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International Journal of Biological... Dec 2022Lentinan (LNT) has been reported to have a wide range of functions, including anti-inflammatory, antioxidant and anticancer properties. LNT may provide a protective...
Lentinan (LNT) has been reported to have a wide range of functions, including anti-inflammatory, antioxidant and anticancer properties. LNT may provide a protective effect in dairy cow mastitis. In this study, we investigated the effect of LNT on lipopolysaccharide (LPS)-induced injury of bovine mammary epithelial cells (BMECs) and the possible mechanism. First, we treated BMECs with different concentrations of LPS to study the effects of LPS on oxidative stress and inflammation in BMECs. Then, we examined the effects of LNT by dividing the cells into seven groups: the control group (CON), LPS treatment group (LPS), Acetyl-l-cysteine (NAC) pretreatment group (NAC + LPS), LNT pretreatment group (LNT + LPS), ML385 and LNT pretreatment group (ML385 + LNT + LPS), LNT treatment group (LNT) and NAC treatment group (NAC). The results showed that LPS-triggered intracellular ROS production and the downregulation of Nrf-2 and HO-1 in BMECs were blocked by LNT pretreatment. LNT inhibited the expression of inflammatory genes and proteins by inhibiting of NF-κB and MAPK. In addition, LNT attenuated LPS induced-apoptosis in BMECs. However, ML385 reversed the protective effect of LNT. Taken together, LNT can be used as a natural protective agent against LPS-triggered BMECs damage through its anti-inflammatory, antioxidant and antiapoptotic effects through modulation of the Nrf2 pathway.
Topics: Animals; Cattle; Female; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Epithelial Cells; Inflammation; Lentinan; Lipopolysaccharides; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Signal Transduction; Mammary Glands, Animal
PubMed: 36243161
DOI: 10.1016/j.ijbiomac.2022.10.024 -
Journal of Controlled Release :... Apr 2023Recently, lentinan (LNT) has been utilized for its diversified potential in research with an extended role from nutritional or medicinal applications to a novel... (Review)
Review
Recently, lentinan (LNT) has been utilized for its diversified potential in research with an extended role from nutritional or medicinal applications to a novel biomaterial. LNT is a biocompatible, multifunctional polysaccharide employed as a pharmaceutical additive in engineering customized drug or gene carriers with an improved safety profile. Its triple helical structure containing hydrogen bonding offers more extraordinary binding sites for the attachments of dectin-1 receptors and polynucleotide sequences (poly(dA)). Hence, the diseases expressing dectin-1 receptors can be specifically targeted through so-designed LNT-engineered drug carriers. Gene delivery using poly(dA)-s-LNT complexes and composites has exhibited greater targetability and specificity. The achievement of such gene applications is assessed through the pH and redox potential of the extracellular cell membrane. The steric hindrance-acquiring behavior of LNT shows promise as a system stabilizer in drug carrier engineering. LNT shows viscoelastic gelling behavior temperature-dependently and therefore needs to explore more to meet topical disease applications. The immunomodulatory and vaccine adjuvant properties of LNT help in mitigating viral infections too. This review highlights the new role of LNT as a novel biomaterial, particularly in drug delivery and gene delivery applications. In addition, its importance in achieving various biomedical applications is also discussed.
Topics: Lentinan; Gene Transfer Techniques; Genetic Therapy; Drug Carriers
PubMed: 36863692
DOI: 10.1016/j.jconrel.2023.02.034 -
Surgical Oncology Mar 2015It has been shown that chemotherapy has limited antitumor activity against advanced urothelial bladder cancer (UBC). Consequently, there is an urgent need to develop... (Comparative Study)
Comparative Study Review
It has been shown that chemotherapy has limited antitumor activity against advanced urothelial bladder cancer (UBC). Consequently, there is an urgent need to develop effective therapeutic methods for patients with advanced UBC. In the present study, the inhibitory effects of lentinan alone, gemcitabine alone, or lentinan combined with gemcitabine on the proliferation of the UBC cell line, T24, were investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, annexin V fluorescein isothiocyanate/propidium iodide staining, and flow cytometry were used to determine the proliferation and apoptosis of T24 cells in each treatment group. Survival-related protein expression was analyzed by western blotting. Increased concentrations of lentinan, or lentinan combined with gemcitabine, positively correlated with decreased T24 cell proliferation. Lentinan combined with gemcitabine chemotherapy significantly inhibited UBC cell proliferation. Gemcitabine has the ability to induce T24 cell apoptosis, and this effect is enhanced when it is combined with lentinan.
Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Line, Tumor; Deoxycytidine; Enzyme-Linked Immunosorbent Assay; Humans; Lentinan; Urinary Bladder Neoplasms; Urothelium; Gemcitabine
PubMed: 25434982
DOI: 10.1016/j.suronc.2014.11.002 -
Journal of Cancer Research and Clinical... Nov 2018Lentinan is a polysaccharide extracted from Shiitake mushrooms that have been used to improve general health for thousands of years in Asia. Lentinan injection is a... (Review)
Review
PURPOSE
Lentinan is a polysaccharide extracted from Shiitake mushrooms that have been used to improve general health for thousands of years in Asia. Lentinan injection is a clinically approved drug in several countries in Asia. The purpose of this study is to review the structure, preclinical and clinical studies, and molecular mechanisms of lentinan. Most importantly, the clinical effectiveness of lentinan as an adjuvant therapeutic drug in treating patients with lung cancer in China during the past 12 years is analyzed statistically.
METHODS
We carried out literature search of randomized controlled trials (RCTs) published from 2004 to 2016 based on CNKI (China National Knowledge Infrastructure), VIP (Chongqing VIP Chinese Scientific Journals Database) and Wanfang database, and 38 eligible RCTs of lentinan-associated lung cancer treatment were identified, containing 3,117 patients.
RESULTS
The structure and function relationship and underlying molecular mechanism of lentinan as an immunostimulant has been summarized. The mean value of overall response rate in treating lung cancer was increased from 43.3% of chemotherapy alone to 56.9% of lentinan plus chemotherapy [p < 0.001, 95% confidence interval (CI) 0.102-0.170]. Compared with chemotherapy alone, lentinan plus chemotherapy showed more efficacy in treating lung cancer (pooled RR 0.79, 95% CI 0.74-0.85) and no statistical heterogeneity was found among studies (I = 11%).
CONCLUSION
Clinical data presented in the past 12 years shows that lentinan is effective not only in improving quality of life, but also in promoting the efficacy of chemotherapy during lung cancer treatment.
Topics: Adjuvants, Immunologic; Asian People; China; Humans; Lentinan; Lung; Lung Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30043277
DOI: 10.1007/s00432-018-2718-1 -
European Journal of Medical Research Jan 2024Shiitake 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... (Review)
Review
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.
Topics: Humans; Lentinan; Stomach Neoplasms; Lung Neoplasms; Treatment Outcome; Prognosis
PubMed: 38172925
DOI: 10.1186/s40001-023-01585-7 -
Progress in Molecular Biology and... 2019Lentinula edodes has been used to improve general health for thousands of years in Asia. It is the second largest cultivated and the most popular edible mushroom in the... (Review)
Review
Lentinula edodes has been used to improve general health for thousands of years in Asia. It is the second largest cultivated and the most popular edible mushroom in the world known as "Xianggu" in China and "Shiitake" in Japan. Lentinan is a polysaccharide extracted from Lentinula edodes. β-Glucan is the major bioactive component in lentinan with immunostimulatory effect. The antitumor property of lentinan was reported in 1960s. Biochemical studies indicate that immunocytes can be activated by lentinan through multiple signaling pathways, such as TLR4/Dectin1-MAPK and Syk-PKC-NFκB pathways. Though it has been approved as an adjuvant therapeutic drug both in China and Japan for treating cancers since 1980s, a systematic review of clinical studies of lentinan has not been conducted elaborately. In this review, over 9474 reported lentinan-associated cancer treatment cases are evaluated and summarized from 135 independent studies in China during the past 12 years (2004-2016) based on CNKI (China National Knowledge Infrastructure), VIP (Chongqing VIP Chinese Scientific Journals Database) and Wanfang database. The 9474 reported lentinan-associated cancer treatment cases include lung cancer (3469 cases), gastric cancer (3039 cases), colorectal cancer (1646 cases), ovarian cancer (183 cases), cervical cancer (130 cases), Non-Hodgkin lymphoma (70 cases), pancreatic cancer (15 cases), cardiac cancer (15 cases), nasopharyngeal cancer (14 cases), duodenal cancer (1 case) and 110 cancer cases with no classifying patient information. Overall clinical data show solid effect of lentinan on improving the quality of life and on promoting the efficacy of chemotherapy and radiation therapy during cancer treatment.
Topics: Adjuvants, Pharmaceutic; Agaricales; China; Clinical Trials as Topic; Humans; Immunologic Factors; Lentinan; Neoplasms
PubMed: 31030752
DOI: 10.1016/bs.pmbts.2019.02.013 -
Phytotherapy Research : PTR Sep 2023Lentinan, a natural drug with wide-ranging pharmacological activities, can regulate autophagy-the process through which Schwann cells (SCs) eliminate myelin fragments...
