學術論文


Academic papers

抗發炎

論文出處:Curr Mol Pharmacol. 2021 Jan 20. doi: 10.2174/1874467214666210120152140.

論文名稱:Protective Effects of Antrodia cinnamomea and Its Constituent Compound Dehydroeburicoic Acid 32 against Alcoholic Fatty Liver Disease.

作  者:Xu L, Peng AK, Cao YN, Qiao X, Yue SS, Ye M, Qi R.

出 版 年:2021

分  類:抗發炎

論文結論:Background: Alcoholic fatty liver disease (AFLD), a leading chronic hepatic disease, affects an increasing number of people, and no effective drugs for the treatment of AFLD are available. Antrodia cinnamomea (AC) can inhibit AFLD, but its mechanisms and the effective compound in AC are unknown.
Objective: We aimed to explore the anti-AFLD mechanism of AC and the active compound within AC.
Methods: Wild-type (WT) C57BL/6J mice underwent 4 weeks of daily ethanol (EtOH) feeding to induce AFLD. AC or dehydroeburicoic acid 32 (DEA32), a compound in AC, was given to the mice. Parallel experiments to assess the effect of AC were conducted in aldehyde dehydrogenase 2 (ALDH2)-knockout (KO) mice. Primary mouse hepatocytes were incubated with ethanol and Alda-1 (an ALDH2 agonist), AC or DEA32.
Results: In WT mice with AFLD, AC reduced lipid deposition, increased the expression and activity of ALDH2, reduced the acetaldehyde content, and downregulated the expression of lipogenic and inflammatory genes in the liver. These effects of AC disappeared in ALDH2 KO mice. DEA32 was identified as an active compound in AC, as its effects on EtOH-treated WT hepatocytes were similar to those of AC, which were comparable to the effects of Alda-1. These effects of DEA32 disappeared in EtOH-treated ALDH2 KO hepatocytes. Furthermore, in WT mice with AFLD, DEA32 reduced lipid deposition, increased the activity of ALDH2 and reduced the accumulation of acetaldehyde in the liver. DEA32 also downregulated the mRNA expression of genes related to lipogenesis and inflammation.
Conclusion: AC and its constituent compound DEA32 inhibit AFLD by upregulating ALDH2 activity, accelerating acetaldehyde metabolism and suppressing lipogenesis and inflammation in the liver.
 

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論文出處:Front Pharmacol. 2018 Jul 18;9:780. doi: 10.3389/fphar.2018.00780. eCollection 2018.

論文名稱:Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways.

作  者:Chen SY, Lee YR, Hsieh MC, Omar HA, Teng YN, Lin CY, Hung JH

出 版 年:2018

分  類:抗癌

論文結論:

The cocultivation of Antrodia cinnamomea (AC) with ginger significantly induced the production of important triterpenoids and EACG was significantly more potent than EAC in targeting HCC cell lines.
1. Inhibited cancer cells growth via the induction of cell cycle arrest at G2/M phase and induction of apoptosis in Huh-7 and HepG2 cells and the activation of caspase-3. 
2. EACG modulated cyclin proteins expression and mitogen-activated protein kinase (MAPK) signaling pathways in favor of the inhibition of cancer cell survival. 

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論文出處:臺北醫學大學 牙醫學系碩博士班

論文名稱:牛樟芝萃取物經由IL-6/STAT3途徑抑制二氫咇啶誘發牙齦增生纖維母細胞增生之探討

作  者:廖士緯

出 版 年:2018

分  類:抗發炎

論文結論:內文尚未公開

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論文出處:Int J Mol Sci. 2020 Sep 22;21(18):6971. doi: 10.3390/ijms21186971.

論文名稱:4-Acetylantroquinonol B Inhibits Osteoclastogenesis by Inhibiting the Autophagy Pathway in a Simulated Microgravity Model.

作  者:Wu CH, Ou CH, Yen IC, Lee SY.

