Bitter melon to control diabetes

Recently here in the land of Oz there was a report on a local current affairs program call the “7:30 report” about some compounds that were isolated from the Chinese bitter melon. Aside from the howling mistake of the structure of the compounds “being solved by scanning electron microscope” (Well bugger me!) these babies have some interesting activity. For those of you that are unaware, Traditional Chinese Medicines (TCM) are currently all the rage in the world of natural products. And why not! TCM’s have been a drug lead bonanza over recent years, and have yielded such gems as artemisinin, the current antimalarial drug of choice for treating malaria that was isolated from the Chinese shrub Artemisia annua, which is fast acting and highly effective against multi-drug resistant falicparum malaria.
So for me it comes as no surprise that the latest “wonder drug lead” comes from some form of Chinese vegetation. The bitter melon has long been known to exhibit antidiabetic activity. As you know doubt are aware type II diabetes is almost at epidemic proportions as we in the western world gorge ourselves and get fatter and fatter. Currently, the two drug classes of choice are the thiazolidinediones and the biguanides. The thiazolidinediones have the rather unfortunate side effect of weight gain – not the greatest side effect in the world for treating diabetes, so novel treatments are a must. A group at the Garvan Institute in Sydney, working with dudes from Bayer in Germany and the Shanghai Institute of Materia Medica got together and explored the old bitter melon and found a whole heap of cucurbitane glycosides that accounted for the activity of the extract. Check out the structures below, and here is the reference for the journal article: Min-Jia Tan, Ji-Ming Ye, Nigel Turner, Cordula Hohnen-Behrens, Chang-Qiang Ke, Chun-Ping Tang, Tong Chen, Hans-Christoph Weiss, Ernst-Rudolf Gesing, Alex Rowland, David E. James and Yang Y, “Antidiabetic Activities of Triterpenoids Isolated from Bitter Melon Associated with Activation of the AMPK Pathway” Chemistry and Biology, 2008, 15, 263 – 273

This got me thinking. Do we analyse the “drugability” of compounds to much. In terms of further development, these guys are a medicinal chemists worst nightmare. To lipophilic, to many chiral centres, etc etc etc. Do we rationalise everything far to much in western medicine at the expense of both serendipity and more traditional pharmacognosy based drug discovery? For me the answer is a resounding YES! These cucurbitane glycosides got me thinking of another triterpene glycoside isolated from the Hoodia cactus, the imaginatively called p57 (see below). This fella has great appetite suppressant activity, and the San people in southern Africa eat the cactus before they go out on their long hunting and gathering capers. There is also considerable overlap at the molecular target level between obesity and type II diabetes, with drugs against one therapeutic area having activity against the other.

Could the western world fatties turn to the good ‘ol triterpene glycoside to solve the obesity/diabetes problems? Should somebody undertake a massive screening campaign looking at trying to identify as many of this structure class as possible that is active against molecular targets implicated in these two disease states? Is this a nail in the coffin of such stupidity as the screening of vast arrays of synthetic libraries to find novel drugs? Has (as I suspect) nature done all the work for us, and all we have to do is conserve a little bit of it, explore it chemically and biologically, and let the medicinal chemists use their skills and talents at manipulating and tinkering around the edges with what nature has provided us to come up with ultimate drug winners? I think so. And just think of the medicinal opportunities that have been lost through the mindless slaughter and marginalisation of Australian aboriginals. It certainly makes me sick.