维生素C对DFraction的协同增效作用可能作为癌症的替代疗法.docx

1、维生素C对DFraction的协同增效作用可能作为癌症的替代疗法声明：本文摘自International Journal of General Medicine，即国际全科医学杂志该杂志属于Dove Medical Press Ltd，其中的文章涉及病理学、流行病学、综合内科医学以及诊断学等，是一本国际开放性期刊。为方便广大读者阅读，我们对论文摘要进行了中文翻译，译文仅供参考，如有不足之处，敬请指正。-本文摘自舞茸D-fraction官方网站，转载请注明【参考译文】Synergistic potentiation of D-fraction with vitamin C as possible

2、 alternative approach for cancer therapy 维生素C对D-Fraction的协同增效作用可能作为癌症的替代疗法摘 要 舞茸D-Fraction（PDF）是一种从舞茸中提取的活性物质，其活性成分是蛋白多糖，它更多的为人所知是一种葡聚糖。PDF已被广泛的研究，其大量的药用潜质（特性）被发现，这包括各种生理学上的益处，从免疫调节作用和抗肿瘤活性到治疗高血压、糖尿病、高胆固醇血症、病毒感染（乙肝病毒和HIV病毒）以及肥胖。尤其是PDF的两个主要生物活性，免疫调节和抗肿瘤活性，已经成为科学和临床的两个主要研究目标。为揭示和证实这些生物活性，进行了大量的体外、体内以及

3、临床试验。这些实验结果显示PDF确实能调整免疫学和血液学的指标，抑制癌细胞生长，甚至能改变癌症患者的生活质量。体外试验中维生素C与PDF的协同增效作用被证明非常令人关注，且具有临床意义，因为这一联合疗法看起来能改善现有的癌症治疗方法的效果。近来，经常用静脉注射维生素C来提高其生理浓度，这一有效的过程使这种联合疗法可行。由此可见，PDF在癌症治疗中单独使用或与其他药物一起使用时均有巨大的潜能。在此，我们将从一个特殊的角度来描述和讨论相关试验中PDF和维生素C联合使用这一可行的治疗方法。关键词： 舞茸D-Fraction，PDF，维生素C，协同作用，癌症疗法论文原文 International J

4、ournal of General Medicine 2009：2 91-108 Synergistic potentiation of D-fraction with vitamin C as possible alternative approach for cancer therapy Sensuke Konno Department of Urology, New York Medical College, valhalla, NY, USAAbstract: Maitake D-fraction or PDF is the bioactive extract of maitake m

5、ushroom (Grifola frondosa) and its active constituent is the protein-bound polysaccharide (proteoglucan), or more specifically known as -glucan. PDF has been extensively studied and a number of its medicinal potentials/properties have been unveiled and demonstrated. Those include various physiologic

6、al benefits ranging from immunomodulatory and antitumor activities to treatment for hypertension, diabetes, hypercholesterolemia, viral infections (hepatitis B and human immunodeficiency virus), and obesity. Particularly, two major biological activities of PDF, immunomodulatory and antitumor activit

7、ies, have been the main target for scientific and clinical research. To demonstrate and confirm such biological activities, numerous studies have been performed in vitro and in vivo or in clinical settings. These studies showed that PDF was indeed capable of modulating immunologic and hematologic pa

8、rameters, inhibiting or regressing the cancer cell growth, and even improving quality of life of cancer patients. Synergistic potentiation of PDF with vitamin C demonstrated in vitro is rather interesting and may have clinical implication, because such combination therapy appears to help improve the

9、 efficacy of currently ongoing cancer therapies. Recently, intravenous administration of vitamin C has been often used to increase its physiological concentration and this useful procedure may further make this combination therapy feasible. Therefore, PDF may have great potential, either being used

10、solely or combined with other agents, for cancer therapy. Such relevant and detailed studies will be described and discussed herein with a special focus on the combination of PDF and vitamin C as a viable therapeutic option.Keywords: maitake D-fraction, PDF, vitamin C, synergism, cancer therapyIntro

11、ductionMushrooms have been known for centuries particularly among Chinese and Japanese people who consumed or utilized them for dietary or medicinal purposes. However, Western people have neither known these mushrooms nor gained their potential health benefits until recently. One reason for this dis

12、parity may arise from misunderstanding or misconception about the nature and properties of mushrooms. As mushrooms belong to the family of “fungi”, many (Western) people have a general perception that mushrooms have little nutritional value while others think that eating mushrooms may make one vulne

13、rable to some yeast infections. We now know these concepts are invalid, and to the contrary, mushrooms have great nutritional value including vitamins, minerals, amino acids, and fibers;1 they are indeed healthy food. As a number of mushrooms are now cultivated worldwide, their products or extracts

14、have become easily available to the public and sold mainly as dietary supplements. The market Number of times this article has been viewed value of such mushroom supplement products worldwide is nearly US$56 billion annually.2 In addition to their dietary value, the medicinal aspects of mushrooms ha

