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1.
Nutrients ; 15(17)2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37686763

RESUMO

Auricularia auricula is a traditional medicinal and edible mushroom with anti-aging effects. Many studies focused on polysaccharides and melanin. However, the anti-aging effects and mechanism of the nutritional supplementation of Auricularia auricula peptides (AAPs) were not elucidated. In this study, AAPs were prepared by enzymolysis of flavor protease and the protective effects on H2O2-induced senescence of HepG2 cells were explored for the first time. The potential mechanism was also investigated. AAPs were mostly composed of low molecular weights with less than 1000 Da accounting for about 79.17%, and contained comprehensive amino acids nutritionally, including seven essential amino acids, aromatic, acidic, and basic amino acids. AAPs nutritional supplementation could significantly decrease the levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA), and increase the activities of antioxidant enzymes (SOD, CAT, and GSH-Px). In addition, the senescence-associated-ß-galactosidase (SA-ß-gal) activity was restrained, and the expression levels of senescence-associated secretory phenotype (SASP) (IL-6, IL-8, IL-1ß, and CXCL2) were also decreased. Ribonucleic acid sequencing (RNA-Seq) was carried out to screen the differentially expressed genes (DEGs) between different groups. GO and KEGG enrichment analysis showed that the mechanism was related to the MAPK/NF-κB signaling pathways. Quantitative real-time PCR (qRT-PCR) analysis and Western blot were carried out to verify the key genes and proteins in the pathways, respectively. AAPs nutritional supplementation resulted a significant down-regulation in key the genes c-fos and c-jun and up-regulation in DUSP1 of the MAPK signaling pathway, and down-regulation in the key genes CXCL2 and IL-8 of the NF-κB signaling pathway. The results of Western blot demonstrate that AAPs nutritional supplementation could inhibit MAPK/NF-κB pathways by reducing the expression levels of IKK, IκB, P65, and phosphorylation of ERK, thus decreasing the inflammatory reaction and delaying cell senescence. It is the first time that AAPs nutritional supplementation was proved to have protective effects on H2O2-induced oxidative damage in HepG2 cells. These results implicate that dietary AAPs could be used as nutrients to reduce the development or severity of aging.


Assuntos
Peróxido de Hidrogênio , NF-kappa B , Humanos , Interleucina-8 , Células Hep G2 , Peptídeos/farmacologia , Suplementos Nutricionais , Transdução de Sinais
2.
Food Sci Biotechnol ; 32(11): 1541-1549, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37637845

RESUMO

Pyrraline, one of advanced glycation end-products, is formed in advanced Maillard reactions. It was reported that the presence of pyrraline was tested to be associated with nephropathy and diabetes. Pyrraline might result in potential health risks because many modern diets are heat processed. In the study, an integrated metabolomics by ultra-high-performance liquid chromatography with mass spectrometry was used to evaluate the effects of pyrraline on metabolism in rats. Thirty-two metabolites were identified as differential metabolites. Linolenic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, tyrosine metabolism and glycerophospholipid metabolism were the main perturbed networks in this pathological process. Differential metabolites and metabolic pathways we found give new insights into studying the toxic molecular mechanisms of pyrraline. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01256-7.

3.
J Spinal Cord Med ; 46(5): 798-806, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-35792817

RESUMO

PURPOSE: Warm acupuncture (WA) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The current study attempted to explore the WA therapy on neuronal apoptosis of SCI and the relationship with the extracellular signal-regulated kinase (ERK) signaling pathway. METHODS: The rat SCI models were established by the impact method. SCI rat models were subjected to WA treatment at Dazhui (GV14) and Jiaji points (T10), Yaoyangguan (GV3), Zusanli (ST36), and Ciliao (BL32). The rat SCI models were established by the impact method. WA and U0126 treatments were performed on the SCI rats. Motor function and neuronal apoptosis were detected. The relative mRNA of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), the phosphorylation level of ERK 1/2 and levels of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), and caspase-3 in spinal cord tissue were tested. RESULTS: After WA treatment, the Basso, Beattie & Bresnahan locomotor rating scale (BBB scale) of SCI rats in the WA treatment was significantly raised from 7 to 14 days after SCI. WA and U0126 treatment significantly diminished apoptotic cells and preserved the neurons in the injured spinal cord. WA and U0126 treatment alleviated the production of inflammatory cytokines in the spinal cord. The distinct increase of p-ERK 1/2 induced by SCI was reversed in WA and U0126 treatment groups. WA and U0126 treatment augmented the level of Bcl-2 and reversed the elevated cleaved caspase-3 protein level after SCI. CONCLUSION: Our study demonstrated that WA might be associated with the downregulation of the ERK signaling pathway. In summary, our findings indicated that WA promotes the recovery of SCI via the protection of nerve cells and the prevention of apoptosis. Meanwhile, the anti-apoptotic effect of WA might be associated with the downregulation of the ERK signaling pathway, which could be one of the mechanisms of WA in the treatment of SCI.