出 版 年:2020

分  類:抗發炎

論文結論:Astronauts suffer from 1–2% bone loss per month during space missions. Targeting osteoclast differentiation has been regarded as a promising strategy to prevent osteoporosis in microgravity (μXg). 4-acetylantroquinonol B (4-AAQB), a ubiquinone from Antrodia cinnamomea, has shown anti-inflammatory and anti-hepatoma activities. However, the effect of 4-AAQB on μXg-induced osteoclastogenesis remains unclear. In this study, we aimed to explore the mechanistic impact of 4-AAQB on osteoclast formation under μXg conditions. The monocyte/macrophage-like cell line RAW264.7 was exposed to simulated μXg (Rotary Cell Culture System; Synthecon, Houston, TX, USA) for 24 h and then treated with 4-AAQB or alendronate (ALN) and osteoclast differentiation factor receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoclastogenesis, bone resorption activity, and osteoclast differentiation-related signaling pathways were analyzed using tartrate-resistant acid phosphatase (TRAP) staining, actin ring fluorescent staining, bone resorption, and western blotting assays. Based on the results of TRAP staining, actin ring staining, and bone resorption assays, we found that 4-AAQB significantly inhibited μXg-induced osteoclast differentiation. The critical regulators of osteoclast differentiation, including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, and dendritic cell-specific transmembrane protein (DC-STAMP), were consistently decreased. Meanwhile, osteoclast apoptosis and cell cycle arrest were also observed along with autophagy suppression. Interestingly, the autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) showed similar effects to 4-AAQB. In conclusion, we suggest that 4-AAQB may serve as a potential agent against μXg-induced osteoclast formation.

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論文出處:Front Pharmacol. 2018 Dec 17;9:1449. doi: 10.3389/fphar.2018.01449. eCollection 2018.

論文名稱:Antrodia camphorata Mycelia Exert Anti-liver Cancer Effects and Inhibit STAT3 Signaling in vitro and in vivo.

作  者:Zhu PL, Fu XQ, Li JK, Tse AK, Guo H, Yin CL, Chou JY, Wang YP, Liu YX, Chen YJ, Hossen MJ, Zhang Y, Pan SY, Zhao ZJ, Yu ZL.

出 版 年:2018

分  類:抗癌

論文結論:

The ethyl acetate fraction of an ethanolic extract of Antrodia camphorata mycelia (EEAC) reduced cell viability, induced apoptosis, and retarded migration and invasion in cultured hepatocellular carcinoma cells (HCC),  HepG2 and SMMC-7721. hepatocellular carcinoma cell lines (HepG2 and SMMC-7721).
1. EEAC downregulated protein levels of phosphorylated and total STAT3 and JAK2 (an upstream kinase of STAT3) in HCC cells. STAT3, but not JAK2, mRNA levels were decreased by EEAC. 
2. EEAC also lowered the protein level of nuclear STAT3, decreased the transcriptional activity of STAT3, and downregulated protein levels of STAT3-targeted molecules, including anti-apoptotic proteins Bcl-xL and Bcl-2, and invasion-related proteins MMP-2 and MMP-9. 
3. In SMMC-7721 cell-bearing mice, EEAC (100 mg/kg, i.g. for 18 days) significantly inhibited tumor growth. EEAC induced apoptosis and suppressed JAK2/STAT3 activation/phosphorylation in the tumors.

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論文出處:國立宜蘭大學 生物技術與動物科學系生物技術碩士班

論文名稱:探討皿培牛樟芝萃取物對 NLRP3 發炎體的作用

作  者:林祖丞

出 版 年:2018

分  類:抗發炎

論文結論:牛樟芝的甲醇萃取物 (MEAC)抑制由LPS刺激巨噬細胞所誘導的 NLRP3 及 proIL-1β 表現,其中的機制是經由減少 ERK1/2 磷酸化及 ROS。MEAC 也具有抑制 caspase-1 活化的效果,而其中機制為減少 ROS 產生、粒線體損傷 及 ASC oligomerization。此外,由 caspase-1 所誘導的 pyroptosis 也會受到 MEAC 抑制。然而也發現由 MEAC 分離出的三萜類化合物 Antcin H 為其中有效的NLRP3 inflammasome 抑制劑,Antcin H 不僅抑制巨噬細胞中的NLRP3 inflammasome,也在小鼠實驗中發現具有改善由葡聚糖硫酸 (DSS) 所誘導的急性結腸炎。

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論文出處:Molecules. 2020 Sep 14;25(18):4213. doi: 10.3390/molecules25184213.

論文名稱:Antrodia cinnamomea Extraction Waste Supplementation Promotes Thermal Stress Tolerance and Tissue Regeneration Ability of Zebrafish.

作  者:Chang CC, Lu YC, Wang CC, Ko TL, Chen JR, Wang W, Chen YL, Wang YW, Chang TH, Hsu HF, Houng JY.

