoprenyl-3- methoxyxanthone (26), 1,3-dihydroxy-2-isoprenyl-7-methoxyxanthone (27), 1,5-dihydroxy-2-isoprenyl-3-methoxyxanthone (28), mangostenone A (29), cowaxanthone D (30), -sitosterol (31), and stigmasterol (32). The structures of above isolates were determined through spectral analyses and comparison of their physical and spectral data with literature. Among the isolated compounds, 13,14-didehydoxyisoxanthochymol (2) and sampsonione B (9) exhibited inhibition against lipopolysaccharide (LPS)-induced NF-B activation in macrophages at a concentration of 30 M with relative luciferase activity values (inhibition %) of 0.75 ± 0.03 (24 ± 4 %) and 0.12 ± 0.03 (88 ± 4 %), respectively. 5-O-Prenylmorusignin J (4), morusignin J (16), xanthochymon B (18), -mangostin (24), calocalabaxanthone (25), mangostenone A (29), and cowaxanthone D (30) exhibited inhibition with IC50 values in a range of 0.66–39.00 M on superoxide anion generation by human neutronnphils in response to fMet-Leu-Phe (fMLP). In addition, 9-hydroxy- calabaxanthone (19), -mangostin (24), and 1,3-dihydroxy-2- isoprenyl-7-methoxyxanthone (27) inhibited U46619-induced platelet aggregation with IC50 values of 33.77 ± 2.38, 29.99 ± 0.21, and 31.50 ± 0.10 M, respectively. Furthermore, garcimultiflorone K (1) exhibited the potent anti-angiogenic activity by exerting the inhibitory effect on tube formation (IC50 = 14.3 ± 1.4 M).

並列關鍵字

Garcinia multiflora ； Garcinia mangostana ； Guttiferae ； bio-activities

參考文獻

1. Robson NKB. Guttiferae in Flora of Taiwan. 2nd ed. Editorial Committee of the Flora of Taiwan: Taipei, Taiwan: 1996; Vol. 2, pp 694-714.

2. Editorial Committee of Flora of China. ‘Garcinia mangostana’ in ‘Flora of China’, Institute of Botany, Chinese Academy of Sciences: Beijing, China, 2007; Vol. 13 (http://www.eFloras.org)

3. 山竹狸團隊:山竹狸歷史沿革。2018年10月20日，取自http://taiwan-mangosteen-forest.tw/About

4. 楊遠波，劉和義，呂勝由，台灣維管束植物簡誌，第二卷，行政院農委會，台北，1997，p 198.

5. Malech HL, Gallin JI. Current concepts: immunology neutrophils in human diseases. N. Engl. J. Med. 1987, 317, 687-694.