Protective effect and mechanism of lycium barbarum polysaccharide against UVB-induced skin photoaging.

BACKGROUND: Cellular senescence can be categorized into two main types, including exogenous and endogenous aging. Photoaging, which is aging induced by ultraviolet (UV) radiation, significantly contributes to exogenous aging, accounting for approximately 80% of such cases. Superoxide Dismutase (SOD) is a class of antioxidant enzymes, with SOD2 being predominantly localized in the mitochondrial matrix. Ultraviolet radiation (UVR) inhibits SOD2 activity by acetylating the key lysine residues on SOD2. Sirtuin3 (SIRT3), the principal mitochondrial deacetylase, enhances the anti-oxidant capacity of SOD2 by deacetylating. Lycium barbarum polysaccharide (LBP) is the main bioactive component extracted from Lycium barbarum (LB). It has been reported to have numerous potential health benefits, such as anti-oxidation, anti-aging, anti-inflammatory and anti-apoptotic properties. Furthermore, LBP has been shown to regulate hepatic oxidative stress via the SIRT3-SOD2 pathway. The aim of this study was to construct a UVB-Stress-induced Premature Senescence (UVB-SIPS) model to investigate the protective effects and underlying mechanisms of LBP against UVB-induced skin photoaging. METHODS: Irradiated with different UVB doses to select the suitable dose for constructing the UVB-SIPS model. Cell morphology was observed using a microscope. The proportion of senescent cells was assessed by senescence-associated ß-galactosidase (SA-ß-gal) staining. Cell viability was studied using the Cell Counting Kit-8 (CCK-8). Intracellular levels of reactive oxygen species (ROS) were observed using flow cytometry and an inverted fluorescence microscope. Expression of γ-H2AX was investigated using flow cytometry. Western blot (WB) was used to verify the expression of senescence-associated proteins (p21, p53, MMP-1, and MMP-3). Enzyme-Linked Immunosorbnent Assay (ELISA) was used to measure pro-inflammatory cytokines levels (IL-6, TNF-α). WB was also used to analyze the expression of SIRT3, SOD2, and Ac-SOD2, and a specific kit was employed to detect SOD2 activity. RESULTS: Our results suggested that the UVB-SIPS group pre-treated with LBP exhibited a reduced proportion of cells positive for SA-ß-gal staining, mitigated production of intracellular ROS, an amelioration in γ-H2AX expression, and down-regulated expression of senescence-associated proteins and pro-inflammatory cytokines as compared to the UVB-SIPS group. Moreover, in contrast to the control group, the UVB-SIPS group showed regulated SIRT3 expression and SOD activity, elevated Ac-SOD2 expression and an increased ratio of Ac-SOD2/SOD2. However, the UVB-SIPS group pre-treated with LBP showed an upregulation of SIRT3 expression and enhanced SOD activity, a reduction in AC-SOD2 expression, and a decreased ratio of AC-SOD2/SOD2, compared to the untreated UVB-SIPS group. Additionally, the photo-protective effect of LBP was diminished following treatment with 3-TYP, a SIRT3-specific inhibitor. This study suggested that LBP, a natural component, exhibits anti-oxidant and anti-photoaging properties, potentially mediated through the SIRT3-SOD2 pathway.

Mechanistic insights into the interaction of Lycium barbarum polysaccharide with whey protein isolate: Functional and structural characterization.

Protein-polysaccharide interactions are crucial for food system structure and stability. This study investigates the interaction of Lycium barbarum polysaccharide (LBP) at 0-2.00 % concentrations with whey protein isolate (WPI), focusing on functionality and structural changes. LBP covalently grafted onto WPI, as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), forming WPI-LBP complexes with a maximum degree of grafting (DG) of 44.58 % at 2.00 % LBP. This grafting reduced WPI's surface hydrophobicity (H0) and improved solubility, emulsifying properties, and digestibility under certain conditions, with optimal antioxidant activity at 1.00 % LBP. Multispectral analysis and microscopy showed LBP grafting alters WPI's secondary, tertiary, crystalline, and micro/nanostructures. The comprehensive analysis indicates that the interaction between LBP and WPI involves covalent bonding, hydrogen bonding, hydrophobic interactions, and electrostatic forces, as supported by zeta potential and chemical forces results. These findings suggest LBP-protein complexes as promising food materials for enhancing functionality and stability in the food industry.

