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

Abstract

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 KATP–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.

In vitro antioxidant, analgesic and cytotoxic activities of Sepia officinalis ink and Coelatura aegyptiaca extracts

“…As no single analgesic drug is ideal for all pains (Pirmohamed et al, 2004), additional therapies are always being sought. According to Raffa and Pergolizzi (2011), natural products might contain ingredients that offer such alternatives by acting through novel mechanisms of action or by interacting additively or synergistically through known mechanisms of action. The results of the present study revealed that, IE and CE extracts showed analgesic action in mice, by inhibiting the acetic acid-induced writhing as compared to the positive drug indomethacin.…”

Indole diterpene alkaloids as novel inhibitors of the Wnt/β-catenin pathway in breast cancer cells

“…Although, an intact ring H and a free C-25-OH group are both essential for overall in vitro activity (proliferation, migration and invasion assays), their modification does not necessarily abolish molecular mechanisms. These results point both to the complex structural requirement and molecular mechanisms through which penitrems exert their effects, which is the case with most natural products [39,40]. …”

A Randomized, Double‐Blind Comparison Shows the Addition of Oxygenated Glycerol Triesters to Topical Mentholated Cream for the Treatment of Acute Musculoskeletal Pain Demonstrates Incremental Benefit Over Time

“…An OGT‐product has been commercially available in Europe for over a decade and has recently become available in the United States (OxyRub™; Creomed). Although its exact mechanism of action remains to be elucidated, its analgesic and anti‐inflammatory effects may involve the reduction in one or both of the mechanisms of lipid peroxidation of the arachidonic acid cascade 46 . Lipid peroxidation is pathological and reactive oxygen scavengers can be used pharmacologically to interrupt this process.…”