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1.
Carbohydr Polym ; 268: 118214, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34127216

ABSTRACT

Phellinus baumii is used to treat inflammatory bowel disease (IBD) and gastroenteritis. In this study, a 46 kDa heteropolysaccharide SHPS-1 was isolated from fruiting bodies of P. baumii. SHPS-1 consisted of arabinose, mannose, glucose, and galactose at a molar ratio of 2.2:15.7:49.3:32.8. SHPS-1 had a backbone containing 1,3-linked ß-D-Glcp and 1,6-linked α-D-Galp residues, and Araf, Manp and Galp units were attached as oligosaccharidic side chains to the backbone at C-6 of some glucopyranoses. SHPS-1 decreased phosphorylation level of STAT-1 and expression levels of STAT-1 targeted genes such as iNOS and TNF-α in lipopolysaccharide-stimulated macrophage RAW 264.7 cells. Furthermore, SHPS-1 promoted the expression of IL-10 and macrophage mannose receptor CD 206, markers of tissue repairing macrophages. SHPS-1 alleviated ulcerative colitis in mice by decreasing pro-inflammatory genes and increasing anti-inflammatory and tissue repairing genes. Collectively, SHPS-1 polysaccharide from P. baumii had anti-inflammatory activity and can potentially treat IBD.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Basidiomycota/chemistry , Colitis, Ulcerative/drug therapy , Fungal Polysaccharides/therapeutic use , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Carbohydrate Sequence , Colitis, Ulcerative/chemically induced , Cytokines/metabolism , Dextran Sulfate , Fruiting Bodies, Fungal/chemistry , Fungal Polysaccharides/chemistry , Fungal Polysaccharides/isolation & purification , Male , Mice , Mice, Inbred C57BL , Phosphorylation/drug effects , RAW 264.7 Cells , STAT1 Transcription Factor/chemistry , STAT1 Transcription Factor/metabolism , Signal Transduction/drug effects
2.
BMC Complement Altern Med ; 19(1): 272, 2019 Oct 21.
Article in English | MEDLINE | ID: mdl-31638956

ABSTRACT

BACKGROUND: This study aimed to investigate the effect of the Phellinus linteus (Mesima) decoction on podocyte injury in a rat model of focal and segmental glomerulosclerosis (FSGS) and evaluate the potential mechanisms. METHODS: FSGS resembling primary FSGS in humans was established in rats by uninephrectomy and the repeated injection of doxorubicin. The FSGS rats were randomly divided into the model group, low-dose group of P. linteus decoction (PLD-LD), medium-dose group of P. linteus decoction (PLD-MD), and high-dose group of P. linteus decoction (PLD-HD). Blood and urine analysis were performed after 12 weeks and the molecular indicators of renal function and the renal pathological changes were examined. RESULTS: FSGS developed within 12 weeks in the test group and showed progressive proteinuria and segmental glomerular scarring. Urinary protein, serum creatinine, urea nitrogen, triglycerides and cholesterol were significantly reduced following the 12-week intervention with P.linteus decoction, especially in the PLD-LD group. Renal nephrin and podocin were markedly increased. Moreover, the pathological damage in the renal tissue was alleviated by the PLD-LD intervention. CONCLUSION: The P. linteus decoction alleviated the podocyte injury in the FSGS rat model, thus minimizing the progression of glomerular sclerosis and improving renal function.


Subject(s)
Glomerulosclerosis, Focal Segmental/drug therapy , Plant Extracts/administration & dosage , Podocytes/drug effects , Animals , Disease Models, Animal , Glomerulosclerosis, Focal Segmental/metabolism , Glomerulosclerosis, Focal Segmental/physiopathology , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Kidney/drug effects , Kidney/metabolism , Kidney/physiopathology , Male , Membrane Proteins/metabolism , Phellinus , Podocytes/metabolism , Rats , Rats, Sprague-Dawley
3.
PLoS One ; 13(10): e0205007, 2018.
Article in English | MEDLINE | ID: mdl-30289941

