GC-MS Profiling and Molecular Docking of Pistachio Shell (Pistacia vera): Insights into its Anticancer Potential Against Cervical Cancer Targets

Abstract

Background: Cervical cancer is one of the leading causes of cancer-related morbidity and mortality among women worldwide, particularly in low- and middle-income countries. The limitations of current therapies indicate that there is an urgent need for affordable, plant-derived alternatives. Pistacia vera (pistachio), a widely consumed nut crop valued for its nutritional and economic importance, generates shells as an agro-industrial byproduct. Rich in phenolics, fatty acids, sterols, and terpenoids, pistachio shells remain underexplored for their anticancer potential.

Objectives: The present study undertakes the first systematic evaluation of pistachio shell methanolic extracts against cervical cancer molecular targets. GC–MS profiling was employed to catalog the phytoconstituents, followed by molecular docking against HPV E6 (PDB: 4XR8) and tumor suppressor p53 (PDB: 1TUP).

Methods: Methanolic extracts of pistachio shells were subjected to GC–MS profiling to identify phytoconstituents. The detected metabolites were docked against cervical cancer–relevant targets, HPV E6 oncoprotein (4XR8) and tumor suppressor p53 (1TUP). ADMET and drug-likeness analyses were performed to evaluate pharmacokinetic feasibility and safety.

Results: GC–MS analysis revealed 32 bioactive constituents, including catechol, oleic acid, stigmasterol, betulin, and nimbin. Among them, 1,2-cyclopentanedione exhibited the strongest interaction with HPV E6 (–9.34 kcal/mol), while catechol showed the highest affinity for p53 (–9.45 kcal/mol). Other metabolites such as nimbin, d-mannose, and oleic acid demonstrated multi-target binding potential. ADMET predictions indicated favorable pharmacokinetic properties, with high gastrointestinal absorption, no CYP450 inhibition, and non-toxic profiles for most candidates, supporting their suitability for oral formulations.

Conclusions: This study provides the first integrated GC-MS and in silico evaluation of pistachio shell, identifying 1,2-cyclopentanedione and catechol as promising dual modulators of HPV E6 and p53. These findings emphasize the intriguing possibility of valuing pistachio agro-waste as a plant-based therapeutic against cervical cancer, warranting further preclinical and clinical investigations