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

Abstract

Diseases such as cancer, neurological pathologies and chronic pain represent currently unmet needs. The existing pharmacotherapeutic options available for treating these conditions are limited by lack of efficiency and/or side effects. Transient receptor potential vanilloid 1 ion channel emerged as an attractive therapeutic target for developing new analgesic, anti-cancer and antiepileptic agents. Furthermore, various natural ingredients were shown to have affinity for this receptor. The aim of this narrative review was to summarize the diverse natural scaffolds of TRPV1 modulators based on their agonistic/antagonistic properties and to analyze the structure–activity relationships between the ligands and molecular targets based on the results of the existing molecular docking, mutagenesis and in vitro studies. We present here an exhaustive collection of TRPV1 modulators grouped by relevant chemical features: vanilloids, guaiacols, phenols, alkylbenzenes, monoterpenes, sesquiterpenoids, alkaloids, etc. The information herein is useful for understanding the key structural elements mediating the interaction with TRPV1 and how their structural variation impacts the interaction between the ligand and receptor. We hope this data will contribute to the design of novel effective and safe TRPV1 modulators, to help overcome the lack of effective therapeutic agents against pathologies with high morbidity and mortality.

Targeting NF-κB Signaling: Selected Small Molecules Downregulate Pro-Inflammatory Cytokines in Both Food Allergen and LPS-Induced Inflammation

“…One of the suggested mechanisms is that vanilloids and their counterparts bind to transient receptor potential vanilloid 1 (TRPV1) [ 41 ]. TRPV1 is primarily expressed in sensory neurons, but it has also been found in non-neuronal cells and immune cells such as dendritic cells, macrophages, and T-cells [ 41 , 42 ]. The difference in TRPV1 expression levels between macrophages and epithelial cells could be one of the reasons why we observe a slightly different immunomodulatory potential of these small molecules in different cell lines.…”

Bioactives and their roles in bone metabolism of osteoarthritis: evidence and mechanisms on gut-bone axis

“…Blockage of TRPV1 led to significant inhibition of joint pain and proved to be a promising therapeutic against osteoarthritis ( 53 ). Various agonists of TRPV1, such as capsaicin, resiniferatoxin, allicin, gingerol, and piperine, have been shown to interact and bind to TRPV1 ( 54 , 55 ). Several clinical studies have shown the effect of topical or intra-articularly administered capsaicin in alleviating OA-related pain ( 56 , 57 ).…”