RESUMO
Dendrobium huoshanense flowers have been widely used for liver protection in China. This work was aimed to discover the natural products with activity of mitigating alcoholic hepatocyte injury from Dendrobium huoshanense flowers via bioactivity-guided isolation, and to clarify the underlying mechanisms of these natural products. As a result, three flavonoids, 3'-O-methylquercetin-3-O-ß-D-galactopyranoside (1), 3'-O-methylquercetin-3-O-ß-D-glucopyranoside (2) and quercetin-3-O-ß-D-glucopyranoside (3), were firstly isolated from D. huoshanense flowers. Results exhibited that flavonoids 1-3 could enhance the cell viability, decrease the expression of ALT and AST, inhibit the cell apoptosis, alleviate the oxidative stress, and mitigate the inflammatory response of alcohol-induced L02 cells. Mechanism study exhibited that flavonoids 1-3 could increase the expression of Nrf2 as well as its downstream antioxidation genes of alcohol-induced L02 cells, while ML-385 (Nrf2 inhibitor) could abolish the inhibitory effects of 1-3 on alcohol-induced hepatocyte injury. Flavonoids 1-3 could also reduce the phosphorylation levels of IκBα and NF-κB p65 of alcohol-induced L02 cells, while SC75741 (NF-κB inhibitor) could not enhance the inhibitory effects of 1-3 on alcohol-induced L02 cells injury. The data above indicated that flavonoids 1-3 could inhibit alcohol-induced hepatocyte injury, which might be attributed to alleviating oxidative stress and mitigating inflammatory response by activating Nrf2 and inhibiting NF-κB pathways.
Assuntos
Produtos Biológicos , Dendrobium , Produtos Biológicos/farmacologia , Etanol/farmacologia , Flavonoides/farmacologia , Flores/metabolismo , Hepatócitos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse OxidativoRESUMO
Three bibenzyls 1-3 and six other compounds 4-9 were firstly isolated from Dendrobium huoshanense stems. They were identified as 3',4-dihydroxy-3,5'-dimethoxybibenzyl(1), batatasin â ¢(2), 3,4'-dihydroxy-5-methoxy bibenzyl(3), dihydroconiferyl dihydro-p-coumarate(4), syringaresinol(5), 3-(4-hydroxyphenyl)-propionic acid ethyl ester(6),(3-ethylphenyl)-1,2-ethanediol(7),(S)-5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one(8) and loliolide(9). Anti-inflammation assay showed that bibenzyls 1-3 could significantly inhibit the production of nitric oxide(NO) and the expression of tumor necrosis factor α(TNF-α) and interleukin 1ß(IL-1ß) mRNA in LPS-induced RAW264.7 macrophages. Mechanism study exhibited that the phosphorylation of nuclear factor kappa B(NF-κB) p65, inhibitor of κB(IκB), extracellular regulatedprotein kinase(ERK), c-Jun N-terminalkinase(JNK), p38 and Akt of LPS-induced RAW264.7 macrophages could be remarkably reduced by 1. These results suggested that the inflammatory response of LPS-induced RAW264.7 macrophages could be significantly inhibited by 1-3. Additionally, the anti-inflammatory effect of 1 might be contributed to its ability on the regulation of NF-κB, MAPKs and Akt signaling pathways.
Assuntos
Dendrobium , Anti-Inflamatórios/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Lipopolissacarídeos , Macrófagos , NF-kappa B , Óxido Nítrico , Óxido Nítrico Sintase Tipo IIRESUMO
Chronic renal failure (CRF) is a major public health problem worldwide. In this work, we investigated the effects of a purified Laminaria japonica polysaccharide (LJP61A) on renal function using an adenine-induced CRF mice model. Results exhibited that adenine treatment caused serious renal pathological damages and elevation of serum creatinine and blood urea nitrogen of mice. However, these changes could be significantly reversed by the administration of LJP61A in a dose-dependent manner. Additionally, LJP61A could dramatically reduce weight loss, improve the urine biochemical index, and regulate the electrolyte disturbance of CRF mice. These results suggest that the renal function of adenine-induced CRF mice can be improved by LJP61A, which might be developed into a potential therapeutic agent for CRF patients.
