Journal of ethnopharmacology · 2025
Inhibition of an endocannabinoid catabolizing enzyme is a potential mechanism for the anxiolytic effect of chamomile.
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El-Alfy Abir T, Almeida Kristine, Vaidya Nidhi, Abourashed Ehab A
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: German chamomile (Matricaria recutita L.) is reputed for its calming effect in humans. Clinical trials demonstrate the role of the endocannabinoid system in modulating emotional homeostasis.
AIM OF THE STUDY: To identify secondary metabolites in chamomile that indirectly modulate the endocannabinoid system through inhibition of fatty acid amide hydrolase (FAAH) enzyme.
MATERIALS AND METHODS: Total methanolic chamomile extract was fractionated using solvents with increasing polarity. All fractions were fingerprinted using high performance liquid chromatography (HPLC) and subsequently evaluated for inhibition of FAAH using an in vitro microplate assay. The fraction with the highest FAAH inhibition was further chromatographed to identify active compound(s). The most potent compound (FAAH inhibition) was investigated in the elevated plus maze (EPM) rodent anxiety model using CD1 adult mice.
RESULTS: In the initial FAAH inhibition screening, the hexane fraction showed the highest activity. Multiple assay-guided chromatography of the hexane fraction resulted in the identification of linoleic acid as the main active constituent. Time course inhibition showed that linoleic acid sustained >50 % inhibition up to 48h post treatment. The IC50 of linoleic acid FAAH inhibition was 0.32 ± 0.03 mM. The compound showed a dose-dependent anxiolytic activity in the EPM assay, evidenced by a significant increase in open arm permanence time at 120 mg/kg dose (p < 0.05).
CONCLUSIONS: The study demonstrates FAAH inhibition activity for chamomile hexane fraction and identifies linoleic acid as its main active constituent. This indicates that chamomile plays a role in modulating the endocannabinoid system and supports its traditional use as a calming herbal dietary supplement to reduce stress and anxiety. The identification of linoleic acid as an endocannabinoid modulating molecule may provide access to lead compounds with therapeutic potential against various mood disorders.
AIM OF THE STUDY: To identify secondary metabolites in chamomile that indirectly modulate the endocannabinoid system through inhibition of fatty acid amide hydrolase (FAAH) enzyme.
MATERIALS AND METHODS: Total methanolic chamomile extract was fractionated using solvents with increasing polarity. All fractions were fingerprinted using high performance liquid chromatography (HPLC) and subsequently evaluated for inhibition of FAAH using an in vitro microplate assay. The fraction with the highest FAAH inhibition was further chromatographed to identify active compound(s). The most potent compound (FAAH inhibition) was investigated in the elevated plus maze (EPM) rodent anxiety model using CD1 adult mice.
RESULTS: In the initial FAAH inhibition screening, the hexane fraction showed the highest activity. Multiple assay-guided chromatography of the hexane fraction resulted in the identification of linoleic acid as the main active constituent. Time course inhibition showed that linoleic acid sustained >50 % inhibition up to 48h post treatment. The IC50 of linoleic acid FAAH inhibition was 0.32 ± 0.03 mM. The compound showed a dose-dependent anxiolytic activity in the EPM assay, evidenced by a significant increase in open arm permanence time at 120 mg/kg dose (p < 0.05).
CONCLUSIONS: The study demonstrates FAAH inhibition activity for chamomile hexane fraction and identifies linoleic acid as its main active constituent. This indicates that chamomile plays a role in modulating the endocannabinoid system and supports its traditional use as a calming herbal dietary supplement to reduce stress and anxiety. The identification of linoleic acid as an endocannabinoid modulating molecule may provide access to lead compounds with therapeutic potential against various mood disorders.