Towards the Development of a New "Red Propolis" Based on Sichuan Pepper (Hua Jiao)

A few years ago we found that Hua Jiao fruits (Chinese red peppercorns)
contain an anti-PAK ingredient which can be extracted by 70% ethanol (or
warm-water), and suppress the growth of cancers and NF tumor xenografts
in mice (Hirokawa, Y. et al, 2006). Since this extract has a rather bitter
(not spicy) taste, we tried to commercialize the dried power of this extract
blended with an NZ honey to add a sweet taste under the brand name "Honey
Pepper" as the first effective therapeutic for NF (neurofibromatosis) and
PAK-dependent cancers such as pancreatic and colon cancers, for which no
effective therapeutic was available on the market. However, no company
got interested in this project. Perhaps it might be too "inexpensive" for
the commercialization.

A year later we found that one of NZ propolis extracts called "Bio 30" also
suppresses the growth of PAK-dependent cancers and NF tumor xenografts in
mice (Demestre, M. et al, 2009). Bio 30 is an inexpensive CAPE (caffeic
acid phenethyl ester)-rich water-miscible extract of NZ propolis from Manuka
Health based in Auckland, NZ, and selectively blocks the oncogenic kinase
PAK by down-regulating the GTPase RAC. One minor problem with this extract
is that its major anti-cancer ingredient (CAPE) causes a skin allergy to
1-2% of population including myself (!).

Shortly thereafter we found that another propolis extract called GPE, Brazilian
green propolis extract from Yamada Bee Farm in Japan, also suppresses the
growth of NF tumors and PAK-dependent cancers by blocking the kinase PAK
(Messerli, S. et al, 2009). GPE contains no CAPE, but another anti-cancer
polyphenol called ARC (artepillin C) that inactivates PAK. This extract
does not cause any allergic reaction, but is far more expensive than Bio
30 (which costs only a dollar for daily treatment).

Interestingly, Brazilian "red propolis" extract (RPE) also appears to inactivate
the kinase PAK, as it suppresses the growth of pancreatic cancer, although
it contains neither CAPE nor ARC. These findings strongly suggest that
honey bees have a natural instinct to collect anti-PAK ingredients from
a variety of trees (or shrubs) such as poplar to make propolis (bee hive)
for protecting their larva from a variety of harmful pathogens such as bacteria,
fungi, viruses, etc. However, RPE is as expensive as GPE. More recently,
I heard that there is another "red propolis" in China which appears to be
based on CAPE. However, this Chinese red propolis is not available on the
market as yet.

Thus, I got a new idea that honey bees could collect the anti-PAK ingredient
from red fruits (peppercorns) of the Chinese "Hua Jiao" to produce an inexpensive
"red propolis" which would be useful for the therapy of both NF and cancers.
The key for this future project would be how to condition honey bees towards
this red peppercorn. Honey bees can memorize colors (in particular yellow
and violet), sweet taste of sugars and aromatic scent. So if the aromatic
alcohol extract of Hua Jiao is mixed with honey and spotted on a red paper,
in theory honey bees would approach this sweet aromatic red paper, learning
that the aromatic red fruits could be among their potentially favorable sources
of sweet honey. Once they could locate Hua Jiao, they would become addicted
to its anti-PAK ingredient whose chemical nature nobody has identified as
yet. Once the new "red propolis" is produced in my garden (bee farm), we
shall make the ethanol extract of this propolis to confirm its anti-PAK
and anti-cancer potential in vitro and in vivo.

However, commercialization of this OZ red propolis extract called "HJ propolis"
would eventually need the chemical identification of this anti-PAK ingredient
in this propolis (or Hua Jiao) to standardize its content in this new propolis
product. Thus, it might be a life-long (certainly time-consuming) project
towards the commercialization. Generally speaking, natural anti-PAK products
including "Natto" and propolis would have a potentially huge market value,
simply because they would be useful not only for cancers and NF, but also
several other PAK-dependent formidable diseases such as Alzheimer's (AD),
Huntington's (HD), AIDS, inflammatory diseases (Asthma and arthritis), epilepsy,
type-2 diabetes, hypertension, HCM (hypertrophic cardiomyopathy ) and malaria.

We prefer to developing an inexpensive one if possible, because it would
be far more "democratic", as it could offer a benefit not only the very
rich people, but also the very poor, even for a life-long treatment if
necessary. These diseases never discriminate the rich and the poor. So the
therapeutics should not. Thus, it would be worth trying to develop this
inexpensive red propolis in my own garden.