Podocarpus nagi (Thunb), in the family Podocarpaceae, is a tropical hard tree native to China, Japan, and Taiwan, of which about 30 kinds of roots, stems, leaves, flowers are used as traditional medicines for treatment of fevers, asthma, coughs, cholera, distemper, chest complaints and venereal diseases. To identify bioactive constituents, phytochemical investigation was carried out on the chloroform and n-butanol fractions of the EtOH extract of the seeds of P. nagi. A total of 31 compounds were isolated with comprehensive chromatography technologies, and identified with 1D and 2D-NMR spectra and other spectroscopic studies. Among them, seventeen compounds were new, including fourteen totarane diterpenoids, namely 1-deoxy-2β-hydroxynagilactone A (1), 2-oxo-nagilactone A (2), 7β-hydroxynagilactone D (3), 3-epi-nagilactone D (4), nagilactones K and L (5 and 6), 3β-hydroxynagilactone L(7), 2β-hydroxynagilactone L (8), 3-epi-15-hydroxynagilactone D (9), 2α,3β,15-trihydroxynagilactone L (10), 15-hydroxynagilactone L (11), 2-epi nagilactone B (12), 3-epi-15-methoxycarbonyl nagilactone D (13) and nagilactone B 3-glucoside (14), and three abietane diterpenoids, namely 16-hydroxyllambertic acid (15), 7-oxo-l8-hydroxyferruginol (16), and 11-deoxy-5a,11,12-trihydroxy-6-oxaabieta-8,11,13-trien-7-one (17). 14 known compounds were identified by 1D-NMR and MS data. Among them, three compounds nagilactone G, 6α-hydroxysugiol and lambertic acid were found from genus Podocarpus for the first time were found from genus Podocarpus for the first time. Pharmacological studies found that many diterpenoids from P. nagi had potent anti-inflammatory and antitumor activities. In the current study, anti-tumor and anti-inflammatory activities of those diterpenoids were tested. Among them, 2β-hydroxynagilactone L (8) showed the most significant anti-tumor activity on A2780 lung cancer cell and HEY ovarian cancer cell, respectively. This compound showed the autophagy inducer activity through the JNK/c-Jun pathway. And the viii compound 16-hydroxylambertic acid (15) showed the anti-inflammatory effect on LPS-stimulated RAW264.7 cells. In the current thesis, 17 novel diterpenoids were identified from P. nagi, and the chemical principles for its anti-inflammatory and antitumor activities were achieved. These findings supply the first key step for the further development of P. nagi and its constituents as drugs or healthy food.

竹柏是羅漢松科竹柏屬的一種常綠植物，主要分佈于中國和日本的南部以 及台灣部分地區，在中國，竹柏的種子、根、莖、葉子、果實、花一直被用作 傳統藥物，用於治療炎癥、哮喘、霍亂、腹瀉、濕疹、發熱、性病、犬瘟熱、 胸部不適等。 本文主要對竹柏種子的化學成份以及其藥理活性進行了系統的研究。採用 矽膠柱層析色譜、葡聚糖凝膠柱色譜（Sephadex LH-20）、ODS 及製備型高效 液相色譜（Prep-HPLC）等分離純化技術，對竹柏種子乙醇提取物正丁醇部位 和乙酸乙酯部位的化學成份進行了研究，從中分離得到 31 個化合物。其中，分 离得到了十七個新化合物，包括 14 個新西兰罗汉松二萜类化合物，命名為 1-deoxy-2β-hydroxynagilactone A (1), 2-oxo-nagilactone A (2), 7β-hydroxynagilactone D (3), 3-epi-nagilactone D (4), nagilactones K and L (5 and 6), 3β-hydroxynagilactone L(7), 2β-hydroxynagilactone L (8), 3-epi-15-hydroxynagilactone D (9), 2α,3β,15-trihydroxynagilactone L (10), 15-hydroxynagilactone L (11), 2-epi nagilactone B (12), 3-epi-15-methoxycarbonyl nagilactone D (13) and nagilactone B 3-glucoside (14), 及三個松香烷二萜類化合 物，命名為 116-hydroxyllambertic acid (15), 7-oxo-l8-hydroxyferruginol (16), and 11-deoxy-5a,11,12-trihydroxy-6-oxaabieta-8,11,13-trien-7-one (17)。通過一維和二 維的核磁共振波譜以及其他譜學技術鑒定了結構。另外，通過一維核磁共振波 譜、質譜和理化方法鑒定了 14 個已知化合物的結構，其中有竹柏内酯 G，6α- 羟基柳杉酚和薄荷酸為第一次在竹柏属中發現。 活性筛选研究表明從竹柏種子中的竹柏内酯類化合物在抗炎、抗腫瘤方面 均有較好的活性。本课题针对 14 个主要竹柏内酯化合物进行抗炎、抗癌活性 筛选，对所分到的25个diterpenoids化合物进行抑制肿瘤细胞增殖作用的实验。 其中，发现 8 号化合物化合物 2β-hydroxynagilactone L 具有通過 JNK/c-Jun 通 路激活自噬的作用，15 号化合物 16-hydroxylambertic acid 具有抗炎作用。課題 對竹柏種子化學成分和藥理活性的研究，為進一步開發健康產品和藥物提供了 基礎。