ABSTRACT

Phellinus igniarius, which is called Sanghuang in Chinese, is a fungal herb widely used in Traditional Chinese Medicine to treat stomachache, inflammation and tumors. Recent studies have demonstrated the antitumor, anti-diabetic, anti-inflammatory and immunity-modulating activities of P. igniarius. In the present study, we investigated that ameliorating effect of the aqueous extract of P. igniarius fruiting body (SH) on dextran sodium sulfate (DSS)-induced colitis in C57BL/6 mice. Treatment with SH (250 and 400 mg/kg) for 8 weeks effectively alleviated the pathological indicators of colitis such as bodyweight reduction, disease activity index score, shortening of colon length and abnormal colon histology. The plasma levels of lipopolysaccharide (LPS) and inflammatory factors such as interleukin-6 (IL-6), IL-1ß and tumor necrosis factor (TNF)-α were all significantly reduced. Supplementation of SH (10 mg/L) also inhibited LPS-elicited IL-1ß production by RAW264.7 macrophages. Real-time PCR and western blot showed that treatment with SH significantly inhibited the phosphorylation of nuclear factor kappa B inhibitor alpha (IκBα) and decreased the expression of IL-6/IL-1ß-maturation genes such as apoptosis-associated speck-like protein (ASC3) and caspase-1 in the colon of DSS-induced colitis mice. These results suggest that SH is adequate for the treatment of colitis. Inhibiting the expression and release of inflammatory factors may participate in the colitis-ameliorating effect of SH.


Subject(s)
Basidiomycota/chemistry , Colitis/chemically induced , Colitis/drug therapy , Dextran Sulfate/adverse effects , Animals , Caspase 1/genetics , Colitis/genetics , Colitis/metabolism , Colon/drug effects , Colon/metabolism , Colon/pathology , Interleukin-1beta/biosynthesis , Interleukin-6/blood , Macrophages/drug effects , Macrophages/metabolism , Mice , Mice, Inbred C57BL , NF-KappaB Inhibitor alpha/metabolism , Phosphorylation/drug effects , RAW 264.7 Cells , Transcription, Genetic/drug effects , Tumor Necrosis Factor-alpha/blood
4.
J Ethnopharmacol ; 150(1): 187-95, 2013 Oct 28.
Article in English | MEDLINE | ID: mdl-24001891

ABSTRACT

ETHNOPHARMACOLOGY RELEVANCE: Our previous study showed that the proteoglycan P1 from Phellinus linteus (Mesima) exhibits significant anti-tumor activity against human hepatocellular carcinoma cells (HepG2); however, its molecular mechanism remains unknown. This study aims to provide insights into the mechanism of the anti-tumor activity of P1 against HepG2 cells. METHODS: We examined the effects of P1 on HepG2 cell proliferation in vitro and in vivo. Flow cytometry was used to analyze the cell cycle distribution and apoptosis. Proteomic analysis, real-time (RT)-PCR, and Western blot were carried out to observe the expression of several cell cycle control proteins in HepG2 cells. RESULTS: Both the volume and the weight of solid tumors were significantly decreased in P1-treated mice (200mg/kg) compared with the control. The HepG2 cells in the P1-treated tumors were significantly decreased, irregularly shaped, and smaller. P1 slightly increased the body weight of the tumor-bearing mice, which indicates that P1 is nontoxic to mammals at 200mg/kg. P1 also caused a significant dose-dependent increase in S phase arrest, but no apoptosis was observed in HepG2 cells. The results of the proteomic analysis, RT-PCR, and Western blot analysis showed that significantly downregulated expression of calreticulin, cyclin D1, cyclin E, and CDK2 and upregulated expression of P27 kip1 and cyclin A in the P1-treated HepG2 cells (200 µg/ml). CONCLUSION: These results suggest that calreticulin expression and the P27 kip1-cyclin A/D1/E-CDK2 pathway were involved in P1-induced S-phase cell cycle arrest in HepG2 cells.


Subject(s)
Antineoplastic Agents/pharmacology , Basidiomycota , Fungal Polysaccharides/pharmacology , Animals , Antineoplastic Agents/therapeutic use , Calreticulin/metabolism , Cell Proliferation/drug effects , Cyclin-Dependent Kinase 2/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Cyclins/metabolism , Female , Fungal Polysaccharides/therapeutic use , Hep G2 Cells , Humans , Mice , Mice, Nude , Proteomics , S Phase/drug effects , Xenograft Model Antitumor Assays
5.
PLoS One ; 8(6): e65892, 2013.
Article in English | MEDLINE | ID: mdl-23755289

