Low-molecular-weight fucoidan increases telomere length and immunostimulatory effects on NK-92 cells following inhaled anesthetic injury.

Inhaled anesthetics, such as isoflurane, may cause side effects, including short-term immunosuppression and DNA damage. In contrast, low molecular weight fucoidan (LMF), derived from brown seaweed, exhibits promising immunomodulatory effects. In this study, we determined the effect of isoflurane on telomeres and examined the potential of LMF to ameliorate the harmful effects of isoflurane. Male Lewis rats, the mouse lymphoma cell line YAC-1, and the human nature killer cell line NK-92 MI were exposed to isoflurane. The relative telomere length (T/S) ratio and mRNA expression were determined by quantitative PCR. The viability assay was used to assess cell viability. In vivo, 2% isoflurane exposure, which is a clinically relevant concentration, reduced telomere length, and correlated with exposure frequency and duration. Isoflurane concentrations above 2% shortened YAC-1 telomeres, with minimal impact on cell viability. LMF pre-treatment enhanced NK-92 MI cell survival resulting from isoflurane exposure and exerted superior telomere protection compared with LMF post-treatment. Furthermore, adding LMF during isoflurane exposure resulted in a significant increase in IFN-γ, TNF-α, and IL-10 mRNA compared with the untreated group. LMF protected against isoflurane-induced telomere shortening, enhanced NK cell viability, and modulated cytokine expression, thus mitigating postoperative immune suppression and risk of tumor metastasis.

Electrospun nanofiber composite mat based on ulvan for wound dressing applications.

Wound dressings can be used to create a temporary healing environment and expedite the wound healing process. Ulvan (ULV) is a sulfated polysaccharide with potent antiviral and anti-inflammatory activities. Polycaprolactone (PCL) is a hydrophobic biodegradable polyester that exhibits slow degradation, strong mechanical strength, and excellent biocompatibility. Electrospun nanofiber matrices mimic the microstructure of the extracellular matrix, allowing them to promote cell proliferation and differentiation. Therefore, the primary objective of this study was to fabricate a polycaprolactone-ulvan fibrous composite mat (PCL-ULV) using the electrospinning technique and to investigate its physical and chemical properties. To assess the characteristics of PCL-ULV, scanning electron microscopy (SEM) was utilized to examine its morphology and diameter distribution. Fourier transform infrared (FTIR) spectroscopy, calcofluor white staining, and monosaccharide analysis were employed to analyze the components of PCL-ULV. Additionally, the water contact angle was measured to evaluate the hydrophilicity. Furthermore, the proliferation and morphology of and gene expression in NIH3T3 fibroblasts on PCL-ULV were assessed. The results showed that the average PCL-ULV fiber diameter was significantly smaller than that of the PCL fibers. The water contact angle measurements indicated that PCL-ULV exhibited better hydrophilicity than the PCL mat. FTIR, calcofluor white staining, and monosaccharide analyses demonstrated that ULV could be successfully coelectrospun with PCL. NIH3T3 fibroblasts cultured on PCL and PCL-ULV showed different cellular behaviors. On PCL-ULV, cell adhesion, proliferation, and stretching were greater than those on PCL. Moreover, the behavior of NIH3T3 fibroblasts on PCL and PCL-ULV differed, as the cells on PCL-ULV exhibited higher proliferation and more stretching. Furthermore, NIH3T3 fibroblasts cultured on ULV-PCL showed higher α-SMA and MMP-9 gene expression and a lower ratio of TIMP-1/MMP-9 than those cultured on PCL. Notably, scarless wounds display lower TIMP/MMP expression ratios than scarring wounds. Thus, the fibrous composite mat PCL-ULV shows potential as a wound dressing for scarless wound healing.

A Comparison of Cooking Conditions of Rhizoclonium Pulp as a Substitute for Wood Pulp.

