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Acute lung injury (ALI) is a devastating condition caused by sepsis, pneumonia, trauma, and more recently, COVID-19. SH003, an herbal formula consisted of Astragalus membranaceus, Angelica gigas and Trichosanthes kirilowii , is known for its effects on cancer and immunoregulation. Previous studies show SH003 exerts a promising anti-inflammatory effect. This study investigates the effect of modified SH003 on ALI using in silico, in vivo , and in vitro models. We performed in silico -based analysis of SH003 on ALI-related pathways. C57BL/6 mice were intraperitoneally subjected to lipopolysaccharide (LPS) to induce septic ALI, followed by oral administration of SH003 for 2 weeks. Dexamethasone was used as the positive control. Human peripheral blood-derived polymorphonuclear neutrophils (PMN) were used to investigate the effect and mechanisms of SH003 on neutrophil extracellular trap (NET) formation. Network pharmacology analysis suggested SH003 regulates lung inflammation by modulating NET formation. SH003 significantly reduced mortality in sepsis in vivo by inhibiting local and systemic inflammation, likely via nuclear factor kappa B and mitogen-activated protein kinase pathways-mediated inflammasome suppression. SH003 also decreased NET-related markers in lung tissues and inhibited LPS- and phorbol myristate acetate-induced NET formation in PMN. Cytometry time-of-flight analysis confirmed regulation of NETosis-related pathways by SH003. SH003 effectively inhibits excessive immune responses in the lung by suppressing inflammasome activation and NET formation. These findings suggest SH003 as a potential therapeutic agent for septic ALI. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of the 1,3,4-oxadiazole based derivatives were synthesized. • All the oxadiazole compounds demonstrate good tyrosinase inhibitory activity. • Among the series, 2-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-ylthio)- N -phenylacetamide exhibit more potent activity than standard drug. • Most potent compound exhibit non-toxic behavior against B16F10 melanoma cells. • The in-vitro results are in support of molecular docking studies. In this research work, we have designed and synthesized some biologically useful of 1,3,4-Oxadiazoles. The structural interpretation of the synthesized compounds has been validated by using FT-IR, LC-MS, HRMS, 1H NMR and 13C NMR techniques. Moreover, the in-vitro mushroom tyrosinase inhibitory potential of the target compounds was assessed. The in-vitro study reveals that, all compounds demonstrate an excellent tyrosinase inhibitory activity. Especially, 2-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-ylthio)- N -phenylacetamide (IC 50 = 0.003 ± 0.00 µM) confirms much more significant potent inhibition activity compared with standard drug kojic acid (IC 50 = 16.83 ± 1.16 µM). Subsequently, the most potent five oxadiazole compounds were screened for cytotoxicity study against B16F10 melanoma cells using an MTT assay method. The survival rate for the most potent compound was more pleasant than other compounds. Furthermore, the western blot results proved that the most potent compound considerably decreased the expression level of tyrosinase at 50 µM (P < 0.05). The molecular docking investigation exposed that the utmost potent compound displayed the significant interactions pattern within the active region of the tyrosinase enzyme and which might be responsible for the decent inhibitory activity towards the enzyme. A molecular dynamic simulation experiment was presented to recognize the residual backbone stability of protein structure. [ABSTRACT FROM AUTHOR]