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Hi<br>
I shall forward your request to the medicinal plants working group. To be
honest I don't understand the chemistry at all but I am sure others on
this list serve do.<br>
Bob<br>
At 01:33 PM 2/22/2005 -0800, you wrote:<br>
<blockquote type=cite class=cite cite>Bob,<br>
<br>
I am the organic chemist who emailed you a few months ago regarding my
experience with spearmint as migraine prophylaxis. Thank you for
submitting my story to the Google Search; I received a couple of
inquiries. <br>
<br>
While studying natural antimigraine remedies, some of Dennis Awang's
articles about parthenolide (e.g.: Parthenocide: The demise of a facile
theory of feverfew activity, <i>J. of Herbs, Spices and Medicinal Plants,
</i>5(4), 1998, 95-98 and his recent comments that appeared in
HerbalGram:65, 36-37) surfaced and caused me to study that component of
feverfew. I emailed my chemcial interpretation of that substance to
Mark Blumenthal of ABC and indirectly to Awang (as I do not have his
email address), and subsequently to Patricia deAngelis. I received
nothing from anyone. <br>
<br>
Below is my chemical interpretation of parthenolide. I wonder if you
think it is worthy of placing it in the Google Search? I certainly would
like some feedback. Please let me know.<br>
<br>
<br>
The recent comments indicating that parthenolide may not the active
constituent in feverfew caught my interest and curiosity. <br>
<br>
Considerable animal studies have been done on parthenolide for its
anti-inflammatory activity and its ability to inhibit the Nuclear Factor
kappaB (NF-kB), a molecular biology term that "it is a transcription
factor that mediates the _expression of genes necessary for the cell to
fight inflammation." Accordingly, scientists, e.g. Dr. M. A.
Moskowitz of Harvard Medical School and Mass. Gen. Hospital suggests that
"blockade of NF-kB activity provides a novel transcriptional target
for the development of anitmigraine drugs." (M.A. Moskowitz et al.:
NF-kB as a molecular target for migraine therapy; Ann Neurol. 2002; 51:
507-516).<br>
<br>
The activity of parthenolide and similar sesquiterpene lactones is
primarily due to the exocyclic methylene moiety as a part of alpha,
beta-unsaturated lactone. There is a proposed mechanism for
degradation of parthenolide: <br>
<br>
In addition to its being an alpha-beta-unsaturated lactone, parthenolide
has a fairly reactive epoxide ring, which can be opened by proton
followed by transannular cyclization and by attacks of sulphydryl groups
in protein (e.g. cysteine), resulting in an entirely different
sesquiterpene lactone. (Paul M. Dewick's "Medicinal Natural
Products, a Biosynthetic Approach," 2nd ed., 2002, Wiley, p.
195). This molecule, that is irreversibly bound to protein, no
longer has the alpha-methylene-gamma-lactone moiety. <br>
<br>
Indeed, when the exocyclic methylene group of parthenolide is reduced,
i.e. no more unsaturation, this "reduced parthenolide" no
longer inhibits the NF-kB activation. (Kwok, Crews, C., et al.: The
anti-inflammatory natural product parthenolide from the medicinal herb
feverfew directly binds to and inhibits IkB kinase; Chemistry &
Biology 8 (2001) 759-766). <br>
<br>
It appears that parthenolide itself might be the active constituent in
feverfew. However, the degraded molecule no longer has its
effect. Perhaps it is due to its degradation, as a consequence of
plant thiols attacking parthenolide, that several commercial preparations
of feverfew have been shown to contain little parthenolide on storage.
(P. Dewick)<br>
<br>
It is certainly important to have standardized QC on feverfew
preparations. Several articles indicate using HPLC (High Performance
Liquid Chromotography). I think perhaps UV-VIS might work as well, as
parthenolide has a distinct peak in the UV region. <br>
<br>
The above is my chemical interpretation, being new to the feverfew area.
I would like inputs and comments.<br>
<br>
Marjorie Nieh<br><br>
<br>
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