Lycium Barbarum Polysaccharide-Derived Nanoparticles Protect Visual Function by Inhibiting RGC Ferroptosis and Microglial Activation in Retinal Ischemia‒Reperfusion Mice.

Retinal ischemia‒reperfusion (IR) is a major contributor to vision impairment and irreversible vision loss due to retinal ganglion cell (RGC) injury or loss. Contemporary therapeutic approaches predominantly focus on the amelioration of symptoms rather than addressing the fundamental etiological factors. Oxidative stress is a notable feature and an important mediator of IR damage. Lycium barbarum polysaccharide (LBP), the main active ingredient of Lycium barbarum, has various pharmacological effects, including antioxidation, immunoregulation, and neuroprotective effects. In this study, the ROS-consumable moiety phenylboronic acid pinacol ester (PBA) is introduced to LBP molecules, which can self-assemble into nanoparticles in aqueous solution. This nanoparticle (termed PLBP) can reduce the cellular ROS levels and enhance the antioxidant capability of RGCs by activating the NRF2 pathway, thus protecting RGCs from ferroptosis and preserving visual function in response to IR injury. PLBP also reduces neuroinflammation by inhibiting the ability of microglia to phagocytose, migrate, secrete inflammatory cytokines, and activate the NF-κB pathway. In conclusion, this approach can be used as an inspiration for the future development of neuroprotective drugs.

Effect of Lycium barbarum polysaccharide on osteoblast proliferation and differentiation in postmenopausal osteoporosis.

OBJECTIVE: We aimed to investigate the effect of Lycium barbarum polysaccharide (LBP) on the proliferation and differentiation of osteoblasts in postmenopausal individuals with osteoporosis using in vitro cell experiments. METHODS: We assessed the effect of long-term LBP consumption on the intestinal metabolites of individuals using a simulation of the human intestinal microbiota ecosystem. We also tested the capacity of LBP in proliferating MC3T3-E1 cells using the cell counting kit-8 (CCK-8) method and analyzed the effect of intestinal metabolites on the osteogenic differentiation of MC3T3-E1 cells by testing bone metabolism viability with relevant indicators. RESULTS: The level of short-chain fatty acids (SCFAs) significantly increased (p < 0.05), and the concentrations of acetic acid, propionic acid, and butyric acid all showed an upward trend after the treatment using LBP. At appropriate concentrations, the fermentation supernatant can enhance osteoblast proliferation by significantly increasing the active expression of bone-alkaline phosphatase (B-ALP) and osteocalcin (OCN) in osteoblasts (p < 0.05). CONCLUSION: By modulating the metabolites of intestinal microbiota, production of SCFAs, the prebiotic properties of LBP can enhance osteoblast differentiation through in vitro simulation experiment and cell-based assay.

Regulation of mouse digestive function, intestinal mucosal barrier function, and inflammatory reaction by lycium barbarum polysaccharide pathway through myosin light chain kinase.

This research investigated the impacts of lycium barbarum polysaccharide (LBP) on the digestive function, intestinal mucosal barrier function, inflammatory response, and myosin light chain kinase (MLCK) signaling pathway in immunosuppressed mice. 70 mg/kg cyclophosphamide was injected into abdomen for the preparation of immune suppression model. Healthy BALB/c mice served as control for the analysis of the differences in gastrointestinal motility and absorptive capacity, intestinal mucosal barrier function, the phagocytic ability of abdominal macrophages, serum immune factor and inflammatory factor levels, and the activation status of the MLCK signaling pathway after continuous gavage with 100 mg/kg LBP. Results revealed a decrease in d-xylose content, phagocytic rate, index of abdominal macrophages, and spleen index in the serum and urine of model mice compared to those of controls. In addition, levels of IgA, IgG, IgM, IL-6 (interleukin-6), IL-12, and interferon-γ (IFN-γ) decreased, while MLCK and myosin light chain (MLC) levels rose (P < 0.01). Versus those in Model group, urine d-xylose content, phagocytic rate, index of abdominal macrophages, spleen index, and the levels of IgA, IgG, IgM, IL-6, IL-12, and IFN-γ of mice undergoing the gavage with LBP increased, while MLCK and p-MLC levels declined (P < 0.05). In conclusion, LBP improved digestive absorption and immune function of immunosuppressed mice and regulated intestinal mucosal barrier immune system by inhibiting MLCK signaling pathway activation.

