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.
Phytomedicine
; 114: 154753, 2023 Jun.
Article
in English
| MEDLINE | ID: covidwho-2302077
ABSTRACT
BACKGROUND:
Dehydroandrographolide (Deh) from Andrographis paniculata (Burm.f.) Wall has strong anti-inflammatory 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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Acute Lung Injury
/
COVID-19
Type of study:
Experimental Studies
Topics:
Traditional medicine
Limits:
Animals
Language:
English
Journal:
Phytomedicine
Journal subject:
Complementary Therapies
Year:
2023
Document Type:
Article
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