Assuntos
Adenina/efeitos adversos , Falência Renal Crônica/etiologia , Falência Renal Crônica/prevenção & controle , Laminaria/química , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Peso Corporal , Modelos Animais de Doenças , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/patologia , Masculino , Camundongos , Polissacarídeos/química , Substâncias Protetoras/químicaRESUMO
Books on Chinese herbal medicines have shown that Dendrobium has the effect of nourishing Yin and reinforcing Yin,usually used for constipation induced by spleen Yin deficiency in clinical application. D. huoshanense,as an independent species among many species of Dendrobium,has no experimental studies about its effects on spleen Yin deficiency-type constipation. The purpose of this experiment was to illustrate the therapeutic effect of D. huoshanense on the constipation of spleen Yin deficiency type in rats,investigate its preliminary mechanism,and compare it with the D. officinale and D. nobile contained in the Chinese Pharmacopoeia to clarify its characteristics. The spleen Yin deficiency model was replicated in 70 rats by the composite factor method,and then the model rats were randomly divided into 7 groups: model group,Liuwei Dihuang Pills group( LWDHP),D. huoshanense high( DHS-H),medium( DHS-M),low( DHS-L) dose groups,D. nobile group( DNS),and D. officinale group( DOS),and another 10 rats were used as normal group( Normal). After 7 continuous days of administration,the fecal water content and intestine propulsion rate of each group were detected. HE staining was used to observe the pathological damage of ileum and colon in each group. Immunohistochemistry and Western blot were used to detect aquaporin 3( AQP3) expressions,while the expression levels of the somatostatin( SS) and motilin( MTL) in the ileum of each group were detected by enzyme-linked immunosorbent assay. The results showed that as compared with the model group,the rats in each drug-administered group had increased number of fecal pellets,increased fecal water content,and the increased intestinal propulsion rate( P<0. 01),while the pathological damage of the ileum and colon was significantly reduced; the expression of AQP3 protein was significantly decreased( P<0. 01); the level of MTL was significantly increased and the level of SS was decreased( P<0. 01). All DHS groups showed a good dose-effect relationship,and the same dose treatment effect was equivalent to that of DOS,but it was superior to DNS. Therefore,DHS has a significant therapeutic effect on constipation of spleen Yin deficiency type,and its mechanism may be related to intestinal motility and water-liquid metabolism,with a good therapeutic effect.
Assuntos
Constipação Intestinal/tratamento farmacológico , Dendrobium/química , Medicamentos de Ervas Chinesas/farmacologia , Plantas Medicinais/química , Deficiência da Energia Yin/tratamento farmacológico , Animais , Intestinos , Distribuição Aleatória , Ratos , BaçoRESUMO
Dendrobium nobile Lindl., an epiphytic herb distributed in the Southeast Asia, is used as a tonic and antipyretic herbal medicine in China. In this study, a water-soluble acidic heteropolysaccharide, DNP-W4, containing mannose, glucose, galactose, xylose, rhamnose, and galacturonic acid, in the molar ratios of 1.0:4.9:2.5:0.5:1.0:0.9, was obtained from the stems of Dendrobium nobile Lindl. Using methylation analysis, partial acid hydrolysis, pectolyase treatment, NMR, and ESI-MS, the structure of DNP-W4 was elucidated. The obtained data indicated that DNP-W4 was a complex heteropolysaccharide and possessed a backbone composed of (1â4)-linked ß-d-Glcp, (1â6)-linked ß-d-Glcp, and (1â6)-linked ß-d-Galp, with substitutes at O-4/6 of Glcp residues and O-3 of Galp. The branches of DNP-W4 were composed of terminal Manp, (1â6)-linked ß-d-Manp, (1â3)-linked ß-d-Glcp, ß-d-Glcp, ß-d-Galp, (1â4)-linked α-d-GalAp, (1â2)-linked α-L-Rhap, and Xylp. DNP-W4 had little immunological activities, but its derivatives had immuno-stimulating activities to some extent.
