Phytomedicine Plus · Published 2026-05-29 · DOI 10.1016/j.phyplu.2026.101005
Priyam Singh, Vishwjeet Jadaun, Mohd Sharib Warsi, Mohd Talha, Jyotsana Dwivedi, Khushtar Anwar Salman
Background: Chronic respiratory conditions, such as asthma and chronic obstructive pulmonary disease (COPD), are primarily caused by persistent oxidative stress and inflammation of the airway epithelium. Although Terminalia chebula, also known as Haritaki, is a well-known Ayurvedic medicinal fruit that has long been utilized in formulations for respiratory health and inflammatory illnesses, its mechanistic function in oxidative stress-driven airway epithelium injury remains insufficiently characterized. Objective: This study examined the potential protective effects of Terminalia chebula fruit extract against oxidative stress-induced damage to human lung epithelial cells, as well as the involvement of the KEAP1–Nrf2 antioxidant pathway. Methods: Terminalia chebula showed the most promising overall bioactivity profile among the studied herbal extracts (H1-H11), with substantial antioxidant capacity and superior cytoprotective properties in A549 cells under oxidative stress. As a result, it was chosen for an elaborate mechanistic evaluation. An oxidative stress damage model was created by exposing A549 cells to H2O2. The MTT assay was used to measure cytocompatibility, DCF-DA and DHE staining were used to measure intracellular and mitochondrial reactive oxygen species, and the comet assay and fluorescence-based nuclear morphology analysis were used to quantify DNA/nuclear damage. RT-qPCR was used to examine the expression of inflammatory and oxidative stress-responsive genes. Major phytochemical contents were identified using LC-ESI-MS/MS profiling, and interactions with KEAP1, IL-6, and IL-8 related targets were investigated using molecular docking. Results: H10 protected against oxidative genotoxic and nuclear damage, enhanced cell viability, and decreased ROS production. Additionally, it suppressed oxidative stress-associated pro-inflammatory mediators IL-6 and IL-8 at the transcript and secretory levels while upregulating Nrf2-associated cytoprotective genes such NQO1 and TXNRD1. Punicalagin, chebulagic acid, terflavin derivatives, and terchebulin were among the polyphenolic tannins discovered by LC-ESI/MS that shown substantial in silico binding affinities for KEAP1 and pro-inflammatory cytokine targets. Conclusion: In an in vitro model of oxidative lung epithelial injury, Terminalia chebula fruit extract has notable cytoprotective, antioxidant, and anti-inflammatory properties that are consistent with KEAP1–Nrf2 axis regulation. These results justify additional validation in sophisticated airway models and in vivo respiratory inflammatory research, and they offer molecular support for its traditional therapeutic value.
Abstract from DOAJ. Public domain (CC0 1.0).
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Singh, P., Jadaun, V., Warsi, M., et al. (2026). Terminalia chebula fruit extract activates the KEAP1–Nrf2 antioxidant axis and attenuates oxidative stress–induced inflammatory injury in human lung epithelial cells. Phytomedicine Plus. https://doi.org/10.1016/j.phyplu.2026.101005