論文出處：Cancers (Basel). 2018 Dec 31;11(1). pii: E34. doi: 10.3390/cancers11010034.
論文名稱：Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling Pathways.
作 者：Chen YA, Tzeng DTW, Huang YP, Lin CJ, Lo UG, Wu CL, Lin H, Hsieh JT, Tang CH, Lai CH.
出 版 年：2018
論文結論：Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, ensitizes prostate cancer (PCa) to radiation through constitutive suppression of IGF-1R downstream signaling. Antrocin downregulated PI3K/AKT and MAPK signaling pathways as well as suppressed type 1 insulin-like growth factor 1 receptor (IGF-1R)-mediated induction of β-catenin to regulate cell cycle and apoptosis.
論文出處：Sci Rep. 2018 Nov 27;8(1):17424. doi: 10.1038/s41598-018-35780-y.
論文名稱：Antrodia cinnamomea induces autophagic cell death via the CHOP/TRB3/Akt/mTOR pathway in colorectal cancer cells.
作 者：Tsai DH, Chung CH, Lee KT.
出 版 年：2018
論文出處：Biomed Pharmacother. 2021 Jun;138:111504. doi:10.1016/j.biopha.2021.111504.
論文名稱：4-Acetylantroquinonol B ameliorates nonalcoholic steatohepatitis by suppression of ER stress and NLRP3 inflammasome activation.
作 者：Yen IC, Tu QW, Chang TC, Lin PH, Li YF, Lee SY.
出 版 年：2021
Nonalcoholic fatty liver disease (NAFLD) is an inflammatory lipotoxic disorder with a prevalence of over 25% worldwide. However, safe and effective therapeutic agents for the management of NAFLD are still lacking. We aimed to investigate the hepatoprotective effect and molecular mechanism of 4-acetylantroquinonol B (4-AAQB), a natural ubiquinone derivative obtained from the mycelia of Antrodia cinnamomea.
RAW264.7 and J774A.1 cells were treated with 4-AAQB and then stimulated with LPS or tunicamycin (TM) for 24 h. Inflammatory responses, markers of endoplasmic reticulum (ER) stress, and NOD-like receptor protein 3 (NLRP3) inflammasome were analyzed in both cell lines. In the applied in vivo model, male C57BL/6J mice were fed with chow or a methionine/choline-deficient (MCD) diet along with vehicle or 4-AAQB (10 mg/kg, i.p. injected, once a day) for 10 consecutive days. Plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Liver tissues were analyzed using histological techniques; protein levels involved in ER stress, NLRP3 inflammasome, and inflammatory responses were measured.
4-AAQB significantly ameliorated the plasma levels of ALT and AST as well as the NAFLD activity score (NAS) in mice fed the MCD diet. In addition, 4-AAQB suppressed inflammatory responses, ER stress, and NLRP3 inflammasome activation, but increased the nuclear factor erythroid 2-related factor 2 (Nrf2) and Sirtuin 1 (SIRT1) signaling pathways in both in vitro and in vivo models.
We suggest that 4-AAQB treatment might be a tangible therapeutic strategy in the management of NAFLD/NASH.
論文出處：Carbohydr Polym. 2018 Dec 15;202:536-544. doi: 10.1016/j.carbpol.2018.09.009. Epub 2018 Sep 6.
論文名稱：Chemical identification of a sulfated glucan from Antrodia cinnamomea and its anti-cancer functions via inhibition of EGFR and mTOR activity.
作 者：Lu MK, Lin TY, Chang CC.
出 版 年：2018
論文結論：AC-SPS-F3, a sulfated glucan from Antrodia cinnamomea, reduced lung cancer cell viability via inhibition of EGFR and mTOR activity.
論文出處：J Am Coll Nutr. 2021 May-Jun;40(4):349-357. doi:10.1080/07315724.2020.1779850.
論文名稱：Hepatoprotective Effect of Antrodia cinnamomea Mycelium in Patients with Nonalcoholic Steatohepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial.
作 者：Chiou YL, Chyau CC, Li TJ, Kuo CF, Kang YY, Chen CC, Ko WS.
