Title

香杉芝菌絲體化學成分之抗氧化、抗發炎與抗癌活性

Translated Titles

Antioxidant, anti-inflammatory and anti-cancer activities of chemical constituents from Antrodia salmonea mycelium

Authors

林蘭閔

Key Words

香杉芝 ; 化學成分 ; 抗氧化能力 ; 抗發炎 ; 人類肝癌細胞SK-Hep-1 ; Antrodia salmonea ; chemical constituent ; antioxidant activity ; anti-inflammatory activity ; SK-Hep-1 cell

PublicationName

中興大學食品暨應用生物科技學系所學位論文

Volume or Term/Year and Month of Publication

2016年

Academic Degree Category

碩士

Advisor

毛正倫

Content Language

繁體中文

Chinese Abstract

香杉芝(Antrodia salmonea)為生長於中空腐朽香杉木內的一種台灣特有種真菌,被證實為是薄孔菌屬(Antrodia)中的新物種,其外型與牛樟芝(Antrodia cinnamomea)相似,且皆帶有苦味,這種苦味被認為是生理活性成分的來源。在先前的文獻當中已經證實牛樟芝所含的活性成分具有抗病毒、抗發炎與抗癌功效,但牛樟芝子實體價格非常地昂貴,所以近年來香杉芝被試圖作為牛樟芝的替代品,然而,目前關於香杉芝的研究文獻並不多,對其生理活性成分仍尚待研究。 本實驗探討香杉芝菌絲體中分離出的化學成分之抗氧化能力、抗發炎活性與抗癌活性。抗氧化能力測定為清除DPPH能力、螯合亞鐵離子能力、還原力與總抗氧化能力;抗發炎活性評估則將化合物與經LPS誘導的巨噬細胞RAW 264.7共同培養後,測定其一氧化氮(NO)含量與活性氧(ROS)含量;抗癌活性則將化合物與人類肝癌細胞SK-Hep-1共同培養,測定其對癌細胞之毒殺活性。 將香杉芝菌絲體70%乙醇萃取物(AS extract)與乙酸乙酯分配萃取,獲得香杉芝70%乙醇萃取物之乙酸乙酯層(ASE),之後利用矽膠管柱層析法分離ASE中化學成分,分離出的三種化合物經紅外線吸收光譜圖、紫外光可見光光譜圖、質譜圖與核磁共振光譜圖比對分析,證實化合物為2-methoxy-6-methyl-1,4-benzoquinone (C1)、3-(4-hydroxy-phenol)-4-isobutyl-1H-pyrrole-2,5-dione (C2)與3-hydroxy-3-methyl-1-(3,4,5-trihydroxy-2-methylphen-yl)butan-1-one (C3),其中C3為首次從自然界分離出的新化合物。 抗氧化能力中,以C3清除DPPH能力效果最好,其EC50小於12.5 µg/mL;還原力中僅C3具有還原力;總抗氧化能力中以C3效果最佳,其EC50為39.56 µg/mL;而這三種化合物皆不具有螯合亞鐵離子能力。 抗發炎活性評估中,當C1為1 µg/mL、C2與C3為15 µg/mL時,對於NO生成量之抑制率分別為38.96%、14.51%與72.03%;當C1為1 µg/mL與C3為15 µg/mL時,對於ROS生成量之抑制率分別為62.91%與161.94%,而C2不具有抑制效果,結果顯示C3顯著抑制NO與ROS生成量。 抗癌活性評估中,C1顯著抑制SK-Hep-1細胞之增生,其IC50於細胞培養24小時與48小時,分別為44.35 µM與40.96 µM。 綜合以上結果,C1具有良好的抗發炎活性,同時對於人類肝癌細胞SK-Hep-1具有毒殺活性;C3有最佳的抗氧化能力與抗發炎活性。 關鍵字:香杉芝、化學成分、抗氧化、抗發炎、人類肝癌細胞SK-Hep-1

English Abstract

Antrodia salmonea is a peculiar fungus in Taiwan, growing in the hollow rotten trunk of Cunninghamia konishii Hayata. It is a basidiomycete identified as a new species of the genus Antrodia. This fungus is similar to Antrodia cinnamonea. They both have a strong bitter taste, which is believed that could be the potent bioactive compounds. Many studies indicated that the bioactive compounds extracted from A. cinnamomea had an extensive range of biological activities, including antiviral, antioxidant and anticancer abilities. However, A. cinnamomea is very precious and expensive. A. salmonea is thus expected to substitute for the former as the medicinal fungus, yet very few biological activities of this fungus have been reported in the open literatures. The present study was aimed to investigate the antioxidant, anti-inflammatory, and anti-cancer effects of the chemical constituents which were isolated from A. salmonea mycelium. Chemical constituents were evaluated for their antioxidant activities in scavenging ability on DPPH radicals, chelating ability on ferrous ion, reducing power and trolox equivalent antioxidant capacity (TEAC), respectively. To investigate potential anti-inflammatory properties of these compounds, it was that using lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and then the production of nitric oxide (NO) and reactive oxygen species (ROS) were measured. As for the anti-cancer effects, these compounds were culture with SK-Hep-1 cells, a human hepatoma cell line, to measure cell viability. 70% ethanolic extract of A. salmonea mycelium (AS extract) partitioned between ethyl acetate and water to afford organic and aqueous parts. The organic part was ethyl acetate fraction of 70% ethanolic extract from A. salmonea mycelium(ASE). ASE was subjected to silica gel chromatography. Three com-pounds, 2-methoxy-6-methyl-1,4-benzoquinone (C1), 3-(4-hydroxy-phenol)-4-isobutyl-1H-pyrrole-2,5-dione (C2) and 3-hydroxy-3-methyl-1-(3,4,5-trihydro-xy-2-methylphenyl)butan-1-one (C3), were isolated from A. salmonea mycelium. C3 was the first time to isolated from nature products. Their structure were elucidated by spectrometric analysis including IR, UV-VIS, MS and NMR spectra. In the antioxidant activities, the results showed that scavenging ability on DPPH radicals of C3 was the most effective. The EC50 was less than 12.5 µg/mL. Only C3 had the reducing power. In TEAC, C3 had the greatest activity. Its EC50 was 39.56 µg/mL. But none of these compounds had the chelating ability on ferrous ion. In the anti-inflammatory activity, when C1 was at 1 µg/mL, the inhibition percentage of NO production was 38.96%. When C2 and C3 were both at 15 µg/mL, the inhibition percentages of NO production were 14.51% and 72.03%, respectively. When C1 was at 1 µg/mL and C3 was at 15 µg/mL, the inhibition percentages of ROS production were 62.91% and 161.94%, respectively. Never-theless, C2 had no effect on the inhibition of ROS production. As a result, C3 significantly inhibited the NO and ROS production. In the anti-cancer activity, the results showed that C1 had significantly effects on cell viability of SK-Hep-1. The IC50 of C1 on cell viability of SK-Hep-1 for 24 hours and 48 hours were 44.35 µM and 40.96 µM, respectively. In conclusion, C1 has good anti-inflammatory effect on macrophage-mediated, meanwhile, exhibites the most potent cytotoxicity against SK-Hep-1 cell. C3 has the most effective both in antioxidant activities and anti-inflammatory effect on macrophage-mediated. Keywords: Antrodia salmonea、chemical constituent、antioxidant activity、anti-inflammatory activity、SK-Hep-1 cell

Topic Category 農業暨自然資源學院 > 食品暨應用生物科技學系所
生物農學 > 生物科學
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