Shahrekord University of Medical Sciences Journal of Herbmed Pharmacology 2345-5004 15 2 2026 04 01 Unveiling the anticancer potential of Ziziphus mauritiana seeds: A multi-targeted approach integrating network pharmacology, molecular docking, and in vitro validation 207 216 10.34172/jhp.2026.53282 EN Rajashekar Shivananda Chavan https://orcid.org/0000-0002-9049-1127 Santhosh Gangaraj https://orcid.org/0009-0003-1099-2410 Manasa Gopal https://orcid.org/0009-0004-5794-4448 Sai Prasad Kaparthi Karthik https://orcid.org/0009-0008-6059-5356 Shivam Anand https://orcid.org/0009-0004-7793-313X Journal Article 10.34172/jhp.2026.53282 2025 07 14 2025 09 04 Introduction: Breast cancer is a major cause of mortality in women, and conventional therapies often face limitations such as toxicity, resistance, and recurrence. The seeds of Ziziphus mauritiana, although traditionally valued for their anti-inflammatory and immune-modulating properties, remain largely understudied for their anticancer potential compared to the leaves, fruits, and bark. This study aimed to evaluate the multi-target activity of the seed extract against breast cancer. Methods: Bioactive compounds identified by gas chromatography-mass spectrometry (GC-MS) were analyzed via network pharmacology to predict targets and enriched pathways. Molecular docking (Schrödinger Maestro) was used to assess interactions with the mTOR kinase (PDB: 4JT6) and PI3Kγ (PDB: 4RA4), with an emphasis on hydrogen bonding and hydrophobic contacts. Antioxidant activity was evaluated using the DPPH assay, and cytotoxicity was assessed against MCF-7 cells using the MTT assay. Results: Beta-D-Glucopyranose showed strong hydrogen bonding with mTOR (−8.56 kcal/mol), and Stigmasterol exhibited hydrophobic interactions with PI3Kγ (−6.30 kcal/mol). Network pharmacology revealed significant enrichment in PI3K-Akt signaling (false discovery rate [FDR] = 1.0E−28), NF-κB signaling (FDR = 1.0E−20), and oxidative stress response (FDR = 1.0E−34). The extract displayed moderate antioxidant capacity (IC₅₀ = 68.86 µg/mL) and dose-dependent cytotoxicity against MCF7 cells (IC₅₀ = 45.63 µg/mL). Conclusion: This first integrative study on Z. mauritiana seed extract highlights its potential as a natural anticancer agent through multi-pathway modulation, antioxidant effects, and cytotoxicity, supporting further preclinical development for breast cancer treatment.