Antioxidative and Analgesic Effects of Naringin through Selective Inhibition of Transient Receptor Potential Vanilloid Member 1

Abstract

Transient receptor potential vanilloid member 1 (TRPV1) is activated in response to capsaicin, protons, temperature, and free reactive oxygen species (ROS) released from inflammatory molecules after exposure to harmful stimuli. The expression level of TRPV1 is elevated in the dorsal root ganglion, and its activation through capsaicin and ROS mediates neuropathic pain in mice. Its expression is high in peripheral and central nervous systems. Although pain is a response evolved for survival, many studies have been conducted to develop analgesics, but no clear results have been reported. Here, we found that naringin selectively inhibited capsaicin-stimulated inward currents in Xenopus oocytes using a two-electrode voltage clamp. The results of this study showed that naringin has an IC50 value of 33.3 μM on TRPV1. The amino acid residues D471 and N628 of TRPV1 were involved in its binding to naringin. Our study bridged the gap between the pain suppression effect of TRPV1 and the preventive effect of naringin on neuropathic pain and oxidation. Naringin had the same characteristics as a model selective antagonist, which is claimed to be ideal for the development of analgesics targeting TRPV1. Thus, this study suggests the applicability of naringin as a novel analgesic candidate through antioxidative and analgesic effects of naringin.

The Efficacy of Camelina sativa Defatted Seed Meal against Colitis-Induced Persistent Visceral Hypersensitivity: The Relevance of PPAR α Receptor Activation in Pain Relief

“…The rich profile of flavonoids found in camelina DSM contains high levels of vitexin and naringenin, which account together for more than 99% of total flavonoids. Both vitexin and naringenin were considered in the recent literature for their neuroprotective effects and inhibition of inflammatory and neuropathic pain [ 41 , 42 , 43 ].…”

“…We observed that pre-treating the animals with the selective PPAR-α receptor antagonist GW6471 almost completely prevented the acute pain-relief offered by camelina administration in DNBS animals. The effect was independent of the activation of PPAR-Ƴ receptor or the CB1 and CB2 receptors, which are involved in pain regulation as well [ 43 , 49 , 50 , 67 , 68 ]. Interestingly, PPAR-α is involved in the modulation of pain signalling [ 69 ], as well as in several pathophysiological mechanisms, some of which contribute to pain development such as neuroinflammation and oxidative stress [ 70 ].…”

“…Camelina sativa DSM has a high content of vitexin and naringenin. These flavonoids are endowed with a neuroprotective potential, attested to by their ability to counteract inflammatory and neuropathic pain [ 42 , 43 , 44 ]. Behind the anti-inflammatory effects, vitexin-enriched plants exhibited remarkable pain-relieving activities.…”

Natural Active Ingredients and TRPV1 Modulation: Focus on Key Chemical Moieties Involved in Ligand–Target Interaction

“…Various flavonoids induced TRPV1-mediated antinociceptive effects, such as reduction in carrageenan-, capsaicin- and chronic complete Freund’s adjuvant (CFA)-induced mechanical and thermal hyperalgesia [ 164 , 165 , 166 , 167 ]. Flavonoids with TRPV1 antagonistic properties included various compounds: naringenin [ 168 ], cochinchinemin A and B, loureirin B [ 169 ], gomisin A [ 170 ], eriodictyol [ 165 ], quercetin [ 171 ] and vitexin [ 164 ].…”

Oxidative Damage in Korean Medicine

“…Eom et al showed that naringin acted in a concentration-dependent and voltageinsensitive manner, reversibly inhibited the interaction with transient receptor potential cation channel subfamily V member 1 at the cellular and molecular levels, and had an IC 50 value of 33.33 µM. Naringin only inhibited inward peak current without affecting inward peak current [15]. They cross-checked the results from TEVC and docking experiments and found that D471 and N628 of transient receptor potential cation channel subfamily V member 1 were involved in binding with naringin.…”