Shiitake mushroom-induced flagellate dermatitis: The first case reported in Nepal.

Shiitake mushroom-induced flagellate dermatitis is a rare but important condition to consider in patients presenting with pruritic skin lesions following mushroom ingestion, especially in regions where such cases are uncommon. Early recognition and appropriate management with oral and topical steroids are crucial for effective symptom resolution and preventing complications. Clinicians should be aware of the characteristic rash and the temporal relationship between mushroom consumption and rash onset. Educating patients about the risks associated with consuming raw or undercooked shiitake mushrooms is essential to prevent recurrence.

Lentinan Ameliorates ß-Hydroxybutyrate-Induced Lipid Metabolism Disorder in Bovine Hepatocytes by Upregulating the Expression of Acetyl-coenzyme A Acetyltransferase 2.

Ketosis in dairy cows is often accompanied by the dysregulation of lipid homeostasis in the liver. Acetyl-coenzyme A acetyltransferase 2 (ACAT2) is specifically expressed in the liver and is important for regulating lipid homeostasis in ketotic cows. Lentinan (LNT) has a wide range of pharmacological activities, and this study investigates the protective effects of LNT on ß-hydroxybutyrate (BHBA)-induced lipid metabolism disorder in bovine hepatocytes (BHECs) and elucidates the underlying mechanisms. BHECs were first pretreated with LNT to investigate the effect of LNT on BHBA-induced lipid metabolism disorder in BHECs. ACAT2 was then silenced or overexpressed to investigate whether this mediated the protective action of LNT against BHBA-induced lipid metabolism disorder in BHECs. Finally, BHECs were treated with LNT after silencing ACAT2 to investigate the interaction between LNT and ACAT2. LNT pretreatment effectively enhanced the synthesis and absorption of cholesterol, inhibited the synthesis of triglycerides, increased the expression of ACAT2, and elevated the contents of very low-density lipoprotein and low-density lipoprotein cholesterol, thereby ameliorating BHBA-induced lipid metabolism disorder in BHECs. The overexpression of ACAT2 achieved a comparable effect to LNT pretreatment, whereas the silencing of ACAT2 aggravated the effect of BHBA on inducing disorder in lipid metabolism in BHECs. Moreover, the protective effect of LNT against lipid metabolism disorder in BHBA-induced BHECs was abrogated upon silencing of ACAT2. Thus, LNT, as a natural protective agent, can enhance the regulatory capacity of BHECs in maintaining lipid homeostasis by upregulating ACAT2 expression, thereby ameliorating the BHBA-induced lipid metabolism disorder.

A General Strategy toward Self-assembled Nanovaccine Based on Cationic Lentinan to Induce Potent Humoral and Cellular Immune Responses.

Adjuvants play a critical role in the induction of effective immune responses by vaccines. Here, a self-assembling nanovaccine platform that integrates adjuvant functions into the delivery vehicle is prepared. Cationic Lentinan (CLNT) is mixed with ovalbumin (OVA) to obtain a self-assembling nanovaccine (CLNTO nanovaccine), which induces the uptake and maturation of bone marrow dendritic cells (BMDCs) via the toll-like receptors 2/4 (TLR2/4) to produce effective antigen cross-presentation. CLNTO nanovaccines target lymph nodes (LNs) and induce a robust OVA-specific immune response via TLR and tumor necrosis factor (TNF) signaling pathways, retinoic acid-inducible gene I (RIG-I) receptor, and cytokine-cytokine receptor interactions. In addition, CLNTO nanovaccines are found that promote the activation of follicular helper T (Tfh) cells and induce the differentiation of germinal center (GC) B cells into memory B cells and plasma cells, thereby enhancing the immune response. Vaccination with CLNTO nanovaccine significantly inhibits the growth of ovalbumin (OVA)-expressing B16 melanoma cell (B16-OVA) tumors, indicating its great potential for cancer immunotherapy. Therefore, this study presents a simple, safe, and effective self-assembling nanovaccine that induces helper T cell 1 (Th1) and helper T cell (Th2) immune responses, making it an effective vaccine delivery system.

