Ganoderma lucidum polysaccharides reduce the severity of acute liver injury by improving the diversity and function of the gut microbiota.

Acute liver injury (ALI) is an abnormal liver function caused by oxidative stress, inflammation and other mechanisms.The interaction between intestine and liver plays an important role in ALI, and natural polysaccharides can participate in the regulation of ALI by regulating the composition of intestinal flora. In this study, Ganoderma lucidum polysaccharide was used as the research object, and ICR mice were used to construct an acute liver injury model induced by carbon tetrachloride (CCl4). 16S rRNA sequencing technology was used to analyze the flora structure abundance and detect the changes of intestinal flora. The effective reading of 8 samples was obtained by 16S rRNA sequencing technology, and a total of 1233 samples were obtained. The results of alpha diversity analysis showed that the sequencing depth was sufficient, the abundance of species in the samples was high and the distribution was uniform, and the sequencing data of the samples was reasonable. Nine species with significant differences were screened out by abundence analysis of intestinal flora structure at genus level. Beta diversity analysis showed that species composition was different between the model group and the treatment group. Ganoderma lucidum polysaccharide can maintain the integrity of mucosal barrier by promoting the proliferation of intestinal epithelial cells and anti-oxidative stress injury, thereby improving the intestinal mucosal inflammation of mice, regulating intestinal flora, and effectively alleviating CCl4-induced acute liver injury.

Electrochemiluminescence assay for the impact of Ganoderma lucidum polysaccharides on resisting arsenic-induced apoptosis.

Ganoderma lucidum (G. lucidum) is a traditional edible fungus with strong medicinal value. G. lucidum polysaccharides (GLP) encapsulate many of the key beneficial properties of this species, providing a valuable tool for the treatment of a range of diseases. The present study was developed to explore the protective benefits of GLP treatment in the context of arsenic poisoning. Through microscopy and flow cytometry experiments, NaAsO2 was found to induce rat tracheal epithelial (RTE) cell apoptosis, together with reductions in cell surface epidermal growth factor receptor (EGFR) expression. GLP treatment, however, was able to reduce apoptosis rates and elevate the expression of EGFR relative to NaAsO2-treated cells. GLP extracts (50, 100, 200 mg·mL-1) prepared from four types of G. lucidum were administered to RTE cells damaged with arsenic, revealing limited differences in position resistance among these varieties. This work provides reference for the pharmaceutical and medical research of G. lucidum.

Ganoderma lucidum Polysaccharides Ameliorate Acetaminophen-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Apoptosis along the Nrf2 Pathway.

The excessive employment of acetaminophen (APAP) is capable of generating oxidative stress and apoptosis, which ultimately result in acute liver injury (ALI). Ganoderma lucidum polysaccharides (GLPs) exhibit hepatoprotective activity, yet the protective impact and potential mechanism of GLPs in relation to APAP-induced ALI remain ambiguous. The intention of this research was to scrutinize the effect of GLPs on APAP-induced ALI and to shed light on their potential mechanism. The results demonstrated that GLPs were capable of notably alleviating the oxidative stress triggered by APAP, as shown through a significant drop in the liver index, the activities of serum ALT and AST, and the amounts of ROS and MDA in liver tissue, along with an increase in the levels of SOD, GSH, and GSH-Px. Within these, the hepatoprotective activity at the high dose was the most conspicuous, and its therapeutic efficacy surpassed that of the positive drug (bifendate). The results of histopathological staining (HE) and apoptosis staining (TUNEL) indicated that GLPs could remarkably inhibit the necrosis of hepatocytes, the permeation of inflammatory cells, and the occurrence of apoptosis induced by APAP. Moreover, Western blot analysis manifested that GLPs enhanced the manifestation of Nrf2 and its subsequent HO-1, GCLC, and NQO1 proteins within the Nrf2 pathway. The results of qPCR also indicated that GLPs augmented the expression of antioxidant genes Nrf2, HO-1, GCLC, and NQO1. The results reveal that GLPs are able to set off the Nrf2 signaling path and attenuate ALI-related oxidative stress and apoptosis, which is a potential natural medicine for the therapy of APAP-induced liver injury.

