Sterilized fermented beverage targets obesity and type 2 diabetes pathways in computational study

By Vijay Kumar MalesuReviewed by Susha Cheriyedath, M.Sc.Dec 9 2025

By analysing the drink people would actually consume, researchers reveal how sterilised plant-based ferments could theoretically influence insulin, lipid, and inflammatory pathways, setting the stage for future experimental testing.

Study: Bioactive aporphines and flavonoids from a fermented beverage target metabolic inflammatory pathways in obesity and type 2 diabetes. Image Credit: Hanasaki / Shutterstock

A recent study in the journal Scientific Reports identified, characterized, and evaluated bioactive molecules in a terminally sterilized, probiotic-fermented medicinal-food-homologous (MFH) beverage that may counter obesity and type 2 diabetes (T2D) through in silico multi-target modulation of metabolic inflammation.

Global Burden of Obesity and Type 2 Diabetes

More than 1 in 8 adults live with obesity, and over 500 million with T2D, a syndemic that fuels heart disease, kidney failure, and lost productivity. Families feel this at the grocery checkout and pharmacy counter. Effective drugs such as glucagon-like peptide-1 (GLP-1) receptor agonists work, but costs, side effects, and access limit real-world use.

Traditional Chinese Medicine (TCM) guided foods and ferments are inexpensive, shelf-stable options that people can drink daily.

Yet most research characterizes raw herbs, not the final sterilized beverage people actually consume. Clarifying which molecules survive processing, and how they act on insulin, lipids, and inflammation, requires integrated chemical and systems analyses. 

Further research should test these mechanisms in cells and humans, as current findings are derived solely from computational analyses.

Profiling Bioactives in a Sterilized MFH Beverage

Investigators analyzed a ready-to-drink, terminally sterilized fermented beverage (FH03FS) produced from five MFH plants, such as Radix of Millettia speciosa, lotus leaf, monk fruit, tangerine peel, and Cinnamomi cortex. They are first heat-treated for safety, then fermented with Lacticaseibacillus paracasei and Lactiplantibacillus plantarum, and finally pasteurized for stability.

Phytochemicals were profiled using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Compounds with relative abundance >0.1% were screened for oral bioavailability and drug-likeness.

 In silico Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) predictions included gastrointestinal (GI) absorption, blood-brain barrier permeability, P-glycoprotein (P-gp) substrate status, and cytochrome P450 (CYP) inhibition.

Systems analyses used network pharmacology to intersect predicted compound targets with obesity and T2D gene sets, protein-protein interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to define core nodes and pathways.

Molecular docking quantified binding (kcal/mol) between prioritized compounds and hub proteins, Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA), guided molecular dynamics (MD) simulations (100 ns) assessed stability via root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), and solvent-accessible surface area (SASA).

Together, this pipeline connects “what is in the bottle” to “what it might do” in metabolic-inflammatory networks as predicted by computational modeling rather than experimental testing.

Chemical Profiling Identifies Ten Key Bioactives

UPLC-MS/MS detected 3,387 molecules spanning phenylpropanoids/polyketides, organoheterocycles, lipids, benzenoids, and alkaloids. From these, ten pharmacokinetically favorable actives emerged, dominated by aporphine alkaloids (nuciferine, asimilobine) and flavonoids (isosinensetin, morin, 5,7,3′,4′-tetramethoxyflavone, 7,4′-di-O-methylapigenin, 3,3′,4′,5,6,7,8-heptamethoxyflavone, 5-desmethylsinensetin), plus (S)-coclaurine and the lignan eudesmin.

ADMET suggested high GI absorption and generally low safety concerns; most compounds did not raise human ether-à-go-go–related gene (hERG) or Ames test (AMES) mutagenicity flags, while some showed CYP interactions worth monitoring in polypharmacy.

Systems Modeling Links Bioactives to Metabolic Inflammation

Target prediction intersected 338 putative compound targets with thousands of obesity and T2D genes, yielding 144 overlapping nodes. Network topology distilled 20 core proteins central to metabolic inflammation and insulin signaling, including peroxisome proliferator-activated receptor gamma (PPARG), estrogen receptor 1 (ESR1), RAC-alpha serine/threonine-protein kinase (AKT1), tumor necrosis factor (TNF), interleukin-1 beta (IL1B), signal transducer and activator of transcription 3 (STAT3), apoptosis regulator B-cell lymphoma 2 (BCL2), cellular tumor antigen p53 (TP53), proto-oncogene tyrosine-protein kinase Src (SRC), mechanistic target of rapamycin (MTOR), and matrix metalloproteinases (MMP2/MMP9).

GO and KEGG enrichment highlighted pathways relevant to metabolic disease biology, including insulin resistance, lipid and atherosclerosis signaling, advanced glycation end-products-receptor for AGE (AGE-RAGE) pathways, and core cascades such as phosphoinositide 3-kinase-Akt (PI3K-Akt), mitogen-activated protein kinase (MAPK), cyclic adenosine monophosphate (cAMP), TNF, and estrogen signaling.

These networks reflect statistically enriched pathway associations and plausibly link a daily beverage to improved glucose transport via glucose transporter type 4 (GLUT4), reduced hepatic gluconeogenesis via forkhead box protein O1 (FOXO1), attenuated inflammatory signaling, and altered lipid handling in computational network models.

Docking and Simulations Demonstrate Binding Stability

Molecular docking supported multi-target engagement. Morin bound ESR1, BCL2, and SRC with high affinity; several flavonoids and (S)-coclaurine favored PPARG, and 5-desmethylsinensetin targeted AKT1. Notably, nuciferine exhibited broad predicted binding across several metabolic hubs.

Two representative complexes underwent MD simulations. Morin-ESR1 stabilized quickly (RMSD ≈ 0.26 nm), maintained hydrogen bonds, and showed van der Waals–driven binding by MM-PBSA with consistent SASA and Rg, features of a low-energy binding pose.

Asimilobine-PPARG exhibited similar stability (RMSD ≈ 0.28 nm) with greater electrostatic contributions and persistent hydrophobic contacts after minor mid-trajectory optimization.

Together, the trajectories displayed a single deep minimum in the free-energy landscape, indicating durable binding modes within the simulated systems.

Potential for Accessible, Fermented Metabolic Support

In communities weighing food budgets against pharmacy bills, a shelf-stable fermented beverage that survives sterilization with intact aporphines and flavonoids and that, in silico, engages PPARG, AKT1, ESR1, and inflammatory nodes, offers a plausible, accessible adjunct to diet and exercise as a hypothesis generated by computational analysis. It does not replace GLP-1 or sodium-glucose cotransporter-2 (SGLT2) therapies, but it could help households nudge glucose, lipids, and inflammation in the right direction if future experimental and clinical studies confirm biological relevance.

Conclusions and Future Experimental Directions

A terminally sterilized MFH fermented beverage (FH03FS) contains aporphine alkaloids and flavonoids with favorable ADMET profiles, high predicted GI absorption, and multi-target actions across insulin, lipid, and inflammatory pathways identified using integrated in silico approaches.

Network pharmacology, molecular docking, and 100-ns MD simulations (with MM-PBSA) indicate stable binding to core hubs like PPARG, ESR1, AKT1, TNF, and others, aligned with KEGG pathways for insulin resistance, PI3K-Akt, MAPK, and AGE-RAGE signaling.

These computational findings generate testable hypotheses that a daily, affordable beverage could complement lifestyle change and conventional care, pending validation in experimental and human studies. Next steps should include biophysical assays, cell models, and human trials to confirm efficacy, safety, dose, and interactions in real-world settings.