Polysaccharide Peptide Research Articles

The Role of β-1.3/1.6-D-Glucan From Ganoderma lucidum Mycelium Extract in Ulcerative Colitis

Ulcerative colitis (UC) is an idiopathic inflammatory disease that affects the colon. Current pharmacological modalities to treat UC have various side effects; therefore, there is a demand to develop a new alternative medicine that can reduce side effects and increase drug efficacy. One candidate for alternative therapy is Polysaccharide Peptide which is extracted from Ganoderma lucidum mycelium. This Polysaccaharide has an active compound of Β-1,3/1,6-D-Glucan which has strong immunomodulatory and anti-inflammatory properties. Various studies have reported that Ganoderma lucidum polysaccharides can reduce inflammatory markers such as TNF-α, IFN-γ, and IL-17A, which is produced by colonic mucosal inflammation. In addition, β-1,3/1,6-D-Glucan has shown improvements in inflammatory parameters and intestinal immunological barrier function animal studies with artificial colitis and requires further research in humans before clinical applications.

Ganoderma lucidum polysaccharide peptide alleviates hyperuricemia by regulating adenosine deaminase and urate transporters.

Hyperuricemia (HUA) affects human health and is involved in the pathogenesis of common chronic diseases. Previous studies showed that Ganoderma lucidum extract lowered HUA in animals. However, the active ingredient and pharmacological mechanism of Ganoderma lucidum extract in the improvement of HUA are unknown. The purpose of this study was to determine the anti-HUA efficacy and related mechanism of Ganoderma lucidum polysaccharide peptide (GLPP) using a potassium oxonate (PO)-induced mouse model and an adenosine-induced cell model. The experimental results showed that blood uric acid (UA) was decreased up to 40.6% by GLPP in HUA mice in a dose-dependent manner. Additionally, GLPP significantly reduced UA production by inhibiting the hepatic and blood adenosine deaminase (ADA) activity and increased UA excretion by decreasing the expression of glucose transporter 9 (GLUT9) and increasing the expression of organic anion transporter 1 (OAT1) in kidney. The adenosine-induced cell model showed that the inhibitory effect of GLPP on ADA activity may be the main reason for the alleviation of HUA by GLPP. Furthermore, PO-induced renal histopathological damage was also alleviated by GLPP in a dose-dependent manner. The experimental results in this study indicated that GLPP exerted anti-HUA effects via regulating the UA production and excretion, suggesting that GLPP could be developed into a therapeutic agent for HUA.

Oral Presentation Award Winner: Polysaccharide Peptide of Ganoderma lucidum Reduces Endothelial Injury in Stable Angina and High-risk Patients.

Oral Presentation Award Winner: Polysaccharide Peptide of Ganoderma lucidum Reduces Endothelial Injury in Stable Angina and High-risk Patients.

Antimetastatic Effects of Ganoderma lucidum Polysaccharide Peptide on B16-F10-luc-G5 Melanoma Mice With Sleep Fragmentation.

Ganoderma lucidum (Lingzhi) polysaccharide peptide (GL-pp) is a component of the globally acknowledged traditional Chinese medicine Ganoderma lucidum; Ganoderma lucidum is known for its sedative, hypnotic, immune regulatory, antitumor, and other pharmacological effects. In recent years, sleep disorders have been linked to many diseases and human body disorders, including cancer. Some experimental studies in mice found that sleep fragmentation could promote tumor development and progression. However, effects on GL-pp on tumor metastasis under circumstances of sleep disorders have rarely been studied. Thus, in this study, we used mice with sleep fragmentation (SF) bearing B16-F10-luc-G5 melanoma tumors to investigate the effect of SF on melanoma metastasis. Furthermore, we investigated the antitumor and antimetastatic effects of GL-pp (80 mg/kg) in mice suffering from SF and bearing B16-F10-luc-G5. Then, whole proteomics was used to analyze the differences in protein expression in the lung tissue between SF mice bearing B16-F10-luc-G5 with and without GL-pp administration. High-throughput pyrosequencing of 16S rRNA was also used to analyze the impact of GL-pp on the gut microbiota composition in SF mice bearing B16-F10-luc-G5. Last, the effects of GL-pp on macrophage polarization and TNF-α serum levels were detected. Collectively, we found that SF significantly facilitated the B16-F10-luc-G5 melanoma tumor metastasis in mice, while GL-pp significantly reduced B16-F10-luc-G5 melanoma tumor metastasis under the condition of SF, in which proteomics and gut microbiota had been changed greatly.