Assuntos
Dendrobium/química , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Fatores Imunológicos/isolamento & purificação , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Análise Espectral , Relação Estrutura-AtividadeRESUMO
The aim was to assess prognostic value of serum 25-hydroxyvitamin D (25[OH] D) levels in older Chinese patients with hip fracture. From June, 2012 to February, 2014, older patients with hip fracture were included. Serum 25(OH) D levels were measured at admission. The functional evaluation at the time of discharge was performed by the Barthel Index. In the 66 patients with an unfavorable outcome, serum 25(OH) D levels were lower compared with those with a favorable outcome. In multivariate analyses, there was an increased risk of unfavorable outcome associated with serum 25(OH) D levels ≤ 20 ng/ml (OR 5.25, 95% CI: 3.12-8.16). Our data supported an association between serum 25[OH] D levels at admission and short-term prognosis in Chinese older patients with hip fracture.
Assuntos
Fraturas Espontâneas/fisiopatologia , Fraturas do Quadril/fisiopatologia , Vitamina D/análogos & derivados , Fatores Etários , Idoso , Feminino , Fraturas Espontâneas/sangue , Fraturas do Quadril/sangue , Humanos , Masculino , Alta do Paciente , Prognóstico , Recuperação de Função Fisiológica , Vitamina D/sangueRESUMO
Dendrobium huoshanense is a precious herbal medicine in China, which exhibits a variety of restorative and therapeutic effects. This study aimed at investigating the hepatoprotective effects of a polysaccharide (DHP1A) isolated from D. huoshanense via water extraction, diethylaminoethyl (DEAE) cellulose anion exchange and size exclusion chromatography. The animal experiment indicated that the oral administration of DHP1A obviously reduced the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and 8-hydroxy-2'-deoxyguanosine in the serum of mice treated with carbon tetrachloride (CCl4), suggesting the hepatoprotective potential of this polysaccharide. Moreover, DHP1A decreased the expressions of tumor necrosis factor-α, interleukin-1ß, monocyte chemoattractant protein-1, macrophage inflammatory protein-2, CD68 and phosphorylated IκBα (p-IκBα) in the CCl4-treated mice. These results revealed that the hepatoprotective effect of DHP1A was partly attributed to its anti-inflammatory action.
RESUMO
BACKGROUND: Tea is one of the most popular beverages in the world. Many species in the Thea section of the Camellia genus can be processed for drinking and have been domesticated. However, few investigations have focused on the genetic consequence of domestication and geographic origin of landraces on tea plants using credible wild and planted populations of a single species. Here, C. taliensis provides us with a unique opportunity to explore these issues. RESULTS: Fourteen nuclear microsatellite loci were employed to determine the genetic diversity and domestication origin of C. taliensis, which were represented by 587 individuals from 25 wild, planted and recently domesticated populations. C. taliensis showed a moderate high level of overall genetic diversity. The greater reduction of genetic diversity and stronger genetic drift were detected in the wild group than in the recently domesticated group, indicating the loss of genetic diversity of wild populations due to overexploitation and habitat fragmentation. Instead of the endangered wild trees, recently domesticated individuals were used to compare with the planted trees for detecting the genetic consequence of domestication. A little and non-significant reduction in genetic diversity was found during domestication. The long life cycle, selection for leaf traits and gene flow between populations will delay the emergence of bottleneck in planted trees. Both phylogenetic and assignment analyses suggested that planted trees may have been domesticated from the adjacent central forest of western Yunnan and dispersed artificially to distant places. CONCLUSIONS: This study contributes to the knowledge about levels and distribution of genetic diversity of C. taliensis and provides new insights into genetic consequence of domestication and geographic origin of planted trees of this species. As an endemic tea source plant, wild, planted and recently domesticated C. taliensis trees should all be protected for their unique genetic characteristics, which are valuable for tea breeding.
