Fig 2: Working model representing the potential mechanism that arachidonate acid metabolism involved in hypoxia response. (A), Abundance of four proteins related to arachidonate acid metabolism based on proteomics dataset. (B), Relative abundance of metabolites related to arachidonate acid metabolism based on metabolism dataset. (C, D), Relative expression of three genes related to arachidonate acid metabolism based on qPCR experiments. (E), Working model representing the biological roles of arachidonate acid metabolism involved in hypoxia response in mouse spleen. Different colors stand for the relative values of HST vs PSC for either protein or metabolite abundances. Alox15: arachidonate 15-lipoxygenase; Hpgds: hematopoietic prostaglandin D synthase; Ptgs2: Prostaglandin G/H synthase; Pld3: phospholipase D. arachidonic acid (peroxide free) (M303T39); 1-stearoyl-2-oleoyl-sn-glycerol 3-phosphocholine (M855T142_1); 20-hydroxyarachidonic acid (M303T70); 15-deoxy-delta-12,14-PGJ2 (M315T42); 8-iso-prostaglandin A2 (M333T42); prostaglandin D2 (M335T120). For panels A–E, each bar of data represents the mean (±SE) of 3 different biological replicates. In panel (E), FC represents fold change.

Fig 3: Suppression of autophagy enhances BBR-induced HSC ferroptosis.A HSC-LX2 cells were treated with BBR (21 µM), erastin (10 µM), RSL3 (1 µM), sorafenib (10 µM), or specific inhibitors of different cell death pathways (necrostatin-1 10 µM, Fer-1 1 µM, liproxstatin-1 100 nM, DFO 25 µM, Z-VAD-FMK 10 µM, and calpeptin 10 µM). Cell viability was assayed by CCK-8. B HSC-LX2 was exposed to BBR (21 µM) for 24 h; a whole-cell lysate was taken for cellular Fe2+, ROS production, MDA generation, and GSH depletion investigation. C HSC-LX2 were treated with or without BBR (21 µM) for 24 h; transmission electron microscopic ultrastructural features of mitochondria are shown. D, E Costained a-SMA with GPx4 or Ptgs2 in TAA-induced mouse liver fibrosis. F HSC-LX2 cells were treated with BBR (21 µM) for the indicated time, a whole-cell lysate was analyzed by western blot using antibodies against the indicated proteins. The results are expressed as mean ± SD. Data are representative of three independent experiments; n = 3–6 in every group; Scales: 1 µm, 100 µm, or 500 nm. Representative photographs are shown. Compared with the control group, *P < 0.05, **P < 0.01; compared with the BBR group, ##P < 0.01.

Fig 4: Molecular docking of effective component-hub target protein. (a) A heat map of affinity energy (kcal/mol). (b–h) shows the molecular docking 3D diagram. (B–H) shows the 2D diagram. Among them, (b-B) IL-1ß-quercetin, (c-C) CXCL2-quercetin, (d-D) CXCL8-kaempferol, (e-E) CXCL8-luteolin, (f-F) CCL20-quercetin, (g-G) PTGS2-quercetin, and (h-H) PTGS2-luteolin.

Fig 5: PD-related biochemical analysis. (A–C) PGF2a, PGE2, and their ratio changes in serum. (D–F) PGF2a, PGE2, and their ratio changes in uterine tissue. (G) COX-2 expression changes in uterine tissue during the experiment. # Model group compared with corresponding control group. # p < 0.05; ## p < 0.01; * p < 0.05; ** p < 0.01. ns, no significance (n = 6 per group). The statistical values are presented in Table S1.