Luteolin blocks the ROS/PI3K/AKT pathway to inhibit mesothelial-mesenchymal transition and reduce abdominal adhesions

Background: Postoperative abdominal adhesion (PAA) is a common postoperative complication. Clinically, various methods have been used to prevent the occurrence of PAA, such as drugs and physiotherapy; however, no satisfactory results have been obtained. Luteolin (LUT) is a natural flavonoid that reduces inflammation and acts as an antioxidant. This research aimed to examine the impact and mechanism of LUT in reducing PAA. Methods: C57/BL6 mice were used in vivo experiments. PAA model was established using a brush friction method. Visual scoring and hematoxylin and eosin staining were used to score the severity of adhesions. Network pharmacology was used to infer potential targets and core pathways of LUT. Hydrogen peroxide (H2O2) was used to induce oxidative stress in vitro, while the reactive oxygen species (ROS) assay kit was used to evaluate oxidative stress levels. Western blotting, cell immunofluorescence, and multiple immunofluorescence assays were used to detect alpha-SMA, vimentin, E-cadherin, collagen I, or AKT phosphorylation level. Scratch assay was used to detect cell migration. Results: LUT reduced the degree of PAA in mice. It attenuated H2O2-induced ROS production and reversed mesothelial-mesenchymal transition (MMT) in HMrSV5 cells. Network pharmacology analysis showed that LUT likely exerted anti-adhesion activity by regulating the PI3K-Akt signaling pathway. Phosphorylated Akt levels were significantly reduced in LUT-treated HMrSV5 cells. LUT also significantly reduced the expression of vimentin and collagen I in adherent tissues and upregulated E-cadherin expression. Conclusion: LUT blocks the ROS/PI3K/AKT pathway, thereby inhibiting MMT and reducing PAA. To this end, LUT has potential in PAA therapy.