Potent protective effects of polysaccharide peptide on vascular endothelium and cardiac remodelling in post myocardial infarction patients: A prospective double-blind randomized controlled trial

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Indonesia"s Ministry of Research and Technology/National Research and Innovation Agency grants Background Inflammation and oxidative stress contribute to endothelial dysfunction leading to progression of atherosclerosis and myocardial infarction (MI). Purpose To evaluate the effect of polysaccharide peptide of Ganoderma lucidum mycelium extracts (β-1,3/1,6-D-Glucan) as protective vascular endothelium and cardiac reverse remodelling in post MI. Methods This is a prospective, randomized double-blind clinical trial in 45 post MI patients. Treated group (TG) was given 3 divided dose of 540 mg β-1,3/1,6-D-Glucan daily for 90 days, and control group (CG) received placebo. Variable measured were EPC,CEC,IL-1,IL-6,TNF-α,hsCRP,NO,SOD,MDA and echocardiography parameters. Results β-1,3/1,6-D-Glucan administration significantly increased EPCs (P = 0.000), but not significantly reduced CECs (P = 0.069). Significant suppression was found in IL-1, IL-6 and TNF-α (all P < 0.05), but not in hsCRP (P = 0.064). TG exhibited significant elevation of NO (P = 0.02) and SOD (P = 0.023), and reduction of MDA (P = 0.001). TG revealed significant improvement of LVEF, LVMI, LVIDd, RWT, RWMA and LV diastolic dysfunction (all P < 0.05); but not in FS and TAPSE (P = 0.24, P = 0.20; respectively). Conclusions Polysaccharide peptide exhibits potent protective vascular endothelium and cardiac reverse remodelling in post MI patients, hence promising as add-on medication on top of standard medical regiment. Result comparison between study groupsVariableMeanPretestMean Difference Post-testP valuePolysaccharide peptide (β-1,3/1,6-D-Glucan)PlaceboVascular Endothelium BiomarkersCECsEPCs87.99 ± 76.7398.32 ± 44.52-48.01 ± 64.0714.90 ± 24.05-13.84 ± 58.67-17.65 ± 27.870.0690.000Oxidative Stress MarkersSODMDANitric Oxide2.93 ± 0.5419.68 ± 9.9737.98 ± 14.440.26 ± 0.74-5.52 ± 10.756.04 ± 9.27-0.23 ± 0.685.75 ± 10.29-0.62 ± 3.300.0230.0010.02Proinflammatory BiomarkershsCRPTNF-αIL-1IL-62512.90 ± 1332.11348.58 ± 85.0392.14 ± 29.62259.40 ± 125.52-6.78 ± 1099.60-44.98 ± 100.94-15.77 ± 27.06-29.63 ± 104.30-1.42 ± 795.35-1.34 ± 104.893.42 ± 33.1475.77 ± 130.830.0640.0060.0420.005Echocardiographic ParametersLVEFFSLVMITAPSELVIDdRWT57.20 ± 11.3930.85 ± 7.07114.07 ± 59.612.14 ± 0.354.86 ± 0.820.54 ± 0.352.30 ± 9.770.73 ± 7.59-4.55 ± 14.460.99 ± 0.49-0.49 ± 0.45-0.14 ± 0.29-2.08 ± 3.353.74 ± 9.2711.48 ± 23.94-0.17 ± 0.340.23 ± 0.430.03 ± 0.040.0080.2480.0430.2020.0000.017Abstract Figure. Comparison among pre- and post-treatment

Ganoderma lucidum Polysaccharide Peptide Reduce Inflammation and Oxidative Stress in Patient with Atrial Fibrillation