出 版 年:2020

分  類:抗發炎

論文結論:Antrodia cinnamomea (AC) has been shown to have anti-inflammatory, anti-tumor, and immunomodulation activities. It is estimated that hundreds of metric tons of AC extraction waste (ACEW) are produced per year in Taiwan. This study aims to assess the feasibility of applying ACEW as feed supplement in the aquaculture industry. ACEW significantly inhibited the growth of microorganisms in the water tank, by around 39.4% reduction on the fifth day with feed supplemented of 10% ACEW. The feed conversion efficiency of zebrafish with 10% ACEW supplementation for 30 days was 1.22-fold compared to that of the control. ACEW dramatically improved the tolerances of zebrafish under the heat and cold stresses. When at water temperature extremes of 38 °C or 11 °C, compared to the 100% mortality rate in the control group, the 10% ACEW diet group still had 91.7% and 83.3% survival rates, respectively. In a caudal fin amputation test, the fin recovery of zebrafish was increased from 68.4% to 93% with 10% ACEW diet after 3-week regeneration. ACEW effectively down-regulated the gene expression of TNF-α, IL-1β, IL-6, and IL-10, and up-regulated the gene expression of IL-4/13A. Additionally, the supplement of ACEW in the feed can maintain and prevent the fish’s body weight from dropping too much under enteritis. Taken together, ACEW has beneficial potential in aquaculture.

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論文出處:Cancers (Basel). 2018 Dec 5;10(12). pii: E491. doi: 10.3390/cancers10120491.

論文名稱:The Disruption of the β-Catenin/TCF-1/STAT3 Signaling Axis by 4-Acetylantroquinonol B Inhibits the Tumorigenesis and Cancer Stem-Cell-Like Properties of Glioblastoma Cells, In Vitro and In Vivo.

作  者:Liu HW, Su YK, Bamodu OA, Hueng DY, Lee WH, Huang CC, Deng L, Hsiao M, Chien MH, Yeh CT, Lin CM.

出 版 年:2018

分  類:抗癌

論文結論:

4-Acetylantroquinonol B (4-AAQB), a bioactive isolate of Antrodia cinnamomea, suppresses the tumor-promoting catenin/LEF1/Stat3 signaling, and inhibited stem cells (CSCs)-induced oncogenic activities in Glioblastoma (GBM) in vitro, with in vivo validation; thus projecting 4-AAQB as a potent therapeutic agent for anti-GBM target therapy. human glioblastoma cell lines (U87MG, DBTRG-05MG). 
1. 4-AAQB significantly downregulated β-catenin and dysregulated the catenin/LEF1/Stat3 signaling axis in U87MG and DBTRG-05MG cells, dose-dependently. 4-AAQB⁻induced downregulation of catenin positively correlated with reduced Sox2 and Oct4 nuclear expression in the cells. 
2. 4-AAQB markedly reduced the viability of U87MG and DBTRG-05MG cells, effectively inhibited the nuclear catenin, limited the migration and invasion of GBM cells, with concurrent downregulation of catenin, vimentin, and slug; similarly, colony and tumorsphere formation was significantly attenuated with reduced expression of c-Myc and KLF4 proteins.

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論文出處:國立虎尾科技大學 生物科技系碩士班

論文名稱:固態培養牛樟芝抗發炎成分之研究

作  者:廖志紘

出 版 年:2018

分  類:抗發炎

論文結論:固態培養牛樟芝菌絲體的乙醇萃取物(ANCI-E)溶於水中以氯仿分配萃取後,分別獲得氯仿層(ANCI-C)和水層(ANCI-W)。其中ANCI-C用高效液相色譜法進行分離,共得到11個化合物:分別為4,7-dimethoxy-5-methyl-1,3-benzodioxole (1)、1,2-dihydroxy-3,6-dimethoxy-4-methylbenzene (2)、antrodin B (3)、24-methylenelanost-8-en-3-ol (4)、dehydroeburicoic acid (5)、antcin A (6)、ubiquinone-3 (7)、4-acetylantroquinonol B (8)、antrocamol LT2 (9)、4-acetylantrocamol LT3 (10) 與 4-acetylantroquinonol K (11)。抗發炎活性評估結果顯示,能抑制LPS刺激RAW 264.7細胞的NO產生,而在細胞訊息傳遞機制探討則發現ANCI-C會顯著抑制誘導型一氧化氮合成酶(iNOS)的表達,也會顯著抑制環氧合酶-2(COX-2)的表達,推測ANCI之抗發炎機制可能經由抑制iNOS及COX-2來達成。

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論文出處:Nutrients. 2020 Sep 11;12(9):2778. doi: 10.3390/nu12092778.

