Fine particulate matter (PM2.5) is the critical cause of lung cancer and can further promote tumor cell migration and invasion. This study investigated the effects of luteolin, an antiangiogenic flavonoid agent, on blocking aqueous extract PM2.5-prompted cancer progression. We observed that luteolin reduced cell migration and the expression of pro-metastatic factors pro-matrix metalloproteinase (MMP)-2 and intercellular adhesion molecule (ICAM)-1 in PM2.5-exposed H460 lung cancer cells. Luteolin treatment also reduced the transduction of PM2.5-induced epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) cascade signaling. Furthermore, the reduction of MMP-2 expression and ICAM-1 production by luteolin in PM2.5-stimulated H460 cells is EGFR-PI3K-AKT pathway dependent. These results suggest that luteolin exhibits antitumor progression by inhibiting EGFR-PI3K-AKT pathway.

It is well known that age-related macular degeneration (AMD) is an irreversible neurodegenerative disease that can cause blindness in the elderly. Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is a part of the pathogenesis of AMD. In this study, we evaluated the protective effect and mechanisms of alpha-mangostin ($\mathsf{\alpha }$-mangostin, $\mathsf{\alpha }$-MG) against NaIO₃-induced reactive oxygen species (ROS)-dependent toxicity, which activates apoptosis in vivo and in vitro. MTT assay and flow cytometry demonstrated that the pretreatment of ARPE-19 cells with $\mathsf{\alpha }$-MG (0, 3.75, 7.5, and 15 $\mathsf{\mu }$M) significantly increased cell viability and reduced apoptosis from NaIO₃-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cleaved PARP-1, cleaved caspase-3 protein expression, and enhancement of Bcl-2 protein. Furthermore, pre-incubation of ARPE-19 cells with $\mathsf{\alpha }$-MG markedly inhibited the intracellular ROS and extracellular H₂O₂ generation via blocking of the abnormal enzyme activities of superoxide dismutase (SOD), the downregulated levels of catalase (CAT), and the endogenous antioxidant, glutathione (GSH), which were regulated by decreasing PI3K-AKT-PGC-1$\mathsf{\alpha }$-STRT-3 signaling in ARPE-19 cells. In addition, our in vivo results indicated that $\mathsf{\alpha }$-MG improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer by inhibiting the expression of cleaved caspase-3 protein. Taken together, our results suggest that $\mathsf{\alpha }$-MG effectively protects human ARPE-19 cells from NaIO₃-induced oxidative damage via antiapoptotic and antioxidant effects.

Brain inflammation, a pathological feature of neurodegenerative disorders, exhibits elevated microglial activity and increased levels of inflammatory factors. The present study was aimed at assessing the anti‐inflammatory response of tetrahydrocurcumin (THC), the primary hydrogenated metabolite of curcumin, which was applied to treat Pseudomonas aeruginosa (P.a.) lipopolysaccharide‐ (LPS‐) stimulated BV2 microglial cells. THC reduced P.a. LPS–induced mortality and the production of inflammatory mediators IL‐6, TNF‐α, MIP‐2, IP‐10, and nitrite. A further investigation revealed that THC decreased these inflammatory cytokines synergistically with JAK/STAT signaling inhibitors. THC also increased Nrf2/HO‐1 signaling transduction which inhibits iNOS/COX‐2/pNFκB cascades. Additionally, the presence of the HO‐1 inhibitor Snpp increased the levels of IP‐10, IL‐6, and nitrite while THC treatment reduced those inflammatory factors in P.a. LPS–stimulated BV2 cells. In summary, we demonstrated that THC exhibits anti‐inflammatory activities in P.a. LPS‐induced inflammation in brain microglial cells by inhibiting STAT1/3‐dependent NF‐κB activation and inducing Nrf2‐mediated HO‐1 expression.

Previous studies showed that NaIO₃ can induce oxidative stress-mediated retinal pigment epithelium (RPE) damage to simulate age-related macular degeneration (AMD). Lemon peel is rich in antioxidants and components that can penetrate the blood–retinal barrier, but their role in retinal oxidative damage remains unexplored. Here, we explore the protection of lemon peel ultrasonic-assisted water extract (LUWE), containing large amounts of flavonoids and polyphenols, against NaIO₃-induced retinal degeneration. We initially demonstrated that LUWE, orally administered, prevented retinal distortion and thinning on the inner and outer nuclei layers, downregulating cleaved caspase-3 protein expression in RPE cells in NaIO₃-induced mice. The effect of LUWE was achieved through the suppression of apoptosis and the associated proteins, such as cleaved PARP and cleaved caspase-3, as suggested by NaIO₃-induced ARPE-19 cell models. This is because LUWE reduced reactive oxygen species-mediated mitochondrial fission via regulating p-Drp-1 and Fis1 expression. We further confirmed that LUWE suppresses the expression of p-MEK-1/2 and p-ERK-1/2 in NaIO₃-induced ARPE-19 cells, thereby providing the protection described above, which was confirmed using PD98059 and U0126. These results indicated that LUWE prevents mitochondrial oxidative stress-mediated RPE damage via the MEK/ERK pathway. Elucidation of the molecular mechanism may provide a new protective strategy against retinal degeneration.

Tetrahydrocurcumin (THC), a major curcuminoid metabolite known for its antioxidant and anti-inflammatory properties, has potential for reducing brain inflammation. This study investigated THC's anti-inflammatory responses and molecular mechanisms against Pseudomonas aeruginosa LPS (P.a. LPS)-induced NLRP3 inflammasome and ROS-producing cell pyroptosis. In the current study, we showed that THC significantly attenuated P.a. LPS-induced inflammasome factor IL-18 production through lysosomal dysfunction and leakage of cathepsin B. Importantly, THC reduced the levels of NLRP3 inflammasome and pyroptosis-related proteins, including NLRP3, active caspase-1, ASC, N-GSDMD, and IL-18. We also demonstrate that the inhibition of NLRP3 inflammasome activation by THC is ROS-dependent, via inhibition of H₂O₂ production, SOD activity, and enhancement of GSH activity. Subsequently, we demonstrated that THC treatment significantly reduced LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and increased heme oxygenase-1 (HO-1) expression in BV-2 cells. Furthermore, we used MAPKs (SB203580, SP600125, and U0126) and HO-1 (SnPP) inhibitors to demonstrate that THC modulated inflammasome-mediated pyroptosis may be related to p38 and JNK MAPK and HO-1-dependent inflammatory signaling. Overall, THC can inhibit ROS-triggered NLRP3 inflammasome-mediated pyroptosis by promoting GSH activity and HO-1 expression via modulating the p38 and JNK signaling pathways in P.a. LPS-treated BV-2 cells.