出 版 年：2021
論文結論：Nonalcoholic steatohepatitis (NASH) has become a prominent liver disease in contemporary society because of the changing dieting styles. Complicated syndromes often accompanied by obesity and diabetes makes no standard treatment for NASH. Therefore, we investigated the potential role of Antrodia cinnamomea mycelium (ACM) as nutraceutical supplementation in the treatment of NASH in this 6-month randomized, double-blind, placebo-controlled study.
28 Participants were treated with three capsules per day containing either 420 mg of ACM or 420 mg of starch as a placebo. The participants were required to follow a predetermined regular visit to hospital every three months during the intervention period (6 months). During each study visit, subjects underwent anthropometric measurements and blood testing for biochemical analysis, immune function assay, inflammatory cytokines assay, and FibroMax test.
The ACM supplemented group had a significant improvement in steatosis and decreased in the inflammatory marker of TNF-α after three and six months. NASH patients who received ACM showed a significant decrease in the SteatoTest mean value from 0.66 at baseline to 0.49 at 6 months (p < 0.029) and the ActiTest mean value decreased from 0.46 at baseline to 0.30 at 6 months (p < 0.029).
This is the first clinical investigation that explores the hepatoprotective effect of A. cinnamomea mycelium in patients with NASH. No participants experienced any adverse events during the study, which suggested that ACM is a safe alternative treatment for NASH.
論文出處：Int J Biol Macromol. 2018 Aug 22. pii: S0141-8130(18)32863-0. doi: 10.1016/j.ijbiomac.2018.08.112. [Epub ahead of print]
論文名稱：Microelements induce changes in characterization of sulfated polysaccharides from Antrodia cinnamomea.
作 者：Lin TY, Tseng AJ, Chao CH, Lu MK
出 版 年：2018
論文結論：Microelements play pivotal roles for fungal/plant development and end-use properties. CuSO4 and ZnSO4 increased the mycelium yields and promoted sulfated polysaccharides (SPS) production. Anticancer function studies showed that those SPSs inhibit the cell viability of lung cancer A549 cells via downregulation of EGFR signaling.
論文出處：Front Immunol. 2021 May 14;12:664425. doi: 10.3389/fimmu.2021.664425.
論文名稱：2,4-Dimethoxy-6-Methylbenzene-1,3-diol, a Benzenoid From Antrodia cinnamomea, Mitigates Psoriasiform Inflammation by Suppressing MAPK/NF-kappaB Phosphorylation and GDAP1L1/Drp1 Translocation.
作 者：Chuang SY, Chen CY, Yang SC, Alalaiwe A, Lin CH, Fang JY.
出 版 年：2021
論文結論：Antrodia cinnamomea exhibits anti-inflammatory, antioxidant, and immunomodulatory activities. We aimed to explore the antipsoriatic potential of 2,4-dimethoxy-6-methylbenzene-1,3-diol (DMD) derived from A. cinnamomea. The macrophages activated by imiquimod (IMQ) were used as the cell model for examining the anti-inflammatory effect of DMD in vitro. A significantly high inhibition of IL-23 and IL-6 by DMD was observed in THP-1 macrophages and bone marrow-derived mouse macrophages. The conditioned medium of DMD-treated macrophages could reduce neutrophil migration and keratinocyte overproliferation. DMD could downregulate cytokine/chemokine by suppressing the phosphorylation of mitogen-activated protein kinases (MAPKs) and NF-κB. We also observed inhibition of GDAP1L1/Drp1 translocation from the cytoplasm to mitochondria by DMD intervention. Thus, mitochondrial fission could be a novel target for treating psoriatic inflammation. A psoriasiform mouse model treated by IMQ showed reduced scaling, erythema, and skin thickening after topical application of DMD. Compared to the IMQ stimulation only, the active compound decreased epidermal thickness by about 2-fold. DMD diminished the number of infiltrating macrophages and neutrophils and their related cytokine/chemokine production in the lesional skin. Immunostaining of the IMQ-treated skin demonstrated the inhibition of GDAP1LI and phosphorylated Drp1 by DMD. The present study provides insight regarding the potential use of DMD as an effective treatment modality for psoriatic inflammation.