The green macroalga Rhizoclonium was cooked with 5%, 10%, and 20% sodium hydroxide (NaOH) for 4 h (5-N, 10-N, and 20-N groups, respectively); with 5%, 10%, and 20% sodium sulfite (Na2SO3) for 4 h (5-NS, 10-NS, and 20-NS groups, respectively); and with 5%, 10%, and 20% NaOH for 2 h and 1% hydrogen peroxide (H2O2) for 2 h (5-NH, 10-NH, and 20-NH groups, respectively). The 5-NH handsheet showed the best mechanical properties; however, the 10-NH pulp was easier to separate than 5-NH during handsheet making, and 10-NH was more suitable for the industrial process. Thus, the 10-NH group showed the optimal production conditions with an optimal length/width ratio, crystallinity index (CI%), three-dimensional (3D) configuration, and mechanical strength. Substituting 20% 10-NH Rhizoclonium pulp with wood pulp had no significant effect on the mechanical properties of the 100% wood pulp handsheet. However, the fibers of the NS group were flatter and lost their 3D configuration, resulting in low mechanical strength. Overall, Rhizoclonium had its own optimal cooking condition, which was not the same as for wood pulp, and it has potential as a substitute for wood pulp in papermaking.

Influence of the Components and Orientation of Hydroxyapatite Fibrous Substrates on Osteoblast Behavior.

Synthetic hydroxyapatite has good biocompatibility, bioactivity and osteoconductive ability because its chemical properties and biological properties are similar to those of bioapatite in bone tissue. Strontium-substituted hydroxyapatite has better degradability than hydroxyapatite and can both promote osteogenesis and inhibit adipogenesis in mesenchymal stem cells. Hence, hydroxyapatite and strontium-substituted hydroxyapatite are widely used as bone graft materials, cell carriers and drug/gene delivery carriers. In addition, osteoblasts cultured on aligned nanofibrous substrates had higher expression of osteogenesis-related genes than did those cultured on random nanofibrous substrates. However, to date, no study has explored the effects of the components and orientation of hydroxyapatite nanofibrous substrates on osteoblastic behavior. In this study, a random hydroxyapatite nanofibrous substrate (R-HANF), a random strontium-substituted hydroxyapatite nanofibrous substrate (R-SrHANF), an aligned hydroxyapatite nanofibrous substrate (A-HANF) and an aligned strontium-substituted hydroxyapatite nanofibrous substrate (A-SrHANF) were successfully fabricated by using the electrospinning technique. The effect of fiber composition on osteoblast-like MG63 cells was assessed by evaluating cell morphology, cell proliferation and osteogenesis-related gene expression. The results showed that MG63 cells cultured on A-SrHANF had higher osteogenesis-related gene expression than those cultured on A-HANF. Additionally, MG63 cells were cultured on R-SrHANF and A-SrHANF to evaluate the effects of fiber orientation on cell behavior. On A-SrHANF, the cells aligned along the direction of the nanofibers, with typical bipolar morphologies, and exhibited higher osteogenesis-related gene expression than cells on R-SrHANF. Hence, the components and orientation of hydroxyapatite nanofibrous substrates are critical parameters affecting the osteogenesis process.

Oligo-Fucoidan supplementation enhances the effect of Olaparib on preventing metastasis and recurrence of triple-negative breast cancer in mice.