Dietary Lycium barbarum Polysaccharide Modulates Growth Performance, Antioxidant Capacity, and Lipid Metabolism in Common Carp (Cyprinus carpio) Fed with High-Fat Diet.

To investigate the ameliorative effects and mechanism of Lycium barbarum polysaccharide (LBP) on growth performance, oxidative stress, and lipid deposition in common carp (Cyprinus carpio) fed with high-fat diets, fish with an initial weight of 5.29 ± 0.12 g were divided into five experimental groups-including normal-fat diets, high-fat diets, and high-fat diets-supplemented with LBP (0.5, 1.0, and 2.0 g/kg) for 8 weeks. The results showed that high-fat diets resulted in significant decreases in final body weight, weight gain rate, and specific growth rate of fish, as well as causing a significant decrease in hepatic total antioxidant capacity, catalase, and glutathione peroxidase activities. These changes were accompanied by a significant decrease in lipase activity and ATP level and a significant increase in malondialdehyde content. The expression levels of lipid metabolism-related genes (acetyl coenzyme A carboxylase 1, stearoyl coenzyme A desaturase 1, fat synthase, peroxisome proliferator-activated receptor-γ, fructofuranose bisphosphatase, and glucose-6-phosphatase) were also markedly elevated by high-fat diets. Supplementation with 0.5-2.0 g/kg LBP in high-fat diets improved the reduced growth performance, increased hepatic total antioxidant enzymes, catalase, and glutathione peroxidase activities, and lowered malondialdehyde level in fish fed with high-fat diets. Additionally, dietary supplementation with LBP significantly downregulated hepatic gene expression levels of acetyl coenzyme A carboxylase 1, stearoyl coenzyme A desaturase 1, fat synthase, sterol regulatory element-binding protein 1, peroxisome proliferator-activated receptor-γ, fructofuranose bisphosphatase, and glucose-6-phosphatase. In conclusion, fish fed with high-fat diets demonstrated impaired growth performance, antioxidant capacity, and lipid metabolism, and dietary supplementation with 0.5-2.0 g/kg LBP ameliorated the impairments induced by high-fat diets.

Lycium barbarum polysaccharide reverses drug resistance in oxaliplatin-resistant colon cancer cells by inhibiting PI3K/AKT-dependent phosphomannose isomerase.

