從2005年至今，清水邦義（Kuniyoshi Shimizu）率領的團隊在國際期刊發表的靈芝論文已有四十篇，可說是當今日本靈芝研究者的標竿。其研究均以同一種靈芝子實體乙醇萃取物為核心，除了證明它有改善攝護腺肥大、減緩骨質疏鬆、防治糖尿病及相關併發症（白內障）、降血壓、抗癌、抗流感病毒等多元功效，亦探討萃取物中五十幾種單一三萜化合物與各種功效間的關係，並針對其中幾種單一三萜化合物進行化學結構與構效關係的分析，釐清它們如何調控細胞內的微管蛋白來發揮作用。同時他們亦對靈芝不同生長階段所生成的三萜種類與含量，進行深入的分析。
整理／吳亭瑤
1. Fujita R, Liu J, Shimizu K, Konishi F, Noda K, Kumamoto S, Ueda C, Tajiri H, Kaneko S, Suimi Y, Kondo R. Anti-androgenic activities of Ganoderma lucidum. J Ethnopharmacol. 2005; 102(1):107-12.
2. Liu J, Fujita R, Sato M, Shimizu K, Konishi F, Noda K, Kumamoto S, Ueda C, Tajiri H, Kaneko S, Suimi Y, Kondo R. The effect of strain, growth stage and cultivationg condition of Ganoderma lucidum on 5a-reductase inhibition. J Wood Sci. 2005; 51(2), 189-192.
3. Liu J, Shimizu K, Kondo R. Ganoderic acid TR, a new lanostanoid with 5a-reductase inhibitory activity from the fruiting body of Ganoderma lucidum. Nat Prod Commun. 2006; 1(5), 345-350.
4. Jiu J, Kurashiki K, Shimizu K, Kondo R. 5alpha-reductase inhibitory effect of triterpenoids isolated from Ganoderma lucidum. Biol Pharm Bull. 2006; 29(2):392-5.
5. Liu J, Kurashiki K, Shimizu K, Kondo R. Structure-activity relationship for inhibition of 5alpha-reductase by triterpenoids isolated from Ganoderma lucidum. Bioorg Med Chem. 2006;14(24):8654-60.
6. Jiu J, Shimizu K, Konishi F, Kumamoto S, Kondo R. The anti-androgen effect of ganoderol B isolated from the fruiting body of Ganoderma lucidum. Bioorg Med Chem. 2007; 15(14):4966-72.
7. Liu J, Shimizu K, Konishi F, Noda K, Kumamoto S, Kurashiki K, Kondo R. Anti-androgenic activities of the triterpenoids fraction of Ganoderma lucidum. Food Chem. 2007; 100: 1691-1696.
8. Noguchi M, Kakuma T, Tomiyasu K, Kurita Y, Kukihara H, Konishi F, Kumamoto S, Shimizu K, Kondo R, Matsuoka K. Effect of an extract of Ganoderma lucidum in men with lower urinary tract symptoms: a double-blind, placebo-controlled randomized and dose-ranging study. Asian J Androl. 2008; 10(4): 651–658.
9. Noguchi M, Kakuma T, Tomiyasu K, Yamada A, Itoh K, Konishi F, Kumamoto S, Shimizu K, Kondo R, Matsuoka K. Randomized clinical trial of an ethanol extract of Ganoderma lucidum in men with lower urinary tract symptoms. Asian J Androl. 2008; 10 (5): 777-785.
10. Masanori Noguchi, Katsuro Tomiyasu, Makoto Nakiri, Kei Matsuoka, Tatsuyuki Kakuma, Fumiko Konishi, Shoichiro Kumamoto, Kuniyoshi Shimizu, Ryuichiro Kondo. An extract of ganoderma lucidum in men with lower urinary tract symptoms: A double-blind, placebo-controlled randomized and dose-ranging study. Nishinihon Journal of Urology, 2008, 70(9): 466-472.