BACKGROUND: Seaweed polysaccharides have been recommended as anticancer supplements and for boosting human health; however, their benefits in the treatment of triple-negative breast cancers (TNBCs) and improving immune surveillance remain unclear. Olaparib is a first-in-class poly (ADP-ribose) polymerase inhibitor. Oligo-Fucoidan, a low-molecular-weight sulfated polysaccharide purified from brown seaweed (Laminaria japonica), exhibits significant bioactivities that may aid in disease management. METHODS: Macrophage polarity, clonogenic assays, cancer stemness properties, cancer cell trajectory, glucose metabolism, the TNBC 4T1 cells and a 4T1 syngeneic mouse model were used to inspect the therapeutic effects of olaparib and Oligo-Fucoidan supplementation on TNBC aggressiveness and microenvironment. RESULTS: Olaparib treatment increased sub-G1 cell death and G2/M arrest in TNBC cells, and these effects were enhanced when Oligo-Fucoidan was added to treat the TNBC cells. The levels of Rad51 and programmed death-ligand 1 (PD-L1) and the activation of epidermal growth factor receptor (EGFR) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) facilitate drug resistance and TNBC metastasis. However, the combination of olaparib and Oligo-Fucoidan synergistically reduced Rad51 and PD-L1 levels, as well as the activity of EGFR and AMPK; consistently, TNBC cytotoxicity and stemness were inhibited. Oligo-Fucoidan plus olaparib better inhibited the formation of TNBC stem cell mammospheroids with decreased subpopulations of CD44high/CD24low and EpCAMhigh cells than monotherapy. Importantly, Oligo-Fucoidan plus olaparib repressed the oncogenic interleukin-6 (IL-6)/p-EGFR/PD-L1 pathway, glucose uptake and lactate production. Oligo-Fucoidan induced immunoactive and antitumoral M1 macrophages and attenuated the side effects of olaparib, such as the promotion on immunosuppressive and protumoral M2 macrophages. Furthermore, olaparib plus Oligo-Fucoidan dramatically suppressed M2 macrophage invasiveness and repolarized M2 to the M0-like (F4/80high) and M1-like (CD80high and CD86high) phenotypes. In addition, olaparib- and Oligo-Fucoidan-pretreated TNBC cells resulted in the polarization of M0 macrophages into CD80(+) M1 but not CD163(+) M2 macrophages. Importantly, olaparib supplemented with oral administration of Oligo-Fucoidan in mice inhibited postsurgical TNBC recurrence and metastasis with increased cytotoxic T cells in the lymphatic system and decreased regulatory T cells and M2 macrophages in tumors. CONCLUSION: Olaparib supplemented with natural compound Oligo-Fucoidan is a novel therapeutic strategy for reprogramming cancer stemness, metabolism and the microenvironment to prevent local postsurgical recurrence and distant metastasis. The combination therapy may advance therapeutic efficacy that prevent metastasis, chemoresistance and mortality in TNBC patients.

Skin proteomic profiling of irradiation-induced fibrosis and its modulation by low molecular weight fucoidan via tight junction pathway.

Fucoidans, sulfated and fucosylated polysaccharides extracted from brown seaweed, were found to inhibit radiotherapy-induced cell damage and fibrosis through the TGF-ß1 pathway. However, the comprehensive molecular response during irradiation-induced fibrosis and fucoidan-assisted recovery still remain unclear. Rat hind limbs were irradiated and smeared with low molecular weight fucoidan (LMF). Protein profiles were examined by a mass spectrometry-based proteomics analysis. Out of a total of 4625 proteins, 233 were found to be significantly up-regulated after irradiation and down-regulated after LMF treatment. Pathway and protein-protein interaction network analyses further indicated that four proteins including Actb, Ezr, Msn and Cdc42 were clustered into the tight junction and regulation of actin cytoskeleton pathways. These four proteins may serve as biomarkers for the detection of skin fibrosis induced by irradiation or TGF-ß1, and for the recovery following LMF treatment.

Preparation of a Fucoidan-Grafted Hyaluronan Composite Hydrogel for the Induction of Osteoblast Differentiation in Osteoblast-Like Cells.

