The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis
Zhichen Pu, Bangzhi Sui, Xingwen Wang, Wusuan Wang, Lingling Li, Haitang Xie
Phytomedicine, doi:10.1016/j.phymed.2023.154753
Background: Dehydroandrographolide (Deh) from Andrographis paniculata (Burm.f.) Wall has strong antiinflammatory and antioxidant activities. Purpose: To explore the role of Deh in acute lung injury (ALI) of coronavirus disease 19 (COVID-19) and its inflammatory molecular mechanism. Methods: Liposaccharide (LPS) was injected into a C57BL/6 mouse model of ALI, and LPS + adenosine triphosphate (ATP) was used to stimulate BMDMs in an in vitro model of ALI. Results: In an in vivo and in vitro model of ALI, Deh considerably reduced inflammation and oxidative stress by inhibiting NLRP3-mediated pyroptosis and attenuated mitochondrial damage to suppress NLRP3-mediated pyroptosis through the suppression of ROS production by inhibiting the Akt/Nrf2 pathway. Deh inhibited the interaction between Akt at T308 and PDPK1 at S549 to promote Akt protein phosphorylation. Deh directly targeted PDPK1 protein and accelerated PDPK1 ubiquitination. 91-GLY, 111-LYS, 126-TYR, 162-ALA, 205-ASP and 223-ASP may be the reason for the interaction between PDPK1 and Deh. Conclusion: Deh from Andrographis paniculata (Burm.f.) Wall presented NLRP3-mediated pyroptosis in a model of ALI through ROS-induced mitochondrial damage through inhibition of the Akt/Nrf2 pathway by PDPK1 ubiquitination. Therefore, it can be concluded that Deh may be a potential therapeutic drug for the treatment of ALI in COVID-19 or other respiratory diseases.
The datasets used and/or analyzed of this study are from
Authorship contribution statement The effects and mechanisms of the anti-covid-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall presented acute lung injury by the inhibition of NLRP3mediated pyroptosis. Zhichen Pu and Haitang Xie conceived the study, designed the study and prepared the manuscript. Zhichen Pu, Bangzhi Sui, Xingwen Wang, Wusan Wang, Lingling Li and Haitang Xie conducted the experiments and data analysis, involved in preparation of the figures and manuscript. All data were generated in-house, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy.
Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.
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