Assuntos
Camellia/genética , Repetições de Microssatélites/genética , Camellia/classificação , DNA de Plantas/genética , Variação Genética/genética , Filogenia , Análise de Sequência de DNA , Theaceae/classificação , Theaceae/genéticaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum, a renowned tonic traditional Chinese medicine, is widely recognized for the exceptional activity in soothing nerves and nourishing the brain. It has been extensively employed to alleviate various neurological disorders, notably Parkinson's disease (PD). AIM OF THE STUDY: To appraise the antiparkinsonian effect of GAA, the main bioactive constituent of G. lucidum, and clarify the molecular mechanism through the perspective of ferritinophagy-mediated dopaminergic neuron ferroptosis. MATERIALS AND METHODS: PD mouse and cell models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+), respectively. Cell viability, behavioral tests and immunofluorescence analysis were performed to evaluate the neurotoxicity, motor dysfunction and dopaminergic loss, respectively. Biochemical assay kits were used to determine the levels of iron, lipid reactive oxygen species (ROS), malondialdehyde (MDA), total ROS and glutathione (GSH). Western blot and immunofluorescence were applied to detect the expressions of nuclear receptor co-activator 4 (NCOA4), ferritin heavy chain 1 (FTH1), p62 and LC3B. Additionally, NCOA4-overexpressing plasmid vector was constructed to verify the inhibitory effect of GAA on the neurotoxicity and ferroptosis-related parameters in PD models. RESULTS: GAA significantly mitigated MPP+/MPTP-induced neurotoxicity, motor dysfunction and dopaminergic neuron loss (pï¼0.01 or pï¼0.05). In contrast to MPP+/MPTP treatment, GAA treatment decreased the levels of iron, MDA, lipid and total ROS, while increasing the GSH level. GAA also reduced the levels of NCOA4 and LC3B, and enhanced the expressions of FTH1 and p62 in PD models (pï¼0.01 or pï¼0.05). However, the protective effect of GAA against the neurotoxicity, NCOA4-mediated ferritinophagy and ferroptosis in PD model was abolished by the overexpression of NCOA4 (pï¼0.01). CONCLUSION: GAA exerted a protective effect on PD, and this effect was achieved by suppressing dopaminergic neuron ferroptosis through the inhibition of NCOA4-mediated ferritinophagy.
Assuntos
Neurônios Dopaminérgicos , Ferritinas , Ferroptose , Camundongos Endogâmicos C57BL , Coativadores de Receptor Nuclear , Animais , Ferroptose/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Coativadores de Receptor Nuclear/metabolismo , Camundongos , Masculino , Ferritinas/metabolismo , Fármacos Neuroprotetores/farmacologia , Autofagia/efeitos dos fármacos , Antiparkinsonianos/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/induzido quimicamente , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Modelos Animais de DoençasRESUMO
Glucagon-like peptide-1 (GLP-1) as a multifunctional hormone is secreted mainly from enteroendocrine L-cells, and enhancing its endogenous secretion has potential benefits of regulating glucose homeostasis and controlling body weight gain. In the present study, a novel polysaccharide (h-DHP) with high ability to enhance plasma GLP-1 level in mice was isolated from Dendrobium huoshanense protocorm-like bodies under the guidance of activity evaluation. Structural identification showed that h-DHP was an acidic polysaccharide with the molecular weight of 1.38 × 105 Da, and was composed of galactose, glucose, arabinose and glucuronic acid at a molar ratio of 15.7: 11.2: 4.5: 1.0 with a backbone consisting of â5)-α-L-Araf-(1â, â3)-α-D-Galp-(1â, â6)-α-D-Galp-(1â, â3,6)-α-D-Galp-(1â, â6)-ß-D-Glcp-(1â and â4,6)-ß-D-Glcp-(1â along with branches consisting of α-L-Araf-(1â, α-D-Galp-(1â, α-D-GlcAp-(1â, ß-D-Glcp-(1â and â4)-ß-D-Glcp-(1â. Animal experiments with different administration routes demonstrated that h-DHP-enhanced plasma GLP-1 level was attributed to h-DHP-promoted GLP-1 secretion in the enteroendocrine L-cells, which was supported by h-DHP-enhanced extracellular GLP-1 level in STC-1 cells. Inhibition of adenylate cyclase and phospholipase C indicated that cAMP and cAMP-triggered intracellular Ca2+ increase participated in h-DHP-promoted GLP-1 secretion. These results suggested that h-DHP has the potential of enhancing endogenous GLP-1 level through h-DHP-promoted and cAMP-mediated GLP-1 secretion from enteroendocrine cells.