A suitable bone substitute is necessary in bone regenerative medicine. Hyaluronan (HA) has excellent biocompatibility and biodegradability and is widely used in tissue engineering. Additionally, research on fucoidan (Fu), a fucose- and sulfate-rich polysaccharide from brown seaweed, for the promotion of bone osteogenic differentiation has increased exponentially. In this study, HA and Fu were functionalized by grafting methacrylic groups onto the backbone of the chain. Methacrylate-hyaluronan (MHA) and methacrylate-fucoidan (MFu) were characterized by FTIR and 1H NMR spectroscopy to confirm functionalization. The degrees of methacrylation (DMs) of MHA and MFu were 9.2% and 98.6%, respectively. Furthermore, we evaluated the mechanical properties of the hydrogels formed from mixtures of photo-crosslinkable MHA (1%) with varying concentrations of MFu (0%, 0.5%, and 1%). There were no changes in the hardness values of the hydrogels, but the elastic modulus decreased upon the addition of MFu, and these mechanical properties were not significantly different with or without preosteoblastic MG63 cell culture for up to 28 days. Furthermore, the cell morphologies and viabilities were not significantly different after culture with the MHA, MHA-MFu0.5, or MHA-MFu1.0 hydrogels, but the specific activity and mineralization of alkaline phosphatase (ALP) were significantly higher in the MHA-MFu1.0 hydrogel group compared to the other hydrogels. Hence, MHA-MFu composite hydrogels are potential bone graft materials that can provide a flexible structure and favorable niche for inducing bone osteogenic differentiation.

Protective Effect of Low-Molecular-Weight Fucoidan on Radiation-Induced Fibrosis Through TGF-ß1/Smad Pathway-Mediated Inhibition of Collagen I Accumulation.

Radiation-induced fibrosis (RIF) occurs after radiation therapy in normal tissues due to excessive production and deposition of extracellular matrix proteins and collagen, possibly resulting in organ function impairment. This study investigates the effects of low-molecular-weight fucoidan (LMF) on irradiated NIH3T3 cells. Specifically, we quantified cellular metabolic activity, fibrosis-related mRNA expression, transforming growth factor beta-1 (TGF-ß1), and collagen-1 protein expression, and fibroblast contractility in response to LMF. LMF pre + post-treatment could more effectively increase cellular metabolic activity compared with LMF post-treatment. LMF pre + post-treatment inhibited TGF-ß1 expression, which mediates negative activation of phosphorylated Smad3 (pSmad3) and Smad4 complex formation and suppresses downstream collagen I accumulation. In addition, LMF pre + post-treatment significantly reduced actin-stress fibers in irradiated NIH3T3 cells. LMF, a natural substance obtained from brown seaweed, may be a candidate agent for preventing or inhibiting RIF.

Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression.

Reactive oxygen species (ROS) produced during intracellular metabolism or triggered by extrinsic factors can promote neoplastic transformation and malignant microenvironment that mediate tumor development. Oligo-Fucoidan is a sulfated polysaccharide isolated from the brown seaweed. Using human THP-1 monocytes and murine Raw264.7 macrophages as well as human HCT116 colorectal cancer cells, primary C6P2-L1 colorectal cancer cells and human MDA-MB231 breast cancer cells, we investigated the effect of Oligo-Fucoidan on inhibiting M2 macrophage differentiation and its therapeutic potential as a supplement in chemotherapy and tumor prevention. We now demonstrate that Oligo-Fucoidan is an antioxidant that suppresses intracellular ROS and mitochondrial superoxide levels in monocytes/macrophages and in aggressive cancer cells. Comparable to ROS inhibitors (DPI and NAC), Oligo-Fucoidan directly induced monocyte polarization toward M1-like macrophages and repolarized M2 macrophages into M1 phenotypes. DPI and Oligo-Fucoidan also cooperatively prevented M2 macrophage invasiveness. Indirectly, M1 polarity was advanced particularly when DPI suppressed ROS generation and supplemented with Oligo-Fucoidan in the cancer cells. Moreover, cisplatin chemoagent polarized monocytes and M0 macrophages toward M2-like phenotypes and Oligo-Fucoidan supplementation reduced these side effects. Furthermore, Oligo-Fucoidan promoted cytotoxicity of cisplatin and antagonized cisplatin effect on cancer cells to prevent M2 macrophage differentiation. More importantly, Oligo-Fucoidan inhibited tumor progression and M2 macrophage infiltration in tumor microenvironment, thus increasing of anti-tumor immunity.

Fabrication and Characteristics of PCL Membranes Containing Strontium-Substituted Hydroxyapatite Nanofibers for Guided Bone Regeneration.

