Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases

Abstract

Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neuro-protective functions. Moreover, emerging data indicate its clinical significance in treating vascular-related diseases, metabolic syndrome, and gastro-protective effects. The dearth of potent drugs for management of such disorders necessitates the urge for further research into the pharmacological aspects of capsaicin. This review summarizes the historical background, source, structure and analogues of capsaicin, and capsaicin-triggered TRPV1 signaling and desensitization processes. In particular, we will focus on the therapeutic roles of capsaicin and its analogues in both normal and pathophysiological conditions.

Keywords: analogues; capsaicin; desensitization; neuropathic pain; therapeutic.

Figure 1

Chemical structure of capsaicin, the primary ingredient of chili pepper, and its three important regions, namely A (aromatic head), B (amide linkage) and C (hydrophobic tail) depicted in different colored boxes.

Figure 2

The general chemical structure of capsaicinoid and capsinoid and their related analogues that differ in the R-group are summarized. Capsaicinoids and capsinoids have a common vanillyl moiety and differ in the central linkage (shown in red) and R-group.