BACKGROUND: Atrial fibrillation (AF) could be triggered by inflammation and oxidative stress. Ganoderma lucidum has an active substance in the form of β-glucan that can reduce inflammatory process and oxidative stress in rats. The objective of this study was to evaluate the effect of Ganoderma lucidum polysaccharide peptide (GLPP) in paroxysmal AF subjects with parameters of anti-inflammatory antioxidant, electrocardiography and health-related quality of life (HRQoL).METHODS: A randomized closed-label clinical trial with pre- and post-test design was conducted. After AF subjects selection, the subjects were randomized, interviewed and veni-punctured to isolate blood plasma. AF Subjects were then treated with placebo or GLPP for 90 days. Post-test blood plasma was collected on the following day after the 90th day. Then anti-inflammatory and antioxidant parameters were measured. After that, echocardiographic and HRQoL assessments were performed.RESULTS: A total of 38 subjects, 11 males and 27 females, completed the study with no significant changes in diets, physical activities, or medications. Comparing to control, the 90-days GLPP-treated subject characteristics were significant difference in systolic blood pressure, heart rate, malondialdehyde, high-sensitivity C-reactive protein, tumor necrosis factor-a, interleukin (IL)-1b, IL-6, primary (P)-wave dispersion, P-max, physical functioning, limitation to physical health, energy/fatigue, pain, and physical limitation.CONCLUSION: GLPP has several potential effects in AF subjects, including anti-inflammatory, antioxidant, and atrial remodelling, so that HRQoL of AF subjects could be improved. Hence, GLPP could suggested as a potential supplementing agent for AF management.KEYWORDS: atrial fibrillation, Ganoderma lucidum, inflammation, antioxidant, atrial remodelling, quality of life

The Role of Ganoderma Lucidum Polysaccharide Peptide in Endothelial Progenitor Cells and Circulating Endothelial Cells as anti Endothelial Dysfunction from Stable Angina Pectoris Patients

Objective: Endothelial dysfunction is the primary initial step for atherogenesis in cardiovascular disease. Stable angina pectoris is a stable form of cardiovascular disease that profoundly alters Endothelial Progenitor Cells (EPC) and Circulating Endothelial Cells (CEC). Both CEC and EPC have a significant role as native homeostasis biomarker of endothelial, which could initiate cytokine storm when homeostasis was altering. Ganoderma Lucidum is known for the antioxidative, anti-inflammatory, and anti-cancer properties and indirect anti endothelial dysfunction. The previous study has proven the Polysaccharide Peptide (PsP) of Ganoderma Lucidum as an effective antioxidant and anti-endothelial dysfunction in atherosclerosis rats and shows no toxicity in an animal model. This study goals to prove the effect of PsP in CEC and EPC in stable angina patients.
 Methods: This is a quasi-experimental trial of 35 Stable Angina patients, determined based on ESC Stable CAD Guidelines with pre and post-test design without a control group. The parameters are CEC and EPC counts. The patients were given PsP 750mg/day in 3 divided doses for 90 days. A paired t-test perform for normally distributed data, and the Wilcoxon test for not normally distributed data, and a significant level of p≤0,05.
 Results: CEC significantly reduced in stable angina patients, with p=0,001. EPC count significantly reduced in stable angina with p=0,001.
 Conclusion: Ganoderma Lucidum PsP is a potent anti-endothelial dysfunction against atherosclerosis's pathogenesis in stable angina.

Polysaccharide–Peptide Conjugates: A Versatile Material Platform for Biomedical Applications

AbstractNatural polymers, such as polysaccharides and proteins, have been widely studied for numerous biomedical applications because of their bioactivity, natural origin, and biodegradability. To address the different needs of a broad spectrum of biomedical applications, natural polymers are modified with or conjugated to small molecular compounds, synthetic and natural polymers, and inorganic nanomaterials and surfaces. Among these hybrid materials, polysaccharide–peptide conjugates have drawn much attention due to their design flexibility, biocompatibility, tunable degradability, and structure similarity to naturally occurring glycoproteins. In the past 20 years, polysaccharide–peptide conjugates have demonstrated the promising potential to address many long‐standing medical challenges. Thus, the design, conjugation chemistry and method, and biomedical applications of polysaccharide–peptide conjugates are summarized and discussed in this review. The conjugation techniques are reviewed from the view of the chemical reactions. Meanwhile, some inspiring examples of polysaccharide–peptide conjugates in biomedical applications, including drug delivery systems, nucleic acid delivery carriers, tissue engineering, and antimicrobial applications, are highlighted. Moreover, the outlook on the challenges and demands of polysaccharide–peptide conjugates is also elaborated.