Immunopotentiating effect of lentinan on chicks and its inhibitory effect on Marek's disease virus infection.

Marek's disease virus (MDV) is a significant tumorigenic virus that causes severe immunosuppression in chickens. Lentinan (LNT) is an immunomodulator containing ß-glucans and is widely used in areas such as antiviral, anticancer, and immune regulation. To investigate the immunomodulatory effects of LNT on specific pathogen-free (SPF) chicks and its potential to inhibit MDV infection, we conducted an MDV challenge experiment and observed the immune-enhancing effect of LNT on SPF chicks. The results showed that LNT promoted the growth and development of SPF chicks and induced the upregulation of cytokines such as Mx protein, interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2). The specific gravity of CD4+ T-lymphocytes and CD8+ T-lymphocytes and their ratios were also significantly upregulated. Prophylactic use of LNT inhibited MDV replication in lymphocytes, liver, and spleen. It also alleviated MDV-induced weight loss and hepatosplenomegaly in SPF chicks. The present study confirms that LNT can enhance the levels of innate and cellular immunity in SPF chicks and contributes to the inhibition of MDV replication in vivo and mitigation of immune organ damage in chicks due to MDV infection. This provides an adjunctive measure for better control of MDV infection.

Lentinan mitigates pemetrexed chemoresistance by the PI3K/Akt pathway in non-small cell lung cancer.

Pemetrexed is a folate analog metabolic inhibitor that is given for therapy of non-small cell lung cancer (NSCLC). Drug resistance affects the efficacy of pemetrexed in NSCLC. Lentinan is a polysaccharide extracted from Shiitake mushrooms which has antitumor roles in multiple cancers, including lung cancer. However, the effects of lentinan on pemetrexed resistance in NSCLC remain unclear. In present study, The pemetrexed-resistant NSCLC cells were established and exposed to pemetrexed and lentinan. Oxidative stress was investigated via mitochondrial membrane potential (JC-1 staining), levels of MDA and SOD.The phosphorylation and total of PI3K and Akt levels were actuated using specific activator 740Y-P and measured through western blot. We observed that Lentinan decreased IC50 of pemetrexed in resistant NSCLC cells. Lentinan aggravated pemetrexed-induced proliferation inhibition of resistant NSCLC cells via reducing PCNA levels. Lentinan exacerbated pemetrexed-triggered oxidative stress through increasing ROS and MDA levels, and reducing mitochondrial membrane potential and SOD levels. Lentinan inhibited PI3K/Akt signaling activation in pemetrexed-treated cells. Activated PI3K/Akt pathway using activator 740Y-P reversed the effects of lentinan on pemetrexed-mediated proliferation inhibition and oxidative stress. Our findings uncover that Lentinan mitigates pemetrexed resistance in NSCLC through inhibiting cell proliferation and inducing oxidative stress by suppressing PI3K/Akt signaling.

The Effects of Lentinan on the Hematological and Immune Indices of Dairy Cows.

In this study, we investigated the effects of lentinan (LNT) on hematological parameters, immune indices, and metabolite levels in dairy cows. We randomly assigned forty Holstein cows to four treatment groups. The treatments consisted of 0, 5, 10, and 15 g/d of LNT. Compared with the control group, the addition of 10 g/d of LNT decreased the content of ALT and IL-8 but simultaneously increased the content of IL-4 in the cows' serum. Supplementation with 10 g/d of LNT decreased the levels of lymphocyte, RDW, ALT, AST, TC, IL-2, and IL-8, but, concurrently, in-creased the levels of granulocytes and IL-4 in their serum. In addition, supplementation with 15 g/d of LNT decreased the levels of RDW, TC, IL-2, and IL-8, but, at the same time, increased the levels of IL-4 and IgM in their serum. For the metabolomic analysis, cows fed with 0 and 10 g/d of LNT were selected. The results showed that 10 metabolites, including reduced nicotinamide riboside and trehalose, were upregulated in the 10 g/d group. These differential metabolites were enriched in tyrosine metabolism and trehalose degradation and altered two metabolic pathways of ubiquinone and other terpene quinone biosynthesis, as well as starch and sucrose metabolism. These findings provide evidence that LNT could be used to reduce the risk of inflammation in dairy cows.