RESUMO
An amyloid-ß (Aß) fibril is a vital pathogenic factor of Alzheimer's disease (AD). Aß fibril disintegrators possess great potential to be developed into novel anti-AD agents. Here, a ligand fishing method was employed to rapidly discover Aß42 fibril disintegrators from Ganoderma lucidum using Aß42 fibril-immobilized magnetic beads, which led to the isolation of six Aß42 fibril disintegrators including ganodermanontriol, ganoderic acid DM, ganoderiol F, ganoderol B, ganodermenonol, and ergosterol. Neuroprotective evaluation in vitro exhibited that these Aß42 fibril disintegrators could significantly mitigate Aß42-induced neurotoxicity. Among these six disintegrators, ergosterol and ganoderic acid DM with stronger protecting activity were further selected to evaluate their neuroprotective effect on AD in vivo. Results showed that ergosterol and ganoderic acid DM could significantly alleviate Aß42-induced cognitive dysfunction and hippocampus neuron loss in vivo. Moreover, ergosterol and ganoderic acid DM could significantly inhibit Aß42-induced neuron apoptosis and Nrf2-mediated neuron oxidative stress in vitro and in vivo.
Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Reishi , Triterpenos , Doença de Alzheimer/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Ligantes , Peptídeos beta-Amiloides , Amiloide , Ergosterol , Fragmentos de Peptídeos/uso terapêuticoRESUMO
This study aims to investigate the ameliorative effect of Codonopsis lanceolata polysaccharide (PCL) on mice with hypogalatia induced by a high-fat diet (HFD) and the potential underlying mechanism. We found that oral administration of PCL demonstrated significant benefits in countering the negative effects of HFD, including weight gain, hepatic steatosis, mesenteric adipocyte hypertrophy, and abnormal glucose/lipid metabolism. In addition, PCL improved mammary gland development and enhanced lactogenesis performance. Histologically, PCL ameliorated the retardation of ductal growth, reduced mammary fat pad thickness, improved the incomplete linear encapsulation of luminal epithelium and myoepithelium, and increased the proliferation of mammary epithelial cells. Flow cytometry analysis showed that PCL mitigated the detrimental effects of HFD on mammary gland development by promoting the proliferation and differentiation of mammary epithelial cells. Mechanistic studies revealed that PCL upregulated the levels of prolactin (PRL) and its receptor (PRLR) in the mammary gland, activated JAK2/STAT5 signaling pathway, and increased the expression of p63, ERBB4, and NRG1. Overall, PCL can ameliorate HFD-induced hypogalactia by activating PRLR-mediated JAK2/STAT5 signaling. Our findings offer a methodological and theoretical foundation for investigating the functional constituents of traditional Chinese medicine in the treatment of hypogalactia.