Developing Herbal Medicine, The Role of β-1,3/1,6-D-Glucan Forms of Polysaccharide Peptide (PsP) from Mycelia Ganoderma lucidum Extracts for Lowering Elevated Total Cholesterol Level in Patients with Heart Failure in Ischaemic Heart Disease

High levels of total cholesterol can worsen the condition of ischemic heart failure. Polysaccharide peptide (PsP) is a capsule of Ganoderma lucidum extract. This study aims to measure changes in total cholesterol levels in patients with ischemic heart failure before and after the administration of PSP and Placebo and to analyze differences in decreases in total cholesterol levels between PSP and Placebo group. This research is a true experiment with a prospective double-blind randomized control method through pre-post test design. The sample consisted of 26 patients, divided into 2 groups and given PSP or placebo capsules per oral interventions carried out every day for 90 days. Venipuncture blood was taken before and after the intervention to measure total cholesterol levels by spectrophotometry methods. Paired T Test was used to determine the average reduction in total cholesterol levels for each group. Independent T Test was used to determine the difference of reduction in total cholesterol average between the two groups. The decrease of total cholesterol average level in PsP group was 24.3 mg/dl (p value 0.001) and an increase of Placebo group was 8.3 mg/dl (p value 0.099). Comparison of the average reduction in total cholesterol levels in PsP : Placebo group was 24.31: -8.31 mg/dl (p value 0.000). There was significant decrease total cholesterol levels in PsP group and neither was of the Placebo group. In addition, there was significant difference in the reduction of total cholesterol levels between PSP and Placebo group.

Ganoderma lucidum spore oil (GLSO), a novel antioxidant, extends the average life span in Drosophila melanogaster

In ancient China, Ganoderma lucidum was believed to be a medical fungus that could increase lifespan. Recently, pharmacologic studies have found that polysaccharide peptides and triterpenoids extracted from Ganoderma lucidum have various physiological effects as active compounds. However, the effects of spore oil isolated from Ganoderma lucidum remains unknown. In this study, the biological effects of Ganoderma lucidum spore oil (GLSO) were evaluated using a Drosophila melanogaster model. Compared with untreated groups, groups treated with GLSO had significantly longer average and maximum lifespan in both normal conditions and under oxidative stress. The activities of various antioxidant enzymes were measured to determine the antioxidant effect of GLSO. GLSO treatment markedly enhanced total superoxide dismutase (SOD) and catalase (CAT) activity and decreased levels of malondialdehyde (MDA). Further, we found dose-dependent increases in the mRNA expression of Cu, Zn-SOD, Mn-SOD, and CAT in GLSO-treated groups. These results suggest that GLSO may effectively eliminate free radicals and extend lifespan in Drosophila. Future work should investigate the value of GLSO as a functional food for the prevention of aging in larger animal models.

Harnessing the immunogenicity of peptide-based glycoconjugate vaccines

Abstract Glycoconjugate vaccines provide enormous health benefits globally, although they have been less successful in some populations at high risk for developing disease. In most cases, conjugation of the sugar antigen to the carrier protein has been done empirically with little attention on variables critical for the immune response. Recent findings offer new insights on their mechanism of actionsuggesting that carbohydrate presentation to T cells by antigen-presenting cells may enhance the efficacy of antibody responses and suggesting the use of a peptide instead a whole protein as carrier. Herein, we have developed a platform to optimize glycopeptide vaccine design by determining optimal polysaccharide chain length, peptide composition and conjugation site. We first determined that the use of a full-length polysaccharide induce optimal immunogenicity. We have further demonstrated the role of the peptide linker and the conjugation site in enhancing both the conjugation efficiency and the immune response to vaccines. When immunizing mice, we found—using GBSIII CPS as a model—that these glycoconjugates induced full protection in the challenge model. We extended the platform to develop a prototype vaccine for Francisella tularensis, coupling the O polysaccharide to an optimized peptide and observing significant protection. Remarkably, protection with a glycoconjugate vaccine against F. tularensis has been only recently obtained by using a genetically enlarged polysaccharide. The results show that peptide glycoconjugate vaccines provide a strong protection against bacterial challenges. We are currently applying the acquired knowledge to create more efficacious and longer lasting immunity to glycoconjugate vaccines.

