从2005年至今,清水邦义(Kuniyoshi Shimizu)率领的团队在国际期刊发表的灵芝论文已有四十篇,可说是当今日本灵芝研究者的标竿。其研究均以同一种灵芝子实体乙醇萃取物为核心,除了证明它有改善摄护腺肥大、减缓骨质疏松、防治糖尿病及相关并发症(白内障)、降血压、抗癌、抗流感病毒等多元功效,亦探讨萃取物中五十几种单一三萜化合物与各种功效间的关系,并针对其中几种单一三萜化合物进行化学结构与构效关系的分析,厘清它们如何调控细胞内的微管蛋白来发挥作用。同时他们亦对灵芝不同生长阶段所生成的三萜种类与含量,进行深入的分析。
整理/吴亭瑶
九州大学农学研究院清水邦义副斆授受邀在中国福州市举办的《2016国际灵芝大会》上演讲。(摄影/吴亭瑶)
灵芝相关之期刊论文(英文)
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.
灵芝相关之论文或文章(日文)
1. 小西史子、隈本正一郎、刘洁、清水邦义、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. 日本临床代替医疗学会志, 2: 14-17, 2003.
2. 清水邦义、立花宏文、佐藤匡央、岛崎洋平. 高齢性ホルモン疾患予防効果を有する「食」の开発. 平成15年度农学研究院教育研究特别経费成果报告书, 2003.
3. 清水邦义、刘洁、宫本以智子、近藤隆一郎. 霊芝の前立腺肥大?骨粗松症改善効果. FFI ジャーナル(Foods & Food Ingredients Journal of Japan), 211(2): 124-133, 2006.
4. 清水邦义、宫本以智子、塩野顺、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松症予防効果. 机能性食品と薬理栄养, 4(1): 29-36, 2006.
5. 清水邦义. 高齢化社会に対応した男性ホルモン调节机能を有するキノコ(霊芝)の开発. 福冈商工会议所ニュース 5月号, 393:16, 2007.
6. 刘洁、清水邦义、近藤隆一郎. 高齢性社会に対応した霊芝の机能性~前立腺肥大症改善?予防効果. ?Green Spirits, 3(3): 3-9, 2007.?
7. 清水邦义、宫本以智子、塩野顺、刘洁、近藤隆一郎. 高齢化社会に対応した霊芝の机能性~骨粗松症予防?改善効果~. ?Green Spirits, 3(4): 3-10, 2008.
8. 野口正典、富安克郎、名切信、松冈啓、角间辰之、小西史子、隈本正一郎、清水邦义、近藤隆一郎. 霊芝中の生理活性物质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开発. 西日本泌尿器科学会志, 70(9): 466-472, 2008.
9. 小西史子、隈本正一郎、野田洁、隈本能光、中嶋裕也、清水邦义、近藤隆一郎. ラットへのGanoderma lucidum (レイシ)抽出物 12周间経口投与による毒性试験. 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. 清水邦义、河野俊亨. 多机能性キノコ「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.