Assuntos
Codonopsis , Transtornos da Lactação , Humanos , Feminino , Camundongos , Animais , Prolactina/metabolismo , Prolactina/farmacologia , Receptores da Prolactina/metabolismo , Codonopsis/metabolismo , Fator de Transcrição STAT5/metabolismo , Dieta Hiperlipídica/efeitos adversos , Transdução de Sinais , Período Pós-Parto , Polissacarídeos/farmacologiaRESUMO
Renal tubular ectopic lipid deposition (ELD) plays a significant role in the development of chronic kidney disease, posing a great threat to human health. The present work aimed to explore the intervention effect and potential molecular mechanism of a purified tea polysaccharide (TPS3A) on renal tubular ELD. The results demonstrated that TPS3A effectively improved kidney function and slowed the progression of tubulointerstitial fibrosis in high-fat-diet (HFD)-exposed ApoE-/- mice. Additionally, TPS3A notably suppressed lipogenesis and enhanced lipolysis, as shown by the downregulation of lipogenesis markers (SREBP-1 and FAS) and the upregulation of lipolysis markers (HSL and ATGL), thereby reducing renal tubular ELD in HFD-fed ApoE-/- mice and palmitic-acid-stimulated HK-2 cells. The AMPK-SIRT1-FoxO1 axis is a core signal pathway in regulating lipid deposition. Consistently, TPS3A significantly increased the levels of phosphorylated-AMPK, SIRT1, and deacetylation of Ac-FoxO1. However, these effects of TPS3A on lipogenesis and lipolysis were abolished by AMPK siRNA, SIRT1 siRNA, and FoxO1 inhibitor, resulting in exacerbated lipid deposition. Taken together, TPS3A shows promise in ameliorating renal tubular ELD by inhibiting lipogenesis and promoting lipolysis through the AMPK-SIRT1-FoxO1 signaling pathway.
Assuntos
Dieta Hiperlipídica , Lipogênese , Lipólise , Camundongos Endogâmicos C57BL , Polissacarídeos , Animais , Lipogênese/efeitos dos fármacos , Camundongos , Lipólise/efeitos dos fármacos , Masculino , Dieta Hiperlipídica/efeitos adversos , Humanos , Polissacarídeos/farmacologia , Polissacarídeos/administração & dosagem , Sirtuína 1/metabolismo , Sirtuína 1/genética , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Túbulos Renais/metabolismo , Túbulos Renais/efeitos dos fármacos , Camellia sinensis/química , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Chá/química , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genéticaRESUMO
A new homogeneous polysaccharide (TPS3A) was isolated and purified from Tianzhu Xianyue fried green tea by DEAE-52 cellulose and Sephacryl S-500 column chromatography. Structural characterization indicated that TPS3A mainly consisted of arabinose, galactose, galacturonic acid and rhamnose in a molar ratio of 5.84: 4.15: 2.06: 1, with an average molecular weight of 1.596 × 104 kDa. The structure of TPS3A was characterized as a repeating unit consisting of 1,3-Galp, 1,4-Galp, 1,3,6-Galp, 1,3-Araf, 1,5-Araf, 1,2,4-Rhap and 1-GalpA, with two branches on the C6 of 1,3,6-Galp and C2 of 1,2,4-Rhap, respectively. To investigate the preventive effects of TPS3A on atherosclerosis, TPS3A was administered orally to ApoE-deficient (ApoE-/-) mice. Results revealed that TPS3A intervention could effectively delay the atherosclerotic plaque progression, modulate dyslipidemia, and reduce the transformation of vascular smooth muscle cells (VSMCs) from contractile phenotype to synthetic phenotype by activating the expression of contractile marker alpha-smooth muscle actin (α-SMA) and inhibiting the expression of synthetic marker osteopontin (OPN) in high-fat diet-induced ApoE-/- mice. Our findings suggested that TPS3A markedly alleviated atherosclerosis by regulating dyslipidemia and phenotypic transition of VSMCs, and might be used as a novel functional ingredient to promote cardiovascular health.
