Fig 2: Effects of BHS on LPS-induced amyloidogenesis, neuroinflammation, NF-?B/MAPK activation, and mRNA expression of inflammatory mediators in the mouse brain. Protein expression levels of (A) APP, C99, and BACE-1 and (B) Iba-1, GFAP, iNOS, and COX-2 were detected by Western blotting. (C) Activation of NF-?B and MAPK pathways. (D) mRNA expression of inflammatory mediators was analyzed by RT-qPCR. Histograms show protein or mRNA levels relative to those of an internal control such as ß-actin or total-type protein. Data represent means ± SEM. # p < 0.05 compared with the Normal group; * p < 0.05, ** p < 0.001, and † p < 0.0001 compared with the LPS group. APP, amyloid-ß precursor protein; BACE-1, ß-secretase-1; BHS, banhasasim-tang; C99, ß-CTF fragment of APP; COX-2, cyclooxygenase-2; ERK, extracellular signal-regulated kinase; GFAP, glial fibrillary acidic protein; HO-1, heme oxygenase; Iba-1, ionized calcium-binding adaptor molecule 1; Indo, indomethacin; iNOS, inducible nitric oxide synthase; IL-1ß, interleukin 1ß; IL-6, interleukin 6; JNK, c-Jun NH2-terminal kinase; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; NF-?B, nuclear factor ?B; TNF-a, tumor necrosis factor alpha.

Fig 3: Illustration of ApoE4 in astrocytes and neurons inducing greater cPLA2 activation than ApoE3 through p38 MAPK pathway, leading to more LTB4, iNOS, and ROS production, increased oxidative stress and neuroinflammation

Fig 4: Possible mechanism of uvaol in alleviating DSS-induced experimental colitis via regulation of macrophage pro-inflammatory responses. DSS treatment induced macrophage infiltration and pro-inflammatory responses in the colon. Upon the stimulation by inflammatory stimulus such as TNF-a, LPS in the inflamed colonic circumstance, ERK/STAT3 signal was activated to promote transcription of pro-inflammatory genes TNF-a, IL-1ß, IL-6, etc. and then the release of pro-inflammatory cytokines TNF-a, IL-6, IL-1ß, COX-2 and iNOS. Uvaol could inhibit ERK and STAT3 activation to suppress the transcription of pro-inflammatory genes and the release of pro-inflammatory cytokines and further improve clinical symptoms and suppress colon inflammation of DSS-treated mice

Fig 5: Blunted iNOS, p65 and CD44 induction in NEU1-hypomorphic (hNEU1) mice after I/R. a Relative neuraminidase activity in LV of hNEU1 and WT mice 3 days after I/R or sham operation after normalization to protein concentration. WT sham N = 8; hNEU1 sham N = 9; WT I/R N = 7; hNEU1 I/R N = 7. b Representative Western blots and relative quantification (c-g), respectively, of the total (WT sham N = 8; hNEU1 sham N = 9; WT I/R N = 10; hNEU1 I/R N = 9) and phosphorylated (S536) p65 (WT sham N = 8; hNEU1 sham N = 9; WT I/R N = 10; hNEU1 I/R N = 9) and the ratio of phosphorylated to total p65 (WT sham N = 8; hNEU1 sham N = 9; WT I/R N = 10; hNEU1 I/R N = 9), CD44 (WT sham N = 11; hNEU1 sham N = 12; WT I/R N = 12; hNEU1 I/R N = 12) and iNOS (WT sham N = 11; hNEU1 sham N = 12; WT I/R N = 12; hNEU1 I/R N = 12) protein levels in the ischemic LV of hNEU1 and WT mice 3 days after sham or I/R injury normalized to Ponceau loading control. All values are depicted as mean ± SD. Statistical analysis was done using or Two-Way-ANOVA with Bonferroni post-test (a, c–g). *P < 0.05 and **P < 0.01 WT I/R 3 days vs. WT sham 3 days; §§P < 0.01 hNEU1 I/R 3 days vs. hNeu1 sham 3 days; #P < 0.05 hNEU1 I/R 3 days vs. WT I/R 3 days