Plant-derived natural compounds for the treatment of acute lung injury: A systematic review of their anti-inflammatory effects in animal models.

BACKGROUNDS AND AIMS Acute lung injury (ALI) is a complex pulmonary disease characterized by a severe inflammatory response. The management of ALI presents a formidable challenge due to the intricate nature of its inflammatory cascade. Numerous studies have highlighted the potential therapeutic benefits of plant-derived natural compounds (PNCs) in treating inflammatory diseases. Our study aims to provide robust current evidence regarding the anti-inflammatory effects and underlying molecular mechanisms of PNCs for ALI treatment. MATERIALS AND METHODS The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the protocol was registered in PROSPERO (CRD42024468401). A comprehensive search was conducted in electronic databases including PubMed, Scopus, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal database (VIP), Wanfang database, and China biomedical literature service system (SinoMed) up until November 2023. Preclinical studies published in both English and Chinese were included. RESULTS Our research encompassed 81 studies, comprising a total of 71 PNCs, including flavonoids, phenylpropanoids, terpenoids, polyphenols, alkaloids, saponins, glycosides, and miscellaneous compounds. This systematic review demonstrated that PNCs played a beneficial role on ALI by regulating the immune response and reducing the release of inflammatory mediators and cytokines. The molecular mechanisms were partially associated with the regulation of Th17/Treg responses, promotion of the polarization of M1-type macrophages to M2-type macrophages, induction of immune cell apoptosis, reversal of microbial dysbiosis in the lungs and the gut, epigenetic modification, and the modulation of inflammatory pathways, including NF-κB, MAPK, TLR4/MyD88, NLRP3/Caspase-1, TGF-β/Smad, Nrf2/HO-1, Rho/ROCK, TLR7/MyD88, and PI3K/AKT, thereby alleviating inflammatory responses and lung damage. CONCLUSION The therapeutic effects of PNCs on ALI are mediated through the modulation of immunity and inflammatory pathways. In light of their potential, PNCs represent a promising pharmacological intervention for the treatment of ALI.