Polysaccharide Peptide (PsP) of Ganoderma lucidum as vasa vasorum anti-Angiogenesis agent in Dyslipidemic state by Measuring Lp-PLA2 and H2O2 Levels: In Vivo Study using wistar strain Rattus novergicus model of Atherosclerosis with Dyslipidemia

Polysaccharide Peptide (PsP) of <i>Ganoderma lucidum</i> as vasa vasorum anti-Angiogenesis agent in Dyslipidemic state by Measuring Lp-PLA2 and H₂O₂ Levels<i>: In Vivo</i> Study using wistar strain <i>Rattus novergicus</i> model of Atherosclerosis with Dyslipidemia

Decreasing angiogenesis vasa vasorum through Lp-PLA2 and H2O2 inhibition by PSP from Ganoderma lucidum in atherosclerosis: in vivo diabetes mellitus type 2

Background Type 2 diabetes mellitus (T2DM) is a major risk factor of atherosclerosis. Hyperglycemia in T2DM causes advanced formation of glycation end products (AGE) which leads to oxidative stress and chronic inflammation. Oxidative stress occurs due to increased levels of reactive oxygen species (ROS) such as H2O2. On the other hand, lipoprotein-associated phospholipase (Lp-PLA2) has pro-inflammatory effects, which cause instability of atherosclerosis plaques. This condition causes hypoxemic cells to stimulate HIFα induced vasa vasorum angiogenesis. This study aims to understand the potential of PSP as an anti-angiogenic agent through decreased levels of H2O2 and Lp-PLA2 leading to the decline of vasa vasorum angiogenesis in diabetic rat model. In addition, this study also measured the lipid profile of diabetic rat model in relation to vasa vasorum angiogenesis. Methods True laboratory experiment with randomized post-test control of group design using 25 wistar rats (Rattus norvegicus) were divided into five groups; one normal group and four group with High Fat Diet (HFD) and low dose streptozotocin (30 mg/kgBW) injection sc, treated with placebo and three various doses of PSP 50, 150, 300 mg/kgBW. Results ANOVA test (p < 0.05) shows that there is a significant influence of polysaccharide peptide (PSP) feeding on the decreased amount of vasa vasorum angiogenesis (p = 0.00), lipid profile (cholesterol total and triglyceride; p = 0.01, p = 0.001), and amount of H202 (p = 0.003). The amount of Lp-PLA2 declined to (p = 0.184). This result indicates that PSP prevents inflammation in atherosclerosis. Conclusions PSP of Ganoderma lucidum is an anti-angiogenic agent in T2DM.

Characterisation of the β-lactam resistance enzyme in Acanthamoeba castellanii

β-Lactams are well known as the best antibiotics for inhibiting the cross-linking between adjacent polysaccharide chains and peptides in the peptidoglycan layer of bacterial cell walls, causing bacterial cell lysis. There are no reports on the action of and resistance mechanisms to β-lactams in protozoa. Acanthamoeba castellanii is a free-living protozoan pathogen capable of causing blinding keratitis and fatal granulomatous encephalitis. When Acanthamoeba is exposed to harsh conditions, it differentiates into the cyst stage to avoid environmental stresses, such as drug treatment. In this study, it was shown that the mature encystation rate of A. castellanii is decreased by treatment with cefotaxime (CTX) and clavulanic acid (CLA); however, the drugs do not kill the amoeba. We hypothesise that β-lactam antibiotics may disturb synthesis of the double cell wall during the encystation process of Acanthamoeba. Interestingly, CTX is considered a powerful β-lactam, whereas CLA is considered a weak β-lactam but an efficient β-lactamase inhibitor. It was demonstrated that Acanthamoeba expresses β-lactamases to prevent inhibition of the encystation process by β-lactams. To reveal the functions of Acanthamoeba β-lactamases, a recombinant Acanthamoeba β-lactamase was produced in Escherichia coli that conferred resistance to β-lactams such as CTX, cefuroxime, penicillin and meropenem. Consequently, we suggest that Acanthamoeba produces enzymes similar to β-lactamases to avoid interference from the environment. Here we provide a new point of view on an important gene responsible for drug resistance and advocate for the development of more efficient treatment against Acanthamoeba infection.

Polysaccharide peptide (PsP) Ganoderma lucidum: a potential inducer for vascular repair in type 2 diabetes mellitus model.

IntroductionThe increasing blood glucose level due to insulin resistance which occurs in diabetes mellitus (DM) may cause vascular damage. This study aims to prove the effect of the polysaccharide peptide (PsP) Ganoderma lucidum on improving vascular damage through an increase of circulating endothelial cells and circulating endothelial cells (CEC) ratio, decreased H2O2, triglyceride (TG), total cholesterol (TC) and insulin resistance in type 2 DM.MethodsOur study is a true experimental study with randomized posttest control group design that used 35 Wistar rats divided into five groups: normal, control (+) and three groups of different variant PsP doses 50, 150 and 300 mg/kg BW (n=7).ResultsBy using one-way ANOVA and post-hoc Duncan test, the results show a significant increase of endothelial progenitor cell (EPC) concentration (p=0.000) and ratio EPC:CEC (0.000) by dose-dependent fashion and also reduced CEC concentration (p=0.001), H2O2 (p=0.03), TG (p=0.001), TC (p=0.01) and insulin resistance (p=0.003).ConclusionIn this study, PsP induced endothelial repairing process and reduced the risk factor with 300 mg/kg BW as optimum dose. However, further research on EPC and CEC detection markers is important. Further research on PsP and clinical trial for commercial uses is also needed.