Objective: Here, we aimed to explore the effect of LBP in combination with Oxaliplatin (OXA) on reversing drug resistance in colon cancer cells through in vitro and in vivo experiments. We also aimed to explore the possible mechanism underlying this effect. Finally, we aimed to determine potential targets of Lycium barbarum polysaccharide (LBP) in colon cancer (CC) through network pharmacology and molecular docking. Methods: The invasion ability of colon cancer cells was assessed using the invasion assay. The migration ability of these cells was assessed using the migration assay and wound healing assay. Cell cycle analysis was carried out using flow cytometry. The expression levels of phosphomannose isomerase (PMI) and ATP-binding cassette transport protein of G2 (ABCG2) proteins were determined using immunofluorescence and western blotting. The expression levels of phosphatidylinositol3-kinase (PI3K), protein kinase B (AKT), B-cell lymphoma 2 (Bcl-2), and BCL2-Associated X (Bax) were determined using western blotting. Forty BALB/c nude mice purchased from Weitong Lihua, Beijing, for the in vivo analyses. The mice were randomly divided into eight groups. They were administered HCT116 and HCT116-OXR cells to prepare colon cancer xenograft models and then treated with PBS, LBP (50 mg/kg), OXA (10 mg/kg), or LBP + OXA (50 mg/kg + 10 mg/kg). The tumor weight and volume of treated model mice were measured, and organ toxicity was evaluated using hematoxylin and eosin staining. The expression levels of PMI, ABCG2, PI3K, and AKT proteins were then assessed using immunohistochemistry. Moreover, PMI and ABCG2 expression levels were analyzed using immunofluorescence and western blotting. The active components and possible targets of LBP in colon cancer were explored using in silico analysis. GeneCards was used to identify CC targets, and an online Venn analysis tool was used to determine intersection targets between these and LBP active components. The PPI network for intersection target protein interactions and the PPI network for interactions between the intersection target proteins and PMI was built using STRING and Cytoscape. To obtain putative targets of LBP in CC, we performed GO function enrichment and KEGG pathway enrichment analyses. Results: Compared with the HCT116-OXR blank treatment group, both invasion and migration abilities of HCT116-OXR cells were inhibited in the LBP + OXA (2.5 mg/mL LBP, 10 µΜ OXA) group (p < 0.05). Cells in the LBP + OXA (2.5 mg/mL LBP, 10 µΜ OXA) group were found to arrest in the G1 phase of the cell cycle. Knockdown of PMI was found to downregulate PI3K, AKT, and Bcl-2 (p < 0.05), while it was found to upregulate Bax (p < 0.05). After treatment with L. barbarum polysaccharide, 40 colon cancer subcutaneous tumor models showed a decrease in tumor size. There was no difference in the liver index after LBP treatment (p > 0.05). However, the spleen index decreased in the OXA and LBP + OXA groups (p < 0.05), possibly as a side effect of oxaliplatin. Immunohistochemistry, immunofluorescence, and western blotting showed that LBP + OXA treatment decreased PMI and ABCG2 expression levels (p < 0.05). Moreover, immunohistochemistry showed that LBP + OXA treatment decreased the expression levels of PI3K and AKT (p < 0.05). Network pharmacology analysis revealed 45 active LBP components, including carotenoids, phenylpropanoids, quercetin, xanthophylls, and other polyphenols. It also revealed 146 therapeutic targets of LBP, including AKT, SRC, EGFR, HRAS, STAT3, and MAPK3. KEGG pathway enrichment analysis showed that the LBP target proteins were enriched in pathways, including cancer-related signaling pathways, PI3K/AKT signaling pathway, and IL-17 signaling pathways. Finally, molecular docking experiments revealed that the active LBP components bind well with ABCG2 and PMI. conclusion: Our in vitro experiments showed that PMI knockdown downregulated PI3K, AKT, and Bcl-2 and upregulated Bax. This finding confirms that PMI plays a role in drug resistance by regulating the PI3K/AKT pathway and lays a foundation to study the mechanism underlying the reversal of colon cancer cell drug resistance by the combination of LBP and OXA. Our in vivo experiments showed that LBP combined with oxaliplatin could inhibit tumor growth. LBP showed no hepatic or splenic toxicity. LBP combined with oxaliplatin could downregulate the expression levels of PMI, ABCG2, PI3K, and AKT; it may thus have positive significance for the treatment of advanced metastatic colon cancer. Our network pharmacology analysis revealed the core targets of LBP in the treatment of CC as well as the pathways they are enriched in. It further verified the results of our in vitro and in vivo experiments, showing the involvement of multi-component, multi-target, and multi-pathway synergism in the drug-reversing effect of LBP in CC. Overall, the findings of the present study provide new avenues for the future clinical treatment of CC.

Lycium barbarum polysaccharide's protective effects against PM2.5-induced cellular senescence in HUVECs.

Fine particulate matter (PM2.5) exposure is strongly associated with vascular endothelial senescence, a process implicated in cardiovascular diseases. While there is existing knowledge on the impact of Lycium barbarum polysaccharide (LBP) on vascular endothelial damage, the protective mechanism of LBP against PM2.5-induced vascular endothelial senescence remains unclear. In this study, we investigated the impact of PM2.5 exposure on vascular endothelial senescence and explored the intervention effects of LBP in human umbilical vein endothelial cells (HUVECs). We found that PM2.5 exposure dose-dependently reduced cell viability and proliferation in HUVECs while increasing the production of reactive oxygen species (ROS), malondialdehyde (MDA), and hydrogen peroxide (H2O2). Additionally, PM2.5 exposure inhibited the activity of superoxide dismutase (SOD). Notably, PM2.5 exposure induced autophagy impairments and cellular senescence. However, LBP mitigated PM2.5-induced cell damage. Further studies demonstrated that correcting autophagy impairment in HUVECs reduced the expression of the senescence markers P16 and P21 induced by PM2.5. This suggests the regulatory role of autophagy in cellular senescence and the potential of LBP in improving HUVECs senescence. These findings provide novel insights into the mechanisms underlying PM2.5-induced cardiovascular toxicity and highlight the potential of LBP as a therapeutic agent for improving vascular endothelial health.