Electrochemiluminescent evaluation of GLUT4 expression in rat adipocytes induced by Ganoderma lucidum polysaccharides.

Glucose transporter 4 (GLUT4) directly facilitates cellular uptake of glucose and plays a crucial role in mammalian adipose tissue glucose metabolism. In this work, we constructed a cytosensor for sensitive electrochemiluminescence (ECL) detection of GLUT4 in rat adipocytes (RA cells). A carbon nanotube sponge (CNTSP) was selected to fabricate a permeable electrode to overcome the steric hindrance of cells on the electrode. The expression of GLUT4 after treatment with Ganoderma lucidum polysaccharide (GLP) was assessed by analyzing the luminescence emitted from cell-surface ECL probes. Our preliminary results suggest that GLP promote the expression of GLUT4, thereby enhancing the uptake of the fluorescent glucose 2-NBDG. Treatment with GLP affected GLUT4 expression in RA cells in a dose-dependent manner. Additionally, the ECL cytosensor contributes to the development of ECL imaging of receptors on the cell surface for clinical drug evaluation.

Novel therapeutic role of Ganoderma Polysaccharides in a septic mouse model - The key role of macrophages.

Ganoderma lucidum polysaccharides (G. PS) have been recognized for their immune-modulating properties. In this study, we investigated the impact of G. PS in a sepsis mouse model, exploring its effects on survival, inflammatory cytokines, Treg cell differentiation, bacterial load, organ dysfunction, and related pathways. We also probed the role of macrophages through chlorphosphon-liposome pretreatment. Using the cecal ligation and puncture (CLP) model, we categorized mice into normal, PBS, and G. PS injection groups. G. PS significantly enhanced septic mouse survival, regulated inflammatory cytokines (TNF-α, IL-17A, IL-6, IL-10), and promoted CD4+Foxp3+ Treg cell differentiation in spleens. Additionally, G. PS reduced bacterial load, mitigated organ damage, and suppressed the NF-κB pathway. In vitro, G. PS facilitated CD4+ T cell differentiation into Treg cells via the p-STAT5 pathway. Chlorphosphon-liposome pretreatment heightened septic mortality, bacterial load, biochemical markers, and organ damage, emphasizing macrophages' involvement. G. PS demonstrated significant protective effects in septic mice by modulating inflammatory responses, enhancing Treg cell differentiation, diminishing bacterial load, and inhibiting inflammatory pathways. These findings illuminate the therapeutic potential of G. PS in sepsis treatment.

A review of Ganoderma lucidum polysaccharides: Health benefit, structure-activity relationship, modification, and nanoparticle encapsulation.

Ganoderma lucidum polysaccharides possess unique functional properties. Various processing technologies have been used to produce and modify G. lucidum polysaccharides to improve their yield and utilization. In this review, the structure and health benefits were summarized, and the factors that may affect the quality of G. lucidum polysaccharides were discussed, including the use of chemical modifications such as sulfation, carboxymethylation, and selenization. Those modifications improved the physicochemical characteristics and utilization of G. lucidum polysaccharides, and made them more stable that could be used as functional biomaterials to encapsulate active substances. Ultimate, G. lucidum polysaccharide-based nanoparticles were designed to deliver various functional ingredients to achieve better health-promoting effects. Overall, this review presents an in-depth summary of current modification strategies and offers new insights into the effective processing techniques to develop G. lucidum polysaccharide-rich functional foods or nutraceuticals.

Ganoderma lucidum polysaccharide peptides GL-PPSQ2 alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps.

Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. ex Fr.) Karst with anti-inflammatory, antioxidant, and immunoregulatory activities. We extracted and characterized a novel GLPP, named GL-PPSQ2, which were found to have 18 amino acids and 48 proteins, connected by O-glycosidic bonds. The monosaccharide composition of GL-PPSQ2 was determined to be composed of fucose, mannose, galactose and glucose with a molar ratio of 1:1.45:2.37:16.46. By using asymmetric field-flow separation technique, GL-PPSQ2 were found to have a highly branched structure. Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ2 significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. Meanwhile, GL-PPSQ2 significantly promoted intestinal tight junction, decreased inflammation, oxidative stress and cellular apoptosis in the ileum and lung. Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. GL-PPSQ2 remarkedly inhibited NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression. GL-PPSQ2 could alleviate intestinal I/R and its induced lung injury via inhibiting oxidative stress, inflammation, cellular apoptosis, and cytotoxic NETs formation. This study proves that GL-PPSQ2 is a novel drug candidate for preventing and treating intestinal I/R injury.

