Inflammation is the first response of the immune system against bacterial pathogens. This study isolated and examined an antioxidant derived from Lactobacillus fermentation products using cultured media with 1% beet powder. The antioxidant activity of the beet culture media was significantly high. Antioxidant activity-guided purification and repeated sample isolation yielded an isolated compound, which was identified as 5-hydoxymaltol using nuclear magnetic resonance spectrometry. We examined the mechanism of its protective effect on lipopolysaccharide (LPS)-induced inflammation of macrophages. 5-Hydroxymaltol suppressed nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. It also suppressed tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS) in the messenger RNA and protein levels in LPS-treated RAW 264.7 cells. Moreover, it suppressed LPS-induced nuclear translocation of NF-κB (p65) and mitogen-activated protein kinase activation. Furthermore, 5-hydroxymaltol reduced LPS-induced reactive oxygen species (ROS) production as well as increased nuclear factor erythroid 2–related factor 2 and heme oxygenase 1 expression. Overall, this study found that 5-hydroxymaltol has anti-inflammatory activities in LPS-stimulated RAW 264.7 macrophage cells based on its inhibition of pro-inflammatory cytokine production depending on the nuclear factor κB signaling pathway, inhibition of LPS-induced reactive oxygen species production, inhibition of LPS-induced mitogen-activated protein kinase induction, and induction of the nuclear factor erythroid 2–related factor 2/heme oxygenase 1 signaling pathway. Our data showed that 5-hydroxymaltol may be an effective compound for treating inflammation-mediated diseases.

Glasswort (Salicornia herbacea L.) is a halophyte that exhibits antioxidant and antidiabetic effects. Only a few studies have been conducted on its antioxidant effects. Here, we isolated an antioxidant using an activity-based purification method, and the resulting compound was identified as (9Z,11E)-13-Oxooctadeca-9,11-dienoic acid (13-KODE). We investigated its ability to suppress inflammatory responses and the molecular mechanisms underlying these abilities using lipopolysaccharide-stimulated RAW 264.7 macrophage cells. We studied the anti-inflammatory effects of 13-KODE derived from S. herbacea L on RAW 264.7 macrophages. 13-KODE inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production by suppressing inducible NO synthase and suppressed LPS-induced tumor necrosis factor and interleukin-1β expression in RAW 264.7 macrophages. LPS-mediated nuclear localization of NF-κB and mitogen-activated protein kinase activation were inhibited by 13-KODE. 13-KODE significantly reduced LPS-induced production of reactive oxygen species and increased the expression of nuclear factor erythroid-2 like 2 (Nfe2I2) and heme oxygenase 1. Overall, our results indicate that 13-KODE may have potential for treating inflammation.

Autophagy and mitophagy are essential survival mechanisms that enable cancer cells to adapt to metabolic stress, particularly during nutrient deprivation. Therefore, targeting these pathways presents a promising therapeutic strategy. Thus, this study aimed to investigate the potential of isopimaric acid (IPA), a diterpenoid compound derived from Torreya nucifera, to disrupt autophagy-related processes in colon cancer cells. Notably, IPA treatment promoted the accumulation of autophagosomes, as indicated by increased LC3-II and p62 protein levels, suggesting an inhibition of autophagic flux rather than an enhancement of initiation. Further analysis revealed that IPA impaired lysosomal function and blocked autophagosome degradation. IPA also suppressed mitophagy by downregulating key regulators, including PINK1 and Parkin, resulting in mitochondrial dysfunction and the accumulation of reactive oxygen species (ROS). Particularly, IPA was non-toxic under nutrient-rich conditions but induced significant cell death under serum starvation conditions. To our knowledge, these findings are the first to show that IPA selectively induces apoptotic cell death in nutrient-deprived colon cancer cells by disrupting both late-stage autophagy and PINK1/Parkin-mediated mitophagy. Furthermore, this research establishes the development of innovative therapeutic strategies that specifically target metabolic stress and combination therapy.

Background/Objectives: Colorectal cancer (CRC) remains a major contributor to cancer-associated deaths globally. Carica papaya L., a tropical fruit species, is reported to contain a wide range of biological properties, along with potential anticancer effects. However, studies evaluating the therapeutic potential and molecular mechanisms of Korean Carica papaya L. cultivars against CRC are limited. Therefore, this study investigated the effect of the hexane fraction of Carica papaya L. on the induction of apoptosis and the underlying mechanisms associated with this effect in human CRC cells. Methods: We performed several in vitro experiments, including cell viability, apoptosis, assessment of autophagic vacuoles, Western blotting, and analysis of autophagic flux. Subsequently, we verified the findings in an animal model of CRC induced by azoxymethane/dextran sulfate sodium. Results: BR 56 Hex F reduced cell viability and induced caspase-7/9-dependent apoptosis accompanied by intracellular and mitochondrial reactive oxygen species elevation. Mechanistically, BR 56 Hex F suppressed phosphatidylinositol 3-kinase (PI3K; p85/p110), p-AKT (Ser473/Thr308), and mammalian target of rapamycin signaling. Although autophagosome formation was initiated, the late-stage autophagic flux was impaired, as evidenced by p62 accumulation, LAMP-1 depletion, and autophagosome accumulation. In vivo, oral administration of BR 56 C. papaya L. extract significantly attenuated azoxymethane/dextran sulfate sodium-induced colon shortening, splenomegaly, histopathological damage, and colonic PI3K and p-AKT expression. Conclusions: BR 56 Hex F inhibited CRC growth by suppressing PI3K/AKT signaling and impairing late-stage autophagic flux, representing a potential natural candidate for CRC treatment.

Triple-negative breast cancer (TNBC) is highly aggressive and lacks targeted therapies. This study investigated the anti-cancer mechanisms of sinapaldehyde (SNAH). The biological effects of SNAH were evaluated in vitro using MDA-MB-231 TNBC cells. Cellular responses, including autophagy, mitochondrial function, apoptosis, cell-cycle progression, migration, and colony formation were investigated. In silico studies explored associated regulatory networks and binding targets. Sinapaldehyde (SNAH) treatment was associated with mitochondrial dysfunction, characterized by alterations in mitochondrial structural and functional markers, increased reactive oxygen species(ROS) production, and loss of mitochondrial membrane potential. SNAH treatment also altered the expression of PINK1 and Parkin and modulated autophagy-associated markers, including LC3B, p62, LAMP1, Beclin-1, and ATG proteins. Time-dependent changes in autophagy- and apoptosis-associated markers were accompanied by increased Annexin V-positive cells and activation of cleaved caspase-9 and caspase-3. SNAH also altered FTH1 and NCOA4 expression, suggesting modulation of ferritinophagy-associated processes, and inhibited migration and colony formation while inducing G2/M cell-cycle arrest. In silico analyses identified potential breast cancer-related molecular targets and signaling pathways associated with SNAH. SNAH induces mitochondrial dysfunction and is associated with alterations in autophagy/mitophagy-associated signaling and activation of apoptosis in MDA-MB-231 TNBC cells. These findings provide insight into the cellular responses to SNAH treatment, while further functional studies are required to establish changes in mitophagic and ferritinophagic flux and the causal relationship between autophagy and apoptosis.