Poly(ε-caprolactone) (PCL) membranes have been widely used in guided tissue regeneration (GTR) and guided bone regeneration (GBR). In addition, hydroxyapatite is the major inorganic component and an essential composition of hard bone and teeth. Recently, numerous studies have demonstrated that strontium-substituted hydroxyapatite (SrHA) not only enhances osteogenesis but also inhibits adipogenesis of mesenchymal stem cells. Therefore, SrHA incorporated into PCL could be an alternative material for GBR. In this study, strontium-substituted hydroxyapatite nanofibers (SrHANFs) were fabricated by a sol-gel route followed by electrospinning. We then fabricated PCL-SrHANF membranes as cell culture substrates and assessed the cellular behavior of osteoblast-like cells. Based on the observations of alkaline phosphatase (ALP) activity, bone sialoprotein (BSP) and osteocalcin (OCN) immunofluorescence staining, and Alizarin Red-S staining of cells cultured on the PCL-SrHANF and PCL membranes, we concluded that SrHANFs can promote the differentiation and mineralization of osteoblast-like cells and that PCL-SrHANF membranes have potential for GBR applications.

Clinical applications of fucoidan in translational medicine for adjuvant cancer therapy.

The chemical composition of fucoidan, a kind of sulfated polysaccharide mainly derived from brown seaweed, includes a substantial percentage of L-fucose. Fucoidan has various biological and pharmacological activities, such as anti-cancer/anti-tumor, anti-proliferation, anti-inflammatory and immune-modulatory functions, and fucoidan-related dietary supplements and nutraceuticals have recently drawn considerable attention. In this review, we aim to provide a current view of different aspects of fucoidan biological activity, with a focus on the anti-cancer regulatory effects of fucoidan on growth signaling mechanisms. First, we discuss historical aspects of fucoidan and fucoidan products, as well as the anti-cancer effects of fucoidan on various cancer cells. Second, we discuss fucoidan's biological activities and induction of cell death in cancer cells, including multiple mechanisms and signal transduction pathways related to its anti-cancer effects. Next, we focus on fucoidan and fucoidan-derived products that have been marketed as dietary supplements or nutraceuticals for cancer, including anti-cancer effects of fucoidan when combined as an adjuvant with clinical drugs. Finally, case studies of fucoidan in complementary therapy and as an alternative medicine in animal and mouse models and human clinical trials to alleviate side effects of anti-cancer chemotherapy are discussed. Combining fucoidan with clinical therapeutic agents in the treatment of cancer patients, dissecting the related signal transduction pathways and investigating their dynamic interactions may reveal potential molecular targets in cancer prevention, therapies and key obstacles in the current development of anti-cancer strategies.

Dietary Supplementation with Low-Molecular-Weight Fucoidan Enhances Innate and Adaptive Immune Responses and Protects against Mycoplasma pneumoniae Antigen Stimulation.

In this study, the low-molecular-weight (LMW) fucoidan, rich in fucose and sulfate, was extracted and purified from the edible brown seaweed, Laminaria japonica. In this study, we orally administered LMW fucoidan to mice for 6 weeks. We then examined fucoidan's effects on innate immunity, adaptive immunity, and Mycoplasma pneumoniae (MP)-antigen-stimulated immune responses. Our data showed that LMW fucoidan stimulated the innate immune system by increasing splenocyte proliferation, natural killer (NK) cell activity, and phagocytic activity. LMW fucoidan also increased interleukin (IL)-2, IL-4, and interferon (IFN)-γ secretion by splenocytes and immunoglobulin (Ig)-G and IgA content in serum, which help regulate adaptive immune cell functions, and decreased allergen-specific IgE. In MP-antigen-stimulated immune responses, the IgM and IgG content in the serum were significantly higher in the LMW fucoidan group after MP-antigen stimulation. Our study provides further information about the immunomodulatory effects of LMW fucoidan and highlights a potential role in preventing M. pneumoniae infection.