Lycium barbarum polysaccharide mitigated methamphetamine addiction and altered methamphetamine-induced gut microbiota dysbiosis.

Methamphetamine (MA) is a highly addictive mental stimulant, and MA abuse remains a significant public health problem worldwide, while effective treatment options are limited. Lycium barbarum polysaccharide (LBP), a major effective component extracted from Lycium barbarum, has potential health-promoting effects on the nervous system; however, its role in MA dependence remains unclear. In this study, the conditioned place preference (CPP) of MA addiction in adult male mice was established to detect changes in gut microbiota profiles after LBP treatment through 16S rRNA gene sequencing. Our results found that LBP administration could alleviate MA-induced CPP and hyperactivity. Interestingly, LBP improved MA-induced gut microbiota dysbiosis by increasing some beneficial autochthonous genus abundances, such as Allobaculum, Gordonibacter, and Ileibacterium. MA exposure induced the co-occurrence network of intestinal microbiota to become weaker and more unstable when compared with the control group, while LBP changed the above effects when compared with the MA group. Bacterial gene function prediction showed that amphetamine addiction, cocaine addiction, and short-chain fatty acid metabolism were enriched. These findings reveal that LBP might regulate MA-induced gut microbiota and behavior changes, which showed potential therapeutic applicability in treating MA addiction by regulating the gut microbiota.

Elevated KDM4D Expression in Pterygium: Impact and Potential Inhibition by Lycium Barbarum Polysaccharide.

Purpose: This study aimed to explore the effects of elevated KDM4D expression and potential therapeutic effects of Lycium barbarum polysaccharide (LBP) on pterygium. Methods: The expression levels of KDM4D in the primary pterygium (n = 29) and normal conjunctiva (n = 14) were detected by immunohistochemistry. The effects of KDM4D on pterygium fibroblasts were detected by the CCK-8 assay, liquid chromatography-mass spectrometry assay, flow cytometry, and scratch wound healing assay. The relative expression of KDM4D in pterygium fibroblasts stimulated by interleukin (IL)-1ß, IL-6, IL-8, and LBP was detected by quantitative real-time PCR and Western blot. The effects of LBP on pterygium fibroblasts were detected using flow cytometry and scratch wound healing assays. Results: The expression level of KDM4D in pterygium was higher than that in normal conjunctiva. KDM4D increased the cell viability of pterygium fibroblasts. The differentially expressed genes identified in the LM-MS assay enriched in "actin filament organization" and "apoptosis." KDM4D promoted migration and inhibited apoptosis of pterygium fibroblasts in vitro. Inflammatory cytokines, including IL-1ß, IL-6, and IL-8, enhanced the expression of KDM4D in pterygium fibroblasts. LBP inhibited the expression of KDM4D in pterygium fibroblasts and decreased their cell viability. Moreover, LBP attenuated the KDM4D effects on migration and apoptosis of pterygium fibroblasts. Conclusions: Elevated KDM4D expression is a risk factor for pterygium formation. LBP inhibits the expression of KDM4D in pterygium fibroblasts and may be a potential drug for delaying pterygium development.

Lycium barbarum polysaccharide inhibits blue-light-induced skin oxidative damage with the involvement of mitophagy.

Although blue light can damage the skin to a certain extent, the pathogenesis of its damage remains still unclear. The available evidence suggests that oxidative stress may be the main cause of its damage. Lycium barbarum polysaccharide (LBP) has antioxidative effects in a variety of cells. In this paper, we investigated the protective role of LBP and its mechanism of action related to mitophagy in blue-light-damaged skin cells. The findings indicated that in HaCaT cells and mouse skin, LBP pretreatment was effective in reducing blue-light-induced apoptosis and ameliorating the elevated level of cellular autophagy/mitophagy caused by excessive blue light exposure. The markers reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were used to assess oxidative stress. LBP could effectively inhibit blue-light-induced oxidative stress. It was also found that blue light exposure caused mitochondrial dysfunction in HaCaT cells, including increased intracellular calcium ion levels and decreased mitochondrial membrane potential. LBP pretreatment significantly relieved mitochondrial dysfunction in HaCaT cells. These findings imply that LBP pretreatment protects skin cells from damage induced by blue light irradiation and that mitophagy may be a significant factor in skin photodamage.

Lycium barbarum polysaccharide inhibits ischemia-induced autophagy by promoting the biogenesis of neural stem cells-derived extracellular vesicles to enhance the delivery of miR-133a-3p.

