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3 Biotech Dec 2019Diabetes and obesity are the most frequently found disease worldwide. Several factors are responsible for obesity, i.e., imbalance in energy expenditure, environmental... (Review)
Review
Diabetes and obesity are the most frequently found disease worldwide. Several factors are responsible for obesity, i.e., imbalance in energy expenditure, environmental factors, feeding habit, lifestyle, etc., which can also be responsible for type 2 diabetes mellitus. There are several synthetic drugs available to combat these diseases which have some side effects on sufferers. Therefore, people are shifting towards inexpensive, effective, widely available natural and herbal medicines. Edible mushrooms, which have been used from ancient time to cure these diseases, contain anti-oxidant, fibers, triterpenoids, alkaloid, and other phytochemicals. Comatin, β-glucan, Tremellastin, and Lentinan KS-2 are active chemicals of mushrooms which show great effect on diabetes mellitus and obesity by modulating either cellular function or biochemical pathways. Here, in this review, we have discussed the potential role of edible mushrooms and its biochemicals in control of diabetes and obesity. Using Bioinformatics, we can find the specific targets of theses biochemicals, so that these can be more effective.
PubMed: 31832297
DOI: 10.1007/s13205-019-1982-3 -
Drug Design, Development and Therapy 2020Chondrocyte-mediated inflammation is an important pathological component of osteoarthritis (OA) development. There are currently no therapies that completely reverse the...
BACKGROUND
Chondrocyte-mediated inflammation is an important pathological component of osteoarthritis (OA) development. There are currently no therapies that completely reverse the development of OA. Lentinan, a type of polysaccharide derived from Lentinus edodes, has been demonstrated to possess significant anti-viral, anti-cancer, and anti-inflammatory effects, and has been recently used in the treatment of several inflammatory diseases. However, little research has focused on the pharmacological effect of lentinan in human OA.
MATERIALS AND METHODS
We evaluated the anti-inflammatory and anti-ROS effects of lentinan in SW1353 chondrocytes treated with AGEs using real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and the nitro oxide-specific stain DAF-FM DA. The regulatory effects of lentinan on NF-κB and MAPK p38 signaling were investigated via promoter assay and Western blot analysis.
RESULTS
We found that lentinan inhibits the production of pro-inflammatory cytokines, including IL-1β, TNF-α, IL-8 and the secretion of PGE and NO, by reducing the expression of COX-2 and iNOS in AGE-challenged chondrocytes. Lentinan also reduces AGE-induced increased expression of matrix metalloproteinases-1, -3, and -13 (MMP-1, MMP-3, MMP-13). Furthermore, lentinan has a similar effect on a disintegrin and metalloproteinase with thrombospondin motifs-4 and -5 (ADAMTS-4, ADAMTS-5). Mechanistically, lentinan reduces the activation of NF-κB.
CONCLUSION
Our findings indicate that lentinan shows a protective effect against AGE-induced inflammatory response in chondrocytes. These findings suggest that lentinan is a promising agent for the treatment of OA that could be used as a dietary supplement for patients with OA.
Topics: Anti-Inflammatory Agents; Cells, Cultured; Chondrocytes; Cytokines; Glycation End Products, Advanced; Humans; Inflammation; Lentinan; Matrix Metalloproteinases; Osteoarthritis
PubMed: 32764881
DOI: 10.2147/DDDT.S243311 -
Journal of Cellular and Molecular... Feb 2019In this study, we investigated the therapeutic potential of lentinan in mouse models of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Lentinan...
In this study, we investigated the therapeutic potential of lentinan in mouse models of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Lentinan decreased the disease activity index and macroscopic and microscopic colon tissue damage in dextran sulphate sodium (DSS)-induced or TNBS-induced models of colitis. High-dose lentinan was more effective than salicylazosulfapyridine in the mouse models of colitis. Lentinan decreased the number of tumours, inflammatory cell infiltration, atypical hyperplasia and nuclear atypia in azoxymethane/DSS-induced CAC model. It also decreased the expression of pro-inflammatory cytokines, such as IL-13 and CD30L, in IBD and CAC model mice possibly by inhibiting Toll-like receptor 4 (TLR4)/NF-κB signalling and the expression of colon cancer markers, such as carcinoembryonic antigen, cytokeratin 8, CK18 and p53, in CAC model mice. In addition, lentinan restored the intestinal bacterial microbiotal community structure in IBD model mice. Thus, it shows therapeutic potential in IBD and CAC model mice possibly by inhibiting TLR4/NF-κB signalling-mediated inflammatory responses and disruption of the intestinal microbiotal structure.
Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Azoxymethane; CD30 Ligand; Carcinoembryonic Antigen; Colitis; Colon; Colonic Neoplasms; Dextran Sulfate; Disease Models, Animal; Female; Gastrointestinal Microbiome; Gene Expression Regulation, Neoplastic; Hyperplasia; Interleukin-13; Keratin-18; Keratin-8; Lentinan; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; NF-kappa B; Signal Transduction; Sulfasalazine; Toll-Like Receptor 4; Tumor Suppressor Protein p53
PubMed: 30472806
DOI: 10.1111/jcmm.13897 -
Frontiers in Pharmacology 2023Lentinan has antiviral, anti-tumor, immunomodulatory, stimulating interferon production, and other pharmacological effects. Previous animal experiments have shown that...
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. 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. 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) ( = 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 ( = 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. Lentinan nasal drops are tolerated well and can shorten the time of virus clearance.
PubMed: 38108068
DOI: 10.3389/fphar.2023.1292479 -
Frontiers in Pharmacology 2021The treatment process of tumor is advanced with the development of immunotherapy. In clinical experience, immunotherapy has achieved very significant results. However,... (Review)
Review
The treatment process of tumor is advanced with the development of immunotherapy. In clinical experience, immunotherapy has achieved very significant results. However, the application of immunotherapy is limited by a variety of immune microenvironment. For a long time in the past, polysaccharides such as lentinan and glycopeptide have been used in clinic as adjuvant drugs to widely improve the immunity of the body. However, their mechanism in tumor immunotherapy has not been deeply discussed. Studies have shown that natural polysaccharides can stimulate innate immunity by activating upstream immune cells so as to regulate adaptive immune pathways such as T cells and improve the effect of immunotherapy, suggesting that polysaccharides also have a promising future in cancer therapy. This review systematically discusses that polysaccharides can directly or indirectly activate macrophages, dendritic cells, natural killer cells etc., binding to their surface receptors, inducing PI3K/Akt, mitogen-activated protein kinase, Notch and other pathways, promote their proliferation and differentiation, increasing the secretion of cytokines, and improve the state of immune suppression. These results provide relevant basis for guiding polysaccharide to be used as adjuvants of cancer immunotherapy.
PubMed: 33935714
DOI: 10.3389/fphar.2021.621813 -
Ecotoxicology and Environmental Safety Oct 2023Fluopyram, 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...
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.
PubMed: 37742572
DOI: 10.1016/j.ecoenv.2023.115510 -
Biomedicine & Pharmacotherapy =... Nov 2023Diabetic cardiomyopathy (DCM), characterized by mitochondrial dysfunction and impaired energetics as contributing factors, significantly contributes to high mortality in...
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 β-(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.
Topics: Mice; Animals; Humans; Diabetic Cardiomyopathies; Lentinan; Caveolin 1; Mitochondria; Diabetes Mellitus; Electron Transport Complex II
PubMed: 37804808
DOI: 10.1016/j.biopha.2023.115645 -
BMC Pharmacology & Toxicology Mar 2022Arsenic, existing ubiquitously in soil, drinking water, or food, is well known to be an environmental pollutants concerned by European Food Safety Authority. Lentinan, a...
BACKGROUND
Arsenic, existing ubiquitously in soil, drinking water, or food, is well known to be an environmental pollutants concerned by European Food Safety Authority. Lentinan, a beta-1,6;1,3-glucan extracts from Lentinus edodes, which has the properties of antioxidant and immunomodulation, present study explored the pharmacological effects of Lentinan on arsenic induced hepatotoxicity in mice.