The anti-tumor activity of brown seaweed oligo-fucoidan via lncRNA expression modulation in HepG2 cells.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death in Asia. HCC is less sensitive to chemotherapy and is known to express multidrug resistant genes to acquire resistance to chemotherapeutic agents, therefore the development of a potent HCC suppressor is essential in treating HCC. Our previous reports demonstrated that oligo-fucoidan from the brown seaweed Sargassum hemiphyllum elevates microRNA-29b to inhibit epithelial-mesenchymal transition in hepatoma cells. In this study, we aimed to examine in vitro effect of oligo-fucoidan in hepatocellular carcinoma through apoptosis and long noncoding RNA (lncRNA) pathway. Oligo-fucoidan was studied for its anti-hepatoma cells by MTT and DNA ladder analysis. And the mechanism was studied by flow cytometry, qPCR and western blot analysis. In this study, oligo-fucoidan induced sub-G1 phase cell cycle arrest and activation of caspases, indicating that the intrinsic and extrinsic apoptotic pathways were involved in the mechanism of oligo-fucoidan-induced cell death. Moreover, oligo-fucoidan significantly increased the expression of p53, p21, and p27, while cyclin-B1 and -D1 were decreased at the mRNA and protein levels. Finally, we showed that targeting apoptosis and cell cycle pathways could also contribute to the induction of the lncRNA-Saf and lncRNA-p21. Through human lncRNA profiler array analysis, the differential expression of lncRNAs in HCC cells following oligo-fucoidan exposure was further examined. These findings indicated that lncRNAs switched oligo-fucoidan-induced apoptosis, which might be potentially valuable in HCC adjuvant therapy.

Fabrication and Characterization of Strontium-Substituted Hydroxyapatite-CaO-CaCO3 Nanofibers with a Mesoporous Structure as Drug Delivery Carriers.

Hydroxyapatite (HAp) is the main inorganic component and an essential part of hard bone and teeth. Due to its excellent biocompatibility, bioactivity, and osteoconductivity, synthetic HAp has been widely used as a bone substitute, cell carrier, and therapeutic gene or drug carrier. Recently, numerous studies have demonstrated that strontium-substituted hydroxyapatite (SrHAp) not only enhances osteogenesis but also inhibits adipogenesis in mesenchymal stem cells. Mesoporous SrHAp has been successfully synthesized via a traditional template-based process and has been found to possess better drug loading and release efficiencies than SrHAp. In this study, strontium-substituted hydroxyapatite-CaO-CaCO3 nanofibers with a mesoporous structure (mSrHANFs) were fabricated using a sol⁻gel method followed by electrospinning. X-ray diffraction analysis revealed that the contents of CaO and CaCO3 in the mSrHANFs decreased as the doping amount of Sr increased. Scanning electron microscopy (SEM) images showed that the average diameter of the mSrHANFs was approximately 200~300 nm. The N2 adsorption⁻desorption isotherms demonstrated that the mSrHANFs possessed a mesoporous structure and that the average pore size was approximately 20~25 nm. Moreover, the mSrHANFs had excellent drug- loading efficiency and could retard the burst release of tetracycline (TC) to maintain antibacterial activity for over 3 weeks. Hence, mSrHANFs have the potential to be used as drug carriers in bone tissue engineering.

Bacteriostatic Effect of a Calcined Waste Clamshell-Activated Plastic Film for Food Packaging.

The addition of calcined waste clamshells (CCS) into polyethylene (PE) plastic bags imparts antibacterial properties due to the presence of CaO. In this study, different proportions of calcined waste clamshells were added to PE to explore its bacteriostatic effects. The PE plastic bags with 9% and 11% of CCS exhibited antibacterial efficacy. Further, total aerobic viable count (TVC) values for raw fish fillet packaging in 9% and 11% CCS-PE plastic bags for five days were similar to the 0% CCS-PE plastic bag group after three days of incubation. In addition, the CCS-PE plastic bag demonstrated stability against solvents when examined using the metal migration test under heptane, ethanol, and acetic acid treatments. The results revealed that the CCS-PE bag retains its CaO bacteriostatic efficacy and that the addition of CCS powder to PE prolongs the shelf life of raw fish fillets, as well as mitigating safety concerns from metal leakage.

