Fig 2: Immunohistochemistry detection on the expression of BDNF, GFAP, NESTIN, NGF, and Tuj-1 proteins. CDD: Changyu Daotan Decoction group; SHT: positive control group; *: Compared to Control group,*P < 0.05, **P < 0.01, ***P < 0.001. #: Compared to Model group, #P < 0.05, ##P < 0.01, ###P < 0.001.

Fig 3: Response of WT and miR-301a-/- mice to caerulein-induced chronic pancreatitis(A) Schematic protocol of the caerulein-induced chronic pancreatitis. (B) Left: representative histological sections of mouse pancreata stained with H&E from caerulein-treated WT (n = 8) and miR-301a-/- (n = 8) mice. Scale bars, 100 µm. Right: Masson staining showed a large increase in fibrosis in caerulein-treated WT and miR-301a-/- mice. Scale bars, 200 µm. (C–E) Immunohistochemical staining of a-SMA (C), desmin (D), and GFAP (E) showed activation of PSCs and increased fibrogenesis of pancreata from caerulein-treated WT (n = 8) and miR-301a-/- (n = 8) mice. Scale bars, 75 µm. (F) Immunohistochemical staining of KRT19 showed strong expression of intact pancreatic ducts over the time course of chronic pancreatitis in caerulein-treated WT (n = 8) and miR-301a-/- (n = 8) mice. Scale bars, 75 µm. Values are mean ± SD. **p < 0.01, *p < 0.05 indicate significant difference between caerulein-treated WT and miR-301a-/- groups.

Fig 4: E. cava reduces glial fibrillary acidic protein (GFAP) expression in mouse brain (A) Astrocyte cells are characterized in GFAP staining (Scale bar, 10 µm). Representative immunohistochemistry (IHC) of cerebrum astrocytes in the mouse brain indicates GFAP (red) and dapi (blue). Quantification of GFAP staining was analyzed by Image J as setting white holes for positive standards. (B) Western blot analysis and quantification of GFAP were evaluated in the cerebrum of each group of male mice. Alpha-Tubulin was used for internal control. (C) Representative immunohistochemistry (IHC) of hippocampus astrocytes in mouse brain indicates GFAP (red) and dapi (blue). Quantification of GFAP staining was analyzed by Image J as setting white holes for positive standards. (D) Western blot analysis and quantification of GFAP were evaluated in the hippocampus of each group of male mice. Alpha-Tubulin was used for internal control. The points on the graph are represented by different shapes, with a white circle indicating the control group, a red square indicating the LPS group, a triangle representing the LPS + E. cava 10 mg/kg group, an inverted triangle indicating the LPS + E. cava 50 mg/kg group, and a rhombus representing the LPS + E. cava 100 mg/kg group. The differences between means were obtained through one-way ANOVA, and then a Tukey post-analysis. The values represent means ± S.D. # p < 0.001 vs. control group and * p < 0.05, *** p < 0.01 vs. LPS group.

Fig 5: CRE reduces the neuroinflammatory state induced by lipopolysaccharide. (A) The experiment outlines the timetable of the animal experiments. The mice were treated with CRE extract orally for 25 d, and the control group was administered distilled water of the same volume as the CRE extract. lipopolysaccharide treatment was given on day 19 at 750 µg/kg/body weight for a week. The mice were sacrificed before 8 h lipopolysaccharide treatment at 1.5 mg/kg body weight, and their organs were collected. (B) The changes in mouse body weight on days 0, 19, and 25. The statistical analysis was performed using one-way analysis of variance (ANOVA) and Tukey post hoc analysis. The results are presented as means ± SD, with * p < 0.05 and ** p < 0.01 indicating significance compared to the lipopolysaccharide group. (C) Serum IL-1ß levels were measured, with the lipopolysaccharide group showing a significant increase compared to the control group and the lipopolysaccharide + CRE 50 mg/kg and lipopolysaccharide + CRE 100 mg/kg groups showing a significant decrease compared to the lipopolysaccharide group. (D) Il-1b mRNA levels were measured in the cerebrum and hippocampus of each group of male mice. (E) GFAP were evaluated in the cerebrum of each group of male mice by Western blot analysis. a-Tubulin was used as an internal control. (F) GFAP were evaluated in the hippocampus of each group of male mice. a-Tubulin was used for internal control. The statistical analysis was performed using one-way ANOVA and Tukey post hoc analysis. The values represent means ± SD # p < 0.001 indicating significance compared to the control group and ** p < 0.01, *** p < 0.001 indicating significance compared to the lipopolysaccharide group.