人々の “健康促進” のために!

人々の “健康促進” のために!
2015年春、沖縄の琉球大学キャンパス内 (産学共同研究棟) に立ち上げた “PAK研究センター” の発足メンバー(左から4人目が、所長の多和田真吉名誉教授)
For detail, click the above image.

2011年2月18日金曜日

Making the Legendary NZ Propolis "CAPE 60":
Blending Bio 30 with a Natural CAPE from API

CAPE (caffeic acid phenethyl ester) is the major anti-cancer polyphenol in propolis produced in Far East, Europe and Oceania. CAPE is now known to block the oncogenic kinase "PAK1" which is essential for the growth of more than 70 % of all human cancers (the majority of solid malignant tumors) , as well as brain tumors such as glioma, NF and TSC tumors. In addition, CAPE activates the tumor suppressing kinase "AMPK", and would be useful for the therapy of Diabetes (type 2) and for the "longevity" (a long life in good health) as well.

According to a 2002 poster on website, NZ propolis shows the highest CAPE content, 60-70 mg/g of dried propolis extract. That is the main reason why I got interested in NZ propolis extracts such as "Bio 30" from Manuka Health. However, in reality we have never seen such a CAPE-rich propolis among NZ propolis as yet. So far the Bio 30 batch that we got during 2006 would be the richest in CAPE, containing 12 mg of CAPE/g. We don't know the precise reason why we could not find the legendary CAPE-rich propolis called "CAPE 60" (containing over 60 mg/g).

Nevertheless, we could create the CAPE 60 artificially, by adding either synthetic or natural CAPE to any propolis. That is what we did during our 2006 in vivo (animal) test, proving that CAPE 60 is more effective than Bio 30 alone in suppressing the growth and metastasis of human NF1 and NF2 tumor xenografts in mice. However, we cannot add "synthetic" CAPE to propolis for medical purposes or human consumption, because the CAPE is not approved by FDA for clinical application. However, if the CAPE sources are among natural products such as propolis or enzymatically synthesized CAPE, there would be no problem for medical use.

Around 2006, a clever Taiwanese student (Chie-Hao Yeh, 23) developed the enzymatic way (esterification) to synthesize CAPE, in collaboration with Dr. Arief Widjaja, an Indonesian senior chemist(1). His thesis is entitled: Enzymatic Synthesis of CAPE. He used an immobilized "lipase B" (Novozym 435) from a fungus called Candida antarctica. The starting materials are CA (caffeic acid) and 2-phenylethanol. According to his recipe, this enzyme catalyzes the esterification of these two natural compounds in isooctane at 70oC for 48 hrs with almost 100% yield! This enzyme is resistant to both heat and organic solvent. After the reaction is completed, only two things remain in solution: CAPE and the solvent. Isooctane could be easily removed by evaporation, leaving basically only CAPE behind (2). Around 2010, a Japanese bee product company called “API” developed a natural source which produces CAPE enzymatically. Although the precise nature of this natural source still remains unknown in public (unpublished), it was filed as a patent.

Originally this company intended to commercialize a Chinese red propolis extract (RPE), because it contains more CAPE than Bio 30 or any other propolis products on the market, around 17 mg/g. Unfortunately, however, they found pesticides as contaminants in this RPE, and abandoned this RPE project. Instead, they developed a natural way to produce CAPE, to create a CAPE-rich propolis by blending this natural source with any “clean” (pesticide-free) propolis such as Bio 30. Thus, I recently contacted the director of API research center, discussing the possibility of commercializing the legendary “CAPE 60” by blending Bio 30 with their natural CAPE source, perhaps under the brand name “Api-Polis”, for the therapy of NF/TSC/cancers. Furthermore, by encapsulating this CAPE-rich propolis in gamma CD (cyclodextrin), a natural ring oligo sugar, we would be able to create a highly “bioavailable” (effectively absorbed through gastrointestinal membranes) CD complex of the CAPE-rich propolis, the “Holy Grail” of api-therapy.


References:

1. Widjaja, A. et al. Enzymatic synthesis of caffeic acid phenethyl ester. J.
Chinese Inst. Chem. Engin. 2008, 39, 413-418

2. Chen, HC., et al. Optimized enzymatic synthesis of CAPE by RSM. New Biotech,
2010, 27, 89-93.

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