Multiple Fingerprint-Activity Relationship Assessment of Immunomodulatory Polysaccharides from Ganoderma lucidum Based on Chemometric Methods.

Polysaccharides with molecular weights ranging from 1.75 × 103 to 1.14 × 104 g/mol were obtained from the fruit bodies of Ganoderma lucidum. The multiple fingerprints and macrophage immunostimulatory activity of these fractions were analyzed as well as the fingerprint-activity relationship. The correlation analysis of molecular weight and immune activity demonstrated that polysaccharides with molecular weights of 4.27 × 103~5.27 × 103 and 1 × 104~1.14 × 104 g/mol were the main active fractions. Moreover, the results showed that galactose, mannose, and glucuronic acid were positively related to immunostimulatory activity. Additionally, partial least-squares regression and grey correlation degree analyses indicated that three peaks (P2, P3, P8) in the oligosaccharide fragment fingerprint significantly affected the immune activity of the polysaccharides. Hence, these ingredients associated with activity could be considered as markers to assess Ganoderma lucidum polysaccharides and their related products, and the study also provides a reference for research on the spectrum-effect relationship of polysaccharides in the future.

Potential Anti-Rheumatoid Arthritis Activities and Mechanisms of Ganoderma lucidum Polysaccharides.

Rheumatoid arthritis (RA) is a chronic and autoimmune disease characterized by inflammation, autoimmune dysfunction, and cartilage and bone destruction. In this review, we summarized the available reports on the protective effects of Ganoderma lucidum polysaccharides (GLP) on RA in terms of anti-inflammatory, immunomodulatory, anti-angiogenic and osteoprotective effects. Firstly, GLP inhibits RA synovial fibroblast (RASF) proliferation and migration, modulates pro- and anti-inflammatory cytokines and reduces synovial inflammation. Secondly, GLP regulates the proliferation and differentiation of antigen-presenting cells such as dendritic cells, inhibits phagocytosis by mononuclear macrophages and nature killer (NK) cells and regulates the ratio of M1, M2 and related inflammatory cytokines. In addition, GLP produced activities in balancing humoral and cellular immunity, such as regulating immunoglobulin production, modulating T and B lymphocyte proliferative responses and cytokine release, exhibiting immunomodulatory effects. Thirdly, GLP inhibits angiogenesis through the direct inhibition of vascular endothelial cell proliferation and induction of cell death and the indirect inhibition of vascular endothelial growth factor (VEGF) production in the cells. Finally, GLP can inhibit the production of matrix metalloproteinases and promote osteoblast formation, exerting protective effects on bone and articular cartilage. It is suggested that GLP may be a promising agent for the treatment of RA.