15、ve been long appreciated in the Far East but are also rapidly gaining a great public attention in the Western world. Because of an easy and abundant availability of many mushrooms by cultivation, not only the public but also scientists can obtain them for scientific and clinical research. Bioactive

16、extracts or metabolites of these medicinal mushrooms are widely being used to treat or prevent a variety of diseases. Since these mushroom products are considered as dietary supplements, they could be individually or personally used for therapeutic purposes without going through a series of “phase t

17、rials” required for an ordinary drug/medicine under the US Food and Drug Administration (FDA). Yet, the sufficient scientific studies have not been performed on most of these mushrooms (or their products) to reveal and confirm their actual medicinal potentials/properties, although some of them have

18、been indeed scientifically investigated. Particularly, one of them is known as “maitake mushroom” (Grifola frondosa) and its bioactive extract is named “Maitake D-fraction.”Maitake D-fraction (PDF)Maitake mushroom is a tasty edible mushroom. Maitake literally means “dancing mushroom” . It is a huge

19、mushroom that can reach 20 inches in diameter and weigh up to 100 pounds. Besides its great taste, it has also been believed to provide health benefits and often used for therapeutic purposes. As maitake was then considered a medicinal mushroom, it has been extensively subjected to scientific studie

20、s for nearly 30 years which has revealed a number of medicinal properties that could provide remarkable health benefits. Various physiological benefits of maitake have been postulated or demonstrated, ranging from immunomodulatory and antitumor activities to treatment for hypertension, diabetes, hyp

21、ercholesterolemia, obesity, and hepatitis B infection.3-11 Its antiviral activity against human immunodeficiency virus (HIV)/AIDS was also confirmed by the US National Cancer Institute in 1992.12 The majority of maitake research described above has been performed using its bioactive extract, namely

22、“Maitake D-fraction (PDF)” . This D-fraction or PDF is the protein-bound polysaccharide or proteoglucan, consisting of -glucan (either -1,6-linked glucan with -1,3 branches or -1,3-linked glucan branched with -1,6 glucosides; see Figure 1) as a main polysaccharide backbone where a few uncharacterize

23、d protein units are attached to. In other words, PDF is not a pure form of -glucan that is yet a core constituent but is a “proteoglucan” having both -glucan (major) and protein (minor) portions. This is a huge proteoglucan with a molecular weight of 1 106 Daltons,3,13 having acid-insoluble, alkali-

24、soluble and hot water-extractable nature.3 In addition, biological activities of PDF have been shown to stem primarily from -glucan, which was thus considered a bioactive component of PDF.3,5,7,9-13 Particularly, its two major biological activities, such as immunomodulatory and antitumor activities,

25、3,7,13 have been well documented and its clinical and therapeutic utilities are known.Immunomodulatory activity of PDFThe innate immune system is the first line of defense against microbial invasion, which immediately recognizes and copes glucose with such infections. Although various -glucans have

26、been known to commonly exhibit immunomodulatory activity for a long time,14 such underlying cellular and molecular mechanisms have not been fully defined but were recently being unveiled. Since PDF has a core -glucan structure for its inherent bioactivities, all immunomodulatory activities demonstra

27、ted with -glucans would be substantially relevant to those exhibited by PDF. Such immunomodulations by -glucans include mitogenecity and activation of immune effector cells such as lymphocytes, macrophages, dendritic cells, and natural killer (NK) cells, stimulating the production of various cytokin

28、es and chemokines such as interleukins (IL-1, IL-6, IL-8, IL-12 etc.), tumor necrosis factor- (TNF-), and interferon- (IFN-).15,16 However, the first step in triggering the immune-modulating effects by -glucans requires the specific cellular receptors that recognize and bind to them. In fact, a numb

29、er of “-glucan receptors” have been identified on both immune and nonimmune cells, including macrophages, NK cells, monocytes, neutrophils, endothelial cells, fibroblasts, etc.17 Those receptors include complement receptor 3 (CR3), lactosylceramide, scavenger receptors, and Dectin-1.18 Particularly,

30、 Dectin-1 appears to be the most interesting receptor, predominantly found on macrophage/monocyte and neutrophil lineages, and can recognize soluble and particulate -glucans.19 It then mediates a variety of cellular immune-modulating effects, such as phagocytosis, endocytosis, and the oxidative burs

31、t, and also induces the production of pro-inflammatory cytokines/chemokines including TNF-, IL-12, and macrophage-inflammatory protein-2 (MIP-2)18,20 although they could work paradoxically in a positive or negative manner, depending on microenvironments where they are regulated or interact with cert

32、ain/specific factors. Nevertheless, -glucans would activate a wide variety of innate host defenses, such as protection against infections with fungal, protozoal, bacterial, and viral pathogens, as well as prevention/protection against cancer development (carcinogenesis). This may well represent how various -glucans or PDF would induce the immunomodulatory effects: ie, binding of -glucans to specific receptors, triggering act