Chemical composition of Callistemon subulatus essential oils and the protective effects against cyclophosphamide-induced lung toxicity: GC/MS metabolic profiling with in vivo and in silico experimental studies

红千层精油的化学成分及其对环磷酰胺诱导的肺毒性的保护作用:GC/MS代谢谱分析结合体内和计算机模拟实验研究

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Abstract

Callistemon is a genus of aromatic plants indigenous to Australia and widely spread for ornamental purposes. In this study, we aimed to investigate the chemical composition of essential oils isolated from the leaves, flowers, stems, and fruits of Callistemon subulatus using gas chromatography-mass spectrometry (GC/MS) analysis, alongside the assessment of the protective effects of the leaf oil against cyclophosphamide (CY)-induced lung toxicity in rats. The leaf oil was rich in oxygenated monoterpenes (51.15%), while the flower oil contained a higher proportion of monoterpene hydrocarbons (72.06%). The stem and fruit oils were predominantly composed of hydrocarbons, accounting for 52.79% and 62.52%, respectively. Interestingly, C. subulatus leaf oil (CLO) showed the highest yield with the highest proportion of eucalyptol (44.36%), a reported anti-inflammatory monoterpene. Thirty rats were divided into five groups and treated for 10 days as follows: group I is a vehicle group, group II was administered CY (200 mg/kg, i. p.), groups III and IV received oral CLO (50 and 100 mg/kg, respectively) in addition to CY (200 mg/kg, i. p.), and group V received only CLO (100 mg/kg, oral). It was found that CLO inhibited the lipid peroxidation level and augmented catalase and glutathione levels. Furthermore, it significantly reduced the overtranscription of α-smooth muscle actin (α-SMA) by preventing fibroblastic cell differentiation into myofibroblasts. The histological appearance of CY-induced lung tissue revealed congestion, epithelial hyperplasia, and inflammatory cell aggregations. However, CLO considerably alleviated these manifestations. The findings demonstrated the preventive function of CLO against the harmful effects of CY on rat lungs. Therefore, C. subulatus oil might be a promising natural candidate for protecting the lung from CY-induced pneumotoxic manifestations.

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