Ameliorative Effect of Morinda Officinalis Oligosaccharides on LPS-Induced Acute Lung Injury.

Acute lung injury (ALI) is a disease characterized by extensive lung damage and rampant inflammation, with a high mortality rate and no effective treatments available. Morinda officinalis oligosaccharides (MOOs), derived from the root of the traditional Chinese medicinal herb Morinda officinalis, known for its immune-boosting properties, presents a novel therapeutic possibility. To date, the impact of MOOs on ALI has not been explored. Our study aimed to investigate the potential protective effects of MOOs against ALI and to uncover the underlying mechanisms through an integrated approach of network pharmacology, molecular docking, and experimental validation. We discovered that MOOs significantly mitigated the pathological damage and decreased the expression of pro-inflammatory cytokines in LPS-induced ALI in mice. Complementary in vitro studies further demonstrated that MOOs effectively attenuated the M1 polarization induced by LPS. Network pharmacology analysis identified HSP90AA1, HSP90AB1, and NF-κB as key overlapping targets within a protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses elucidated the biological processes and signaling pathways implicated in MOOs' therapeutic action on ALI. Subsequently, molecular docking affirmed the binding of MOOs to the active sites of these identified targets. Corroborating these findings, our in vivo and in vitro experiments consistently demonstrated that MOOs significantly inhibited the LPS-induced upregulation of HSP90 and NF-κB. Collectively, these findings suggest that MOOs confer protection against ALI through a multi-target, multi-pathway mechanism, offering a promising new therapeutic strategy to mitigate this severe pulmonary condition.

[Effect of Shenfu injection on expression of lipopolysaccharide --induced microRNA-146a in alveolar macrophages].

OBJECTIVE: To study the effects of Shenfu injection (SF) on the expression of lipopolysaccharide(LPS)-induced microRNA-146a (miR-146a) in rat alveolar macrophages (AMs), and to extrapolate its potential anti-inflammatory mechanisms. METHODS: In vitro cultured rat AMs (NR8383 cells) were randomly divided into control group, LPS stimulation group, and SF stimulation group. The LPS stimulation group was challenged with a final concentration of 1 mg/L LPS, and to the control group an equal volume of phosphate buffer solution (PBS) was added instead. For SF treated group, SF in different concentrations (1 ml/L or 10 ml/L) was used during incubation of AMs for half an hour, and then LPS was added (1 mg/L final concentration). After 6 hours, the cells and were collected. MiRNA-146a expression [reverse transcription-polymerase chain reaction (RT-PCR)] in cells and tumor necrosis factor-α (TNF-α ) content [enzyme-linked immunosorbent assay (ELISA)] in culture supernatant were determined for each group. RESULTS: Both the expression of miR-146a and TNF-α content in LPS stimulation group were significantly elevated compared with control group [miR-146a (expression folds): 5.92 + 1.57 vs. 1.04 +0.38; TNF-α (ng/L): 636.93 _ 30.21 vs. 20.46 + 2.81; both P<0.05]. Compared with LPS stimulation group, the expression of miR-146a was significantly upregulated in cells in both 1 ml/L and 10 ml/L SF stimulation groups, but TNF- α content was significantly reduced in the supernatant [miR-146a (expression folds): 7.02 + 0.91, 8.11 ± 1.07 vs. 5.92 -1.57; TNF-α (ng/L): 447.24 +21.29, 357.83 +19.73 vs. 636.93 +30.21, all P<0.05] in a dose-dependent manner (both P<0.05). CONCLUSION: SF could up-regulate miR-146a expression in AMs in a dose-dependent manner, and it was speculated that miR-146a might be involved in the anti-inflammatory processes with SF treatment.