Deciphering the mechanism(s) of action of natural products: analgesic peroxide oil as example

Summary Background:  There are multiple reports of natural products having therapeutic effect. In an era of evidence‐based medicine, clinical trials inform clinical decisions regarding use of the product, but prevailing preference is to identify and use a single ‘active ingredient’. Yet, the clinical benefit of a natural product might derive from the fortuitous combination of its multiple components. Therefore, the elucidation of the mechanism(s) of action of natural products is important, but presents significant challenges. This article examines this issue using peroxide oil (essential oxygen oil) as an illustrative example. Objective:  To review the published literature of a natural product in an effort to elucidate postulated mechanism(s) of action of a complex mixture. Methods:  The clinical and preclinical literature was reviewed from the perspective of its contribution to elucidating a mechanism of analgesic action of a natural product. Results:  Peroxide oil contains ingredients that are associated with analgesic mechanisms, such inhibition of lipid peroxidation and arachidonic acid metabolism and non‐opioid, glibenclamide‐sensitive receptor‐mediated and K ATP –NO–cGMP channel pathways. Conclusion:  Although its exact mechanism remains unknown, peroxide oil provides an example of how a natural product can be evaluated for plausible mechanistic explanation of its purported therapeutic efficacy. Such an approach seems valuable, since, as in this case, the constituents appear to contribute in an additive or synergistic manner, something not possible with a single substance.