ABSTRACT

We had previously shown that deoxynojirimycin-polysaccharide mixture (DPM) not only decreased blood glucose but also reversed the damage to pancreatic ß-cells in diabetic mice, and that the anti-hyperglycemic efficacy of this combination was better than that of 1-deoxynojirimycin (DNJ) or polysachharide alone. However, the mechanisms behind these effects were not fully understood. The present study aimed to evaluate the therapeutic effects of DPM on streptozotocin (STZ)-induced diabetic symptoms and their potential mechanisms. Diabetic mice were treated with DPM (150 mg/kg body weight) for 90 days and continued to be fed without DPM for an additional 30 days. Strikingly, decrease of blood glucose levels was observed in all DPM treated diabetic mice, which persisted 30 days after cessation of DPM administration. Significant decrease of glycosylated hemoglobin and hepatic pyruvate concentrations, along with marked increase of serum insulin and hepatic glycogen levels were detected in DPM treated diabetic mice. Results of a labeled (13)C6-glucose uptake assay indicated that DPM can restrain glucose absorption. Additionally, DPM down-regulated the mRNA and protein expression of jejunal Na(+)/glucose cotransporter, Na(+)/K(+)-ATPase and glucose transporter 2, and enhanced the activities as well as mRNA and protein levels of hepatic glycolysis enzymes (glucokinase, phosphofructokinase, private kinase and pyruvate decarboxylas E1). Activity and expression of hepatic gluconeogenesis enzymes (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) were also found to be attenuated in diabetic mice treated with DPM. Purified enzyme activity assays verified that the increased activities of glucose glycolysis enzymes resulted not from their direct activation, but from the relative increase in protein expression. Importantly, our histopathological observations support the results of our biochemical analyses and validate the protective effects of DPM on STZ-induced damage to the pancreas. Thus, DPM has significant potential as a therapeutic agent against diabetes.


Subject(s)
1-Deoxynojirimycin/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Polysaccharides/therapeutic use , Streptozocin/toxicity , Animals , Blood Glucose/drug effects , Blotting, Western , Glucose/metabolism , Insulin/blood , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred ICR
6.
J Ethnopharmacol ; 134(3): 961-70, 2011 Apr 12.
Article in English | MEDLINE | ID: mdl-21333726

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: 1-Deoxynojirimycin (DNJ) discovered from mulberry trees has been reported to be a potent inhibitor of intestinal α-glycosidases (sucrase, maltase, glucoamylase), and many polysaccharides were useful in protecting against alloxan-induced pancreatic islets damage through their scavenging ability. This study was aimed to evaluate the therapeutic effect and potential mechanism(s) of the hybrid of DNJ and polysaccharide (HDP) from mulberry leaves on alloxan-induced diabetic mice. MATERIALS AND METHODS: Daily oral treatment with HDP (150 mg/kg body weight) to diabetic mice for 12 weeks, body weight and blood glucose were determined every week, oral glucose tolerance test was performed after 4 and 8 weeks, biochemical values were measured using assay kits and gene expressions were investigated by RT-PCR. RESULTS: A significant decline in blood glucose, glycosylated hemoglobin, triglyceride, aspartate transaminase and alanine transaminase levels and an evident increase in body weight, plasma insulin level and high density lipoprotein were observed in HDP treated diabetic mice. The polysaccharide (P1) showed a significant scavenging hydroxyl radicals and superoxide anion radical effects in vitro, which indicated that P1 could protect alloxan-induced pancreatic islets from damage by scavenging the free radicals and repaired the destroyed pancreatic ß-cells. Pharmacokinetics assay showed that DNJ could be absorbed from the gastrointestinal mucosa and diffused rapidly into the liver, resulted in postprandial blood glucose decrease and alleviated the toxicity caused by sustained supra-physiological glucose to pancreatic ß-cells. RT-PCR results indicated that HDP could modulate the hepatic glucose metabolism and gluconeogenesis by up/down-regulating the expression of rate-limiting enzymes (glucokinase, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in liver and up-regulating the pancreatic and duodenal homeobox factor-1 (PDX-1), insulin-1 and insulin-2 expressions in pancreas. CONCLUSION: These findings suggested that HDP has complimentary potency to develop an antihyperglycemic agent for treatment of diabetes mellitus.


Subject(s)
1-Deoxynojirimycin/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Gene Expression Regulation, Enzymologic/drug effects , Morus/chemistry , Plant Leaves/chemistry , Polysaccharides/therapeutic use , 1-Deoxynojirimycin/pharmacology , Alloxan , Animals , Base Sequence , DNA Primers , Diabetes Mellitus, Experimental/enzymology , Diabetes Mellitus, Experimental/metabolism , Glucokinase/genetics , Glucokinase/metabolism , Glucose Tolerance Test , Glucose-6-Phosphatase/genetics , Glucose-6-Phosphatase/metabolism , Homeodomain Proteins/metabolism , Insulin/metabolism , Male , Mice , Mice, Inbred ICR , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Phosphoenolpyruvate Carboxykinase (ATP)/metabolism , Polysaccharides/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Trans-Activators/metabolism
7.
Alcohol Alcohol ; 45(4): 320-31, 2010.
Article in English | MEDLINE | ID: mdl-20554696