Lentinan inhibits cell invasion via M2 polarization of tumor-associated macrophages and Wnt/ß-catenin signaling in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is an aggressive and devastating cancer due to its metastasis induced by increased invasion. Lentinan is a polysaccharide exerting antitumor roles in multiple cancers, including lung cancer. However, the influence of lentinan on cell invasion in NSCLC remains unclear. Cell invasion was detected by transwell analysis. Matrix metallopeptidase 9 (MMP9) levels were measured through immunofluorescence staining. The markers arginase-1 (Arg-1), CD206 and interleukin (IL)-10 (IL-10) of M2 macrophages, Wnt3a, and ß-catenin levels were measured by western blot or enzyme linked immunosorbent assay. Lentinan did not affect cell viability and proliferation in NSCLC cells. Lentinan suppressed cell invasion and reduced the expression and secretion of MMP9. Lentinan attenuated also M2 polarization of tumor-associated macrophages. Moreover, lentinan mitigated the M2 macrophage conditioned medium-mediated cell invasion and MMP9 alterations in NSCLC cells. Lentinan inhibited the activation of the Wnt/ß-catenin signaling in NSCLC cells. The activated Wnt/ß-catenin pathway reversed the suppressive effects of lentinan on cell invasion and MMP9 level in NSCLC cells. In conclusion, lentinan reduces cell invasion in NSCLC cells by inhibiting the M2 polarization of tumor-associated macrophages and the Wnt/ß-catenin signaling.

The effect of lentinan on dexamethasone-induced immunosuppression in mice.

The immune system acts as a vital defense barrier against pathogenic invasions, and its stable operation is crucial for maintaining body health. Nevertheless, various natural or artificial factors can compromise the body's immune function, leading to immunosuppression, which may interfere with the efficacy of vaccination and increase the susceptibility of the body to disease-causing pathogens. In an effort to ensure successful vaccinations and improve overall physical well-being, the search for appropriate immune regulators to enhance immunity is of paramount importance. Lentinan (LNT) has a significant role in immune regulation and vaccine adjuvants. In the present study, we constructed an immunosuppressive model using dexamethasone (DEX) and demonstrated that LNT could significantly improved antibody levels in immunosuppressive mice and stimulated T-lymphocyte proliferation and differentiation in intestinal Peyer's patches. LNT also increased the production of secretory immunoglobulin A (sIgA) in the duodenal fluid, the number of goblet cells, and the proportion of mucin area. Moreover, LNT modulated the intestinal microbiota and increased the production of short-chain fatty acids. Additionally, LNT promoted the proliferation, differentiation, and pro-inflammatory cytokines production of DEX-treated splenic T lymphocytes in vitro. Thus, the present study highlights the potential of LNT in reversing immunosuppression and avoiding the failure of vaccination.

Lentinan-loaded GelMA hydrogel accelerates diabetic wound healing through enhanced angiogenesis and immune microenvironment modulation.

Diabetic wound healing is a substantial clinical challenge, characterized by delayed angiogenesis and unresolved inflammation. Lentinan, a polysaccharide extracted from shiitake mushrooms, has the potential to regulate both macrophage polarization and angiogenesis, though this aspect remains inadequately explored. To facilitate lentinan's clinical utility, we have developed a GelMA hydrogel encapsulated with lentinan (10 µM), offering a controlled release mechanism for sustained lentinan delivery at the wound site. Application of the lentinan-encapsulated delivery system topically significantly expedites wound closure compared to control groups. Furthermore, histological examination demonstrates enhanced neovascularization and reduced inflammation in lentinan-treated wounds, as evidenced by increased M2 macrophage infiltration. Moreover, our results indicated that lentinan-induced AMPK activation promotes DAF16 expression, enhancing the resistance of macrophages and HUVECs to oxidative stress in high-glucose environments, thereby promoting M2 macrophage polarization and angiogenesis. All these findings underscore lentinan's capacity to modulate macrophage polarization and angiogenesis via the AMPK/DAF16 pathway, ultimately facilitating the healing of diabetic wounds.

