Administration of Gracilariopsis lemaneiformis polysaccharide attenuates cisplatin-induced inflammation and intestinal mucosal damage in colon-26 carcinoma tumor-bearing mice.

BACKGROUND: Our preliminary research revealed that the polysaccharide GP90 from Gracilariopsis lemaneiformis enhanced the antitumor effect of cisplatin, indicating that GP90 may increase the chemotherapeutic sensitivity. However, it is still necessary to fully understand whether GP90 can also improve the intestinal barrier dysfunction and systemic inflammation induced by cisplatin. RESULTS: GP90 has been demonstrated to inhibit the excessive release of nitirc oxide, interleukin (IL)-6, IL-1ß and tumor necrosis factor (TNF)-α induced by lipopolysaccharide in RAW264.7 cells. In vivo, GP90 effectively ameliorated the decrease in the serum CD4+ /CD8+ T-cell ratio induced by cisplatin and significantly reduced the increase in the inflammatory cytokines, CD4+ Foxp3+ , CD4+ granzyme B+ and CD4+ TNF-α induced by cisplatin. Furthermore, when combined with cisplatin, GP90 increases the protein expression levels of mucin-2 and zonula occludens-1 in the mouse small intestine. Additionally, GP90 combined with cisplatin has a modulatory effect on the intestinal microbiota by elevating the Firmicutes-to-Bacteroidetes ratio and the relative abundance of beneficial microorganisms (Lachnospiraceae bacterium), at the same time as reducing the abundance of cisplatin specific Bacteroides acidifaciens and elevating the content of butyric acid and isobutyric acid. CONCLUSION: Collectively, these findings indicate that GP90 potentially mitigates inflammation and protects the intestinal barrier in tumor-bearing organisms undergoing chemotherapy. © 2024 Society of Chemical Industry.

Polysaccharides derived from Spirulina platensis inhibited Singapore grouper iridovirus by impeding the entry of viral particles.

Attributable to the rapid dissemination and high lethality of Singapore grouper iridovirus (SGIV), it has caused significant economic losses for marine fish aquaculture in China and Southeast Asian nations. Hence, there is an urgent need to find antiviral drugs that are both safe and effective. In this study, a novel heteropolysaccharide named Spirulina platensis polysaccharides (SPP) was purified and characterized from S. platensis. The molecular weight of SPP is 276 kDa and it mainly consists of Glc and Rha, followed by minor components such as Gal, Xyl, and Fuc. The backbone of SPP was determined to be →2) -ß-Rhap-(1 â†’ 4) -α-Fucp-(1 â†’ [2) -α-Rhap-(1] 2[→6)-α-Glcp-(1] 4[→ 4) -α-Glcp-(1] 8[→ 4) -ß-Glcp-(1]2→, with branches of ß-Galp, α-Xylp and α-Glcp. SPP significantly inhibited SGIV-induced cytopathic effects (CPEs), viral gene replication and viral protein expression. The antiviral mechanism of SPP was associated with the disruption of SGIV entry to host cells. Furthermore, it was not observed that SPP made statistically significant impact on the expression of interferon-related cytokines. Our results offered novel insights into the potential utilization of spirulina polysaccharides for combating aquatic animal viruses.

Tuna trimmings (Thunnas albacares) hydrolysate alleviates immune stress and intestinal mucosal injury during chemotherapy on mice and identification of potentially active peptides.

In this study, Tuna trimmings (Thunnas albacares) protein hydrolysate (TPA) was produced by alcalase. The anti-tumor synergistic effect and intestinal mucosa protective effect of TPA on S180 tumor-bearing mice treated with 5-fluorouracil (5-FU) chemotherapy were investigated. The results showed that TPA can enhance the anti-tumor effect of 5-FU chemotherapy, as evident by a significant reduction in tumor volume observed in the medium and high dose TPA+5-FU groups compared to the 5-FU group (p < 0.001). Moreover, TPA significantly elevated the content of total protein and albumin in all TPA dose groups (p < 0.01, p < 0.001), indicating its ability to regulate the nutritional status of the mice. Furthermore, histopathological studies revealed a significant increase in the height of small intestinal villi, crypt depth, mucosal thickness, and villi area in the TPA+5-FU groups compared to the 5-FU group (p < 0.05), suggesting that TPA has a protective effect on the intestinal mucosa. Amino acid analysis revealed that TPA had a total amino acid content of 66.30 g/100 g, with essential amino acids accounting for 30.36 g/100 g. Peptide molecular weight distribution analysis of TPA indicated that peptides ranging from 0.25 to 1 kDa constituted 64.54%. LC-MS/MS analysis identified 109 peptide sequences, which were predicted to possess anti-cancer and anti-inflammatory activities through database prediction. Therefore, TPA has the potential to enhance the antitumor effects of 5-FU, mitigate immune depression and intestinal mucosal damage induced by 5-FU. Thus, TPA could be serve as an adjuvant nutritional support for malnourished patients undergoing chemotherapy.

