In vitro and In silico evaluation of Shunthi (Zingiber officinale Roscoe.) to ascertain its role in Functional Dyspepsia

Abstract

Introduction: Functional dyspepsia is a benign gastrointestinal disorder presenting with early satiety, post prandial fullness and discomfort in epigastrium. It is a multifactorial condition due to impaired gastric motility, visceral hypersensitivity and inflammation. Ayurveda classifies Shunthi (Zingiber officinale Roscoe.) under Truptighna group of medicinal plants. It is traditionally used for symptoms similar to FD. But the mechanism of action in functional gastrointestinal disorders is not yet understood. Methodology: Z. officinale rhizome ethanolic extract was assessed for total phenols (Folin-ciocalteu method), flavonoids (Aluminium chloride method) and Antioxidant assay (DPPH method) followed by network pharmacology and molecular docking approach to elucidate the multitargeted mechanism of Shunthi in FD. Results: Z. officinale rhizome showed phenolic content of 76.36 mg GAE/ gm of extract and flavonoid content of 6.55 mg QE/ gm of extract. The extract showed DPPH free radical inhibition activity with IC₅₀ 20.1 µg/mL. 285 phytoconstituents were retrieved from IMPPAT 2.0 and Dr. Duke’s databases. ADME screening via SWISS-ADME was performed and 181 compounds were retained. Binding DB and Uniprot analyses helped to identify 57 bio-actives. Intersection with proteins associated with FD with Venny 2.1 revealed 34 common targets. A protein-protein interaction network was constructed using STRING database, followed by Gene Ontology and KEGG pathway enrichment analyses. The results identified serotonergic synapse, arachidonic acid metabolism, cancer related pathways and micro-RNA signalling pathways as the primarily modulated pathways. Topological analysis was done using Cytoscape. During molecular docking, it was understood that five key phytoconstituents namely dehydrogingerdione, 8-shagol, 10-shagol, gingerol and 8-gingerdione bind more effectively with stable binding scores (>/= -7 kcal/mol) to core targets PTGS2, TRPV1 and ALOX5. Conclusion: Modulation involving multiple targets and pathways indicates that Shunthi has the ability to act by regulation of inflammation and nociception, by maintaining gastrointestinal homeostasis. The study findings provide a rationale based on systems-pharmacology approach and form the basis for further experimental and clinical validation.