TY - JOUR
T1 - Molecular networking identifies an AHR-modulating benzothiazole from white button mushrooms (Agaricus bisporus)
AU - Chen, Xiaoling
AU - Patterson, Andrew D.
AU - Perdew, Gary H.
AU - Murray, Iain A.
AU - Kellogg, Joshua J.
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/7
Y1 - 2023/7
N2 - Diet-derived aryl hydrocarbon receptor (AHR) ligands have potential to maintain gut health. However, among the myriad bioactive compounds from foods, identifying novel functional ligands which would significantly impact gastrointestinal health is a challenge. In this study, a novel AHR modulator is predicted, identified, and characterized in the white button mushroom (Agaricus bisporus). Using a molecular networking approach, a methylated analog to benzothiazole was indicated in white button mushrooms, which was subsequently isolated and identified as 2-amino-4-methyl-benzothiazole(2A4). Cell-based AHR transcriptional assays revealed that 2-amino-4-methyl-benzothiazole possesses agonistic activity and upregulated CYP1A1 expression. This contrasts with previous findings that whole white button mushroom extract has overall antagonistic activity in vivo, underscoring the importance of studying the roles each chemical component plays in a whole food. The findings suggest that 2-amino-4-methyl-benzothiazole is a previously unidentified AHR modulator from white button mushroom and demonstrate that molecular networking has potential to identify novel receptor modulators from natural products.
AB - Diet-derived aryl hydrocarbon receptor (AHR) ligands have potential to maintain gut health. However, among the myriad bioactive compounds from foods, identifying novel functional ligands which would significantly impact gastrointestinal health is a challenge. In this study, a novel AHR modulator is predicted, identified, and characterized in the white button mushroom (Agaricus bisporus). Using a molecular networking approach, a methylated analog to benzothiazole was indicated in white button mushrooms, which was subsequently isolated and identified as 2-amino-4-methyl-benzothiazole(2A4). Cell-based AHR transcriptional assays revealed that 2-amino-4-methyl-benzothiazole possesses agonistic activity and upregulated CYP1A1 expression. This contrasts with previous findings that whole white button mushroom extract has overall antagonistic activity in vivo, underscoring the importance of studying the roles each chemical component plays in a whole food. The findings suggest that 2-amino-4-methyl-benzothiazole is a previously unidentified AHR modulator from white button mushroom and demonstrate that molecular networking has potential to identify novel receptor modulators from natural products.
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U2 - 10.1016/j.jff.2023.105602
DO - 10.1016/j.jff.2023.105602
M3 - Article
C2 - 37397272
AN - SCOPUS:85161274641
SN - 1756-4646
VL - 106
JO - Journal of Functional Foods
JF - Journal of Functional Foods
M1 - 105602
ER -