Integrated In-Silico Prioritization of Anti-Diabetic Candidates from Helianthus Tuberosus Using Bibliometrics, Target Prediction, Docking, MD, and ADMET Profiling

Diabetes mellitus [DM] is a growing global burden associated with cardiovascular, neurological, and metabolic complications. Helianthus tuberosus [Jerusalem artichoke] contains inulin and bioactive phytochemicals that may modulate DM-related pathways. This study aimed to identify and prioritize candidate antidiabetic compounds through an integrated computational pipeline.

Bibliometric analysis of Web of Science and Scopus records retrieved in February 2025 mapped research trends and prioritized candidate molecules. Protein targets were predicted using SwissTargetPrediction. Lead compounds underwent molecular docking with AutoDock Vina, 10-ns molecular dynamics simulations in GROMACS, pharmacokinetic and drug-likeness assessment using SwissADME, and toxicity prediction using ProTox-3 and Way2Drug.

“Fermentation,” “inulin,” and “metabolism” were the most frequent keywords. Six microbiome-derived metabolites generated through inulin fermentation and five plant phytochemicals were compiled. HDAC3, carbonic anhydrases, PTP1B, and EGLN1 emerged as relevant targets. Butyrate-HDAC3 and ferulic acid-CA XII formed stable complexes during molecular dynamics simulations [average RMSD ≤0.3 nm]. Both compounds had SwissADME bioavailability scores of 0.85, although ferulic acid showed suboptimal solubility. ProTox-3 classified butyrate as Toxicity Class 3 [predicted LD50 approximately 91 mg/kg], with possible blood-brain barrier liability; Way2Drug indicated potential multisystem adverse effects at higher exposures.

These findings suggest complementary antidiabetic mechanisms involving microbiome-derived metabolites and plant phytochemicals, but the computational predictions require experimental confirmation.

Butyrate and ferulic acid were prioritised for mechanism-focused preclinical validation, with attention to butyrate toxicity and ferulic acid formulation.