出 版 年：2020
論文結論：非酒精脂肪肝病（NAFLD）是全世界最常見的慢性肝病，然而還尚未找到一個安全且有效的藥物，值得我們深入探討。本研究探討牛樟芝菌絲體之萃取物（ACE）對於NAFLD的機轉與作用。我們在細胞模型中使用J774A.1 和HepG2 以及Caco-2三種細胞株，實驗方法利用西方墨點法與RT-qPCR分析內質網壓力、NLRP3 inflammasome及緊密連接蛋白相關的蛋白表現量與相關基因表現量。此外於動物模型採用8周齡C57BL/6品系雄性小鼠餵食60%高脂飲食（HFD），同時將ACE混於飲水每日給予，並且記錄其飲食飲水量與體重變化，持續10週後安樂死，血清採集檢測轉胺酶與血脂等，肝臟組織收集後，其中一葉進行組織切片並進行常規染色（H&E）以及油紅染色（Oil red O）評估肝臟內脂質含量，其餘肝臟與迴腸組織均質後利用西方墨點法與RT-qPCR檢測。此外，利用微米級電腦斷層掃描造影系統（Micro CT）和16S rRNA定序分析了活體脂肪組織分佈和腸道菌群組成。我們發現ACE顯著抑制HFD飲食誘導的肥胖症狀，胰島素阻抗，並且不影響進食以及損害腎功能，改善HFD飲食誘導非酒精性肝病的症狀。我們發現不論在細胞及動物的模型中，ACE都顯著抑制內質網壓力及NLRP3 inflammasome 活化，增加自嗜作用，並進一步發現 ACE通過增加緊密連接蛋白修復腸道屏障功能。與肥胖相關的腸道菌群，包括Bifidobacterium, Muribaculaceae, Candidatus Saccharimonas, Eggerthella Ceae, Parabacteroides, Turicibacter, Akkermansia, Alistipes, 和 Enterorhabdus，在給予ACE後顯著的改變腸道菌群的組成。根據這些結果，ACE可能是治療肥胖與NAFLD的潛在藥物。
論文出處：Int J Med Mushrooms. 2018;20(8):727-738. doi: 10.1615/IntJMedMushrooms.2018026983.
論文名稱：Compound of Stout Camphor Medicinal Mushroom, Taiwanofungus camphoratus (Agaricomycetes), Induces Protective Autophagy in SPCA-1 Cells through AMPK Inhibition-Independent Blockade of the Akt/mTOR Pathway.
作 者：Yang H, Zhang J, Zhang H, Yang Y, Liu Y, Sun W, Wang W, Jia W.
出 版 年：2018
論文結論：By-1, a maleimide derivative isolated from Taiwanofungus camphoratus, treatment activated autophagy flux in human lung cancer SPCA-1 cells, which confirmed that autophagy was induced by By-1 treatment. By-1 treatment suppressed the Akt-mammalian target of rapamycin (mTOR) pathway and the AMP-activated protein kinase (AMPK) pathway.
論文出處：Phytother Res. 2021 Mar;35(3):1609-1620. doi: 10.1002/ptr.6928.
論文名稱：Protective effects of Antrodia camphorata extract against hypoxic cell injury and ischemic stroke brain damage.
作 者：Kong ZL, Hsu YT, Johnson A, Tsai TH, Miao S, He JL, Tsou D.
出 版 年：2021
論文結論：Ischemic stroke is the most prevalent stroke condition in the world resulted in either a transient ischemic attack or long-lasting neurological problems due to the interrupted or reduced blood flow to the brain. Antrodia camphorata is a well-known medicinal mushroom native to Taiwan and is familiar due to its medicinal effects. The current study investigated the protective effect of A. camphorata-alcohol extracts (AC-AE) against cobalt (II) chloride (CoCl2)-induced oxidative stress in vitro and ischemia/reperfusion-induced brain injury in vivo. The rats were pre-treated with AC-AE for 4 weeks. Our results showed that AC-AE reduced cell damage and decreased reactive oxygen species (ROS) production in C6 and PC12 cells under CoCl2-induced hypoxic condition. AC-AE doses (385, 770, 1,540 mg/kg/day, 4 weeks) increased nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA expressions and decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expressions in Sprague Dawley rat. Besides, it decreased stroke infarct size and increased the level of antioxidants in both brain and serum. Furthermore, it reduced the formation of malondialdehyde (MDA) after ischemia/reperfusion (I/R). Our results suggested that AC-AE exerted an effective reduction of ischemia stroke by regulating ROS production.dysfunction.