Assuntos
Aterosclerose , Dislipidemias , Animais , Camundongos , Chá , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/análise , Aterosclerose/tratamento farmacológico , Apolipoproteínas ERESUMO
OBJECTIVE: To study the protective effects of polysaccharides from Dendrobium huoshanense (DHP) against CCl4-induced liver injury in mice. METHOD: Eighty male Kunming mice were randomly divided into normal control group, model control group, dextran control group, starch control group, hydrolyzate control group, three different dose of DPH groups consisting of high-dosage group, middle-dosage group and low-dosage group (200, 100, 50 mg x kg(-1)). Each group contained ten mice. The mice were treated with DHP via intragastric administration for 15 days before treatment of 50% CCl4 in olive oil for consecutive two days. Both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum and superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents in liver tissues were determined in all groups. Immunohistochemistry was used to detect the expression of TNF-alpha in hepatic tissue. Hepatic histopathological examination was observed. RESULT: DHP effectively decreased the activities of ALT and AST in serum and the contents of hepatic MDA, and restored hepatic SOD activities in acute liver injury mice. Liver tissue damage induced by CCl4 was ameliorated in mice with DHP administration through histopathology examination. Furthermore, the expression of TNF-alpha was greatly decreased in groups treated with polysaccharides. CONCLUSION: DHP has a significantly hepatoprotective effect on CCl4-induced acute liver injury in mice. Protective effect of DHP on the liver may be related to its function of scavenging free radicals and inhibiting lipid peroxidation and TNF-alpha expression.
Assuntos
Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dendrobium/química , Polissacarídeos/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Polissacarídeos/química , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with unknown etiology and difficult treatment. In this study, the intervention effect of Dendrobium fimbriatum Hook polysaccharide (cDFPW1) on UC was verified by constructing a dextran sulfate sodium (DSS)-induced colitis mouse model, and the protective effect of cDFPW1 on intestinal mucosal integrity in UC was explored by the co-culture system consisting of intestinal organoids and lamina propria lymphocytes (LPLs) combined with the experiment of microbial depletion mice. Results showed that cDFPW1 significantly alleviated UC symptoms in mice and promoted the proliferation of intestinal epithelial cells. Importantly, cDFPW1 could directly improve DSS-induced morphological damage of intestinal organoids and increase the number of epithelial cells, which was validated in mice. During repair, an increase in the number of Lgr5+ cells in intestinal organoids and mouse intestines was promoted by cDFPW1. Meanwhile, cDFPW1 promoted intestinal stem cells (ISCs)-mediated intestinal epithelial regeneration by significantly upregulating IL-22 expression. We further confirmed that the secretion of IL-22 was mediated by LPLs. Together, these findings suggest that cDFPW1 promotes ISCs regeneration by LPLs-mediated up-regulation of IL-22 to protect the intestinal mucosal integrity, thereby playing an important role in improving UC.
Assuntos
Colite Ulcerativa , Colite , Dendrobium , Animais , Camundongos , Colite/induzido quimicamente , Colite Ulcerativa/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Interleucinas/metabolismo , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos C57BL , Células-Tronco , Interleucina 22RESUMO
This study aimed to explore whether Dendrobium huoshanense stem polysaccharide (cDHPS) ameliorates alcohol-induced gastric ulcer (GU) through the strengthening effect of the gastric mucosal barrier in rats and its potential mechanism. In normal rats, the pretreatment of cDHPS effectively strengthened gastric mucosal barrier by increasing mucus secretion and tight junction protein expression. In GU rats, cDHPS supplementation effectively alleviated alcohol-induced gastric mucosal injury and nuclear factor κB (NF-κB)-driven inflammation by strengthening gastric mucosal barrier. Moreover, cDHPS significantly activated nuclear factor E2-related factor 2 (Nrf2) signaling and promoted antioxidant enzymes activities in both normal and GU rats. These results suggested that the pretreatment of cDHPS could strengthen gastric mucosal barrier to inhibit oxidative stress and NF-κB-driven inflammation induced gastric mucosal injury, which was likely related to the activation of Nrf2 signaling.