Ganoderma lucidum polysaccharides improve lipid metabolism against high-fat diet-induced dyslipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: As a kind of traditional medicinal fungi, Ganoderma lucidum has been employed as folk medicine in China against multiple metabolic diseases on account of its superior bioactivities. Recently, accumulated reports have investigated the protective effects of G. lucidum polysaccharides (GLP) on ameliorating dyslipidemia. However, the specific mechanism by which GLP improves dyslipidemia is not completely clear. AIMS OF THE STUDY: This study aimed to investigate the protective effects of GLP on high-fatdiet-induced hyperlipidemia and exploring its underlying mechanism. MATERIALS AND METHODS: The GLP was successfully obtained from G. lucidum mycelium. The mice were conducted with high-fatdiet to establish the hyperlipidemia model. Biochemical determination, histological analysis, immunofluorescence, western blot and real-time qPCR were used to assess the alterations in high-fatdiet-treated mice after the GLP intervention. RESULTS: It was found that GLP administration significantly decreased body weight gain and the excessive lipid levels, and partly alleviated tissue injury. Oxidative stress and inflammations were efficiently ameliorated after the treatment of GLP by activing Nrf2-Keap1 and inhibiting NF-κB signal pathways. GLP promoted cholesterol reverse transport by LXRα-ABCA1/ABCG1 signaling, increased the expressions of CYP7A1 and CYP27A1 responsible for bile acids production, accompanied by inhibition of intestinal FXR-FGF15 levels. Besides, multiple target proteins involved in lipid metabolism were also significantly modulated under the intervention of GLP. CONCLUSION: Taken together, our results suggested that GLP showed potential lipid-lowering effects and its possible mechanism was involved in improving oxidative stress and inflammation response, modulating bile acids synthesis and lipid regulatory factors, and promoting reverse cholesterol transport, thereby suggesting that GLP may possibly used as a dietary supplement or medication for the adjuvant therapy for hyperlipidemia.

A new strategy to improve Ganoderma polysaccharides production by symbiotic fungi elicitors through activating the biosynthetic pathway.

Ganoderma lucidum polysaccharides (GLP) attract growing attention due to their remarkable bioactivities, but the low content in raw materials remains a bottleneck severely restricting their application. We previously found a higher polysaccharides accumulation in Ganoderma lucidum cultured in continuous cropping soil, and soil symbiotic fungi are presumed as the key among many factors. Herein, 33 symbiotic fungi were isolated from the soil, and fungal elicitors were prepared to investigate their biotic eliciting effect on GLP biosynthesis. Most elicitors were found to significantly improve GLP production, among which the NO.16 molecularly identified as Penicillium citrinum, exhibited the optimum eliciting effect with GLP yield increasing by 3.4 times. Differences in the biosynthetic pathway genes expressions and the monosaccharide components of GLP were further analyzed. The transcriptions of the main genes of GLP biosynthetic pathway were up-regulated under PCE treatments, suggesting it improves GLP production by activating transcriptions of the biosynthetic pathway genes. Moreover, PCE eliciting significantly altered the monosaccharide compositions of GLP with Gal, Man, GalA, GlcA, and Fuc increasing by 8.17 %, 5.68 %, 5.41 %, 2.66 %, and 1.51 % respectively, but Glc decreased by 23.43 %, which may result in the activity change. It can serve as a new strategy to improve GLP production.

Immune-enhancing effects of Astragalus polysaccharides and Ganoderma lucidum polysaccharides on Vibrio harveyi flgJ DNA vaccine in grouper.

Astragalus polysaccharides (APS) and Ganoderma lucidum polysaccharides (GLP) have been shown to possess strong immunoregulatory properties in aquatic animals. In this study, the fragment containing Vibrio harveyi flgJ gene was ligated into pcDNA3.1(+) vector and pcDNA3.1(+)-flgJ was constructed as DNA vaccine. APS and GLP were used as DNA vaccine adjuvants to evaluate the immunoregulatory effect by intramuscular injection to pearl gentian grouper (♀Epinephelus fuscoguttatus × â™‚E. lanceolatus). The results showed that pcDNA3.1(+)-flgJ combined with APS or GLP could significantly up-regulate the innate and adaptive immune response in fish, including serum-specific antibody titres, catalase and lysozyme activities. At the same time, DNA vaccine combined with APS or GLP significantly up-regulated the expression levels of CD8α, IgM, IL-1ß, MHC-Iα, MyD88 and TLR3 genes in thymus, head kidney, spleen and liver of pearl gentian grouper in comparison with those of the pFlgJ group. After 42 days post-vaccination, V. harveyi was used to challenge pearl gentian grouper by intraperitoneal injection. The relative percentage of survival (RPS) of pFlgJ, pFlgJ +APS, pFlgJ +GLP and pFlgJ+APS+GLP groups were 69%, 81%, 77% and 88%, respectively. These results suggested APS and GLP were potential adjuvants for DNA vaccine against V. harveyi infection in pearl gentian grouper.

Structural characterization and hepatoprotective activity of an acidic polysaccharide from Ganoderma lucidum.

