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Background Fluorofenidone (AKF-PD) is an anti-fibrotic small-molecule compound. Its mechanism of action on paraquat (PQ)-induced pulmonary fibrosis is still unclear. Material/Methods Forty-eight SD rats were divided into 4 groups: control group, PQ group, PQ+AKF-PD group, and AKF-PD group. The pathological changes of lung tissues were observed by Masson and HE staining. The UPLC-QTOF-MS analysis was performed to detect the differences in metabolites among groups, then the possible mechanisms of the anti-pulmonary fibrosis effects of fluorofenidone were further revealed by network pharmacology analysis. Biological methods were used to verify the results of the network pharmacology analysis. Results The results showed that fluorofenidone treatment significantly alleviated paraquat-induced pulmonary fibrosis. Metabolomics analysis showed that 18 metabolites were disordered in the serum of paraquat-poisoned rats, of which 13 were restored following fluorofenidone treatment. Network pharmacology analysis showed that the drug screened a total of 12 targets and mainly involved multiple signaling pathways and metabolic pathways to jointly exert anti-pulmonary fibrosis effects. Autophagy is the main pathway of fluorofenidone in treatment pulmonary fibrosis. The western blot results showed that fluorofenidone upregulated the expression of LC3-II/I and E-cadherin, and downregulated the expression of p62, α-SMA, and TGF-β1, which validated that fluorofenidone could inhibit the development of paraquat-induced pulmonary fibrosis by increasing autophagy. Conclusions In conclusion, metabolomics combined with network pharmacology research strategy revealed that fluorofenidone has a multi-target and multi-path mechanism of action in the treatment of pulmonary fibrosis.

In this work, quercetin was loaded in the highly-porous lactose via the adsorption of quercetin molecules in ethanol. The method aims to improve the quercetin solubility and the loading capacity of lactose. The method relates to the synthesis of the highly-porous lactose with a particle size of ∼35 μm, a mean pore width of ∼30 nm, a BET surface area of 35.0561 ± 0.4613 m2/g, and a BJH pore volume of ∼0.075346 cc/g. After the quercetin loading in ethanol, BET surface area and BJH pore volume of porous lactose were reduced to 28.8735 ± 0.3526 m2/g and 0.073315 cc/g, respectively. The reduction rate was based on the quercetin loading efficiency of highly-porous lactose. DSC analysis and XRD analysis suggest that the sediments of quercetin in the nanopores of porous lactose are crystalline. FTIR spectroscopy results suggest that there is no significant interaction between quercetin and lactose. The highly-porous lactose had a higher loading efficiency of 20.3% (w/w) compared to the α-lactose (with 5.2% w/w). The release rates of quercetin from the highly-porous lactose tablets were faster compared to the conventional α-lactose carrier.

After paraquat (PQ) poisoning, it is difficult to accurately diagnose patients' condition by only measuring their blood PQ concentration. Therefore, it is important to establish an accurate method to assist in the diagnosis of PQ poisoning, especially in the early stages. In this study, a gas chromatography−mass spectrometry (GC−MS) metabonomics strategy was established to obtain metabolite information. A random forest algorithm was used to search for potential biomarkers of PQ poisoning, and data mining and network pharmacological analysis were used to evaluate the active components, drug−disease targets, and key pathways of Xuebijing (XBJ) injection in the treatment of PQ-induced pulmonary fibrosis. Targets from the network pharmacology analysis and metabolites from plasma metabolomics were jointly analyzed to select crucial metabolic pathways. Finally, molecular docking technology and in vitro experiments were used to verify the pathway targets to further reveal the potential mechanisms underlying the antipulmonary fibrosis effect of XBJ. Metabonomics studies showed that L-valine, glycine, citric acid, D-mannose, D-galactose, maltose, L-tryptophan, and arachidonic acid contributed more to the differentiation of different groups than other metabolites. Compared with the control group, the PQ poisoning group had higher levels of L-valine, glycine, citric acid, L-tryptophan, and arachidonic acid, and lower levels of D-mannose, D-galactose, and maltose. After treatment with XBJ injection, the relative levels of these metabolites were reversed. The network pharmacological analysis screened a total of 180 targets, mainly involving multiple signaling pathways and metabolic pathways, which jointly played an antipulmonary fibrosis effect. Based on the combined analysis of 180 targets and 8 different metabolites, arachidonic acid metabolism was selected as the key metabolic pathway. Molecular docking analysis showed that the XBJ compound had strong binding activity with the target protein. Western blot results showed that XBJ injection could reduce the inflammatory response by downregulating the expressions of p-p65, p-IKBα, and p-IKKβ, thus inhibiting the development of PQ-induced pulmonary fibrosis. In summary, the combined results from metabolomics and network pharmacology studies showed that Xuebijing has the characteristics of multitarget, multichannel, and multicomponent action in the treatment of pulmonary fibrosis caused by PQ.