Letter to the editor: Effect of aqueous extract of Glycyrrhiza glabra on rabbit ileum motility

Dear Editor,

We read with interest the recent publication by Zulfiqar et al.^[1] on the pharmacological effects of Glycyrrhiza glabra on rabbit ileum motility. The in vitro investigation offers valuable insight into the modulatory bidirectional impact of this widely used herb. The use of acetylcholine, atropine, and ondansetron to elucidate the dual cholinergic and serotonergic pathways was scientifically appropriate and well-executed.

However, the dose–response relationship reported in the study raises critical interpretative questions. The non-linear pattern where the 5% extract elicited a stronger contraction than the 15% and 20% concentrations may suggest receptor desensitisation or a dose-dependent shift in the extract’s pharmacodynamic profile. A plausible explanation lies in the presence of isoliquiritigenin, a flavonoid constituent of G. glabra, which has been shown to relax smooth muscle through nitric oxide–cyclic guanosine monophosphate (NO)-cGMP signalling. In a high-impact study, Chen et al. demonstrated that isoliquiritigenin causes vasorelaxation by enhancing cGMP levels through the NO pathway.^[2] Such relaxant activity at higher concentrations could counteract the prokinetic effects observed at lower doses, supporting the hypothesis of a dual or biphasic action. Thus, the study’s conclusion about G. glabra having both spasmogenic and spasmolytic effects may reflect dose-dependent modulation by its phytoconstituents.

The graphical data in the article by Zulfiqar et al.^[1] offered valuable insights; however, in [Figures 1 and 3] presented by them do not give clarity because of inconsistent axis labels and vague legends. A standardised format for displaying contraction force along with proper units (e.g., millinewtons, mN) would enhance clarity.

Another limitation is that the extract was reported only in terms of percentage concentration, without any phytochemical standardisation. Future research should include the quantification of active components, such as glycyrrhizin and isoliquiritigenin, to ensure reproducibility and to correlate specific constituents with the observed pharmacological effects. Earlier studies have demonstrated liquorices’ prokinetic effects in vivo using gastric emptying models and even explored it in clinical trials for functional dyspepsia, reinforcing the importance of standardising extract composition for clinical relevance.^[3]

We recommend that future investigations incorporate intermediate extract concentrations (e.g., 10%), randomise dose administration to avoid fatigue bias, and utilise standardised extracts. In vivo, the validation of gastrointestinal effects would also support translational relevance.

In conclusion, while the current study presents promising preliminary data, further refinement of the methodology and standardisation is necessary to establish G. glabra’s therapeutic potential for gastrointestinal dysmotility firmly.