Lentinan, a natural drug with wide-ranging pharmacological activities, can regulate autophagy-the process through which Schwann cells (SCs) eliminate myelin fragments after peripheral nerve injury (PNI). However, the effect of lentinan after PNI and the role of accelerated myelin debris removal via autophagy in this process are unclear. This study examined the effect of lentinan on rat sciatic nerve repair following crush injury and the underlying mechanisms. After the successful establishment of the sciatic nerve compression injury model, group-specific treatments were performed. The treatment group received 20 mg/kg lentinan via intraperitoneal injection, while the model group was treated with normal saline. The recovery in each group was then evaluated. Further, a rat SC line (RSC96) was cultured in medium with/without lentinan after supplementation with homogenous myelin fractions to evaluate the removal of myelin particles. Our results showed that lentinan promotes autophagic flux in vivo via the AMPK/mTOR signaling pathway, accelerates the clearance of myelin debris by SCs, and inhibits neuronal apoptosis, thereby promoting neurological recovery. Similarly, in vitro experiments showed that lentinan promotes the phagocytosis of myelin debris by SCs. In conclusion, our results suggest that lentinan primarily promotes nerve regeneration by accelerating the autophagic clearance of myelin debris in SCs, and this process is likely regulated by the AMPK/mTOR signaling pathway. Therefore, this study provides compelling evidence that lentinan may be a cost-effective and natural treatment agent for PNI.
Topics: Rats; Animals; Myelin Sheath; Lentinan; Peripheral Nerve Injuries; AMP-Activated Protein Kinases; Autophagy; Sciatic Nerve; TOR Serine-Threonine Kinases
PubMed: 37165703
DOI: 10.1002/ptr.7862 -
Molecular and Cellular Biochemistry Feb 2022Inflammatory responses change several aspects of malignancies such as proliferation, survival, angiogenesis, and metastasis and lead to tumor progression. Lung cancer is...
Inflammatory responses change several aspects of malignancies such as proliferation, survival, angiogenesis, and metastasis and lead to tumor progression. Lung cancer is the leading type of cancer worldwide and cancer-related inflammatory mediators challenge the successful treatments. Lentinan, a polysaccharide derived from Lentinula edodes, has shown anti-inflammatory characteristics in colitis and has been approved as an adjuvant therapy for cancer treatment. In the present study, we explored the mechanism underlying anti-inflammatory function of Lentinan in lung cancer cells. We showed that Lentinan reduced the inflammatory cytokines IL-6 and IL-1β in LPS-stimulated A549 cells at the concentrations much lower than the IC. Lentinan failed to alter the NLRP3 expression profile at transcriptional and translational levels. However, it showed a huge inhibition of caspase-1 activity. Lentinan downregulated the expression of IL-6 and IL-1β at the mRNA level. We also showed that Lentinan altered the oxidative status of the cells by increasing the intracellular ROS content and attenuating the activity of GPx4, the key player in the anti-oxidative defense system. Lentinan-induced ROS generation was associated with caspase-3 activation and induction of DNA breaks. This alteration was also associated with mitochondrial membrane depolarization shown by TMRE staining. Using recombinant caspase-1, we showed that Lentinan did not directly target caspase-1 but it led to caspase-1 inhibition. In conclusion, cytotoxicity and anti-inflammatory functions are separated by the dose of Lentinan. Lentinan increased the ROS and mitochondrial dysfunction in a level that is insufficient to induce cell death, but is sufficient to regulate the NLRP3 activation.
Topics: A549 Cells; Anti-Inflammatory Agents; Humans; Inflammation; Lentinan; Lung Neoplasms; Neoplasm Proteins; Oxidative Stress
PubMed: 34783966
DOI: 10.1007/s11010-021-04293-0 -
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 -
Scientific Reports Nov 2022Gut microbiota dysbiosis is already a global problem after antibiotic overuse. This study was to investigate the therapeutic effect of lentinan and the mechanism of...
Gut microbiota dysbiosis is already a global problem after antibiotic overuse. This study was to investigate the therapeutic effect of lentinan and the mechanism of recovery of intestinal inflammation on broad-spectrum antibiotic-driven gut microbial dysbiosis in mice. Gut microbiota was elucidated by the Illumina MiSeq platform. Gas chromatography/mass spectrometry was used to investigate short-chain fatty acid content. Colon histology, expression of tight-junction associated proteins and pro-inflammatory cytokines levels were evaluated. The results showed that the gut microbiota of diversity and richness were reduced and various taxonomic levels of the gut microbiota were perturbed after antibiotics gavage. The abundance of Firmicutes and Bacteroidetes shifted to Proteobacteria and increased the relative abundance of harmful microbiota (Parabacteroides and Klebsiella) post-antibiotics, whereas lentinan administration reversed the dysbiosis and increased beneficial microbiota, including S24-7, Lactobacillus, Oscillospira, Ruminococcus and Allobaculum. The concentrations of propionic acid and butyric acid were significantly increased by treatment with lentinan. And lentinan improved colon tissue morphology and reduced pro-inflammatory cytokines via altering NF-κB signaling pathway in antibiotic-driven gut microbial dysbiosis mice. Taken together, the results proved that lentinan can be used as a prebiotic and the result provided a theoretical basis for improving the clinical treatment of broad-spectrum antibiotics side effects.
Topics: Mice; Animals; Dysbiosis; Lentinan; Anti-Bacterial Agents; Firmicutes; Bacteroidetes; Tight Junction Proteins; Cytokines; Inflammation; Mice, Inbred C57BL
PubMed: 36380080
DOI: 10.1038/s41598-022-23469-2