論文名稱:Protective Effect of Spore Powder of Antrodia camphorata ATCC 200183 on CCl(4)-Induced Liver Fibrosis in Mice.

作  者:Ren Y, Li HX, Zhou L, Lu ZM, Shi J, Geng Y, Xu ZH.

出 版 年:2020

分  類:抗發炎

論文結論:Liver fibrosis is a pathological process with intrahepatic diffused deposition of the excess extracellular matrix, which leads to various chronic liver diseases. Drugs with high efficacy and low toxicity for liver fibrosis are still unavailable. Antrodia camphorata has antioxidant, antivirus, antitumor and anti-inflammation roles, and has been used to treat liver diseases in the population. However, the hepatoprotective effects of A. camphorata spores and the mechanisms behind it have not been investigated. In this study, we evaluate the hepatoprotective effect of spore powder of A. camphorata (SP, 100 mg/kg/day or 200 mg/kg/day) on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. SP groups reduced serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities compared with the CCl4 group. SP also showed a decrease in hydroxyproline (Hyp) content in liver tissues. SP improved cell damage and reduced collagen deposition by H&E, Sirius red and Masson staining. Furthermore, SP down-regulated the mRNA levels of α-SMA and Col 1, and the protein expression of α-smooth muscle actin (α-SMA), collagen I (Col 1), tumor necrosis factor alpha (TNF-α), toll like receptor 4 (TLR4) and nuclear factor-Κb (NF-κB) p65. In summary, SP has an ameliorative effect on hepatic fibrosis, probably by inhibiting the activation of hepatic stellate cells, reducing the synthesis of extracellular matrix.

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論文出處:Food Funct. 2018 Dec 13;9(12):6517-6525. doi: 10.1039/c8fo02079e.

論文名稱:Alpha-terpineol affects synthesis and antitumor activity of triterpenoids from Antrodia cinnamomea mycelia in solid-state culture.

作  者:Zhang Y, Li D , Wang Z , Zang W , Rao P , Liang Y , Mei Y .

出 版 年:2018

分  類:抗癌

論文結論:To enhance production of Antrodia cinnamomea triterpenoids (ACTs) from mycelia in solid-state culture, α-terpineol was added to the medium as an elicitor at an optimal concentration of 0.05 mL L-1. In assays of in vitro antitumor activity, ACTs-E (from culture with elicitor) produced stronger viability reduction in several tumor cell lines and stronger apoptosis induction in HeLa in a dose-dependent manner. ACTs-E strongly inhibited synthesis of topoisomerase I (TOP1) and tyrosyl-DNA phosphodiesterase I (TDP1), which are involved in DNA repair, at both transcriptional and protein levels.

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論文出處:中華醫事科技大學 醫學檢驗生物技術系碩士班

論文名稱:牛樟芝萃取物對藍光誘導視網膜細胞發炎之研究

作  者:鄭文淇

出 版 年:2018

分  類:抗發炎

論文結論:牛樟芝子實體、菌絲體水和乙醇萃取物,不會影響視網膜上皮細胞(ARPE-19)的存活率。以不同時間的藍光照射後,細胞死亡走入細胞凋亡路徑。以抑制藍光所誘發之IL-1β、IL-6及IL-8的發炎因子及胞內ROS和VEGF分泌量的生物活性。

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論文出處:Asian-Australas J Anim Sci. 2020 Jul;33(7):1167-1179. doi: 10.5713/ajas.19.0393.

論文名稱:Effects of dietary Antrodia cinnamomea fermented product supplementation on metabolism pathways of antioxidant, inflammatory, and lipid metabolism pathways-a potential crosstalk.

作  者:Lee MT, Lin WC, Lin LJ, Wang SY, Chang SC, Lee TT.