A hyaluronan-based polysaccharide peptide generated by a genetically modified Streptococcus zooepidemicus

Polysaccharide peptides (or protein-bound polysaccharides, PSPs) are commonly found in mushrooms and plants and possess important nutritional properties and health benefits. The pathogenic bacterium Streptococcus zooepidemicus does not inherently produce PSPs but secretes the capsular polysaccharide hyaluronan. However, in a previous investigation of the catalytic mechanism of UDP-glucose dehydrogenase (UGDH), a PSP of peptide-bound hyaluronan was found to be produced by S. zooepidemicus through the in vivo expression of a mutant of the gene encoding UGDH. In the present study, this hyaluronan-derived PSP was structurally characterized by FT-IR, NMR, and high-performance liquid chromatography-mass spectrometry (HPLC-MS), and the data confirmed that the polysaccharide backbone, hyaluronan, is covalently bound to the side-chain peptides via an amide linkage. More importantly, the bacterial production of a PSP via this genetic modification method should inspire further research on the in vitro enzymatic synthesis of PSPs or even naturally occurring polysaccharide derivatives and may provide a theoretical foundation for investigating the in vivo synthetic mechanism of PSPs.

Polysaccharide peptides from Ganoderma lucidum ameliorate lipid metabolic disorders and gut microbiota dysbiosis in high-fat diet-fed rats

This study aimed to investigate the effects of polysaccharide peptides from Ganoderma lucidum (GLPP) on hyperlipidaemia and gut microbiota dysbiosis in high-fat diet (HFD)-exacerbated hypercholesterolemic rats. Results showed that oral administrations of GLPP markedly alleviated the dyslipidaemia through decreasing the serum levels of triglyceride (TG), cholesterol (TC), free fatty acids (FFA) and low-density lipoprotein cholesterol (LDL-C), and significantly suppressing hepatic lipid accumulation and steatosis. Metagenomic analysis revealed that GLPP supplementation produced significant structure changes on the intestinal microbiota in HFD-fed rats, in particular modulating the relative abundance of functionally relevant microbial phylotypes compared with the HFD group. The Spearman's correlation analysis revealed that the serum and hepatic lipid profiles were negatively correlated with Jeotgalicoccus, Ignavigranum, Sporosarcina, Bacteroides, Anaerovorax, Parasutterella, Alistipes and Alloprevotella, but positively correlated with Allobaculum, Phascolarctobacterium, Psychrobacter, Enterorhabdus, Blautia and Roseburia. Meanwhile, the GLPP treatment regulated the mRNA expression responsible for hepatic lipid metabolism and promoted fecal excretion of total bile acids (BAs). These findings indicated that GLPP ameliorate lipid metabolic disorders through modulating gut microbiota structure and regulating the genes involved in hepatic lipid and cholesterol metabolism.

Protective effect of polysaccharide peptide on cerebral ischemia‑reperfusion injury in rats.

In the present study, the protective effects and regulatory mechanism of polysaccharide peptide (PSP) were investigated in rats with cerebral ischemia-reperfusion (IR) injury. Neuroblastoma N2a cells were divided into five groups: Negative control; IR injury; PSP low dose treatment; PSP middle dose treatment; and PSP high dose treatment. In vitro, the cell viability was detected by an MTT assay. ELISA was performed to determine the activity of lactate dehydrogenase (LDH) and caspase-3. A cerebral IR injury model in vivo was established, and hematoxylin and eosin (H&E) staining, western blotting, neurological deficit score and cerebral infarction were assessed. The cell viability was markedly improved following treatment with PSP and the activity of LDH and caspase-3 was decreased following PSP administration (P<0.05). The in vivo studies determined that the neurological deficit score and cerebral infarction volume were reduced with the concentration of PSP increasing between 150 and 250 mg/kg. The H&E staining indicated that PSP was able to protect the nerve cells against the cerebral IR injury. In addition, PSP upregulated the decreased silent information regulator protein 1, peroxisome proliferator-activated receptor γ coactivator-1α and apoptosis regulator B-cell lymphoma 2 expression induced by cerebral IR injury. The protein expression level of caspase-3 and apoptosis regulator apoptosis regulator Bcl-2-like protein 4 was downregulated following PSP administration. These results suggested that PSP may improve nerve cell viability, enhance the neuroprotective role in cerebral IR injury and provide a novel approach for the treatment of cerebral IR injury.

