Pharmacological Applications of Capsaicin in the Treatment of Diseases

Capsaicin is the bioactive substance found in Capsicum plants. Pungency is a particular characteristic of such substance. The therapeutic use of chili extracts was made more than 200 years ago, and the properties of capsaicin are still being studied. It is recognized by cells through binding to the transient receptor potential vanilloid 1 (TRPV1) ion channel, being the main receptor agonist. Previous studies described TRV1 expression in afferent neurons and highlighted the essential role of channel activation in the cellular transduction of signs of pain. After interacting with its receptor, capsaicin may modulate substance P release. Interestingly, after prolonged exposure to the agonist, TRPV1 desensitizes and does not respond to capsaicin stimuli and thus promotes pain relief. Additionally, capsaicin modulates the gastrointestinal tract by regulating microbiota that favor short-chain fatty acid production and regulate ghrelin hormone and proinflammatory cytokines. The anti-cancer activity of capsaicin occurs through different pathways. On breast malignant cells capsaicin promote cell death through the cyclin-dependent kinase 8 pathway. In prostate cancer cells the substance impairs androgen receptor (AR) activity while in enterocytes cancer cells it triggers oxidative stress, which will lead to apoptosis. Prevention of oxidative stress and endothelial dysfunction was reported, impairing atherosclerosis development. Currently, researchers are developing new techniques to deliver capsaicin with few side effects. Conventional formulations and nanotechnological strategies have been studied to enhance capsaicin bioavailability. It is noteworthy that capsaicin exerts significant beneficial effects and thus is considered a new strategy for the management of pathological conditions.