11. Miyamoto I, Liu J, Shimizu K, Kukita A, Kukita T, Sato M, Kondo R. Regulation of osteoclastogenesis by ganoderic acid DM isolated from Ganoderma lucidum.Eur J Pharmacol. 2009; 602(1):1-7.
12. Fatmawatia S, Kurashiki K, Takeno S, Kim Y, Shimizu K, Sato M, Imaizumi K, Takahashi K, Kamiya S, Kaneko S, Kondo R. The inhibitory effect on aldose reductase by an extract of Ganoderma lucidum. Phytother Res. 2009; 23(1): 28-32.
13. Shimizu K, Miyamoto I, Liu J, Konishi F, Kumamoto S, Kondo R. Estrogen-like activity of ethanol extract of Ganoderma lucidum. J Wood Sci. 2009; 55(1): 53-59.
14. Liu J, Tamura S, Kurashiki K, Shimizu K, Noda K, Konishi F, Kumamoto S, Kondo R. Anti-androgen effects of extracts and compounds from Ganoderma lucidum. Chem Biodivers. 2009; 6(2): 231-243.
15. Liu J, Shiono J, Shimizu K, Kukita A, Kukita T, Kondo R. Ganoderic acid DM: anti-androgenic osteoclastogenesis inhibitor. Bioorg Med Chem Lett. 2009; 19(8): 2154-7.
16. Liu J, Shiono J, Shimizu K, Kondo R. Ganoderic acids from Ganoderma lucidum: inhibitory activity of osteoclastic differentiation and structural criteria. Planta Med. 2010; 76(2): 137-9.
17. Fatmawati S, Shimizu K, Kondo R. Inhibition of aldose reductase in vitro by constituents of Ganoderma lucidum. Planta Med. 2010; 76(15): 1691-3.
18. Fatmawati S, Shimizu K, Kondo R. Ganoderic acid Df, a new triterpenoid with aldose reductase inhibitory activity from the fruiting body of Ganoderma lucidum. Fitoterapia. 2010 ;81(8): 1033-6.
19. Liu J, Shimizu K, Kondo R. The effects of ganoderma alcohols isolated from Ganoderma lucidum on the androgen receptor binding and the growth of LNCaP cells. Fitoterapia. 2010; 81(8):1067-72.
20. Fatmawati S, Shimizu K, Kondo R. Ganoderol B: a potent α-glucosidase inhibitor isolated from the fruiting body of Ganoderma lucidum. Phytomedicine. 2011 Sep 15;18(12):1053-5.
21. Fatmawati S, Shimizu K, Kondo R. Structure-activity relationships of ganoderma acids from Ganoderma lucidum as aldose reductase inhibitors. Bioorg Med Chem Lett. 2011; 21(24): 7295-7.
22. Liu J, Kurashiki K, Fukuta A, Kaneko S, Suimi Y, Shimizu K, Kondo R. Quantitative determination of the representative triterpenoids in the extracts of Ganoderma lucidum with different growth stages using high-performance liquid chromatography for evaluation of their 5α-reductase inhibitory properties. Food Chemistry, 2012; 133(3): 1034-38.
23. Liu J, Shimizu K, Tanaka A, Shinobu W, Ohnuki K, Nakamura T, Kondo R. Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms. Sci Rep. 2012; 2:905.
24. Fatmawati S, Kondo R, Shimizu K. Structure-activity relationships of lanostane-type triterpenoids from Ganoderma lingzhi as α-glucosidase inhibitors. Bioorg Med Chem Lett. 2013; 23(21): 5900-3.
25. Hai Bang T, Suhara H, Doi K, Ishikawa H, Fukami K, Parajuli GP, Katakura Y, Yamashita S, Watanabe K, Adhikari MK, Manandhar HK, Kondo R, Shimizu K. Wild Mushrooms in Nepal: Some Potential Candidates as Antioxidant and ACE-Inhibition Sources. Evid Based Complement Alternat Med. 2014; 2014:195305.