BACKGROUND: Neural stem cell-derived extracellular vesicles (NSC-EVs) mediated endogenous neurogenesis determines a crucial impact on spontaneous recovery after stroke. Here, we checked the influence of Lycium barbarum polysaccharide (LBP) on the biogenesis of NSC-EVs and then focused on studying mechanisms of LBP in ameliorating ischemic stroke outcome. METHODS: LBP was prepared to precondition NSCs and isolate EVs. MCAO models and primary NSCs were administrated to evaluate the therapeutic effect. RT-PCR, western blot, flow cytometry, and immunofluorescence techniques were performed to explore the mechanism. RESULTS: LBP pretreatment increased the production of NSC-EVs and improved the neuroprotective and recovery effects of NSC-EV in ischemic stroke mice. LBP-pretreated NSC-EV in a dose-dependent manner substantially reduced neuronal death compared with NSC-EV. Screening of the signaling cascade involved in the interaction between NSC-EV and neurons revealed that AMPK/mTOR signaling pathway inhibited autophagic activity in neurons receiving either treatment paradigm. NSC-EVs but not EVs collected from NSCs pretreated with the anti-miR-133a-3p oligonucleotide reduced cell death, whereas the anti-oligonucleotide promoted autophagy activity and cell death by modulating AMPK/mTOR signaling in OGD-induced primary neurons. CONCLUSION: LBP activated AMPK/mTOR signaling pathway by increasing the enrichment and transfer of miR-133a-3p in NSC-EVs to inhibit stroke-induced autophagy activity.

Neuroprotective effects of Lycium barbarum polysaccharide on light-induced oxidative stress and mitochondrial damage via the Nrf2/HO-1 pathway in mouse hippocampal neurons.

Light at night (LAN) induced cognitive impairment associated with oxidative stress in mice has been reported. Lycium barbarum polysaccharide (LBP) exhibits anti-tumor, anti-oxidant and neuroprotective effects, yet the neuroprotective effect on light-induced neuron damage still unclear. Here, mice exposed to LAN displayed cognitive impairment and depressive like behavior, which was reversed by LBP treatment. Meanwhile, LBP alleviated light-induced higher apoptosis and mitochondrial damage in HT-22 cells. Also, LBP prevented the decreased of mitochondrial membrane permeabilization (MMP) level in light-treated cells. Additionally, LBP demonstrated its antioxidant potential by reducing ROS production and malondialdehyde (MDA) level, while simultaneously enhancing the levels of superoxide dismutase (SOD) and glutathione peroxidases (GSH-Px) in both light-treated mice and HT-22 cells. Furthermore, the mRNA and protein expression of Nrf2 (NF-E2-related factor 2), heme oxygenease-1 (HO-1), and NAD(P)H quinone oxidoreductase (NQO1) were decreased in both light-treated mice and cells. Additionally, LBP treatment reversed light-induced the inhibition of Nrf2/HO-1 signaling pathway in both mice and cells. Moreover, Nrf2 antagonist ML385 significantly eliminated the neuroprotection of LBP on cell apoptosis, oxidative stress and mitochondrial damage in light-treated cells. These results indicate that LBP can rescue light-induced neurotoxicity in mice and HT-22 cells by activating the Nrf2/HO-1 signaling pathway.

Lycium barbarum polysaccharide-glycoprotein ameliorates ionizing radiation-induced epithelial injury by regulating oxidative stress and ferroptosis via the Nrf2 pathway.

Radiation-induced oral mucositis (RIOM) is considered to be the most common acute side effect of radiation therapy and occurs during intentional or accidental radiation exposure. Antioxidant synthesis agents have been reported to protect against or alleviate the development of mucositis, but the resulting side effects of chemical synthesis agents limit their use in clinical practice. Lycium barbarum polysaccharide-glycoprotein (LBP), a polysaccharide extract of the Lycium barbarum fruit, has superior antioxidant capacity and biosafety and is a potential option for radiation prevention and treatment. Here, we aimed to investigate whether LBP conferred radioprotection against ionizing radiation-induced oral mucosal damage. We found that LBP exerted radioprotective effects in irradiated HaCaT cells, improving cell viability, stabilizing mitochondrial membrane potential, and decreasing cell death. LBP pretreatment reduced oxidative stress and ferroptosis in radioactivity-damaged cells by activating the transcription factor Nrf2 and promoting its downstream targets, such as HO-1, NQO1, SLC7A11, and FTH1. Knockdown of Nrf2 eliminated the protective effects of LBP, implying the essential role of Nrf2 in LBP activity. Additionally, the topical application of LBP thermosensitive hydrogel on rat mucosa resulted in a significant decrease in ulcer size in the irradiated group, suggesting that LBP oral mucoadhesive gel may be a potential tool for the treatment of irradiation. In conclusion, we demonstrated that LBP attenuates ionizing radiation-induced oral mucosa injury by reducing oxidative stress and inhibiting ferroptosis via the Nrf2 signaling pathway. LBP may be a promising medical countermeasure against RIOM.

