Invasive breast cancer is highly regulated by tumor-derived cytokines in tumor microenvironment. The development of drugs that specifically target cytokines are promising in breast cancer treatment. In this study, we reported that arctigenin, a bioactive compound from Arctium lappa L., could decrease tumor-promoting cytokines GM-CSF, MMP-3, MMP-9 and TSLP in breast cancer cells. Arctigenin not only inhibited the proliferation, but also the invasion and stemness of breast cancer cells via decreasing GM-CSF and TSLP. Mechanistically, arctigenin decreased the promoter activities of GM-CSF and TSLP via reducing the nuclear translocation of NF-κB p65 which is crucial for the transcription of GM-CSF and TSLP. Furthermore, arctigenin-induced depletion of GM-CSF and TSLP inhibited STAT3 phosphorylation and β-catenin signaling resulting in decreased proliferation, invasion and stemness of breast cancer cells in vitro and in vivo. Our findings provide new insights into the mechanism by which tumor-promoting cytokines regulate breast cancer progression and suggest that arctigenin is a promising candidate for cytokine-targeted breast cancer therapy.

Sappanone A (SAP), a high-isoflavone compound derived from the traditional Chinese medicine Sumu, exhibits various pharmacological activities, including anti-inflammatory and anti-oxidant effects. However, its protective effects on the liver have rarely been reported. The aim of this study was to investigate the effects of SAP on immune-mediated liver injury induced by concanavalin A (Con A) in mice and to explore the underlying molecular mechanisms. Mice were administered SAP intraperitoneally (50 mg/kg body weight). Three hours later, Con A (18 mg/kg) was injected via the tail vein to induce liver damage. Livers and blood were collected 12 h after Con A challenge. Liver cell apoptosis, oxidative stress, and M1 macrophage activation in vivo were investigated. Bone marrow-derived macrophages were used to confirm the effects of SAP on M1 polarization in vitro. The results indicated that SAP decreased transaminase levels, inhibited apoptosis, and improved oxidative stress in mouse livers. Furthermore, SAP significantly reduced the proportion of macrophages, inhibited the expression of CD86, and downregulated the expression of M1 macrophage-related inflammatory cytokines. Moreover, SAP-treated macrophages alleviated liver damage caused by Con A compared to non-SAP-treated macrophages. Mechanistically, SAP inhibited the phosphorylation of key molecules in the MAPK and NF-κB signaling pathways in macrophages, resulting in an inhibitory effect on M1 macrophage activation. Taken together, SAP alleviates immune-mediated liver injury induced by Con A by suppressing M1 macrophage polarization, which is partially associated with NF-κB and MAPK signaling pathways.

5-hydroxymethylfurfural (5-HMF) has been shown to exert neuroprotective effects in a global cerebral ischemia mouse model in our previous study, where it demonstrated antioxidant and anti-inflammatory properties. However, studies on its antidepressant mechanisms remain scarce. Since oxidative stress and neuroinflammation are closely associated with depression, this study investigated the antidepressant effects of 5-HMF, focusing on its potential inhibition of oxidative stress via the Nrf2 pathway and its role in microglial M1 polarization-mediated neuroinflammation. An acute depression mouse model induced by intraperitoneal injection of lipopolysaccharide (LPS) was utilized. Mice received 5-HMF (12 mg/kg) or an equal volume of vehicle via intraperitoneal injection 30 min prior to and 5 min after LPS administration. At 24 h post-modeling, behavioral tests (sucrose preference, forced swim, and open field tests) were conducted to evaluate the antidepressant effect of 5-HMF. Histological damage in the hypothalamus was assessed using Nissl staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Immunofluorescence was performed to evaluate M1 polarization of hypothalamic microglia. Oxidative stress damage was assessed by measuring malondialdehyde (MDA), carbonyl groups, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. Nrf2 DNA-binding activity was examined using an ELISA-based assay. The expression of inflammatory cytokines, Nrf2, and downstream antioxidant proteins was analyzed by ELISA kits and Western blotting. 5-HMF significantly alleviated LPS-induced depression-like behaviors, reduced hypothalamic neuronal damage, decreased oxidative stress, and inhibited microglial M1 polarization. It also regulated the expression of inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-4, and IL-10) and activated the Nrf2 signaling pathway, enhancing nuclear translocation efficiency. Notably, these effects were significantly attenuated by the Nrf2 inhibitor brusatol. In conclusion, 5-HMF exerts neuroprotective effects by modulating Nrf2-mediated oxidative stress responses and suppressing microglial M1 polarization-driven neuroinflammation. These findings suggest that 5-HMF may provide therapeutic potential for alleviating depression symptoms induced by acute inflammation.

The authors wish to make the following correction to this paper