Abstract
Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) have high mortality rates. Though corticosteroids are commonly used for the treatment of these conditions, their efficacy has not been conclusively demonstrated and their use can induce various adverse reactions. Hence, the application of corticosteroids as therapeutic modalities for ALI/ARDS is limited. Meanwhile, the aporphine alkaloid oxocrebanine isolated from Stephania pierrei tubers has demonstrated anti-inflammatory efficacy in murine/human macrophage cell lines stimulated by lipopolysaccharide (LPS). Accordingly, the primary objectives of the present study are to investigate the anti-inflammatory effects of oxocrebanine on LPS-induced murine alveolar epithelial (MLE-12) cells and its efficacy against LPS-induced murine ALI. Results show that oxocrebanine downregulates the abundance of interleukin (IL)-1beta, IL-6, and inducible nitric oxide synthase, as well as the phosphorylation of nuclear factor-kappaB (NF-κB), stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), p38, protein kinase B (Akt), and glycogen synthase kinase-3beta signalling proteins in LPS-induced MLE-12 cells. Moreover, in a murine ALI model, oxocrebanine lowers lung injury scores and lung wet/dry weight ratios while reducing inflammatory cell infiltration. It also suppresses LPS-induced tumour necrosis factor-alpha and IL-6 in the bronchoalveolar lavage fluid and plasma. Moreover, oxocrebanine downregulates NF-κB, SAPK/JNK, p38, and Akt phosphorylation in the lung tissues of LPS-treated mice. Taken together, the foregoing results show that oxocrebanine provides significant protection against LPS-induced ALI in mice primarily by suppressing various inflammatory signalling pathways in alveolar epithelial cells and lung tissues. Hence, oxocrebanine might prove effective as an anti-inflammatory agent for the treatment of lung inflammation.
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Acknowledgements
This research was supported by the Royal Patronage of Her Royal Highness Princess Maha Chakri Sirindhorn (grant no. WUBG-018/2565). W. Chulrik acknowledges the support of the Walailak University Graduate Research Fund (grant no. CGS-RF-2021/05) and the Walailak University Ph.D. Excellence Scholarship (grant no. 04/2020). The Center of Excellence for Innovation in Chemistry, Ministry of Higher Education, Science, Research, and Innovation provided partial funding for this study to A. Suksamrarn and W. Chaichompoo. We would like to thank Editage (www.editage.com) for English language editing.
Funding
This research was financed by the Royal Patronage of Her Royal Highness Princess Maha Chakri Sirindhorn (grant no. WUBG-018/2565). W. Chulrik thanks the Walailak University Graduate Research Fund (grant no. CGS-RF-2021/05) and a Walailak University Ph.D. Excellence Scholarship (grant no. 04/2020). The Center of Excellence for Innovation in Chemistry, Ministry of Higher Education, Science, Research, and Innovation provided partial funding for this study to A. Suksamrarn and W. Chaichompoo.
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Conceptualisation: WC and WC; methodology: WC and WC; validation: AT and CP; formal analysis: WC and CJ; investigation: WC, CJ, WC, NS, and RK; resources: KR and AS; writing—original draft preparation; WC and WC; writing—review and editing: WC, KR, AS, and WC; supervision and funding acquisition: WC and AS. All authors read and approved the final manuscript.
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Chulrik, W., Jansakun, C., Chaichompoo, W. et al. Protective effects of Stephania pierrei tuber-derived oxocrebanine against LPS-induced acute lung injury in mice. Inflammopharmacol 31, 2023–2035 (2023). https://doi.org/10.1007/s10787-023-01231-y
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DOI: https://doi.org/10.1007/s10787-023-01231-y