Medicinal Mushrooms as Multicomponent Mixtures-Demonstrated with the Example of Lentinula edodes.

Medicinal mushrooms are multicomponent mixtures (MOCSs). They consist of a large number of individual compounds, each with different chemical structures, functions, and possible pharmacological activities. In contrast to the activity of an isolated pure substance, the effects of the individual substances in a mushroom or its extracts can influence each other; they can strengthen, weaken, or complement each other. This results in both advantages and disadvantages for the use of either a pure substance or a multicomponent mixture. The review describes the differences and challenges in the preparation, characterization, and application of complex mixtures compared to pure substances, both obtained from the same species. As an example, we use the medicinal and culinary mushroom Lentinula edodes, shiitake, and some of its isolated compounds, mainly lentinan and eritadenine.

Lentinan progress in inflammatory diseases and tumor diseases.

Shiitake mushrooms are a fungal food that has been recorded in Chinese medicine to nourish the blood and qi. Lentinan (lLNT) is an active substance extracted from shiitake mushrooms with powerful antioxidant, anti-inflammatory, anti-tumor functions. Inflammatory diseases and cancers are the leading causes of death worldwide, posing a serious threat to human life and health and posing enormous challenges to global health systems. There is still a lack of effective treatments for inflammatory diseases and cancer. LNT has been approved as an adjunct to chemotherapy in China and Japan. Studies have shown that LNT plays an important role in the treatment of inflammatory diseases as well as oncological diseases. Moreover, clinical experiments have confirmed that LNT combined with chemotherapy drugs has a significant effect in improving the prognosis of patients, enhancing their immune function and reducing the side effects of chemotherapy in lung cancer, colorectal cancer and gastric cancer. However, the relevant mechanism of action of the LNT signaling pathway in inflammatory diseases and cancer. Therefore, this article reviews the mechanism and clinical research of LNT in inflammatory diseases and tumor diseases in recent years.

A novel method for detecting conformation-dependent ß-glucans-single, double, and triple-helical from Shiitake mushroom.

This pioneering study explores the structural intricacies of therapeutic ß-glucan in Shiitake (Lentinula edodes), i.e. Lentinan (LNT). Lentinan, a neutral polysaccharide [ß-(1,3; 1,6) glucan], exists in three forms; single, double, and triple-helical, but conformation-dependent bioactivity studies are lacking. In this context, we meticulously assessed indigenous Shiitake accessions from Northeast India, unveiling the conformational spectrum of LNT through an innovative pipeline. The experiment approached the simultaneous estimation of total glucan (TG), triple helical glucan (THG), and single-double helical glucan (SDG). Profiling revealed the exceptional LNT content in DMRO-623 (TG: 46.74%, SDG: 9.34%, THG: 37.39%) which emerged as the highest documented to date. Beyond the culinary delight, this research and the novel approach to LNT quantification will create a pivotal platform for advanced mushroom research, offering prospects for novel discoveries, innovative applications, and therapeutic potential.

Dextrans, Pullulan and Lentinan, New Scaffold Materials for Use as Hydrogels in Tissue Engineering.

