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Forskolin: from an ayurvedic remedy to a modern agent.

Forskolin is a labdane diterpene extracted from Indian Coleus plant (Coleus
forskohlii). Forskolin has been shown to directly activate adenylyl cyclase
and raises the intracellular levels of cyclic Adenosine Monophosphate
(cyclic AMP or cAMP). in a wide variety of cell types. [1] On the other hand,
forskolin has been shown to inhibit a number of membrane transport
proteins and channel proteins through a mechanism that does not involve
the production of cAMP. [2] Thus, it is believed that supplement of forskolin
may have board variety of health benefits.

In 1980s, researchers have already shown its potential health benefits or
effects. In the intact rat myometrium, forskolin stimulate cAMP generation
and markedly potentiated increases in cAMP caused by isoproterenol,
prostaglandin E2 and prostacyclin. Activation of cyclic AMP generation by
forskolin was biphasic with respect to concentration; the major response
being mediated by a low affinity interaction (Kapp 28 microM) and a minor
effect being due to an interaction with a high affinity site (Kapp 0.5 microM).

At the lower dosages of 3-4 micrograms/kg/min, forskolin had no effect on
dP/dtmax, cardiac index, ejection fraction, or myocardial oxygen
consumption in patients suffered from dilated cardiomyopathy. However,
forskolin administered at a dosage of 4 micrograms/kg/min induced an
increase in dP/dtmax by 19% and a 16% rise in heart rate. However, these
changes were associated with symptomatic flush syndromes. Therefore,
forskolin may serve as a vasodilating substance in lower concentrations, but
cannot be used as a positive inotropic compound. [4]

It is unclear if forskolin has health benefits on curing cancers, but
experiments showed that forskolin might affect the pancreatic cancer cell
development. Researchers from University of California (USSF) San
Francisco demonstrated that stimulation of adenylyl cyclase and the protein
kinase A pathway by forskolin and vasoactive intestinal peptide increased
MUC5AC antigen expression and release from pancreatic cancer cells.
MUC5AC mucin is not expressed in normal pancreas but is expressed in
tumors. Their study showed that the protein kinase A pathway may
contribute to the up-regulation of MUC5AC expression seen in pancreatic
tumors. [5]

Here is another reason why people think forskolin may benefit people at risk
of pancreatic cancer, at least, for diagnostic purpose. The circulating
antigen sialyl-Lewis(a) is used in serological tests for malignancy.
Researchers from Osaka City University Medical School, Japan, found
forskolin could increase the release of sialyl-Lewis(a) from SW1990 cells. In
addition, forskolin could also increase the cellular content of antigen and
MUC1 mRNA. [6]

Platelet aggregation probably plays an important role in implantation of
tumor cells into the target organ during the early phase of tumor metastasis.
In a study of nude mice, researchers from Jikei University School of
Medicine, Tokyo, Japan, prepared a hepatic metastasis model by
intrasplenic implantation of 3-4 x 10(6) of HT29LMM human colon cancer
cells in nude mice. They also supplied 10 mg/kg of forskolin 30 minutes
before and 24 hours, after implantation of tumor cells, respectively. They
found the total weight of hepatic metastasis lesions and the occupied rate
were significantly low, compared to a control group. In a vitro inhibitory
study, forskolin was found to be a platelet aggregation inhibitor.
Researchers believe that forskolin inhibits hepatic metastasis from human
colon cancer by preventing platelet aggregation during the metastatic tumor
formation. [7]


[1] Insel PA, Ostrom RS. Forskolin as a tool for examining adenylyl cyclase
expression, regulation, and G protein signaling. Cell Mol Neurobiol 2003
Jun;23(3):305-14. [2] Laurenza A, Sutkowski EM, Seamon KB, Forskolin: a
specific stimulator of adenylyl cyclase or a diterpene with multiple sites of
action? Trends Pharmacol Sci. 1989 Nov;10(11):442-7. [3] Mokhtari A, Do
Khac L, Tanfin Z, Harbon S. Forskolin modulates cyclic AMP generation in
the rat myometrium. Interactions with isoproterenol and prostaglandins E2
and I2. J Cyclic Nucleotide Protein Phosphor Res. 1985;10(3):213-27. [4]
Schlepper M, Thormann J, Mitrovic V. Cardiovascular effects of forskolin
and phosphodiesterase-III inhibitors. Basic Res Cardiol. 1989;84 Suppl
1:197-212. [5] Ho JJ, Crawley S, Pan PL, Farrelly ER, Kim YS. Secretion of
MUC5AC mucin from pancreatic cancer cells in response to forskolin and
VIP. Biochem Biophys Res Commun. 2002 Jun 14;294(3):680-6. [6]
Yamashita Y, Ho JJ, Farrelly ER, Hirakawa K, Sowa M, Kim YS.Forskolin and
phorbol ester have opposite effects on the expression of mucin-associated
sialyl-Lewis(a) in pancreatic cancer cells. Eur J Cancer. 2000
Jan;36(1):113-20. [7] Yoshizawa J, Yoshida K, Fujikawa T, Tanabe A,
Sakurai K. Inhibitory effects of Forskolin on hepatic metastasis from human
colon cancer in nude mice. Nippon Geka Gakkai Zasshi. 1995