26. Tran HB, Yamamoto A, Matsumoto S, Ito H, Igami K, Miyazaki T, Kondo R, Shimizu K. Hypotensive effects and angiotensin-converting enzyme inhibitory peptides of reishi (Ganoderma lingzhi) auto-digested extract. Molecules. 2014; 19(9): 13473-85.
27. Bang TH, Shimizu K. Structure-Activity Relationship and Inhibition Pattern of Reishi-derived (Ganoderma lingzhi) Triterpenoids against Angiotensin-Converting Enzyme. Phytochem Lett. 2015; 12: 243-247.
28. Zhu Q, Bang TH, Ohnuki K, Sawai T, Sawai K, Shimizu K. Inhibition of neuraminidase by Ganoderma triterpenoids and implications for neuraminidase inhibitor design. Sci Rep. 2015; 5:13194.
29. Amen YM, Zhu Q, Tran HB, Afifi MS, Halim AF, Ashour A, Mira A, Shimizu K. Lucidumol C, a new cytotoxic lanostanoid triterpene from Ganoderma lingzhi against human cancer cells. J Nat Med. 2016; 70(3): 661-6.
30. Sakamoto S, Kohno T, Shimizu K, Tanaka H, Morimoto S. Detection of Ganoderic Acid A in Ganoderma lingzhi by an Indirect Competitive Enzyme-Linked Immunosorbent Assay. Planta Med. 2016; 82(8): 747-51.
31. Amen YM, Zhu Q, Afifi MS, Halim AF, Ashour A, Shimizu K. New cytotoxic lanostanoid triterpenes from Ganoderma lingzhi. Phytochem Lett. 2016; 17: 64-70.
32. Sakamoto S, Kikkawa N, Kohno T, Shimizu K, Tanaka H, Morimoto S. Immunochromatographic strip assay for detection of bioactive Ganoderma triterpenoid, ganoderic acid A in Ganoderma lingzhi. Fitoterapia. 2016; 114:51-55.
33. Shimizu K, Amen YM, Kaifuchi S. Methoxyflavones from New Lingzhi Medicinal Mushroom, Ganoderma lingzhi (Agaricomycetes).Int J Med Mushrooms. 2016;18(8):713-719.
34. QinchQinchang Zhu, Yhiya M. Amen, Koichiro Ohnuki, Kuniyoshi Shimizu, et al. Anti-influenza effects of Ganoderma lingzhi: An animal study. J Funct Foods. 2017; 34: 224-28.
35. Amen Y, Zhu Q, Tran HB, Afifi MS, Halim AF, Ashour A, Shimizu K. Partial contribution of Rho-kinase inhibition to the bioactivity of Ganoderma lingzhi and its isolated compounds: insights on discovery of natural Rho-kinase inhibitors. J Nat Med. 2017; 71(2):380-388.
36. Kohno T, Hai-Bang T, Zhu Q, Amen Y, Sakamoto S, Tanaka H, Morimoto S, Shimizu K. Tubulin polymerization-stimulating activity of Ganoderma triterpenoids. J Nat Med. 2017; 71(2): 457-462.
37. Yusakul G, Nuntawong P, Sakamoto S, Ratnatilaka Na Bhuket P, Kohno T, Kikkawa N, Rojsitthisak P, Shimizu K, Tanaka H, Morimoto S. Bacterial Expression of a Single-Chain Variable Fragment (scFv) Antibody against Ganoderic Acid A: A Cost-Effective Approach for Quantitative Analysis Using the scFv-Based Enzyme-Linked Immunosorbent Assay. Biol Pharm Bull. 2017;40(10):1767-1774.
38. Satria D, Amen Y, Niwa Y, Ashour A, Allam AE, Shimizu K. Lucidumol D, a new lanostane-type triterpene from fruiting bodies of Reishi (Ganoderma lingzhi). Nat Prod Res. 2019 Jan;33(2):189-195.