The development of hydrogels based on dextrans, pullulan and lentinan to be used in biomedical applications including tissue engineering is reported. Despite the fact that selected polysaccharides such as hyaluronic acid are well established, little is known, how these polysaccharides can be chemically modified to create hydrogels under controlled conditions. In this study we present a small library of chemically modified polysaccharides which are used for a divergent approach to achieve biomedical relevant hydrogels. In this case the crosslinking is based on thio ether formation between thiol modified donor and vinylsulfone or maleimide modified acceptor components. Successful synthesis of the linker systems and coupling at the polysaccharides, hydrogel formation takes place under physiological conditions. We extended the study by coupling small molecules like adhesion factors for increasing cell compatibility as well as a dye for further studies. The different hydrogels were studied to their rheological properties, water uptake, their permeability, biodegrability and their cytotoxicity.

Single-injection subunit vaccine for rabies prevention using lentinan as adjuvant.

Current rabies vaccines require 5 doses to provide full protection from the deadly virus, which significantly reduce the compliance of recipients. To minimize the number of immunizations herein single injection vaccines were developed. First a single injection vaccine was designed using rabies virus glycoprotein (G protein) as antigen. A time-controlled release system which uses dynamic layer-by-layer films as erodible coating was employed to accomplish multiply pulsatile releases of G protein. The single-injection vaccine elicits potent humoral and cellular immune responses comparable to the corresponding multi-dose ordinary vaccines because of their similar release pattern of G protein. To further improve its performance, a second single injection vaccine, in which lentinan was added as adjuvant, was designed. This single-injection vaccine again elicits humoral and cellular immune responses comparable to the corresponding multi-dose ordinary vaccines because of their similar release pattern of antigen and adjuvant. In addition, the second single-injection vaccine elicits higher level immune response and provides higher efficiency on virus inhibition than the first one because lentinan can booster immune response.

Systematic review and meta-analysis on the efficacy and safety of Injectable Lentinan combined with chemotherapy in the treatment of gastric cancer.

BACKGROUND: This study employed a meta-analysis to evaluate the efficacy and safety of adjunctive treatment with injectable Lentinan (LNT) in combination with chemotherapy for gastric cancer (GC). METHODS: Computer-based searches of 6 databases were performed to identify randomized controlled trials (RCTs) relevant to the treatment of GC with LNT through mid-March 2023. Two independent researchers performed risk of bias assessment and trial sequential analysis(TSA), extracted the data and used Revman 5.3 software for data analysis. The certainty of evidence was graded based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS: A total of 31 RCTs with 2729 patients were included in the analysis. The results revealed that adjunctive therapy with LNT was associated with improved treatment efficacy (RR = 1.48, 95%CI: 1.36 ∼ 1.61, p < 0.00001), improvement in clusters of differentiation (CD3+, CD4+, and CD4+/CD8+), natural killer (NK) cells, and quality of life assessment (RR = 1.32, 95%CI: 1.20 ∼ 1.45, p < 0.00001) compared to using chemotherapy alone. In addition, there was a reduction in CD8+ levels, incidence of white blood cell decline, gastrointestinal reactions, and platelet decline. TSA results indicated that there was sufficient evidence to draw firm conclusions about these outcomes, and the GRADE scores showed 'high' or 'moderate' quality of evidence for these outcomes. CONCLUSION: The efficacy of treatment of GC with LNT in combination with chemotherapy was found to be better than chemotherapy alone. And no serious adverse effects were observed. However, further RCTs are needed to further validate the results of this study.

Lentinan has a beneficial effect on cognitive deficits induced by chronic Toxoplasma gondii infection in mice.