Structural characterization of a sulfated polysaccharide from Gracilariopsis lemaneiformis and its potentiation of cisplatin antitumor activity in Colon-26 carcinoma tumor-bearing mice by inducing ferroptosis.

Ferroptosis, a form of regulated cell death caused by iron-mediated lipid peroxidation, has become a potential strategy to overcome drug resistance and improve the efficacy of traditional cancer treatments. In this study, we investigated whether treatment with the combination of Gracilariopsis lemaneiformis polysaccharides and cisplatin (CP) potentiated the antitumor activity in a Colon-26 carcinoma tumor-bearing mouse model by ferroptosis activation. The G. lemaneiformis polysaccharide GP90 was mainly composed of (1→3) linked 4-O-sulfate-ß-D-galactose and (1→4) linked 3,6-anhydro-α-L-galactose with a molecular weight of 12.45 kDa. Compared with the CP group, the combination of GP90 and CP significantly suppressed tumor growth. Based on the transcriptomic and metabolomic analyses of tumor tissue, GP90 enhanced the antitumor effect of CP by promoting ferroptosis and regulating ferroptosis-related metabolic pathways. Moreover, the accumulation of 4-hydroxy-2-nonenal (4-HNE) and down-regulation of the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (Gpx4) were verified by immunohistochemistry staining. Finally, gene set enrichment analysis showed that positive immunoregulatory pathways were significantly enriched in the GP90 and CP combination group. Our results indicate that GP90 potentiates chemotherapy sensitivity by targeting the transferrin receptor and SLC7A11/Gpx4 pathway to induce ferroptosis, which might be a useful therapeutic target in colorectal cancer patients.

Antidiabetic effects of protein hydrolysates from Trachinotus ovatus and identification and screening of peptides with α-amylase and DPP-IV inhibitory activities.

In the present study, the antidiabetic properties of Trachinotus ovatus protein hydrolysates (TOH) in streptozotocin-induced diabetic mice were investigated, and peptides with α-amylase (AAM) and dipeptidyl peptidase IV (DPP-IV) inhibitory activities were identified and screened. The results showed that TOH alleviated body weight loss, polyphagia, blood glucose elevation and insulin secretion decline in diabetic mice. After 4 weeks of TOH administration, random blood glucose (RBG) decreased significantly. The TOH groups showed a dose-dependent reduction in fasting blood glucose (FBG), especially in the high-dose TOH group, which reduced FBG by 58% versus the effect of metformin. Moreover, TOH exerted a remarkable protective effect on hepatorenal function, as evidenced by increased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) and decreased serum urea levels. Histopathological studies confirmed that TOH can significantly protect the kidney and pancreas from histological changes, which was of great benefit for ensuring the normal secretion of insulin and preventing the occurrence of complications such as diabetic nephropathy. Two fractions with higher inhibitory activity against AAM and DPP-IV, F4 and F6, were obtained from the ultrafiltration of TOH-2 (≤3 kDa). A total of 19 potentially active peptides from F4 and 3 potentially active peptides from F6 were screened by LC‒MS/MS combined with bioinformatic analysis. These peptides are small molecular peptides composed of 2-6 amino acids, rich in characteristic amino acids such as proline, arginine, phenylalanine and asparagine, and contain high proportions of peptides (68% for F4, 67% for F6) with hydrophobicity ≥50%. They offer potent antidiabetic potential and could potentially bind to the active sites in the internal cavities of the target enzymes AAM and DPP-IV. In summary, this study revealed for the first time the antidiabetic effects of protein hydrolysates of Trachinotus ovatus and their derived peptides, which are promising natural ingredients with the potential to be used for the treatment or prevention of diabetes.

Structural characterization, and in vitro immunostimulatory and antitumor activity of an acid polysaccharide from Spirulina platensis.

In this study, a novel heteropolysaccharide named SP90-1 with immunostimulatory and antitumor activity was purified and characterized from Spirulina platensis. SP90-1 has a molecular weight of 63.92 kDa and mainly consists of rhamnose (Rha), glucose (Glc), galactose (Gal) and glucuronic acid (GlcA), followed by the minor components Fuc and Xyl. The backbone of SP90-1 was determined to be →2)-α-d-Rhap-(1 â†’ 2,3)-α-d-Rhap-(1 â†’ 4)-ß-d-Glcp-(1 â†’ [3)-ß-d-Rhap-(1→]3, with branches at the O-3 of Rha, consisting of the side chains 4-Galp and 4-GlcpA. SP90-1 was found to significantly enhance phagocytic capacity, promote the secretion of nitric oxide (NO), interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in RAW264.7 cells, and remarkably inhibit the growth of A549 lung cancer cells. These findings demonstrate that SP90-1 could potentially be further explored for immunomodulatory biomedical applications.