ABSTRACT

AIMS: The purpose of this study was to investigate the possible mechanism(s) of saponins from Panax japonicus (SPJ) on alcohol-induced hepatic damage in mice. METHODS: SPJ were identified by high performance liquid chromatography-evaporative light scattering detection-mass spectrometry (LC-ELSD-MS). Non-toxic concentrations of SPJ were assayed on alcohol-induced hepatic injury in male ICR mice and human hepatic cells. The protective effects were evaluated by biochemical values, histopathological observations and the relative gene expression. Results. In vitro, SPJ showed significant hydroxyl radical scavenging capacity. In vivo, SPJ (50 mg/kg) could rectify the pathological changes of aspartate transaminase, alanine transaminase, malondialdehyde, reduced glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) caused by alcohol metabolism to normal levels except for hepatic GSH and CAT. In hepatic cells, the results were in agreement with foregoing results determined in mice after pretreatment of SPJ (100 microg/ml). RT-PCR results showed that CAT, GPX and SOD mRNA decreased by alcohol metabolism were reversed, in which GPX3, SOD1 and SOD3 could return to a normal level, but CAT, GPX1 and SOD2 mRNA were still evidently lower than the control. Histopathological observations provided supportive evidence for biochemical analyses. CONCLUSIONS: SPJ plays an important role in the protection of the structure and function of hepatic mitochondria and karyon by directly scavenging reactive oxygen species/free radicals and up-regulating the expression of antioxidant enzymes (SOD, GPX and CAT), especially to GPX3, SOD1 and SOD3.


Subject(s)
Glutathione Peroxidase/genetics , Liver Diseases, Alcoholic/prevention & control , Liver/drug effects , Panax/chemistry , Saponins/pharmacology , Superoxide Dismutase/genetics , Up-Regulation/drug effects , Animals , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Free Radical Scavengers/chemistry , Free Radical Scavengers/isolation & purification , Free Radical Scavengers/pharmacology , Free Radicals/metabolism , Glutathione Peroxidase/metabolism , Humans , Lipid Peroxidation/drug effects , Liver/enzymology , Liver/metabolism , Male , Mice , Mice, Inbred ICR , Reactive Oxygen Species/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Saponins/chemistry , Saponins/isolation & purification , Superoxide Dismutase/metabolism , Superoxide Dismutase-1
8.
Zhongguo Zhong Yao Za Zhi ; 32(21): 2282-5, 2007 Nov.
Article in Chinese | MEDLINE | ID: mdl-18309674

ABSTRACT

OBJECTIVE: To study the protective effects of Panax japonics (PJ) on alcohol-induced gastric lesion in mice and the possible mechanisms. METHOD: Male ICR mice were randomized into six groups: normal, control, PJ (1.5, 3.0, 6.0 g x kg(-1)) and Yinduoan (1.5 g x kg(-1)). The mice were pretreated with PJ before administering ethanol to observe the effect on the concentration of ethanol in serum and urine. The contents of MDA, GSH and GSH-PX, CAT and SOD activities were measured in serum and gastric mucosa, and subsequently, the pathological evaluation of stomach was also observed. RESULT: The concentration of ethanol in serum was evidently decreased after PJ (1.5, 3.0 g x kg(-1)) was administrated because the ethanol was eliminated fleetly through urine. Synchronously the PJ reduced the content of MDA and increased the GSH increased in serum and gastric, besides, it increased the enzymatic activities of GSHPX, CAT and SOD, and the ethanol-induced gastric mitochondria structure injury were ameliorated so as to make the function to normal. CONCLUSION: Based on these observations, one could conclude that the PJ is a potent protective agent against ethanol-induced gastric damages. One mechanism may be related with inhibiting the absorbability of ethanol at gastrointestinal tract, decreasing the concentration of ethanol in serum, and accelerating the ethanol elimination through urine so as to alleviate the ethanol-induced damage to gastrointestinal mucosal, enhancing the first-pass metabolism in stomach, and particularly increasing the antioxidant levels in serum and gastric. These gastroprotective effects might be, at least partly, through ameliorating the gastric mitochondria structure.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Panax/chemistry , Protective Agents/pharmacology , Stomach Diseases/prevention & control , Animals , Catalase/blood , Catalase/metabolism , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/therapeutic use , Ethanol , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Glutathione/blood , Glutathione/metabolism , Glutathione Peroxidase/blood , Glutathione Peroxidase/metabolism , Male , Malondialdehyde/blood , Malondialdehyde/metabolism , Mice , Mice, Inbred ICR , Microscopy, Electron , Mitochondria/drug effects , Mitochondria/ultrastructure , Phytotherapy , Plants, Medicinal/chemistry , Protective Agents/isolation & purification , Protective Agents/therapeutic use , Random Allocation , Stomach Diseases/blood , Stomach Diseases/chemically induced
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