CAP and Metabolic Diseases: A Mini Review on Preclinical Mechanisms and Clinical Efficacy

Abstract

Capsaicin (CAP) is the chief active ingredient of natural chili peppers. It has culinary and medicinal benefits. CAP activates its receptor, transient receptor potential vanilloid subfamily 1 (TRPV1), which is expressed in the sensory and motor neurons, adipocytes, liver, vascular smooth muscle cells, neuromuscular junction, skeletal muscle, heart and brain. The specificity of CAP to activate TRPV1 is the fundamental mechanism for its medicinal benefits to treat pain, obesity, hypertension, and other diseases. Preclinical data from rodent model of high fat diet-induced obesity collectively suggest that CAP exerts its effects by activating TRPV1 signaling pathway, which stimulates thermogenic mechanisms in the white and brown adipose tissues to induce browning of white adipose tissues and brown adipose tissue thermogenesis. This leads to enhancement of metabolic activity and thermogenesis to counter obesity. Although CAP and its pungent and nonpungent analogs are used in human clinical studies, their effects on satiety and energy expenditure have been the highlights of such studies. The precise mechanism of action of CAP has not been evaluated in humans. This article summarizes these data and suggests that long-term safety and tolerance studies are important for advancing CAP to treat human obesity.

Binding Efficacy and Thermogenic Efficiency of Pungent and Nonpungent Analogs of Capsaicin

“…The common interactions of the vanillyl groups in CAP and Capsiate (L553, L515, and S512) could explain how the latter ligand can activate TRPV1. However, it is possible that the extra interactions displayed by the vanillyl group in Capsiate (N551 and T550) produce structural changes in TRPV1 different than those elicited by CAP, leading to the lower level of activation evinced through the physiologic and thermogenic actions in mice described previously [9,10,11]. Regarding CAP-β- d gluco, the low degree of activation displayed by this ligand can be attributed to its binding outside the binding channel.…”

“…CAP-induced rise in intracellular Ca 2+ via TRPV1 is suggested to facilitate its thermogenic effect [10]. Also, clinical research has demonstrated the enhancement of energy expenditure in humans by CAP and Capsiate [11]. Although similar studies have been performed with several combinations of capsinoids and capsaicinoids in rodent models, such studies have used divergent doses and concentrations of these compounds [7,11], which make the interpretation of the results difficult and challenging.…”

“…Also, clinical research has demonstrated the enhancement of energy expenditure in humans by CAP and Capsiate [11]. Although similar studies have been performed with several combinations of capsinoids and capsaicinoids in rodent models, such studies have used divergent doses and concentrations of these compounds [7,11], which make the interpretation of the results difficult and challenging. Published work suggests that Capsiate exerts an anti-obesity effect [7,12], while it is also shown to activate other forms of TRP proteins like TRPA1 [5].…”

Assessment of Pharmacology, Safety, and Metabolic activity of Capsaicin Feeding in Mice

“…Capsaicin (CAP) is a key ingredient of natural chili peppers. The benefits of CAP to treat neuropathic pain 1–3 , cancer 4–7 and metabolic syndrome 8–14 have been extensively researched in the recent years. Previous experimental studies using CAP patches applied locally on rats and rabbits suggest that CAP was safe and well tolerated 15 .…”