E-Stilbenes: General Chemical and Biological Aspects, Potential Pharmacological Activity Based on the Nrf2 Pathway

Abstract

Stilbenes are phytoalexins, and their biosynthesis can occur through a natural route (shikimate precursor) or an alternative route (in microorganism cultures). The latter is a metabolic engineering strategy to enhance production due to stilbenes recognized pharmacological and medicinal potential. It is believed that in the human body, these potential activities can be modulated by the regulation of the nuclear factor erythroid derived 2 (Nrf2), which increases the expression of antioxidant enzymes. Given this, our review aims to critically analyze evidence regarding E-stilbenes in human metabolism and the Nrf2 activation pathway, with an emphasis on inflammatory and oxidative stress aspects related to the pathophysiology of chronic and metabolic diseases. In this comprehensive literature review, it can be observed that despite the broad number of stilbenes, those most frequently explored in clinical trials and preclinical studies (in vitro and in vivo) were resveratrol, piceatannol, pterostilbene, polydatin, stilbestrol, and pinosylvin. In some cases, depending on the dose/concentration and chemical nature of the stilbene, it was possible to identify activation of the Nrf2 pathway. Furthermore, the use of some experimental models presented a challenge in comparing results. In view of the above, it can be suggested that E-stilbenes have a relationship with the Nrf2 pathway, whether directly or indirectly, through different biological pathways, and in different diseases or conditions that are mainly related to inflammation and oxidative stress.

Dietary Phenolic Compounds—Wellbeing and Perspective Applications

“…Stilbenes can be observed in their free, glycosylated, prenylated, and methoxylated forms and are characterized by a variety of chemical compounds [48]. Stilbenes are present in small amounts in plant organs and tissues.…”

O Pentáculo Do Bem Estar Como Instrumento De Avaliação Do Modo De Vida Na Atenção Primária a Saúde

“…O piceatanol (trans-3,3,4,5-tetrahidroxiestilbeno, PIC), pertence ao grupo dos estilbeno, que fazem parte de um amplo grupo de polifenóis, que ocorre naturalmente em muitas espécies vegetais, principalmente através do mecanismo de defesa contra agentes agressores e patógenos (MENDONÇA et al, 2024). Foi isolado pela primeira vez em 1956, em uma planta chamada Vouacapoua americana (CRAVEIRO et al, 1970;DUBROVINA;KISELEV, 2017).…”

Induction of Semaphorin 3A by Resveratrol and Pinostilbene via Activation of the AHR-NRF2 Axis in Human Keratinocytes

“…Tapinarof is a natural stilbene compound [ 27 , 28 ], and some stilbenes have been reported to activate AHR and NRF2 [ 29 , 30 ]. Thus, there may be stilbenes that potentially produce as much or more SEMA3A than tapinarof.…”