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<p>Lung cancer (LC) remains the foremost cause of cancer-related mortality worldwide. Exposure to the carcinogen diethylnitrosamine (DEN) results in significant toxicity across various organs, with the lungs being especially affected. Rosmanol (RML), a well-known phenolic diterpenoid derived from several medicinal plants, especially <i>Rosmarinus officinalis</i> L. (rosemary), has been reported to exhibit potent anti-proliferative, antioxidant, anti-inflammatory, and anticancer activities. Therefore, the present-day study investigated the antineoplastic potential of RML in contrast to DEN-induced LC in a Wistar rat model by modulating the Nrf2/NF-κB/PI3K/Akt and COX-2/CYP2E1/VEGF signalling pathways. Rats were categorised into six experimental groups: normal control (NC), DEN (150&#xa0;mg/kg b.w., i.p.), DEN + RML at different concentrations, and RML alone (20&#xa0;mg/kg b.w.). The findings revealed that RML administered DEN-induced rat decreased BW, elevation in LW and LW/BW ratio, hepatic enzyme leakage, serum glycoproteins, oxidative stress, inflammation, and structural disruption of pulmonary and hepatic tissues. In addition, RML enhanced antioxidant enzyme activities, lung tissue glycoproteins, and the expression of Nrf2, IL-10, p53, Bax, and caspases, while significantly suppressing Bcl-2, inflammatory cytokines, COX-2, CYP2E1, and VEGF mRNA levels. The RML-alone group exhibited biochemical and histological profiles similar to those of the NC group. Collectively, the results suggest that RML confers strong antitumor protection against DEN-induced LC, primarily through its antioxidant, anti-inflammatory, and pro-apoptotic actions via regulation of the Nrf2/NF-κB/PI3K/Akt signalling network.</p>

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Protective effects of rosmanol on DEN-induced lung cancer via targeting Nrf2/NF-κB/PI3K/Akt and COX-2/CYP2E1/VEGF pathways: in vivo approach

  • 期刊论文

  • 发表日期：

    2026年2月23日

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  • Ji Chang,
  • Wu Xiaoran,
  • Zhao Lisha,
  • Zhang Shiran,
  • Zhang Hui

摘要

Lung cancer (LC) remains the foremost cause of cancer-related mortality worldwide. Exposure to the carcinogen diethylnitrosamine (DEN) results in significant toxicity across various organs, with the lungs being especially affected. Rosmanol (RML), a well-known phenolic diterpenoid derived from several medicinal plants, especially Rosmarinus officinalis L. (rosemary), has been reported to exhibit potent anti-proliferative, antioxidant, anti-inflammatory, and anticancer activities. Therefore, the present-day study investigated the antineoplastic potential of RML in contrast to DEN-induced LC in a Wistar rat model by modulating the Nrf2/NF-κB/PI3K/Akt and COX-2/CYP2E1/VEGF signalling pathways. Rats were categorised into six experimental groups: normal control (NC), DEN (150 mg/kg b.w., i.p.), DEN + RML at different concentrations, and RML alone (20 mg/kg b.w.). The findings revealed that RML administered DEN-induced rat decreased BW, elevation in LW and LW/BW ratio, hepatic enzyme leakage, serum glycoproteins, oxidative stress, inflammation, and structural disruption of pulmonary and hepatic tissues. In addition, RML enhanced antioxidant enzyme activities, lung tissue glycoproteins, and the expression of Nrf2, IL-10, p53, Bax, and caspases, while significantly suppressing Bcl-2, inflammatory cytokines, COX-2, CYP2E1, and VEGF mRNA levels. The RML-alone group exhibited biochemical and histological profiles similar to those of the NC group. Collectively, the results suggest that RML confers strong antitumor protection against DEN-induced LC, primarily through its antioxidant, anti-inflammatory, and pro-apoptotic actions via regulation of the Nrf2/NF-κB/PI3K/Akt signalling network.