In this study, Ganoderma lucidum crude polysaccharide (GLP) was found to have protective effect on liver damage in mice caused by restraint stress through improving oxidative status. Two polysaccharides, including a neutral ß-glucan (GLPB2) and an acidic ß-glucan (GLPC2) were purified from GLP through anion-exchange chromatography (AEC) combined with gel permeation. GLPC2, with an average molecular weight of 20.56 kDa, exhibited stronger hepatoprotective effect against H2O2-induced liver injury in HepG2 cells compared to GLPB2. Glycosidic residues and NMR analysis comprehensively revealed that GLPC2 contained d-Glcp-(1→, →3)-d-Glcp-(1→, →4)-d-Glcp-(1→, →6)-d-Glcp-(1→, →3, 6)-d-Glcp-(1 â†’ and â†’ 4)-d-GlcpA-(1 â†’ . AEC can be an effective technique for separating ß-glucans into neutral and acidic fractions by different ionic strength buffer. The findings provided a theoretical basis for the potential application of G. lucidum polysaccharides as a hepatoprotective in food and pharmaceutical industry.

Gastroprotective Effects of Ganoderma lucidum Polysaccharides with Different Molecular Weights on Ethanol-Induced Acute Gastric Injury in Rats.

Ganoderma lucidum is known as a medicine food homology that can ameliorate gastrointestinal diseases. To evaluate the gastroprotective effects on different Ganoderma lucidum polysaccharides (GLPs), GLP was separated into three parts with different molecular weights using 100 kDa, 10 kDa, and 1 kDa membranes. The mitigation effects of different GLPs on ethanol-induced acute gastric injury were observed in rats. After pretreatment with different GLPs, especially GLP above 10 kDa, the symptoms of gastric mucosal congestion and bleeding were improved; serum myeloperoxidase, inflammatory factor, and histamine were decreased; and antioxidant activity and defense factors (NO and EGF) were increased. Results showed that GLP with different molecular weights had a dose-dependent effect in alleviating alcohol-induced gastric injury. The underlying mechanism might be related to regulating anti-oxidation, promoting the release of related defense factors, reducing inflammatory factors, and reducing the level of histamine in serum. The current work indicated that GLPs above 10 kDa could be applied as natural resources for producing new functional foods to prevent gastric injury induced by ethanol.

The Pharmacological Rationales and Molecular Mechanisms of Ganoderma lucidum Polysaccharides for the Therapeutic Applications of Multiple Diseases.

As a versatile Chinese herb, Ganoderma lucidum (Leyss. ex Fr.) Karst (G. lucidum) has been applied to treat multiple diseases in clinics and improve the quality of life of patients. Among all of its extracts, the main bioactive components are G. lucidum polysaccharides (GLPs), which possess many therapeutic effects, such as antitumor, immunoregulatory, anti-oxidant, antidiabetic, antibacterial, and antifungal effects and neuroprotection activities. This review briefly summarized the recent studies of the pharmacological rationales of GLPs and their underlying molecular signaling transmission mechanisms in treating diseases. Until now, the clear mechanisms of GLPs for treating diseases have not been reported. In this review, we used the keywords of "Ganoderma lucidum polysaccharides" and "tumor" to search in PubMed (years of 1992-2020), then screened and obtained 160 targets of antitumor activities in the literatures. The network pharmacology and mechanism framework were employed in this study as powerful approaches to systematically analyze the complicated potential antitumor mechanisms and targets of GLPs in cancer. We then found that there are 69 targets and 21 network pathways in "Pathways in cancer". Besides, we summarized the effects of GLPs and the models and methods used in the research of GLPs. In conclusion, GLPs have been studied extensively, but more in-depth research is still needed to determine the exact mechanisms and pathways. Therefore, this review might provide new insights into the vital targets and pathways for researchers to study the pharmacological mechanisms of GLPs for the treatment of diseases.

Ganoderma lucidum polysaccharides protect against sepsis-induced cardiac dysfunction by activating SIRT1.

