Synthesis of resveratrol derivatives as new analgesic drugs through desensitization of the TRPA1 receptor

Nakao, Syuhei; Mabuchi, Miyuki; Wang, Shenglan; Kogure, Yoko; Shimizu, Tadashi; Noguchi, Koichi; Tanaka, Akito; Dai, Yi

doi:10.1016/j.bmcl.2017.05.025

Cited by 17 publications

(8 citation statements)

References 24 publications

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“…The natural stilbenoids resveratrol and pinosylvin inhibit TRPA1 activation by AITC and decrease AITC-induced paw inflammation and production of the proinflammatory cytokine interleukin-6 (IL-6) in mice (542,570,930). A more recent study showed that from a series of 20 stilbenoids, none modulates TRPV1 and most of them have stronger action than resveratrol, with maximal potency observed with ortho monoxygenated stilbenes 6 and 17 (572).…”

Section: Trpa1 Antagonismmentioning

confidence: 99%

Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

Talavera

Startek

Alvarez‐Collazo

et al. 2020

Physiological Reviews

269

274

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The transient receptor potential ankyrin (TRPA) channels are Ca2+-permeable nonselective cation channels remarkably conserved through the animal kingdom. Mammals have only one member, TRPA1, which is widely expressed in sensory neurons and in non-neuronal cells (such as epithelial cells and hair cells). TRPA1 owes its name to the presence of 14 ankyrin repeats located in the NH2 terminus of the channel, an unusual structural feature that may be relevant to its interactions with intracellular components. TRPA1 is primarily involved in the detection of an extremely wide variety of exogenous stimuli that may produce cellular damage. This includes a plethora of electrophilic compounds that interact with nucleophilic amino acid residues in the channel and many other chemically unrelated compounds whose only common feature seems to be their ability to partition in the plasma membrane. TRPA1 has been reported to be activated by cold, heat, and mechanical stimuli, and its function is modulated by multiple factors, including Ca2+, trace metals, pH, and reactive oxygen, nitrogen, and carbonyl species. TRPA1 is involved in acute and chronic pain as well as inflammation, plays key roles in the pathophysiology of nearly all organ systems, and is an attractive target for the treatment of related diseases. Here we review the current knowledge about the mammalian TRPA1 channel, linking its unique structure, widely tuned sensory properties, and complex regulation to its roles in multiple pathophysiological conditions.

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Section: Trpa1 Antagonismmentioning

confidence: 99%

Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

Talavera

Startek

Alvarez‐Collazo

et al. 2020

Physiological Reviews

269

274

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“…There is a heterologous desensitization of TRPA1 via a TRPV1 pathway [170, 171]. Resveratrol or AITC act as activators and desensitizers of TRPA1 channels [153]. High concentrations of para-benzoquinone caused rapid activation of TRAP1 followed by fast decline in a cysteine-dependent desensitization mechanism [172].…”

Section: Activation and Desensitization Of Trpa1 And Trpv1mentioning

confidence: 99%

Potential Interplay between Nrf2, TRPA1, and TRPV1 in Nutrients for the Control of COVID-19

Bousquet

Czarlewski²,

Zuberbier

et al. 2021

Int Arch Allergy Immunol

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In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1 and TRPV1 induce inflammation and play a key role in the physiology of almost all organs. They may augment sensory or vagal nerve discharges to evoke pain and several symptoms of COVID-19, including cough, nasal obstruction, vomiting, diarrhea, and, at least partly, sudden and severe loss of smell and taste. TRPA1 can be activated by reactive oxygen species and may therefore be up-regulated in COVID-19. TRPA1 and TRPV1 channels can be activated by pungent compounds including many nuclear factor (erythroid-derived 2) (Nrf2)-interacting foods leading to channel desensitization. Interactions between Nrf2-associated nutrients and TRPA1/TRPV1 may be partly responsible for the severity of some of the COVID-19 symptoms. The regulation by Nrf2 of TRPA1/TRPV1 is still unclear, but suggested from very limited clinical evidence. In COVID-19, it is proposed that rapid desensitization of TRAP1/TRPV1 by some ingredients in foods could reduce symptom severity and provide new therapeutic strategies.

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“…Attaching Substituents to Position-2 of Resveratrol. The synthesis of resveratrol derivatives was mainly composed of constructing CC by the Heck 11 or Wittig reaction 12 and of linking substituents with hydroxyl groups of resveratrol. We initially envisioned that introducing substituents into resveratrol directly was a convenient protocol for the preparation of resveratrol derivatives.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…9 The biological activity of resveratrol was related to its hydroxyl groups, which were able to trap free radicals in vivo. 10 In the preparation of resveratrol derivatives, both Heck-Hiyama cross-coupling 11 and Wittig reaction 12 provided with powerful strategies for achieving resveratrol derivatives with various substituents attaching to the stilbene scaffold. As shown in Figure 1, a typical resveratrol derivative was produced by the substitution of one benzene ring in resveratrol by bicyclo[1.1.1]-pentane 13 or deferiprone, 14 or the CC bond in resveratrol was replaced by multiple CC bonds, 15 1,4,2-dioxazole, 16 or selenophene.…”

Section: ■ Introductionmentioning

confidence: 99%

Hybrid of Resveratrol and Glucosamine: An Approach To Enhance Antioxidant Effect against DNA Oxidation

Bao

Liu

2018

Chem. Res. Toxicol.

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Resveratrol exhibits various pharmacological activities, which are dependent upon phenolic hydroxyl groups. In this work, glucosamine, lipoic acid, or adamantanamine moiety was applied for attaching to ortho-position of hydroxyl group in resorcinol moiety of resveratrol (known as position-2). Antioxidant effects of the obtained hybrids were characterized using DNA oxidative systems mediated by OH, Cu/glutathione (GSH), and 2,2'-azobis(2-amidinopropanehydrochloride) (AAPH), respectively. The glucosyl-appended imine and amine at position-2 of resveratrol were found to show higher inhibitory effects than other resveratrol derivatives against AAPH-induced DNA oxidation. The antioxidative effect was quantitatively expressed by stoichiometric factor ( n, the number of radical-propagation terminated by one molecule of antioxidant). The stoichiometric factors of glucosyl-appended imine and amine of resveratrol increased to 4.74 (for imine) and 4.97 (for amine), respectively, higher than that of resveratrol (3.70) and glucoside of resveratrol (3.49). It was thereby concluded that the combination of resveratrol with glucosamine at position-2 represented a novel pathway for modifying resveratrol structure in the protection of DNA against peroxyl radical-mediated oxidation.

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Synthesis of resveratrol derivatives as new analgesic drugs through desensitization of the TRPA1 receptor

Cited by 17 publications

References 24 publications

Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

Potential Interplay between Nrf2, TRPA1, and TRPV1 in Nutrients for the Control of COVID-19

Hybrid of Resveratrol and Glucosamine: An Approach To Enhance Antioxidant Effect against DNA Oxidation

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