Alleviative effect of fucoxanthin-containing extract from brown seaweed Laminaria japonica on renal tubular cell apoptosis through upregulating Na+/H+ exchanger NHE1 in chronic kidney disease mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Brown seaweed is a common food for Asians, and the bioactive ingredient fucoxanthin exerts anti-apoptotic activities in several cell types. Renal tubular cell apoptosis is one of the common cellular events leading to renal fibrosis and chronic kidney disease (CKD). However, the influence of fucoxanthin-containing brown seaweed extract on CKD is still unknown. We intended to evaluate the inhibitory effect of fucoxanthin-containing extract from brown seaweed on renal apoptosis under CKD condition and its molecular mechanism. MATERIALS AND METHODS: The fucoxanthin-containing brown seaweed extract (LJE) was prepared from Laminaria japonica. We investigated how LJE influences on both doxorubicin-treated rat renal tubular cells (NRK-52E) and the renal symptoms of nephrectomy-induced CKD mice. RESULTS: LJE inhibited doxorubicin-induced apoptosis and upregulated Na+/H+ exchanger isoform 1 (NHE1) expression in NRK-52E cells, which were blocked by the NHE1 inhibitor cariporide. LJE also upregulated peroxisome proliferator-activated receptor alpha (PPARα). PPARα siRNA transfection inhibited LJE-induced NHE1 expression and anti-apoptotic effect. In CKD mice, LJE increased NHE1 expression in renal tubules and reduced apoptotic renal tubular cells, but not in PPARα knockout mice. The inhibitory effect of LJE on apoptosis also reduced renal tubulointerstitial fibrosis and improved renal function in CKD mice. CONCLUSION: We demonstrated that LJE inhibits renal apoptosis via NHE1 upregulation. The anti-apoptotic effect of LJE also improves renal function in CKD mice. Therefore, fucoxanthin-containing brown seaweed may have a therapeutic potential for CKD patients.

Oligo-Fucoidan prevents IL-6 and CCL2 production and cooperates with p53 to suppress ATM signaling and tumor progression.

Low-molecular-weight Fucoidan (Oligo-Fucoidan) is a sulfated polysaccharide that has a variety of biological effects and has also been shown to have beneficial health effects. However, the molecular mechanisms underlying the therapeutic effects of Oligo-Fucoidan in patients with cancer remain unclear. Using human colorectal cancer HCT116 cells with (p53+/+) or without (p53-/-) normal p53 expression, we found that Oligo-Fucoidan treatment reduces the occurrence of spontaneous DNA lesions. Etoposide induces double strand DNA breaks. Subsequent administration of Oligo-Fucoidan to etoposide-treated cells promotes p53 accumulation, p21 expression and significant decreases in ataxia-telangiectasia-mutated (ATM), checkpoint kinase 1 (Chk1) and γ-H2AX phosphorylation in p53+/+ cells compared with p53-/- cells. Similarly, co-administration of Oligo-Fucoidan with etoposide inhibits ATM, Chk1 and γ-H2AX phosphorylation, particularly in the presence of p53. Furthermore, Oligo-Fucoidan supplementation increases cancer cell death and attenuates the adverse effects induced by etoposide that decreases production of the pro-inflammatory cytokine IL-6 and chemokine CCL2/MCP-1. Importantly, Oligo-Fucoidan decreases the tumor-promoting M2 macrophages in microenvironment as well as collaborates with p53 and works in combination with etoposide to prevent HCT116 tumorigenicity. Our results first demonstrate that p53 enables Oligo-Fucoidan to effectively inhibit tumor progression, and Oligo-Fucoidan minimizes the side effects of chemotherapy and alters tumor microenvironment.

Fabrication and Cytotoxicity of Fucoidan-Cisplatin Nanoparticles for Macrophage and Tumor Cells.