39. Nakagawa T, Zhu Q, Tamrakar S, Amen Y, Mori Y, Suhara H, Kaneko S, Kawashima H, Okuzono K, Inoue Y, Ohnuki K, Shimizu K. Changes in content of triterpenoids and polysaccharides in Ganoderma lingzhi at different growth stages. J Nat Med. 2018 Jun;72(3):734-744.
40. Tamrakar S, Fukami K, Parajuli GP, Shimizu K. Antiallergic Activity of the Wild Mushrooms of Nepal and the Pure Compound Hispidin. J Med Food. 2019 Feb;22(2):225-227.
41. Satria D, Tamrakar S, Suhara H, Kaneko S, Shimizu K. Mass Spectrometry-Based Untargeted Metabolomics and α-Glucosidase Inhibitory Activity of Lingzhi (Ganoderma lingzhi) During the Developmental Stages. Molecules. 2019 May 29;24(11): 2044.
1. 小西史子、隈本正一郎、劉潔、清水邦義、近藤隆一郎、金子周平. マンネンタケGanoderma lucidumによる前立腺肥大の抑制. 日本臨床代替医療学会誌, 2: 14-17, 2003.
2. 清水邦義、立花宏文、佐藤匡央、島崎洋平. 高齢性ホルモン疾患予防効果を有する「食」の開発. 平成15年度農学研究院教育研究特別経費成果報告書, 2003.
3. 清水邦義、劉潔、宮本以智子、近藤隆一郎. 霊芝の前立腺肥大・骨粗鬆症改善効果. FFI ジャーナル(Foods & Food Ingredients Journal of Japan), 211(2): 124-133, 2006.
4. 清水邦義、宮本以智子、塩野順、佐藤匡央、久木田明子、久木田敏夫、近藤隆一郎. マンネンタケ（Ganoderma lucidum）エタノール抽出物による骨粗鬆症予防効果. 機能性食品と薬理栄養, 4(1): 29-36, 2006.
5. 清水邦義. 高齢化社会に対応した男性ホルモン調節機能を有するキノコ（霊芝）の開発. 福岡商工会議所ニュース ５月号, 393:16, 2007.
6. 劉潔、清水邦義、近藤隆一郎. 高齢性社会に対応した霊芝の機能性～前立腺肥大症改善・予防効果. Green Spirits, 3(3): 3-9, 2007.
7. 清水邦義、宮本以智子、塩野順、劉潔、近藤隆一郎. 高齢化社会に対応した霊芝の機能性～骨粗鬆症予防・改善効果～. Green Spirits, 3(4): 3-10, 2008.
8. 野口正典、富安克郎、名切信、松岡啓、角間辰之、小西史子、隈本正一郎、清水邦義、近藤隆一郎. 霊芝中の生理活性物質を利用した中高年男性の下部排尿路排尿障害に対する特定保健用食品の開発. 西日本泌尿器科学会誌, 70(9): 466-472, 2008.
9. 小西史子、隈本正一郎、野田潔、隈本能光、中嶋裕也、清水邦義、近藤隆一郎. ラットへのGanoderma lucidum (レイシ)抽出物 12週間経口投与による毒性試験. 応用薬理, 75(1/2): 7-12, 2008.
10. 霊芝(Ganoderma lingzhi)自己消化物の血圧降下作用について〔Hypotensive effects of Reishi(Ganoderma lingzhi)’s auto-digested extract and it’s potent peptides for the inhibition of angiotensin converting enzyme〕. 日本きのこ学会第17回大会において発表, 2013.09.
11. 清水邦義、河野俊亨. 多機能性キノコ「霊芝」（Ganoderma lingzhi）の更年期症状改善効果. 更年期と加齢のヘルスケア, 13(1): 98-103, 2014.
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