Naturally Derived Anti-HIV Polysaccharide Peptide (PSP) Triggers a Toll-Like Receptor 4-Dependent Antiviral Immune Response.

Aim Intense interest remains in the identification of compounds to reduce human immunodeficiency virus type 1 (HIV-1) replication. Coriolus versicolor's polysaccharide peptide (PSP) has been demonstrated to possess immunomodulatory properties with the ability to activate an innate immune response through Toll-like receptor 4 (TLR4) showing insignificant toxicity. This study sought to determine the potential use of PSP as an anti-HIV agent and whether its antiviral immune response was TLR4 dependent. Materials and Methods HIV-1 p24 and anti-HIV chemokine release was assessed in HIV-positive (HIV+) THP1 cells and validated in HIV+ peripheral blood mononuclear cells (PBMCs), to determine PSP antiviral activity. The involvement of TLR4 activation in PSP anti-HIV activity was evaluated by inhibition. Results PSP showed a promising potential as an anti-HIV agent, by downregulating viral replication and promoting the upregulation of specific antiviral chemokines (RANTES, MIP-1α/β, and SDF-1α) known to block HIV-1 coreceptors in THP1 cells and human PBMCs. PSP produced a 61% viral inhibition after PSP treatment in HIV-1-infected THP1 cells. Additionally, PSP upregulated the expression of TLR4 and TLR4 inhibition led to countereffects in chemokine expression and HIV-1 replication. Conclusion Taken together, these findings put forward the first evidence that PSP exerts an anti-HIV activity mediated by TLR4 and key antiviral chemokines. Elucidating these new molecular mediators may reveal additional drug targets and open novel therapeutic avenues for HIV-1 infection.

Ganoderma lucidum Polysaccharide Peptide Attenuates Skin Flap Ischemia-Reperfusion Injury in a Thioredoxin-Dependent Manner.

Thioredoxin-1 plays an important role in protecting the skin flap from ischemia-reperfusion injury. Ganoderma lucidum polysaccharide peptide is the major component of G. lucidum, which possesses potent antioxidant and antiapoptotic activity. This study aims to determine whether G. lucidum polysaccharide peptide could attenuate skin flap ischemia-reperfusion injury and to investigate possible mechanisms involved. G. lucidum polysaccharide peptide was administered to mice and epidermal cells before ischemia-reperfusion and hypoxia/reoxygenation, respectively. The thioredoxin-1 inhibitor PX-12 was introduced in the counterevidence group. The flap tissues and cells were tested by hematoxylin and eosin and immunohistochemistry staining, terminal deoxynucleotidyl transferase-mediated dUDP end-labeling assay, superoxide dismutase and malonic dialdehyde measurement, and Western blot. The survival rates of ischemia-reperfusion flaps and hypoxia/reoxygenation cells increased significantly following G. lucidum polysaccharide peptide treatment. Mitigated tissue damage, reduced apoptosis, and enhanced antioxidant activity were observed in ischemia-reperfusion flaps replenishing G. lucidum polysaccharide peptide. Western blot analysis revealed thioredoxin-1 depletion and a remarkable increase in ASK-1, phospho-p38, cleaved caspase-3, and cleaved PARP abundance in ischemia-reperfusion flaps and hypoxia/reoxygenation cells, whereas G. lucidum polysaccharide peptide dramatically up-regulated thioredoxin-1 and reduced the apoptosis-related protein expression. However, the rescue effect of G. lucidum polysaccharide peptide was notably blunted by supplementation with PX-12. The current investigation highlights the protective role of G. lucidum polysaccharide peptide in skin flap ischemia-reperfusion injury through a thioredoxin-1-dependent antioxidant and antiapoptotic pathway. This initial foray demonstrates the therapeutic value of G. lucidum polysaccharide peptide against ischemia-reperfusion and facilitates the understanding of its dermoprotective mechanism.