Mechanistic Insights on Dyspepsia Modulation by Salvia rosmarinus Through Network Pharmacology, Molecular Docking, and Molecular Dynamics

Dyspepsia or indigestion is known to be a symptom of several gastrointestinal issues including gastroesophageal reflux disease (GERD) and gastric cancer. With the ever-increasing popularity of traditional herbal medicines, the research selected rosemary, or Salvia rosmarinus, due to its historical ethnopharmacological applications and ease of cultivation. Potential targets of molecules from S. rosmarinus are explored for the molecular pathogenesis of functional dyspepsia. Through a network pharmacology approach, it has been shown that there is a significant interaction between the disease and the plant’s compounds. The pathways involving the target genes of S. rosmarinus that are related to functional dyspepsia were revealed to be implicated in the development of certain diseases like gastric cancer and fibrosis which are both precursors to dyspepsia. Moreover, through molecular docking, the results of the pathway analyses were computationally validated indicating that the compound luteolin has the most significant interaction against dyspepsia-related genes. It effectively promotes apoptosis in cancer pathways, reducing the chances of gastric cancer carcinogenesis. To further validate these findings, molecular dynamics simulation was performed to compare the stability and binding behavior of the top-performing compound against the reference compound. The results of this study could be a possible basis in developing pharmaceuticals against gastrointestinal diseases, specifically, dyspepsia.