Caulerpa chemnitzia polysaccharide exerts immunomodulatory activity in macrophages by mediating the succinate/PHD2/HIF-1α/IL-1ß pathway.

Algal polysaccharide is an important food functional factor with diverse bioactive and low toxicity. Previous studies have confirmed Caulerpa chemnitzia polysaccharides (CRVP) have immunomodulatory activity, but the immunomodulatory mechanism of CRVP in macrophages has not been thoroughly explored yet. In our research, we found that CRVP has outstanding immunomodulatory activity in macrophages, which is reflected in promoting cell proliferation, upregulating cytokines (IL-1ß, IL-6, and TNF-α) expression, and increasing NO and ROS levels. Additionally, the result of joint analysis of untargeted metabolomics showed metabolism played a major role in the immunomodulatory of CRVP and suggested succinic acid was a key metabolite. Further verification indicated that the accumulation of succinic acid in macrophages after administered with CRVP, induced the down-regulation of prolyl hydroxylase domain 2 (PHD2) and up-regulation of hypoxia-inducible factor-1α (HIF-1α), thereby enhancing IL-1ß expression. Together, the immunomodulatory activity of CRVP in macrophages via succinate/PHD2/HIF-1α/IL-1ß pathway.

Bioactive polysaccharides mediate ferroptosis to modulate tumor immunotherapy.

Polysaccharides from diverse origins exhibit notable bioactivities, particularly their capacity to exert antitumor and immune-enhancing effects. Concurrently, ferroptosis emerges as a distinctive form of regulated cell death characterized by iron-dependent lipid peroxidation, potentially influencing the demise of specific tumor cells and organismal homeostasis. Recent scholarly attention has increasingly focused on utilizing polysaccharides to modulate tumor cell ferroptosis and manipulate cellular immune responses. This article provides an in-depth analysis of contemporary research concerning using polysaccharides to augment antitumor immunity and combat malignancies. Central to our discourse is examining the pivotal role of polysaccharides in mediating ferroptosis, bolstering immune surveillance, and elucidating the interplay between polysaccharides and antitumor immunity. Furthermore, a comprehensive synthesis of the multifaceted roles of polysaccharides in antitumor and immunomodulatory contexts is provided. Recent advances in understanding how polysaccharides enhance immune function by inducing ferroptosis cell death are explained. Lastly, unresolved inquiries are outlined, and potential avenues for future research are proposed, focusing on the translational applications of polysaccharides in antitumor immunotherapy.

Puerarin Induces Molecular Details of Ferroptosis-Associated Anti-Inflammatory on RAW264.7 Macrophages.

Puerarin is a natural flavonoid with significant anti-inflammatory effects. Recent studies have suggested that ferroptosis may involve puerarin countering inflammation. However, the mechanism of ferroptosis mediated by the anti-inflammatory process of puerarin has not been widely explored. Herein, puerarin at a concentration of 40 µM showed an anti-inflammatory effect on lipopolysaccharide (LPS)-induced macrophages RAW264.7. The analysis of network pharmacology indicated that 51 common targets were enriched in 136 pathways, and most of the pathways were associated with ferroptosis. Subsequently, the analysis of metabolomics obtained 61 differential metabolites that were enriched in 30 metabolic pathways. Furthermore, integrated network pharmacology and metabolomics revealed that puerarin exerted an excellent effect on anti-inflammatory in RAW264.7 via regulating ferroptosis-related arachidonic acid metabolism, tryptophan metabolism, and glutathione metabolism pathways, and metabolites such as 20-hydroxyeicosatetraenoic acid (20-HETE), serotonin, kynurenine, oxidized glutathione (GSSG), gamma-glutamylcysteine and cysteinylglycine were involved. In addition, the possible active binding sites of the potential targeted proteins such as acyl-CoA synthetase long-chain family member 4 (ACSL4), prostaglandin-endoperoxide synthase 2 (PTGS2), arachidonate 15-lipoxygenase (ALOX15) and glutathione peroxidase 4 (GPX4) with puerarin were further revealed by molecular docking. Thus, we suggested that ferroptosis mediated the anti-inflammatory effects of puerarin in macrophages RAW264.7 induced by LPS.

Anti-Colon Cancer Activity of Dietary Phytochemical Soyasaponin I and the Induction of Metabolic Shifts in HCT116.

Dietary phytochemicals play an important role in the prevention and treatment of colon cancer. It is reported that group B of soyasaponin, derived from dietary pulses, has anti-colonic effects on some colon cancer cell lines. However, it is uncertain which specific soybean saponins play a role. In our study, as one of the group B soyasaponin, the anti-colon cancer activity of soyasaponins I (SsI) was screened, and we found that it had the inhibitory effect of proliferation on colon cancer cell lines HCT116 (IC50 = 161.4 µM) and LoVo (IC50 = 180.5 µM), but no effect on HT29 between 0-200 µM. Then, nine potential targets of SsI on colon cancer were obtained by network pharmacology analysis. A total of 45 differential metabolites were identified by metabolomics analysis, and the KEGG pathway was mainly enriched in the pathways related to the absorption and metabolism of amino acids. Finally, molecular docking analysis predicted that SsI might dock with the protein of DNMT1, ERK1. The results indicated that the effect of SsI on HCT116 might be exerted by influencing amino acid metabolism and the estrogen signaling pathway. This study may provide the possibility for the application of SsI against colon cancer.

Catechin Mediates Ferroptosis to Exert an Anti-Inflammatory Effect on RAW 264.7 Cells.

Catechin possesses a potential anti-inflammatory activity, but its anti-inflammatory mechanism is still unclear. Herein, the analysis of network pharmacology showed that catechin might mediate ferroptosis on macrophages to exhibit a significant anti-inflammatory effect on RAW264.7. The metabolomics further indicated that catechin might influence ferroptosis by activating two pathways of cysteine and methionine metabolism and glutathione metabolism, and inhibiting the pathway of ferroptosis to promote the reduction of l-methionine-s-oxide and s-glutathionyl-l-cysteine, and the reduction and synthesis of γ-glutamylcysteine. Furthermore, related proteins (MSRA, CDR, GSR and GCL) in three metabolic pathways and ferroptosis-related proteins (GPX4 and SLC7A11) might be relevant to catechin through molecular docking. Thus, we speculate that catechin plays an anti-inflammatory effect through mediating ferroptosis on RAW264.7, which still needs further focus on the detailed molecular mechanism.