Molecular Target for Thunder God Vine
Mar21

Molecular Target for Thunder God Vine

This post appeared originally last Friday for my monthly gig at Science-Based Medicine. Thunder god vine may not be a useful herbal medicine but the compounds isolated from it are fascinating – if not as medicines, then most certainly as laboratory tools. Nature Chemical Biology recently published an article where a research team from Johns Hopkins, the University of Colorado at Boulder, and Drew University in New Jersey, has determined the molecular mechanism of action of triptolide, an unusual triepoxide compound from the plant. Tripterygium wilfordii Hook F, or thunder god vine, is known as lei gong teng in Chinese traditional medicine and has a history of use as an anti-inflammatory herb. As with many traditional medicines, usage patterns do not necessarily indicate scientific validity. In fact, a Cochrane review published just last month on herbal therapies for rheumatoid arthritis indicated that the efficacy of thunder god vine was mixed. More concerning is that the herb had significant adverse effects in some trials, from hair loss to one case of aplastic anemia. Nevertheless, the herb’s components have been studied since the 1970s for since they also appears to kill tumor cells in culture with nanomolar potency and have immunosuppresant activity in animal models. The group of the late natural products chemist at the University of Virginia, S. Morris Kupchan, first identified the unusual structures of triptolide and tripdiolide from Tripterygium wilfordii as described in this 1972 paper from the Journal of the American Chemical Society. Cytotoxic activity toward tumor cells in culture was used to guide the chemical fractionation of extracts. The unusual presence of three consecutive epoxides in the structures of both compounds led Kupchan to hypothesize later in Science that they target leukemia cells by covalent binding to cellular targets involved in cellular growth. As an aside for my non-chemistry readers (and I’m sure my chemist readers will correct me): Epoxides are chemically reactive groups composed of an oxygen atom bonded to two carbons; the constraints of this triangular structure and the electrons on the oxygen favor the opening of this ring and attack of other atoms such as sulfur, often present in regulatory regions of enzymes. Dare I say that the Wikipedia entry gives a pretty nice primer. The reactivity of epoxides also makes these compounds highly useful intermediates in industry, particularly in the manufacture of ethylene glycol antifreeze and industrial paints and adhesives (e.g. epoxy resins). Conventional wisdom would drive most scientists to take one look at triptolide and say that this stuff is a royal mess – so chemically reactive that it couldn’t possible have a specific cellular target. It’s probably too “dirty” –...

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