The effect of ethanol extracts of loulu flower on LPS-induced acute lung injury in mice

• Published in: Journal of ethnopharmacology Vol. 334; p. 118515
• Main Authors: Wurentuya, Han, Shan, Mei, Shengtao, Lai, Mulin, Sirigunqiqige, Luoricuo, Yang, Miaohong, Feng, Yulin, Zhong, Guoyue, Zhu, Jixiao, Li, Min
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 15.11.2024
• Subjects: Acute lung injury; Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Acute Lung Injury - pathology; Animals; Anti-Inflammatory Agents - pharmacology; Bronchoalveolar Lavage Fluid; Cytokines - metabolism; Ethanol - chemistry; Flowers - chemistry; Lipopolysaccharide; Lipopolysaccharides - toxicity; Loulu flower; Lung - drug effects; Lung - metabolism; Lung - pathology; Male; Mice; Mice, Inbred BALB C; NF-kappa B - metabolism; Plant Extracts - pharmacology; Signal Transduction - drug effects; Solvents - chemistry; TLR4/NLRP3 signaling pathways; Toll-Like Receptor 4 - metabolism; Lipopolysaccharide; Acute lung injury; Loulu flower; TLR4/NLRP3 signaling pathways
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118515

In Mongolian medicine, Loulu flower (LLF), the dried inflorescence of Rhaponticum uniflorum (L.) DC. from the Compositae family, has been used to clear heat and relieve toxicity for millennia, particularly in the treatment of pneumonia. To reveal the effects of LLF on mice with lipopolysaccharide (LPS)-stimulated acute lung injury (ALI) and elucidate the underlying mechanisms. ALI was established in BALB/c mice via nasal drops administration of LPS (5 mg/kg). The mice were then orally administrated with various doses of LLF extracts and the positive drug dexamethasone (DEX, 5 mg/kg), once daily for seven consecutive days. Last day, after being stimulated with LPS for 6h, the mice were closed dislocation of cervical vertebra, the serum, bronchus alveolar lavage fluid (BALF) and lung tissue were put into the EP tube and stored at −80 °C for further analysis. The changes of histopathology were tested by hematoxylin and eosin stain (H&E), the levels of, IL-1β, IL-18, TNF-α and IL-4 in BALF and serum were measured by ELISA. The pathways related to the treatment of ALI were predicted by network pharmacology. The expression levels of TLR4/NF-κB and NLRP3 signaling pathway-associated proteins, COX-2 and ERK were tested by western blotting. The levels of P65 and NLRP3 in lung tissues were determined by immunofluorescence analysis. LLF total extract and the extract parts could alleviate the inflammatory cell infiltration, thicken the alveolar walls in lung tissues, reduce the levels of IL-18, IL-1β in BALF, the TNF-α in both BALF and serum, meantime enhance the level of IL-4 in BALF and serum in mice with LPS-induced ALI. Our network pharmacology and comprehensive gene ontology analyses revealed the active constituents of LLF and the pathways, including TLR4/NF-κB, NLRP3 and MAPK signaling pathways, which play significant roles in ALI. Furthermore, both the total extract and its extraction portions suppressed the expressions of proteins related with the COX-2, p-ERK and TLR4/NF-κB signaling pathway (TLR4, p-IκB, p-p65), as well as the NLRP3 signaling pathway (NLRP3, cleaved caspase-1, caspase-1, IL-1β). LLF could improve the pathological changes and reducing inflammatory reactions in mice induced by LPS. The mechanism may be related to the modulation of the TLR4/NLRP3 signaling pathways. [Display omitted] •The effect of LLF on LPS-induce ALI in mice were revealed.•The mechanism pathway of LLF on LPS-induce ALI in mice by network pharmacology were predicted.•The potential mechanisms of LLF on LPS-induce ALI in mice were analyzed by western blot and immumofluorescence method.