出 版 年:2020

分  類:抗發炎

論文結論:Objective
This study was conducted to fathom the underlying mechanisms of nutrition intervention and redox sensitive transcription factors regulated by Antrodia cinnamomea fermented product (FAC) dietary supplementation in broiler chickens.
Methods
Four hundreds d-old broilers (41±0.5 g/bird) assigned to 5 groups were examined after consuming control diet, or control diet replaced with 5% wheat bran (WB), 10% WB, 5% FAC, and 10% FAC. Liver mRNA expression of antioxidant, inflammatory and lipid metabolism pathways were analyzed. Prostaglandin E2 (PGE2) concentration in each group were tested in the chicken peripheral blood mononuclear cells (cPBMCs) of 35-d old broilers to represent the stress level of the chickens. Furthermore, these cells were stimulated with 2,2′-Azobis(2-amidinopropane) dihydrochloride (AAPH) and lipopolysaccharide (LPS) to evaluate the cell stress tolerance by measuring cell viability and oxidative species.
Results
Heme oxygenase-1, glutathione S-transferase, glutamate-cysteine ligase, catalytic subunit, and superoxide dismutase, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that regulates the above antioxidant genes were all up-regulated significantly in FAC groups. Reactive oxygen species modulator protein 1 and NADPH oxygenase 1 were both rather down-regulated in 10% FAC group as comparison with two WB groups. Despite expressing higher level than control group, birds receiving diet containing FAC had significantly lower expression level in nuclear factor-kappa B (NF-κB) and other genes (inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3, and cyclooxygenase 2) involving in inflammatory pathways. Additionally, except for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that showed relatively higher in both groups, the WB, lipoprotein lipase, Acetyl-CoA carboxylase, fatty acid synthase, fatty acid binding protein, fatty acid desaturase 2 and peroxisome proliferator-activated receptor alpha genes were expressed at higher levels in 10% FAC group. In support of above results, promoted Nrf2 and inhibited NF-κB nuclear translocation in chicken liver were found in FAC containing groups. H2O2 and NO levels induced by LPS and AAPH in cPBMCs were compromised in FAC containing diet. In 35-d-old birds, PGE2 production in cPBMCs was also suppressed by the FAC diet.
Conclusion
FAC may promote Nrf2 antioxidant pathway and positively regulate lipid metabolism, both are potential inhibitor of NF-κB inflammatory pathway.

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論文出處:Leuk Lymphoma. 2018 Oct 2:1-11. doi: 10.1080/10428194.2018.1512709. [Epub ahead of print]

論文名稱:The JAK inhibitor antcin H exhibits direct anticancer activity while enhancing chemotherapy against LMP1-expressed lymphoma.

作  者:Chen YF, Chang CH, Huang ZN, Su YC, Chang SJ, Jan JS.

出 版 年:2018

分  類:抗癌

論文結論:The latent membrane protein 1 (LMP-1) of EBV constitutively activates the JAK/STAT signaling pathway and contributes to the proliferation of EBV-infected primary human B lymphocytes. Antcin H, an analog of the JAK2 inhibitor zhankuic acid A (ZAA), inhibits LMP-1-induced JAK/STAT related signaling and induces lymphoma cell line apoptosis. Moreover, antcin H enhances low-dose methotrexate (MTX) cytotoxicity against lymphoma cells. Treatment of antcin H with low-dose MTX significantly suppressed tumor growth and prolonged the survival of tumor-bearing mice.

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論文出處:國立清華大學 化學系所

論文名稱:真菌牛樟芝和黑木耳的免疫增強多醣在化學及 生物學上的研究

作  者:皮勒拉

出 版 年:2018

分  類:抗發炎

論文結論:

牛樟芝的冷水萃取物中分離出多醣體,通過氣相層析質譜儀(GC-MS)和核磁共振光譜(NMR)進行分析決定。其免疫活性多醣體 (ACP; 分子量大於7萬) 的化學結構鑑定為galactomannan,為八醣重複序列組成的多醣體,結構解析為{→6)-D-Manp-(α1→2)-D-Manp-(α1→2)[D-Manp-(α1→3)-D-Manp-(α1→2)-D-Manp-(α1→6)-D-Galp (α1→6)]-D-Manp-(α1→6)-D-Galp-(α1→}。可活化小鼠巨噬細胞J774A.1、骨髓來源的小鼠巨噬細胞、以及人類單核細胞衍生的樹突狀細胞,具濃度依賴性的方式產生TNF-α和IL-6。類鐸受體4 (Toll-like receptor 4) 則被鑑定為ACP誘導巨噬細胞活化的主要細胞受體。除了能刺激免疫細胞活化外,ACP也能增強巨噬細胞的吞噬作用以及殺菌能力,同時也會增強對細菌內毒素LPS的耐受力 (LPS tolerance) 。

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