Serum metabolomics combined with 16S rRNA sequencing to reveal the effects of Lycium barbarum polysaccharide on host metabolism and gut microbiota.

Gut microbes and microbial metabolites derived from polysaccharides mediate beneficial effects related to polysaccharides consumption. Lycium barbarum polysaccharide (LBP) is the main bioactive components in L. barbarum fruits and possesses considerable health-promoting effects. In the present study, we aimed to investigate whether LBP supplementation influenced host metabolic responses and gut microbiota in healthy mice, and to identify bacterial taxa associated with the observed beneficial effects. Our results indicated that mice supplied with LBP at 200 mg/kg BW showed lower serum total cholesterol (TC), triglyceride (TG), and liver TG levels. LBP supplementation strengthened the antioxidant capacity of liver, supported the growth of Lactobacillus and Lactococcus, and stimulated short-chain fatty acids (SCFAs) production. Serum metabolomic analysis revealed that fatty acid degradation pathways were enriched, and RT-PCR further confirmed that LBP up-regulated the expression of liver genes involved in fatty acid oxidation. The Spearman's correlation analysis indicated that some serum and liver lipid profiles and hepatic SOD activity were associated with Lactobacillus, Lactococcus, Ruminococcus, Allobaculum and AF12. Collectively, these findings provide new evidence for the potential preventive effect of LBP consumption on hyperlipidemia and nonalcoholic fatty liver disease.

Dietary supplementation with Lycium barbarum polysaccharides conducive to maintaining the health of Luciobarbus capito via the enhancement of enzyme activities and the modulation of gut microbiota.

Lycium barbarum polysaccharide (LBP) is the main active component of Lycium barbarum (L. barbarum), which has important medicinal and nutritional value. However, the effect of LBP treatment on Luciobarbus capito (L. capito) still remains unknown. Given this, the current work aims to probe the underlying effect of different levels of LBP treatment (i.e. 0.10, 0.50 and 1.00 g/L) on L. capito in the context of enzymatic activity analysis, histological observations and gut microbiota analysis. Compared with control group, the activities of hepatic antioxidant enzymes, intestinal digestive enzymes and hepatic immune enzyme were found to be significantly increased after 0.10 g/L LBP and 0.50 g/L LBP treatment (P < 0.05). This result indicated that moderate levels of LBP treatment could dramatically enhance the immunity and antioxidant capacity of L. capito. Furthermore, the compositional structures of the gut microbiota in L. capito were found to be greatly shaped after LBP treatment, whereas the diversity and abundance of the gut microbiota were only found to be slightly changed (P > 0.05). No significant changes were screened in the morphologic structures of gut constructions. This work would provide theoretical and experimental basis for future application of LBP as supplement in the culture process of the farmed fish.

Lycium barbarum polysaccharide protects cardiomyocytes from hypoxia/reoxygenation injury via activation of SIRT3/CypD signaling.

