Computational Evidence for Spirulina–Moringa Phytochemical Chemosensitization of Pancreatic Cancer: An Integrative Network Pharmacology, Molecular Docking, and Transcriptomic Study

Background and Aim. Pancreatic ductal adenocarcinoma (PDAC) exhibits nearuniversal
FOLFIRINOX chemoresistance driven by constitutive NF-κB activation,
mTOR-mediated autophagy suppression, and P-glycoprotein drug efflux. This
study computationally evaluates whether phytochemicals from Spirulina platensis
(Arthrospira platensis Gomont, Oscillatoriaceae) and Moringa oleifera Lam.
(Moringaceae) represent candidate chemosensitisation agents for KRASG12D-mutant
PDAC, generating specific testable hypotheses for subsequent experimental validation.
Methods. An eight-layer computational pipeline was deployed: ADMET/
Lipinski/QED filtering, compound–target–disease network pharmacology, PPI
hub gene identification, AutoDock-GPU v1.6 molecular docking (Lamarckian Genetic
Algorithm), 100 ns molecular dynamics simulation with MM-PBSA, Bliss/Loewe/ZIP
synergy modelling, Boolean/ODE pathway simulation with rule-perturbation sensitivity
analysis, and TCGA-PAAD transcriptomic target validation with GATA6
subtype stratification.
Results. Nine drug-like compounds target 30 PDAC disease genes (96.8% overlap;
Monte Carlo randomisation p < 10−4, 184-fold enrichment). NF-κB1 emerged as
the dominant hub (degree = 10). AutoDock-GPU validated β-sitosterol binding to
EGFR (ΔG = −7.98 kcal/mol) and NF-κB p65/RELA (−7.70 kcal/mol). The triple
combination achieved 87.9% predicted cell death versus 83.3% for FOLFIRINOX
alone (Boolean model robust under 66.4% of permuted rule sets). Hub targets are
specifically hyper-activated in FOLFIRINOX-resistant basal-like PDAC (enrichment
p = 2.94×10−74). Bioavailability-adjusted scoring identifies niazimicin (Foral = 45%)
as the most pharmacologically realistic lead.
Conclusions. Computational evidence supports a “three-pronged siege” hypothesis
in which Spirulina and Moringa phytochemicals may modulate PDAC resistance
pathways. A 48–72 h Moringa washout protocol is proposed to mitigate the identified
CYP3A4–irinotecan herb–drug interaction. These predictions warrant experimental
validation in PANC-1 models before any clinical extrapolation.
Keywords: pancreatic cancer · network pharmacology · molecular docking · Spirulina
platensis · Moringa oleifera · FOLFIRINOX