Apigenin and Structurally Related Flavonoids Allosterically Potentiate the Function of Human α7-Nicotinic Acetylcholine Receptors Expressed in SH-EP1 Cells

Authors

Waheed Shabbir, University of California, San FranciscoFollow
Keun-Hang Susan Yang, Chapman UniversityFollow
Bassem Sadek, UAE UniversityFollow
Murat Oz, Kuwait UniversityFollow

Document Type

Article

Publication Date

5-5-2021

Abstract

Phytochemicals, such as monoterpenes, polyphenols, curcuminoids, and flavonoids, are known to have anti-inflammatory, antioxidant, neuroprotective, and procognitive effects. In this study, the effects of several polyhydroxy flavonoids, as derivatives of differently substituted 5,7-dihydroxy-4H-chromen-4-one including apigenin, genistein, luteolin, kaempferol, quercetin, gossypetin, and phloretin with different lipophilicities (cLogP), as well as topological polar surface area (TPSA), were tested for induction of Ca²⁺ transients by α7 human nicotinic acetylcholine (α7 nACh) receptors expressed in SH-EP1 cells. Apigenin (10 μM) caused a significant potentiation of ACh (30 μM)-induced Ca²⁺ transients, but did not affect Ca²⁺ transients induced by high K⁺ (60 mM) containing solutions. Co-application of apigenin with ACh was equally effective as apigenin preincubation. However, the effect of apigenin significantly diminished by increasing ACh concentrations. The flavonoids tested also potentiated α₇ nACh mediated Ca²⁺ transients with descending potency (highest to lowest) by genistein, gossypetin, kaempferol, luteolin, phloretin, quercetin, and apigenin. The specific binding of α7 nACh receptor antagonist [¹²⁵I]-bungarotoxin remained unchanged in the presence of any of the tested polyhydroxy flavonoids, suggesting that these compounds act as positive allosteric modulators of the α7-nACh receptor in SH-EP1 cells. These findings suggest a clinical potential for these phytochemicals in the treatment of various human diseases from pain to inflammation and neural disease.

Comments

This article was originally published in Cells, volume 10, in 2021. https://doi.org/10.3390/cells10051110

Recommended Citation

Shabbir,W.; Yang, K.-H.S.; Sadek, B.; Oz, M. Apigenin and Structurally Related Flavonoids Allosterically Potentiate the Function of Human 7-Nicotinic Acetylcholine Receptors Expressed in SH-EP1 Cells. Cells 2021, 10, 1110. https://doi.org/10.3390/cells10051110

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