Background: Myocardial ischemia-reperfusion is a common pathological feature of many heart and vascular diseases, but the molecular mechanism of this process is still unclear, and there is no effective way to protect cardiomyocytes. The aim of this study was to examine the effects and underlying molecular mechanisms of Lycium barbarum polysaccharide (LBP) on myocardial ischemia-reperfusion injury in cardiomyocytes. Methods: The cardiomyocyte cell line H9c2 were used to establish an in vitro hypoxia/reoxygenation (H/R) model. After treatment with LBP and/or the SIRT3 inhibitor 3-TYP, cell morphology was observed under the light microscopy. The Cell Counting Kit (CCK)-8 and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to detect cell proliferation, and flow cytometry was performed to assess cell apoptosis. The lysine (166)-acetylation of CypD1 was determined by co-immunoprecipitation assay. Enzyme-linked immunosorbent assay (ELISA) was used to determine the lactate dehydrogenase (LDH) level in the culture medium. Na+-K+-ATPase activity, Ca2+-ATPase activity, and nitric oxide (NO) levels were measured. Results: LBP alleviated cell damage and upregulated STIR3 expression in a dose-dependent manner. Upregulated SIRT3 expression and suppressed acetylation of CypD were also observed in H/R-induced H9c2 cells treated with LBP. Indeed, LBP remarkably reversed the inhibition of proliferation and cell apoptosis in H/R-induced H9c2 cells by activating SIRT3/CypD signaling. Blockade of SIRT3 with SIRT3 inhibitor (3-TYP) inhibited the protective effect of LBP on H9c2 cells. LBP markedly alleviated the H/R-induced increase of LDH release, and the decrease of Na+-K+-ATPase activity, Ca2+-ATPase activity, and NO levels. Inhibition of SIRT3 restored the protective effects of LBP. Conclusions: LPB induced deacetylation of CypD by upregulating SIRT3, thereby protecting mitochondrial function and relieving H/R-induced injury in cardiomyocytes.

Lycium barbarum polysaccharide-glycoprotein promotes osteogenesis in hPDLSCs via ERK activation.

OBJECTIVE: A lack of relevant research on Lycium barbarum polysaccharide-glycoprotein (LBP) application in oral diseases. Here, we focused on the effect of LBP on osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and periodontitis bone loss. METHODS: Human periodontal ligament stem cells (hPDLSCs) were isolated and identified by flow cytometry. Alkaline phosphatase (ALP) activity, Alizarin Red staining, and combined qPCR and Western blot analyses were performed to elucidate the effects of LBP on the osteogenic potential of hPDLSCs. In vivo experiments were performed with the treatment of LBP in rat periodontal model. MicroCT scanning and histological analysis were conducted to evaluate osteogenesis in situ. RESULTS: Human periodontal ligament stem cells (hPDLSCs) were successfully isolated and identified with CD90, CD29, and CD45. LBP enhanced hPDLSCs proliferation and migration and promoted RUNX2, ALP, Collagen I, and Osteocalcin expression through activating the ERK1/2 signaling pathway in vitro. The inflammatory factors, including interleukin 6 (IL-6) and interleukin 8 (IL-8) were reduced after LBP treatment. Alveolar bone resorption was significantly decreased in the LBP-treated groups in vivo, and osteoclast was markedly decreased by LBP application. CONCLUSION: LBP promoted hPDLSC osteogenesis by targeting the ERK1/2 signaling pathway and reverse bone loss by reducing inflammation. These findings provided latent hope for LBP application in periodontal therapy.

Impact of Lycium barbarum polysaccharide on the expression of glucagon-like peptide 1 in vitro and in vivo.

Several studies showed the efficacy of Lycium barbarum polysaccharide (LBP) in diabetic animals and patients with type 2 diabetes mellitus (T2DM). However, the mechanism of LBP in alleviating T2DM based on glucagon-like peptide 1 (GLP1) has not been suitably elucidated. GLP1 is an important peptide that plays a role in blood glucose homeostasis. Inhibition of sodium/glucose cotransporter 1 (SGLT1) can result in a net increase in GLP1 release. We found that LBP could reduce SGLT1 expression. Thus, the effects of LBP on the first- and second-phase secretion of GLP1 were systematically assessed in vitro using STC1 cells and in vivo using diabetic KKAy mice. LBP could induce the first-phase secretion of GLP1 by stimulating calcium ion influx in vitro and by inhibiting alpha-glucosidase activity in vivo. Regulation of Gcg gene expression by modulating the Wnt/ß-catenin and cAMP/Epac pathways, as well as inhibition of alpha-glucosidase activity, was responsible for the second-phase secretion of GLP1. LBP could stimulate GLP1 secretion; however, dipeptidyl peptidase 4 (DPP4) activated by LBP might offset the second-phase secretion of GLP1. Thus, we suggest considering the simultaneous use of LBP and a DPP4 inhibitor to stimulate slow, continuous GLP1 secretion. Further studies are warranted for in-depth mechanistic information.