Capsaicin, The Vanilloid Receptor TRPV1 Agonist in Neuroprotection: Mechanisms Involved and Significance

Abstract

Hot peppers, also called chilli, chilli pepper, or paprika of the plant genus Capsicum (family Solanaceae), are one of the most used vegetables and spices worldwide. Capsaicin (8-methyl N-vanillyl-6-noneamide) is the main pungent principle of hot green and red peppers. By acting on the capsaicin receptor or transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1), capsaicin selectively stimulates and in high doses defunctionalizes capsaicin-sensitive chemonociceptors with C and Aδ afferent fibers. This channel, which is involved in a wide range of neuronal processes, is expressed in peripheral and central branches of capsaicin-sensitive nociceptive neurons, sensory ganglia, the spinal cord, and different brain regions in neuronal cell bodies, dendrites, astrocytes, and pericytes. Several experimental and clinical studies provided evidence that capsaicin protected against ischaemic or excitotoxic cerebral neuronal injury and may lower the risk of cerebral stroke. By preventing neuronal death, memory impairment and inhibiting the amyloidogenic process, capsaicin may also be beneficial in neurodegenerative disorders such as Parkinson's or Alzheimer's diseases. Capsaicin given in systemic inflammation/sepsis exerted beneficial antioxidant and anti-inflammatory effects while defunctionalization of capsaicin-sensitive vagal afferents has been demonstrated to increase brain oxidative stress. Capsaicin may act in the periphery via the vagal sensory fibers expressing TRPV1 receptors to reduce immune oxidative and inflammatory signalling to the brain. Capsaicin given in small doses has also been reported to inhibit the experimentally-induced epileptic seizures. The aim of this review is to provide a concise account on the most recent findings related to this topic. We attempted to delineate such mechanisms by which capsaicin exerts its neuronal protective effects. We also aimed to provide the reader with the current knowledge on the mechanism of action of capsaicin on sensory receptors.

Keywords: Brain stroke; Capsaicin; Capsicum; Epilepsy; Hot peppers; Neurodegenerative diseases; Resiniferatoxin; Sensory neurons; Systemic inflammation; TRPV1.

Fig. 1

Mechanisms underlying protection by systemic administration of capsaicin in small doses in ischaemic/reperfusion brain injury

Fig. 2

Favourable effects of capsaicin administration in cerebrovascular disease

Fig. 3

Protective mechanisms of small dose capsaicin in experimental Parkinson’s disease

Fig. 4

Effects of supplementing diet with capsaicin or systemic injection of small dose capsaicin in experimental Alzheimer’s disease

Fig. 5

Effects of capsaicin in systemic inflammation/sepsis

Fig. 6

Effects of small dose systemic capsaicin in experimental epilepsy