Advancing Functional Dyspepsia Research Through Translational Gastric Motility Testing

Functional dyspepsia is a highly prevalent gastrointestinal disorder, with impaired gastric accommodation recognised as a key underlying mechanism in a substantial proportion of patients. Although herbal medicines are widely used to alleviate dyspeptic symptoms, the mechanistic basis for many multi‑component herbal formulations remains poorly characterised, particularly with respect to gastric smooth muscle function and muscarinic receptor signalling.

Weleda AG sought to generate robust preclinical evidence to understand how a proprietary multi‑herbal Amara extract influences gastric motility, and to identify the molecular pathways involved. This required:

• A physiologically relevant ex vivo model of gastric smooth muscle contraction and relaxation
• Quantitative assessment of dose‑dependent effects across defined gastric regions
• Mechanistic interrogation of muscarinic receptor involvement
• A study conducted under stringent quality and ethical standards, suitable to support peer‑reviewed publication

REPROCELL collaborated with Weleda AG to design and executed an ex vivo organ bath study using guinea pig gastric smooth muscle, integrating established pharmacological controls and sponsor‑specific test compounds.

Study Design

The study assessed the effects of two herbal test extracts supplied by Weleda AG on circular smooth muscle strips dissected from the fundus of adult male Dunkin Hartley guinea pigs. Only macroscopically normal tissues that passed predefined functional viability criteria were included in the study.

Execution

Muscle strips were mounted under controlled tension and allowed to equilibrate before pharmacological testing. Following baseline stabilisation:

1. Carbachol was applied to induce reproducible smooth muscle contraction
2. Test extracts were added cumulatively to assess concentration‑dependent effects on muscle tone
3. Comparative responses were analysed alongside vehicle and positive controls
4. At study completion, papaverine was added to confirm maximal tissue relaxation and viability

Data were captured digitally and analysed using established statistical methods, with results expressed as changes in baseline tone or reversal of carbachol‑induced contraction.

Using REPROCELL’s ex vivo gastric motility platform, the study demonstrated that:

• The lyophilizate of Amara Drops (Amara extract) induced dose‑dependent relaxation of guinea pig gastric fundus smooth muscle
• The extract significantly inhibited carbachol‑induced contraction, supporting a direct effect on cholinergic pathways regulating gastric tone
• Pharmacological interrogation showed that the relaxant effect was independent of M3 muscarinic receptor activity
• Complementary cellular and receptor‑binding assays (performed in parallel by specialist providers) identified inhibition and binding of the M2 muscarinic receptor as the primary mechanism of action

Importantly, REPROCELL’s organ bath data provided the physiological foundation linking receptor‑level findings to functional gastric smooth muscle outcomes.

The collaborative work between Weleda AG and REPROCELL culminated in a peer‑reviewed publication in Neurogastroenterology & Motility (2024), demonstrating for the first time that:

• A complex herbal formulation can induce gastric fundus relaxation via selective modulation of muscarinic signalling
• Ex vivo guinea pig gastric tissue provides a highly informative translational model for studying gastric accommodation
• Mechanistic pharmacology and physiologically relevant tissue assays can be successfully integrated to support evidence‑based phytotherapy research

The study contributes valuable insight into the biological basis of herbal treatments for impaired gastric accommodation and functional dyspepsia.