dehydroandrographolide and Acute-Lung-Injury

Dehydroandrographolide (Deh) from Andrographis paniculata (Burm.f.) Wall has strong anti-inflammatory and antioxidant activities.. To explore the role of Deh in acute lung injury (ALI) of coronavirus disease 19 (COVID-19) and its inflammatory molecular mechanism.. 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.. 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.. 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.

Topics: Acute Lung Injury; Andrographis paniculata; Animals; COVID-19; Inflammasomes; Lipopolysaccharides; Medicine, Chinese Traditional; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein; Proto-Oncogene Proteins c-akt; Pyroptosis; Reactive Oxygen Species

To investigate the effect of dehydroandrographolide succinate (DAS) on oxidative stress and induced nitric oxide synthase (iNOS) expression in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury.. Thirty male BALB/C mice were randomly divided into control group, LPS+DAS group and LPS group (n=10). The levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) in the bronchoalveolar lavage fluid (BALF) were measured. The wet-to-dry ratio (W/D) of the lung tissue was determined to evaluate lung edema. HE staining was used to observe the pathological changes and lung injury scores. The expressions of iNOS mRNA and protein in the lungs were analyzed using RT-PCR and Western blotting, respectively.. IL-1β, IL-6, TNF-α and MDA levels in the BALF, W/D, lung injury scores, and iNOS mRNA and protein expressions increased and SOD in the BALF decreased significantly after intratracheal LPS injection. Compared with those in LPS group, IL-1β, IL-6, TNF-α and MDA in BALF, W/D, lung injury scores and iNOS mRNA and protein expression were significantly reduced and SOD in the BALF significantly increased in LPS+DAS group.. Dehydroandrographolide succinate can alleviate oxidative stress in LPS-induced acute lung injury possibly by inactivating iNOS.

Topics: Acute Lung Injury; Animals; Diterpenes; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Nitric Oxide Synthase Type II; Oxidative Stress; Succinic Acid