Pterostilbene ameliorates benzo[b]fluoranthene-induced lung injury by suppressing Toll-like receptor 4/nuclear factor kappa-B pathway and mitochondria-mediated apoptosis
- Phytomedicine. 2026 Jun 14:159:158405. doi: 10.1016/j.phymed.2026.158405.
- 1. West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.
- 2. West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; College of Polymer Science and Engineering, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
- 3. West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; Health Promotion and Food Nutrition & Safety Key Laboratory of Sichuan Province, Sichuan University, Chengdu 610041, China; Occupational Health and Occupational Medicine Key Laboratory of Sichuan Provincial Health Commission, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; Molecular Toxicology Key Laboratory of Sichuan Provincial Education Office, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
Background: Benzo[b]fluoranthene is a polycyclic aromatic hydrocarbon widely present in grilled, smoked, fried foods and incomplete tobacco combustions, and was reported to impact the cardiovascular and pulmonary health, while pterostilbene, a phytochemical commonly found in grapes, blue berries and Pterocarpus santalinus, is capable of modulating inflammatory responses, oxidative stress, and Apoptosis.
Purpose: This study evaluated if pterostilbene mitigates benzo[b]fluoranthene-induced lung injury through anti-inflammatory, antioxidant, and anti-apoptotic activities.
Methods: In vivo studies utilized C57BL/6J Nifdc mice (n=8 per group). The six experimental groups included: a sham control (corn oil), a benzo[b]fluoranthene group (100 mg/kg), a pterostilbene group (50 mg/kg), and three co-treatment groups receiving both BbF (100 mg/kg) and PT at 12.5, 25, or 50 mg/kg. Concurrent in vitro analyses in BEAS-2B and 16HBE bronchial epithelial cells comprised immunological evaluations, oxidative stress measurements, and mechanistic studies targeting mRNAs and proteins associated with inflammation, antioxidant response, and Apoptosis.
Results: In mice, oral administration of pterostilbene reduced benzo[b]fluoranthene-induced inflammatory cell infiltration in the lung, elevated the expressions of anti-inflammatory and antioxidant factors in both the lung tissues and the serum, and regulated key oxidative stress and inflammatory proteins NF-κB and HO-1. In the BEAS-2B and 16HBE cells, pterostilbene treatment decreased the proportions of sub-G1 phase cells and apoptotic cells, restored mitochondrial membrane potential suppressed by benzo[b]fluoranthene exposure, increased the levels of antioxidant Enzymes (CAT, GSH, GPx), and upregulated the expressions of anti-apoptotic protein Bcl-2 and antioxidant proteins Nrf2 and HO-1.
Conclusion: Pterostilbene can protects the respiratory tract against injury through a multi-mechanism mode of action. Its synergistic anti-inflammatory, antioxidant, and anti-apoptotic activities collectively alleviate oxidative stress, suppress inflammatory responses, and inhibit programmed cell death, thereby preserving respiratory epithelial integrity and function.
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