BACKGROUND: Toxoplasma gondii (T. gondii) is increasingly considered a risk factor for neurodegenerative diseases. However, there is only limited information on the development of drugs for T. gondii infection. Lentinan from Lentinula edodes is a bioactive ingredient with the potential to enhance anti-infective immunity. The present study aimed to investigate the neuroprotective effect of lentinan on T. gondii-associated cognitive deficits in mice. METHODS: A chronic T. gondii infection mouse model was established by administering 10 cysts of T. gondii by gavage. Lentinan was intraperitoneally administered 2 weeks before infection. Behavioral tests, RNA sequencing, immunofluorescence, transmission electron microscopy and Golgi-Cox staining were performed to assess the effect of lentinan on cognitive deficits and neuropathology in vivo. In vitro, the direct and indirect effects of lentinan on the proliferation of T. gondii tachyzoites were evaluated in the absence and presence of BV-2 cells, respectively. RESULTS: Lentinan prevented T. gondii-induced cognitive deficits and altered the transcriptome profile of genes related to neuroinflammation, microglial activation, synaptic function, neural development and cognitive behavior in the hippocampus of infected mice. Moreover, lentinan reduced the infection-induced accumulation of microglia and downregulated the mRNA expression of proinflammatory cytokines. In addition, the neurite and synaptic ultrastructural damage in the hippocampal CA1 region due to infection was ameliorated by lentinan administration. Lentinan decreased the cyst burden in the brains of infected mice, which was correlated with behavioral performance. In line with this finding, lentinan could significantly inhibit the proliferation of T. gondii tachyzoites in the microglial cell line BV2, although lentinan had no direct inhibitory effect on parasite growth. CONCLUSIONS: Lentinan prevents cognitive deficits via the improvement of neurite impairment and synaptic loss induced by T. gondii infection, which may be associated with decreased cyst burden in the brain. Overall, our findings indicate that lentinan can ameliorate T. gondii-related neurodegenerative diseases.

Safety and efficacy of lentinan nasal drops in patients infected with the variant of COVID-19: a randomized, placebo-controlled trial.

Objective: Lentinan has antiviral, anti-tumor, immunomodulatory, stimulating interferon production, and other pharmacological effects. Previous animal experiments have shown that lentinan nasal drops can assist [Corona Virus Disease 2019) COVID-19] vaccine to induce high levels of neutralizing antibodies and can effectively resist the invasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the safety and efficacy of lentinan nasal drops in patients infected with Omicron (SARS-CoV-2 variant) through a dose-escalation study and a placebo-controlled trial. Methods: A randomized, placebo-controlled trial. The study was divided into two phases: Phase I: a dose escalation trial in which 24 COVID-19 patients were enrolled, that is, 12 in the escalation dose group (50, 75, and 100 µg/day) and 12 in the standard treatment group. The aim was to evaluate the safety and tolerance of lentinan nasal drops. The second stage was a placebo-controlled study. The optimal dose group of the first stage was used as the therapeutic dose, and the sample size was expanded to verify the anti-COVID-19 efficacy of lentinan nasal drops. Results: In the dose-increasing study, lentinan nasal drops showed good safety, and no serious adverse reactions occurred. The virus shedding time of the 100 µg dose group was significantly shorter than that in the control group (7.75 ± 1.71 VS 13.41 ± 3.8 days) (p = 0.01), and the 100 µg/day lentinan nasal drops were tolerated well. The results of the placebo-controlled study showed that compared with that in the placebo group, the time for COVID-19 antigen to turn negative was significantly shorter in the 100 µg lentinan nasal drop group (p = 0.0298), but no significant difference was observed in symptom improvement between the two groups. In the placebo-controlled study, two patients experienced mild nasal discomfort with nasal drops, but the symptoms relieved themselves. Conclusion: Lentinan nasal drops are tolerated well and can shorten the time of virus clearance.

Lentinan alleviates diabetic cardiomyopathy by suppressing CAV1/SDHA-regulated mitochondrial dysfunction.