Assuntos
Dendrobium , Úlcera Gástrica , Ratos , Animais , NF-kappa B/metabolismo , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Antioxidantes/farmacologia , Inflamação , Polissacarídeos/efeitos adversosRESUMO
In the present work, we explored the interventional effect and potential mechanism of a purified Laminaria japonica polysaccharide (LJP61A) on podocyte epithelial-mesenchymal transition (EMT) in TGF-ß1-induced podocytes and adriamycin-treated mice. Results showed that compared to the model groups, LJP61A significantly up-regulated the levels of epithelial markers (Nephrin, WT-1, podocin) and down-regulated the levels of mesenchymal markers (α-SMA, FN1) in vitro and in vivo, thus preventing EMT-like morphological changes of podocytes, proteinuria and kidney injury. Smad3 and p38MAPK are two central pathways mediating podocyte EMT activated by TGF-ß1. We found that LJP61A suppressed TGF-ß1-induced activation of Smad3, Smad4 and p38MAPK in vitro and in vivo. Moreover, the inhibitory actions of LJP61A on podocyte EMT were synergistically strengthened by Smad3 inhibitor SIS3 and p38MAPK inhibitor SB203580. Taken together, these findings revealed that LJP61A could prevent podocyte EMT, which might be related to the inhibition of TGF-ß1-mediated Smad3 and p38MAPK pathways.
Assuntos
Laminaria , Podócitos , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Podócitos/metabolismo , Transição Epitelial-Mesenquimal , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Proteína Smad3/metabolismoRESUMO
The Ca2+-calpain signaling plays a pivotal role in regulating the upstream signaling pathway of cellular autophagy. The aim of the current work was to investigate the role of Ca2+-calpain signaling in the regulation of macrophage autophagy by a Laminaria japonica polysaccharide (LJP61A) in Ox-LDL induced macrophages and high fat diet fed atherosclerotic mice. Results revealed that the LJP61A markedly decreased the levels of intracellular Ca2+, calpain1, calpain2 and their downstream effectors (Gsα, cAMP and IP3), and simultaneously enhanced autophagy activity and lipid metabolism, thereby reducing lipid accumulation in the Ox-LDL stimulated macrophages and lipid-laden plaques in atherosclerotic mice. Moreover, BAPTA-AM (a Ca2+ chelator) and calpeptin (a calpain inhibitor) synergistically strengthened the beneficial effects of LJP61A on autophagy and lipid metabolism by decreasing the levels of intracellular Ca2+, calpain1, calpain2, and their downstream effectors (Gsα, cAMP and IP3) induced by Ox-LDL. These findings suggested that the LJP61A suppressed macrophage derived foam cell formation and atherosclerosis by modulating the Ca2+-calpain-mediated autophagy.
Assuntos
Aterosclerose , Laminaria , Animais , Camundongos , Células Espumosas , Laminaria/metabolismo , Calpaína/metabolismo , Calpaína/farmacologia , Macrófagos , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Lipoproteínas LDL/metabolismo , Transdução de Sinais , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , AutofagiaRESUMO
Osteocalcin was reported to regulate muscle energy metabolism, thus fighting fatigue during exercise. The current work aimed to investigate the anti-fatigue effect and the underlying mechanism of a homogeneous polysaccharide (PCPY-1) from Polgonatum cyrtonema after structure characterization. In the exhaustive swimming mouse model and the co-culture system of BMSCs/C2C12 cells, PCPY-1 significantly stimulated BMSC differentiation into osteoblasts as determined by ALP activity, matrix mineralization, and the protein expressions of osteogenic markers BMP-2, phosphor-Smad1, RUNX2, and osteocalcin. Meanwhile, PCPY-1 remarkably enhanced myoblast energy metabolism by upregulating osteocalcin release and GPRC6A protein expression; the phosphorylation levels of CREB and HSL; the mRNA levels of GLUT4, CD36, FATP1, and CPT1B; and ATP production in vitro and in vivo. Accordingly, PCPY-1 exhibited good anti-fatigue capacity in mice as confirmed by fatigue-related indicators. Our findings indicated PCPY-1 could enhance osteocalcin-mediated communication between bones and muscles, which was conducive to muscle energy metabolism and ATP generation, thus alleviating fatigue in exhausted swimming mice.