{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:29:37Z","timestamp":1787138977129,"version":"build-2736575974"},"reference-count":75,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Royal Initiative of Her Royal Highness Princess Maha Chakri Sirindhorn-Botanical Garden of Walailak University","award":["RSPG-WU-26\/2566"],"award-info":[{"award-number":["RSPG-WU-26\/2566"]}]},{"award":["RSPG-WU-26\/2566"],"award-info":[{"award-number":["RSPG-WU-26\/2566"]}],"id":[{"id":"https:\/\/ror.org\/04b69g067","id-type":"ROR","asserted-by":"publisher"}]},{"name":"FCT\/MEC","award":["UID\/50011\/2025"],"award-info":[{"award-number":["UID\/50011\/2025"]}]},{"name":"FCT\/MEC","award":["LA\/P0006\/2020"],"award-info":[{"award-number":["LA\/P0006\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background\/Objectives: Oxidative stress is a major cause of RBC membrane damage, especially in individuals with G6PD deficiency who have impaired antioxidant defenses. Triphala, a phenolic-rich herbal formulation with known antioxidant activity, was evaluated for its phytochemical profile, antioxidant and anti-hemolytic effects, and molecular mechanisms in H2O2-induced oxidative stress models using normal and G6PD-deficient human RBCs. Methods: Triphala aqueous extract was characterized using LC-MS and GC-MS. Antioxidant activity was evaluated by DPPH and ABTS assays. Cytotoxicity, membrane stability, and protection against H2O2-induced hemolysis were assessed in normal and G6PD-deficient RBCs. Network pharmacology, molecular docking and MD simulation analyses were performed to predict antioxidant-related mechanisms. Statistical analysis was conducted using one-way ANOVA (p &lt; 0.05). Results: LC-MS identified gallic acid as the predominant phenolic compound, while GC-MS revealed pyrogallol as the major constituent. The extract showed strong radical scavenging activity and significantly reduced H2O2-induced hemolysis in both normal and G6PD-deficient RBCs without cytotoxicity (p &lt; 0.05). Network pharmacology revealed that G6PD-related antioxidant regulation, oxidative stress response, and inflammatory signaling pathways are the key enriched biological processes. Network pharmacology analysis ranked PPARG, PTGS2, EGFR, MMP9, TLR4, ACE, REN, PPARA, SERPINE1, and MMP2 as the top hub proteins, highlighting their central roles in oxidative stress, inflammation, and metabolic signaling pathways. Kynurenic acid binds strongly to PTGS2 (COX-2) and ACE with binding affinities below \u22127.0 kcal\/mol, forming multiple hydrogen bonds that stabilize its interactions within the active sites. MD simulations confirmed that kynurenic acid binds stably to ACE and PTGS2, with RMSD values plateauing near 2.4 \u00c5 and 3.0 \u00c5, RMSF values mostly below 2 \u00c5, and recurrent hydrogen bonding and electrostatic contacts with key residues, collectively underscoring its conformational stability, adaptive flexibility, and modulatory potential. Conclusions: Triphala aqueous extract exhibits potent antioxidant and anti-hemolytic activities and may serve as a natural adjunct strategy for reducing oxidative damage in G6PD deficiency and related RBC disorders.<\/jats:p>","DOI":"10.3390\/life16081359","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:04:12Z","timestamp":1787137452000},"page":"1359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Phytochemical, Network Pharmacology, and Molecular Docking Analyses of Triphala Extract Reveal Protective Effects Against H2O2-Induced Oxidative Hemolysis in G6PD-Deficient Erythrocytes"],"prefix":"10.3390","volume":"16","author":[{"given":"Aman","family":"Tedasen","sequence":"first","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siriwimon","family":"Ranjuanjit","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nattacha","family":"Srirod","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kingkan","family":"Bunluepuech","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6703-7869","authenticated-orcid":false,"given":"Maria de Lourdes","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veeranoot","family":"Nissapatorn","sequence":"additional","affiliation":[{"name":"Research Excellence Center for Innovation and Health Products (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Futuristic Science Research Center, School of Science, World Union for Herbal Drug Discovery (WUHeDD), Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0351-1178","authenticated-orcid":false,"given":"Chutima","family":"Rattanawan","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Amnatcharoen Campus, Mahidol University, Mueang Amnat Charoen 37000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9054-0665","authenticated-orcid":false,"given":"Naunpun","family":"Sangphech","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Khlong Luang, Pathumthani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9202-1594","authenticated-orcid":false,"given":"Rachasak","family":"Boonhok","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0826-197X","authenticated-orcid":false,"given":"Orawan","family":"Sarakul","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Hematology and Transfusion Sceince Research Center (HTSRC), Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lee, H.Y., Ithnin, A., Azma, R.Z., Othman, A., Salvador, A., and Cheah, F.C. 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