出 版 年：2020
論文出處：Int J Med Mushrooms. 2018;20(4):321-335. doi: 10.1615/IntJMedMushrooms.2018025836.
論文名稱：Autophagy Inhibition Enhances SPCA-1 Cell Proliferation Inhibition Induced by By-1 from the Stout Camphor Medicinal Mushroom, Taiwanofungus camphoratus (Agaricomycetes).
作 者：Yang H, Sun W, Zhang J, Zhang Y, Zhang H, Yang Y, Wu D, Liu Y, Qiankun Z, Min L, Wang WH, Jia W
出 版 年：2018
論文出處：Phytochemistry. 2021 Apr;184:112677. doi: 10.1016/j.phytochem.2021.112677.
論文名稱：Enhancement of antroquinonol production via the overexpression of 4-hydroxybenzoate polyprenyltransferase biosynthesis-related genes in Antrodia cinnamomea.
作 者：Liu X, Xia Y, Zhang Y, Liang L, Xiong Z, Wang G, Song X, Ai L.
出 版 年：2021
論文結論：Antroquinonol (AQ) as one of the most potent bioactive components in Antrodia cinnamomea (Fomitopsidaceae) shows a broad spectrum of anticancer effects. The lower yield of AQ has hampered its possible clinical application. AQ production may potentially be improved by genetic engineering. In this study, the protoplast-polyethylene glycol method combined with hygromycin as a selection marker was used in the genetic engineering of A. cinnamomea S-29. The optimization of several crucial parameters revealed that the optimal condition for generating maximal viable protoplasts was digestion of 4-day-old germlings with a mixture of enzymes (lysing enzyme, snailase, and cellulase) and 1.0 M MgSO4 for 4 h. The ubiA and CoQ2 genes, which are involved in the synthesis of 4-hydroxybenzoate polyprenyltransferase, were cloned and overexpressed in A. cinnamomea. The results showed that ubiA and CoQ2 overexpression significantly increased AQ production in submerged fermentation. The overexpressing strain produced maximum AQ concentrations of 14.75 ± 0.41 mg/L and 19.25 ± 0.29 mg/L in pCT74-gpd-ubiA and pCT74-gpd-CoQ2 transformants, respectively. These concentrations were 2.00 and 2.61 times greater than those produced by the control, respectively. This research exemplifies how the production of metabolites may be increased by genetic manipulation, and will be invaluable to guide the genetic engineering of other mushrooms that produce medically useful compounds.
論文出處：Sci Rep. 2018 Aug 27;8(1):12914. doi: 10.1038/s41598-018-31209-8.
論文名稱：Antrodia cinnamomea boosts the anti-tumor activity of sorafenib in xenograft models of human hepatocellular carcinoma.
作 者：Wu WD, Chen PS, Omar HA, Arafa EA, Pan HW, Jeng J, Hung JH
出 版 年：2018
出 版 年：2018
論文結論：利用幾丁聚醣在酸性溶液中帶正電荷及二氧化矽帶負電荷而形成凝膠來包覆皿培式牛樟芝 (petri-dish cultured Antrodia cinnamomea, PAC)，作成包覆皿培式牛樟芝之幾丁聚醣-氧化矽奈米粒 (PAC encapsulated in chitosan-silica nanoparticles, Nano-PAC) 。在細胞實驗中，大鼠睪丸 Leydig cell 在誘導發炎模式下發現 Nano-PAC 可降低超氧陰離子及一氧化氮濃度。有效改善糖尿病大鼠之多吃、多喝、肝與腎損傷、高血糖、胰島素阻抗、睪丸損傷、精子品質及生殖內分泌失調等問題；另外發現 Nano-PAC也能藉由減少糖化終產物、脂質過氧化物及超氧陰離子生成來改善氧化壓力，進一步減少促發炎因子以及一氧化氮的生成；並增加抗氧化酵素活性而下調 c-Jun N-terminal kinase 訊號路徑。