OBJECTIVE: To investigate whether the silent information regulator 1 (SIRT1) was involved in the protective effects of Ganoderma lucidum polysaccharides (GLP) against sepsis-induced cardiac dysfunction. METHODS: Lipopolysaccharide (LPS)-induced sepsis model was constructed in C57/BL6J mice. Mice were randomly divided into LPS + GLP + EX-527, LPS + EX-527, LPS + GLP, LPS or control group). The levels of serum inflammatory factor markers were examined by ELISA. H&E staining was performed to assess the inflammation. TUNEL staining and bromodeoxyuridine staining were used to observe cell apoptosis and proliferation, respectively. Expression of apoptosis and proliferation-related proteins was detected by western blot. KEY FINDINGS: GLP treatment could significantly increase the expression of SIRT1, reduce levels of serum inflammatory factors (TNF-α, IL-1α and IL-6) and inflammatory cells in mice heart tissue of sepsis models (all Ps < 0.01). Compared with LPS group, GLP treatment inhibited apoptosis and promoted proliferation of myocardial tissues (all Ps < 0.01). Besides, EX-527 (SIRT1 inhibitor) treatment could partially reverse the protective effects of GLP against sepsis-induced cardiac dysfunction (all Ps < 0.01). CONCLUSIONS: GLP might play a protective role in sepsis-induced cardiac dysfunction through regulating inflammatory response, apoptosis and proliferation via activating SIRT1. Therefore, GLP is expected to be a probable novel strategy for treatment of sepsis.

[Ganoderma lucidum polysaccharides promote T lymphocyte infiltration into tumor by regulating expression of ICAM-1 in endothelial cells].

Polysaccharide is among the main active components of Ganoderma lucidum for tumor prevention and treatment. Howe-ver, it remains unclear whether it has synergy with tumor immunotherapy. This study evaluated the effect of G. lucidum polysaccharides(GLP) on the infiltration of T lymphocytes into tumor and the underlying mechanism, in order to provide a reference for its application in tumor immunotherapy. GLP were prepared by water extraction and alcohol precipitation combined with Sevag method and then given(intraperitoneal injection) to the mice bearing B16-F10 cells at 25, 50 and 100 mg kg~(-1), respectively, to evaluate the effect on tumor growth. The infiltration of CD3~+ and CD8~+ T cells and the expression of intercellular cell adhesion molecule-1(ICAM-1) in tumor were detected by immunohistochemistry. EA.hy926 cells were treated with 50, 100 and 200 µg·mL~(-1) GLP, and the expression of ICAM-1 was determined by Western blot. The adhesion of EA.hy926 cells treated with GLP was measured with fluorescence-labeled Jurkat cells. To analyze the mechanism based on NF-κB pathway, this study determined the protein levels of nuclear factor kappa-B(NF-κB) p65, alpha inhibitor of NF-κB(IκBα), p-NF-κB p65 and p-IκBα by Western blot. The results showed that GLP can significantly inhibit the tumor growth in mice bearing B16-F10 cells, promote the infiltration of CD3~+ and CD8~+ T cells in tumor, and increase the expression of ICAM-1 in tumor. Meanwhile, GLP could also enhance the expression of ICAM-1 in EA.hy926 cells, thus strengthen the adhesion to Jurkat cells, induce phosphorylation and protein degradation of IκBα, and raise the expression and phosphorylation level of NF-κB p65. These results suggested that GLP could promote the expression of ICAM-1 through NF-κB pathway and further enhance the infiltration of T lymphocytes into tumor, thereby inhibiting tumor growth. This study lays a foundation for the further application of GLP in tumor immunotherapy.

Self-Assembled pH-Sensitive Nanoparticles Based on Ganoderma lucidum Polysaccharide-Methotrexate Conjugates for the Co-delivery of Anti-tumor Drugs.

