Integrated network pharmacology, metabolomics, and bioinformatics to elucidate the mechanisms of Cimicifuga Rhizoma and Cimicifuga Rhizoma stir-fried with honey bran in protecting against acute lung injury

Background and purpose: Cimicifuga Rhizoma (CR) is commonly used to treat pneumonia. Our study has demonstrated that CR exerts protective effects against acute lung injury (ALI) in vitro. This study aims to systematically investigate the in vivo protective effects of CR and its production (CR stir-fried with honey bran CRHB) on ALI, elucidate their potential mechanisms, and identify the pharmacological substances. Experimental approach: Firstly, UPLC-Q-TOF-MS/MS was used to collect the information on the components absorbed into blood of CR and CRHB. Secondly, the therapeutic effects of them on ALI were evaluated based on various pharmacological indicators. The mechanisms and potential pharmacologically substances of CR and CRHB in the protecting against ALI were investigated through an integrated approach combining serum pharmacochemistry, metabolomics, and bioinformatics analyses. Key results: Both CR and CRHB were capable of ameliorating the inflammatory conditions caused by LPS, and CRHB exhibited better than CR in the treatment of ALI. Integrated analysis reveals that although the mechanisms and active substances of CR and CRHB in protecting against ALI are different, they are related to the NF-κB signaling pathway. The pharmacological substances of CR in protecting against ALI were identified as myristicinaldehyde, isoferulic acid, 1-cinnamoylpyrrolidine, and ferulic acid. For CRHB, the pharmacological substances included farrerol,8-prenylnaringenin, 6,7,8-trimethoxychromen-2-one, sinensetin, and isoferulic acid. Conclusion and implications: CR and CRHB ameliorate LPS-induced ALI, with their mechanisms of action involving the modulation of the NF-κB signaling pathway. The pharmacological substances of CR that confer protection against ALI include myristicinaldehyde, isoferulic acid, 1-cinnamoylpyrrolidine, and ferulic acid. For CRHB, the pharmacological substance are farrerol, 6,7,8-trimethoxychromen-2-one, 8-prenylnaringenin, sinensetin, and isoferulic acid.