Labani · Pharmaceutics 2023 · in vitro pharmacological assay · n=?

Pistacia vera Extract Potentiates the Effect of Melatonin on Human Melatonin MT 1 and MT 2 Receptors with Functional Selectivity.

Cited 7 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

In vitro laboratory study on cell lines without human or animal trials.

PubMed 37514032 · doi:10.3390/pharmaceutics15071845 · record verified 2026-08-29

What was done

Researchers evaluated 25 commercial plant extracts with reputed sleep and anxiety benefits for activity at human melatonin MT1 and MT2 receptors. Using mock-transfected and HEK293 cells expressing MT1 or MT2, they performed cellular assays assessing 2-[125I]iodomelatonin binding, cAMP inhibition, ERK1/2 activation, and beta-arrestin2 recruitment.

What was found

Extract 18 (Ex18) from Pistacia vera dried fruits showed potent melatonin receptor activity, containing 5.28 ± 0.46 mg/g extract of endogenous melatonin. Ex18 was also found to contain an additional active constituent that potentiated the effect of melatonin on Gi protein-dependent signaling pathways but not on beta-arrestin2 recruitment. Potentiating activity was also observed in other tested extracts.

Why it matters

This study shows that pistachio extract provides high endogenous melatonin levels alongside an active component that selectively potentiates melatonin receptor signaling. This functional selectivity may inform future botanical or pharmaceutical development for sleep and circadian disorders.

Limits

The study is entirely in vitro using engineered HEK293 cell models. The abstract does not identify the specific chemical structure of the potentiating constituent, nor does it assess bioavailability, in vivo metabolism, safety, or human efficacy.

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