Essential oil from Inula japonica Thunb. And its phenolic constituents ameliorate pulmonary injury and fibrosis in bleomycin-treated mice

Ethnopharmacological relevance: Pulmonary injury and fibrosis can be caused by various factors because of their inflammatory nature, both can lead to serious clinical consequences. Inula japonica Thunb. is used in traditional Chinese medicine for the treatment of lung diseases. However, the effect and mechanism of action of the essential oil of I. japonica (EOI) on pulmonary injury and fibrosis are not well understood. Aim of the study: To investigate the therapeutic effects of EOI on mice with bleomycin (BLM)-induced acute pulmonary injury and chronic fibrosis formation, as well as its potential mechanism. Materials and methods: A short-term mouse model of pulmonary injury was established by intratracheal injection of BLM to investigate the anti-inflammatory effect of EOI, and a long-term model of pulmonary fibrosis was used to explore the anti-fibrosis effect of EOI. High-dose EOI (200 mg/kg) was administered intragastrically, and lowdose (50 mg/kg) was administered by intratracheal injection. Gas chromatography-mass spectrometry (GC-MS) was used to identify the ingredients in EOI, and high-performance liquid chromatography (HPLC) was performed for the preparation of EOI compounds. Western blot and real-time qPCR were used to verify the effects of EOI and its active composition on inflammation, oxidative stress and fibrosis signaling pathway. Results: Treatment with EOI significantly reduced the inflammation and oxidative stress by reducing the levels of inflammatory and oxidative cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and malondialdehyde in BLM-treated mice with acute pulmonary injury. EOI treatment could also suppress the formation of fibrous tissue in mice with BLM-induced pulmonary fibrosis through inhibiting TGF-beta/Smad and PI3K/Akt pathways. Chromatographic analysis and preparation suggested that fatty acid and phenol derivatives are present in EOI. Based on cellular inflammation and fibrosis models, the phenolic compounds in EOI can represent the anti-inflammatory and anti-fibrotic effects of EOI by regulating pro-inflammatory and pro-fibrotic cytokines such as NO, TNF-alpha, IL-6, TGF-beta 1, and alpha-SMA. Conclusion: EOI ameliorated BLM-induced pulmonary injury and fibrosis in mice by inhibiting the inflammatory response and regulating the redox equilibrium, as well as by mediating TGF beta/Smad and PI3K/Akt, which suggested that EOI has potential to treat pulmonary diseases.

Automated summary

Inula japonica essential oil (EOI) shows potential therapeutic effects on pulmonary injury and fibrosis in mouse models. EOI can inhibit inflammatory response, regulate redox equilibrium, and suppress pulmonary fibrosis by mediating the TGF-beta/Smad and PI3K/Akt signaling pathways.