METHODS
Mice experiments were performed by sodium arsenite (SA) treatment or Lentinan intervention, then histopathology, ELISA, Flow Cytometry, or Western-Blotting were applied to evaluate hepatic injury, oxidative stress, CD4 type 17 helper T (Th17) cells, CD4CD25Foxp3 regulatory T cells (Tregs), T cells receptor OX40/CD134, IL-17A, NLRP3, Nrf2, and NQO1.
RESULTS
SA treatment showed hepatic pathological injury and the elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in serum, and induced the increases of malondialdehyde (MDA), Th17 cells, OX40 or IL-17A in liver tissues, which were consistently ameliorated by Lentinan intervention. Further, immunoblotting experiments showed that Lentinan intervention downregulated the levels of OX40, IL-17A, and NLRP3 signals, while elevated the levels of anti-oxidative Nrf2, NQO1 signals compared to arsenic treatment group. For Tregs, Lentinan intervention showed no significant difference from SA treatment group.
CONCLUSION
Lentinan antagonizes SA-induced hepatotoxicity in mice, may be involved in the downregulations of pro-inflammatory OX40 or IL-17A and the activation of anti-oxidative Nrf2, NQO1 signals.
Topics: Animals; Arsenic; Chemical and Drug Induced Liver Injury; Down-Regulation; Interleukin-17; Lentinan; Mice; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein
PubMed: 35313999
DOI: 10.1186/s40360-022-00557-7 -
Journal of Fungi (Basel, Switzerland) Feb 2024Medicinal mushrooms are multicomponent mixtures (MOCSs). They consist of a large number of individual compounds, each with different chemical structures, functions, and... (Review)
Review
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 , shiitake, and some of its isolated compounds, mainly lentinan and eritadenine.
PubMed: 38392825
DOI: 10.3390/jof10020153 -
Biochemical and Biophysical Research... Nov 2021Liver cancer is one of the most common malignancies that is difficult to treat due to late diagnosis and chemo-resistance. In the present study, we developed and...
Liver cancer is one of the most common malignancies that is difficult to treat due to late diagnosis and chemo-resistance. In the present study, we developed and validated a cell based split nanoLuc biosensor to monitor the Apaf1-Apaf1 interactions in response to apoptosis-inducing drugs such as cisplatin. We showed that the activity of split nanoLuc is reconstituted only in response to apoptotic inducer, cisplatin and in a dose-dependent manner. Apaf1 mutants which were unable to oligomerize failed to recover nanoLuc activity while constitutively active variant increased the nanoLuc activity. Generation of Apaf1 knockout HepG2 and treatment with cisplatin showed dramatic reduction in cell death suggesting that cisplatin mainly targets liver cancer cells through apoptosis. As the natural products are potent sources of compounds for adjuvant therapy, we screened a collection of natural products and identified lentinan as an inducer of apoptosome formation, a key step for induction of apoptosis. Lentinan is a polysaccharide with antitumor, pro-apoptotic properties that functions with poorly understood mechanisms. Lentinan was shown to have cytotoxic effects with the IC of 650 μM. Sub-lethal lentinan concentration doubled the nanoLuc activity when co-treated with cisplatin. We also showed that lentinan hugely reduced the dose of cisplatin to induce certain amount of death and that lentinan co-treatment with cisplatin enhanced the Apaf1 transcription in HepG2 cells while lentinan or cisplatin alone failed to alter the transcription. In addition, lentinan and cisplatin co-treatment induced mitochondrial depolarization. This suggested that lentinan combinatorial therapy with cisplatin engaged a different signalling pathway to kill the liver cancer cells and that adjuvant therapy with lentinan can reduce the dose of cisplatin and thus reduce the possibility of chemo-resistance.
Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptotic Protease-Activating Factor 1; Biosensing Techniques; Carcinoma, Hepatocellular; Cisplatin; Drug Synergism; Hep G2 Cells; Humans; Lentinan; Liver Neoplasms; Mutation
PubMed: 34507064
DOI: 10.1016/j.bbrc.2021.08.030