Diabetic cardiomyopathy (DCM), characterized by mitochondrial dysfunction and impaired energetics as contributing factors, significantly contributes to high mortality in patients with diabetes. Targeting key proteins involved in mitochondrial dysfunction might offer new therapeutic possibilities for DCM. Lentinan (LNT), a ß-(1,3)-glucan polysaccharide obtained from lentinus edodes, has demonstrated biological activity in modulating metabolic syndrome. In this study, the authors investigate LNT's pharmacological effects on and mechanisms against DCM. The results demonstrate that administering LNT to db/db mice reduces cardiomyocyte apoptosis and mitochondrial dysfunction, thereby preventing DCM. Notably, these effects are fully negated by Caveolin-1 (CAV1) overexpression both in vivo and in vitro. Further studies and bioinformatics analysis uncovered that CAV1 bound with Succinate dehydrogenase subunit A (SDHA), triggering the following ubiquitination and degradation of SDHA, which leads to mitochondrial dysfunction and mitochondria-derived apoptosis under PA condition. Silencing CAV1 leads to reduced apoptosis and improved mitochondrial function, which is blocked by SDHA knockdown. In conclusion, CAV1 directly interacts with SDHA to promote ubiquitination and proteasomal degradation, resulting in mitochondrial dysfunction and mitochondria-derived apoptosis, which was depressed by LNT administration. Therefore, LNT may be a potential pharmacological agent in preventing DCM, and targeting the CAV1/SDHA pathway may be a promising therapeutic approach for DCM.

Anti-Inflammatory and Anti-Oxidant Impacts of Lentinan Combined with Probiotics in Ulcerative Colitis.

Multi-methods have been developed to control ulcerative colitis. This research targeted to probe that lentinan combined with probiotics suppresses inflammation and oxidative stress responses in a dextran sulfate sodium (DSS)-induced colitis model. A mouse model of colitis was induced through oral administration with 2.5% DSS and treated with lentinan and probiotics independently or in combination. Then, bodyweight and Disease Activity Index (DAI) of mice were determined. Histopathology of colon tissue was analyzed, and apoptosis, inflammation and oxidative stress in the colon tissue of mice were observed. An HT-29 cell model of colitis was established by DSS stimulation and cultured with lentinan and/or probiotics to examine cell proliferation and apoptosis. The data discovered that after DSS induction of colitis, mice developed weight loss, increased DAI score, and shortened the length of colon. Also, severe histopathology of the colon, and increased apoptosis, inflammation and oxidative stress were recognizable. Lentinan could alleviate DSS-induced colitis, and the highest dose was the most significant. Probiotics could also relieve UC in mice, and mixed probiotics had a better therapeutic effect than single probiotics. Lentinan combined with probiotics could further alleviate DSS-induced colitis damage. In addition, lentinan combined with probiotics impaired apoptosis and enhanced proliferation of DSS-treated HT-29 cells. In a word, lentinan combined with probiotics reduces the inflammatory response and oxidative stress of UC.

Lentinan protects Caenorhabditis elegans against fluopyram-induced toxicity through DAF-16 and SKN-1 pathways.

Fluopyram, a SDH inhibitor fungicide, is widely used in agriculture to control fungi and nematodes. However, fluopyram has been proved toxic that caused damage to organs through oxidative stress. The development of natural extracts that can reduce oxidative damage is a promising method. Lentinan is isolated from Lentinus edodes and has been verified its antioxidant activity. In this study, Caenorhabditis elegans was used to evaluate the protective effects of lentinan against fluopyram-induced toxicity and the possible mechanisms. Results showed that lentinan pretreatment notably increased the survival rate of N2 nematodes by 15.0 % and extended the lifespan by 91.5 %, compared with the fluopyram treatment. Lentinan pretreatment reverted the inhibition of the locomotion and reproduction of C. elegans under the fluopyram stress. In addition, lentinan pretreatment significantly decreased the contents of ROS and MDA in N2 nematodes. Moreover, pretreated with lentinan significantly recovered the decreased activities of CAT, SOD, GST and SDH induced by fluopyram. Lentinan pretreatment enhanced the mRNA levels of daf-16 and skn-1 and their downstream genes in the nematodes compared with the fluopyram group. In daf-16 and skn-1 mutants, the lifespan, ROS and related genes expression were not significantly changed in lentinan pretreatment. Pretreated with lentinan significantly enhanced the fluorescence intensity of SOD-3::GFP and GST-4::GFP, and promoted the nuclear translocation of DAF-16 and SKN-1 under the fluopyram stress. In summary, these findings indicated that lentinan protected C. elegans from fluopyram-induced toxicity via DAF-16 and SKN-1.