1,8-cineole: An Underappreciated Anti-inflammatory Therapeutic

Abstract

The inflammatory response is typically initiated by infection or cellular injury, and provides host protection aimed at clearing the initial triggering event, as well as providing long-term protective immunity. When properly functioning, the inflammatory process is a mediator of acute injury to restore tissue health and is characteristically self-limiting once tissue repair and homeostasis have been restored. If tissue health is not restored, such as if the tissue harbors a continuous low grade inflammatory stimulant, then the inflammatory process becomes a chronic response that continuously damages the surrounding tissue in its attempt to provide repair. Left unchecked, long-term inflammation can result in diseases of chronic inflammation, such as autoimmunity or age-related diseases. Choice of current anti-inflammatory therapies is often limited by patient risk-benefit considerations. Traditional approaches to manage chronic inflammation include non-steroidal anti-inflammatory drugs or corticosteroids which provide short-term benefits, but are often plagued with significant side effects that preclude their use for long-term therapy. The newest classes of anti-inflammatory therapeutics, biologics, are engineered monoclonal antibodies that bind pro-inflammatory mediators and neutralize their effects by preventing pro-inflammatory signaling. Unfortunately, biologic therapies are often prohibitively expensive and have serious, sometimes life-threatening side effects. In lieu of biologics or chemically synthesized small molecules, natural products have provided a rich source of small molecule effectors. One particular natural product, 1,8-cineole, also called eucalyptol, is reported to have anti-inflammatory, anti-microbial, and anti-oxidant activity. Several clinical trials have established potent anti-inflammatory activity for 1,8-cineole, which may suggest its use as a primary treatment, or at the very least, an adjunct therapy for current anti-inflammatory agents. We argue that use of 1,8-cineole as an anti-inflammatory agent needs greater study in other diseases with a chronic inflammatory component, including atherosclerotic cardiovascular disease, type 2 diabetes mellitus, and arthritic complications.