Pterostilbene ameliorates benzo[b]fluoranthene-induced lung injury by suppressing Toll-like receptor 4/nuclear factor kappa-B pathway and mitochondria-mediated apoptosis.

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.