In tumor therapy, polymer nanoparticles are ideal drug delivery materials because they can mask the disadvantages of anti-tumor drugs such as poor solubility in water, high toxicity, and side effects. However, most polymer-based nanoparticles do not themselves have anti-tumor properties. Herein, a novel pH-sensitive nanoparticle drug delivery system based on Ganoderma lucidum polysaccharides (GLPs), which have demonstrated anti-tumor activities, was designed to enable the delivery of methotrexate (MTX) and 10-hydroxycamptothecin (HCPT) to tumor cells, where they could exert synergistic anti-tumor effects. The prepared nanoparticles were irregularly spherical in shape with a uniform particle size of ∼190 nm, and they exhibited a high drug-loading capacity (MTX 21.5% and HCPT 22.6%) and excellent biocompatibility. Moreover, the loaded MTX and HCPT units were rapidly released under acidic conditions within the tumor cells while remaining stable under normal physiological conditions. Meanwhile, compared to free MTX and HCPT, the GLP-APBA-MTX/HCPT nanoparticles presented exhibited better tumor suppressive effects and fewer side effects in vivo, which indicates that they may be an effective anti-tumor treatment strategy.

Ganoderma Lucidum Polysaccharides Enhance the Abscopal Effect of Photothermal Therapy in Hepatoma-Bearing Mice Through Immunomodulatory, Anti-Proliferative, Pro-Apoptotic and Anti-Angiogenic.

Hepatocellular carcinoma is a malignant tumor with high morbidity and mortality, a highly effective treatment with low side effects and tolerance is needed. Photothermal immunotherapy is a promising treatment combining photothermal therapy (PTT) and immunotherapy. PTT induces the release of tumor-associated antigens by ablating tumor and Ganoderma lucidum polysaccharides (GLP) enhance the antitumor immunity. Results showed that Indocyanine Green (ICG) was successfully encapsulated into SF-Gel. ICG could convert light to heat and SF-Gel accelerates the photothermal effect in vitro and in vivo. PTT based on ICG/ICG-SF-Gel inhibited the growth of primary and distal tumors, GLP enhanced the inhibitory efficacy. ICG/ICG-SF-Gel-based PTT and GLP immunotherapy improved the survival time. ICG/ICG-SF-Gel-based PTT induces tumor necrosis and GLP enhanced the photothermal efficacy. ICG/ICG-SF-Gel-based PTT inhibited cell proliferation and angiogenesis, induced cell apoptosis, enhanced cellular immunity, and GLP enhanced these effects. In conclusion, GLP could enhance the abscopal effect of PTT in Hepatoma-bearing mice.

Ganoderma lucidum polysaccharides ameliorated depression-like behaviors in the chronic social defeat stress depression model via modulation of Dectin-1 and the innate immune system.

Major depressive disorder (MDD) is a prevalent, chronic, and recurrent disease. At least one-third of patients have treatment-resistant depression; therefore, there is an urgent need for novel drug development. Cumulative studies have suggested an inflammatory mechanism for the pathophysiology of MDD. Ganoderma lucidum polysaccharides (GLP) is an anti-inflammatory and immunomodulatory agent. Here, we found that an injection of GLP led to a rapid and robust antidepressant effect after 60 min in the tail suspension test. This antidepressant effect remained after 5 days of treatment with GLP in the forced swim test. Unlike psychostimulants, GLP did not show a hyperactive effect in the open field test. After 60 min or 5 days of treatment, GLP exhibited an antidepressant effect in a chronic social defeat stress (CSDS) depression animal model. Moreover, after 5 days of treatment, GLP attenuated the expression of the proinflammatory cytokines IL-1ß and TNF-α, enhanced the expression of the anti-inflammatory cytokine IL-10 and the neurotrophic factor BDNF, and inhibited the activation of microglia and proliferation of astrocytes in the hippocampus of CSDS mice. In addition, after 5 days of treatment, GLP significantly enhanced GluA1 S845 phosphorylation as well as GluA1 and GluA2 expression levels in the hippocampus of CSDS mice. To determine whether the antidepressant effect was mediated by Dectin-1, we found that GLP treatment enhanced Dectin-1 expression in the hippocampus in CSDS mice, and the Dectin-1-specific inhibitor laminarin almost completely blocked the antidepressant effect of GLP. This study identified GLP, an agonist of Dectin-1, as a novel and rapid antidepressant with clinical potential and multiple beneficial mechanisms, particularly in regulating the neuroimmune system and, subsequently, AMPA receptor function.