Capsaicin–TRPV1 Signaling: Therapeutic Potential, Molecular Mechanisms, and Safety Considerations
Abstract
Hot peppers (Capsicum spp.), particularly Capsicum annuum, have been consumed worldwide for centuries as food, medicine, and natural colorants. Their pungency is primarily attributed to capsaicin, a bioactive alkaloid synthesized in the placental tissue of chili fruits. Capsaicin exerts its biological effects mainly through activation of the transient receptor potential vanilloid 1 (TRPV1) receptor, a non-selective cation channel involved in nociception, thermoregulation, and neurogenic inflammation. This review highlights the dual role of capsaicin as both a health-promoting and potentially harmful compound. Numerous experimental and clinical studies demonstrate its beneficial effects, including anti-inflammatory, antioxidant, anti-obesity, anti-diabetic, cardioprotective, neuroprotective, reno-protective, and anticancer properties. Capsaicin has also shown therapeutic potential in conditions such as alopecia areata, colitis, hepatic steatosis, pneumonia, renal injury, and metabolic disorders through modulation of lipid metabolism, oxidative stress, gut microbiota, and cellular apoptosis. Conversely, excessive or prolonged exposure to capsaicin has been associated with adverse outcomes, including gastrointestinal injury, chronic cough hypersensitivity, gut dysbiosis, neurogenic pain, central sensitization, vasoconstriction syndromes, and tissue damage. Additionally, contamination of chili products with aflatoxins poses further health risks. Overall, this review emphasizes the “capsaicin paradox,” underscoring the importance of dosage, exposure duration, and physiological context in determining whether capsaicin functions as a therapeutic agent or a toxic irritant.
