蛹蟲草子實體化學成分與生物活性之研究

Studies on the Chemical Constituents and Biological Activity of the Fruiting Body of Cordyceps militaris

丘錦朋(Ching-Peng Chiu)

指導教授 ： 張芳榮

共同指導教授 ： 吳永昌(Yang-Chang Wu)

高雄醫學大學/藥學院/天然藥物研究所博士班/博士(2018年)

摘要

蛹蟲草(Cordyceps militaris)又稱為北蟲草，是一種珍貴可食用真菌，常被用來替代冬蟲夏草(Cordyceps sinensis)，並應用於發炎、神經系統、代謝和免疫等疾病。本研究利用氣相層析串聯質譜儀(GCMS)、管柱層析及高效能液相層析儀(HPLC)由蛹蟲草乙醇萃取物鑑定分離、純化後得到6個脂肪酸[pentadecanoic acid (H-1)、hexadecanoic acid (H-2)、heptadecanoic acid (H-3)、9,12-octadecadienoic acid (H-4)、cis-9-octadecenoic acid (H-5) 以及stearic acid (H-6)] 、3 個腦苷脂[cordycerebroside A (M-1) 、soyacerebroside I (M-2)和glucocerebroside (M-3)]、2 個核苷酸[adenosine (M-4)和cordycepin (M-5)]及3 個固醇[egrosterol peroxide (M-6)、cerevisterol (M-7) 和 egrosterol (M-8)] 。其中，腦苷脂類化合物為首次從蛹蟲草中分離得到，且cordycerebroside A (M-1)為新化合物。
生物活性方面，9,12-octadecadienoic acid (H-4)和cis-9-octadecenoic acid (H-5)對於superoxide anion generation 和elastase release 具有顯著的抑制活性，IC50 值在1.59¬–3.43 μM 之間。而soyacerebroside I (M-2)對於NO的產生具有顯著的抑制活性(IC50 值為8.4 g/mL)，並且在10 M 濃度下能顯著抑制RAW264.7 巨噬細胞受LPS 誘發之的iNOS以及COX-2表現。此外，透過細胞以及動物實驗也證實soyacerebroside I (M-2)具有抗骨關節炎活性，能抑制抑制單核細胞/巨噬細胞浸潤到滑膜細胞中，並透過減少monocyte chemoattractant protein-1 (MCP-1)的表現來減緩滑膜發炎以及軟骨損傷。

關鍵字

蛹蟲草 ； 冬蟲夏草 ； 脂肪酸 ； 腦苷 ； 脂 ； 核苷 ； 酸 ； 腺苷 ； 蟲草素 ； 固醇 ； 抗發炎 ； 骨關節炎

並列摘要

Cordyceps militaris, also known as bei-chong-chaw and northern worm grass, is valuable edible fungus, which is commonly uses to replace Cordyceps sinensis treating for inflammation, nervous system, metabolism and immunity diseases. In this study, six fatty acids [pentadecanoic acid (H-1), hexadecanoic acid (H-2), heptadecanoic acid (H- 3), 9,12-octadecadienoic acid (H-4), cis-9-octadecenoic acid (H-5) and stearic acid (H-6)], three cerebrosides [cordycerebroside A (M-1), soyacerebroside I (M-2) and glucocerebroside (M-3)], two nucleosides [adenosine (M-4) and cordycepin (M-5)], and three steroids [egrosterol peroxide (M-6), cerevisterol (M-7) and egrosterol (M-8)] were isolated from the ethanolic extract of C. militaris utilizing GC/MS, column chromatography, and HPLC. Among those isolates, M-1 is a new compound, and M-1 to M-3 are first examples of cerebrosides isolated from C. militaris.
In studies of bioactivity, two fitty acids, 9,12-octadecadienoic acid (H-4) and cis-9-octadecenoic acid (H-5), showed better potency in anti-inflammatory effect by inhibiting superoxide anion generation and elastase release with IC50 1.59–3.43 μM. In addition, M-2 inhibited the production of nitric oxide (NO) with an IC50 value of 8.4 μg/mL and reduced the accumulation of pro-inflammatory iNOS protein, and reduce the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophages. Furthermore, M-2 showed the anti-osteoarthritis activity via inhibiting monocyte/macrophage infiltration into synoviocytes and attenuating synovial inflammation and preventing cartilage damage by reducing monocyte chemoattractant protein-1 expression.

並列關鍵字

Cordyceps militaris ； Cordyceps sinensis ； fatty acids ； cerebrosides ； nucleosides ； adenosine ； cordycepin ； steroid ； anti-inflammation ； osteoarthritis

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