Fucoidan, an anionic, sulfated polysaccharide from brown seaweed, is known to exhibit antitumor and immunomodulatory functions. To develop an immune protection and chemotherapeutic agent, fucoidan-cisplatin nanoparticles (FCNPs) were designed. FCNPs were prepared by mixing cisplatin with fucoidan solution or fucoidan with cisplatin solution, followed by dialysis to remove trace elements. The nanoparticles, comprising 10 mg of fucoidan and 2 mg of cisplatin, which exhibited the highest cisplatin content and loading efficiency during the production process, were named as Fu100Cis20. The cisplatin content, cisplatin loading efficiency, nanoparticle size, and zeta potential of Fu100Cis20 were 18.9% ± 2.7%, 93.3% ± 7.8%, 181.2 ± 21.0 nm, and -67.4 ± 2.3 mV, respectively. Immune protection assay revealed that Fu100Cis20-treated RAW264.7 cells were protected from the cytotoxicity of cisplatin. Furthermore, antitumor assay indicated that Fu100Cis20-treated HCT-8 cells showed stronger cytotoxicity than those treated with cisplatin alone. These results suggested that fucoidan-based nanoparticles exhibited suitable particle size and high drug encapsulation, and that Fu100Cis20 has potential application in both immunotherapy and chemotherapy.

Fucoidan ameliorates pancreatic ß-cell death and impaired insulin synthesis in streptozotocin-treated ß cells and mice via a Sirt-1-dependent manner.

SCOPE: Several beneficial biological functions of fucoidan (FO) isolated from brown algae have been demonstrated. The purpose of this study was to investigate whether FO derived from Sargassum hemiphyllum ameliorates pancreatic ß-cell damage and impaired insulin synthesis under diabetic condition. METHODS AND RESULTS: The effects of FO were studied in streptozotocin (STZ)-treated pancreatic ß-cell line, NIT-1cells, and mice. The cell apoptosis, protein analyses, histological examination, and pancreatic function assays were performed. The increased pancreatic ß-cell apoptosis and decreased insulin secretion observed in STZ-treated NIT-1 cells and mice were greatly attenuated by FO. Moreover, FO has an ability to enhance glucagon-like peptide-1 receptor (GLP-1R) and sirtuin 1 (Sirt-1) activity through activation of AMPK/GAPDH/PDX-1 cascade in STZ-treated ß cells. However, the effects of FO were significantly reversed by EX527, a specific Sirt-1 inhibitor. Similarly, the hyperglycemia, lower expression of Sirt-1, PDX-1, and GLP-1R in the pancreas of diabetic mice were markedly improved after FO administration. CONCLUSION: We demonstrated that FO exhibits an anti-diabetic effect mainly through attenuation of ß-cell death, thereby elevating insulin synthesis by upregulating PDX-1 and GLP1-R via a Sirt-1-dependent manner. Therefore, FO-containing food or supplements may have a therapeutic effect for diabetes by preventing ß-cell damage and dysfunction.

Effects of Low-Molecular-Weight Fucoidan and High Stability Fucoxanthin on Glucose Homeostasis, Lipid Metabolism, and Liver Function in a Mouse Model of Type II Diabetes.

The combined effects of low-molecular-weight fucoidan (LMF) and fucoxanthin (Fx) in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism. As for glucose and lipid metabolism in the adipose tissue, the expression of insulin receptor substrate (IRS)-1, glucose transporter (GLUT), peroxisome proliferator-activated receptor gamma (PPARγ), and uncoupling protein (UCP)-1 mRNAs in the adipose tissue of diabetic mice was significantly upregulated by Fx and LMF + Fx, and levels of inflammatory adipocytokines, such as adiponectin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were significantly modulated only by LMF + Fx supplementation. The efficacy of LMF + Fx supplementation on the decrease in urinary sugar and on glucose and lipid metabolism in the white adipose tissue of db/db mice was better than that of Fx or LMF alone, indicating the occurrence of a synergistic effect of LMF and Fx.