Assuntos
Terapia por Acupuntura , Traumatismos da Medula Espinal , Animais , Ratos , Apoptose , Caspase 3/metabolismo , Caspase 3/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Transdução de Sinais , Medula Espinal/patologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia
4.
J Spinal Cord Med ; 45(1): 106-116, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32441569

RESUMO

Objective: Acupuncture combined with moxibustion (AM) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The present study aimed to confirm the effect and mechanism of AM treatment on the recovery of SCI.Design: Male Sprague-Dawley rats were used to establish the SCI model by impact method. SCI rat models were subjected to AM treatment at Dazhui (GV14) and Jiaji points (T7-T12), Yaoyangguan (GV3), Zusanli (ST36) and Ciliao (BL32).Outcome measures: Motor function and cell apoptosis in rats after SCI. The mRNA and protein expression levels of Shh and Gli-1 were determined by real-time quantitative polymerase chain reaction, western blot and immunohistochemistry.Results: After AM treatment, the hindlimb motor function of SCI rats was significantly increased than the SCI group at 7, 9, 11, 14 days (P < 0.05). AM treatment 7 d and 14 d significantly preserved the nissl-stained positive neurons and significantly decreased number of apoptotic cells, compared to that of SCI 7 and 14 d groups (P < 0.05). AM treatment improved the mRNA protein levels of Shh and Gli-1 after 7 and 14 days treatment compared to the SCI group (P < 0.05).Conclusion: AM could improve the expression of Shh and Gli-1 in injured spinal cord of rats. That could be part of underlying mechanisms of AM treatment including recover motor function and preserve the neuron cells and alleviate the apoptosis of nerve cells in rats after SCI.


Assuntos
Terapia por Acupuntura , Moxibustão , Traumatismos da Medula Espinal , Animais , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Transdução de Sinais , Medula Espinal
5.
Plant Physiol ; 181(4): 1600-1614, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31548267

RESUMO

RETINOBLASTOMA-RELATED (RBR) is an essential gene in plants, but its molecular function outside of its role in cell cycle entry remains poorly understood. We characterized the functions of OsRBR1 and OsRBR2 in plant growth and development in rice using both forward- and reverse-genetics methods. The two genes were coexpressed and performed redundant roles in vegetative organs but exhibited separate functions in flowers. OsRBR1 was highly expressed in the floral meristem and regulated the expression of floral homeotic genes to ensure floral organ formation. Mutation of OsRBR1 caused loss of floral meristem identity, resulting in the replacement of lodicules, stamens, and the pistil with either a panicle-like structure or whorls of lemma-like organs. OsRBR2 was preferentially expressed in stamens and promoted pollen formation. Mutation of OsRBR2 led to deformed anthers without pollen. Similar to the protein interaction between AtRBR and AtMSI1 that is essential for floral development in Arabidopsis, OsMSI1 was identified as an interaction partner of OsRBR1 and OsRBR2. OsMSI1 was ubiquitously expressed and appears to be essential for development in rice (Oryza sativa), as the mutation of OsMSI1 was lethal. These results suggest that OsRBR1 and OsRBR2 function with OsMSI1 in reproductive development in rice. This work characterizes further functions of RBRs and improves current understanding of specific regulatory pathways of floral specification and pollen formation in rice.


Assuntos
Genes de Plantas , Morfogênese/genética , Oryza/genética , Proteínas de Plantas/genética , Pólen/genética , Retinoblastoma/genética , Sequência de Bases , Regulação da Expressão Gênica de Plantas , Modelos Biológicos , Mutação/genética , Especificidade de Órgãos/genética , Oryza/ultraestrutura , Fenótipo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Pólen/ultraestrutura , Ligação Proteica , Frações Subcelulares/metabolismo
6.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(1): 50-56, 2018 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926659

RESUMO

OBJECTIVE: To investigate the effects of Coriaria Sinica Maxim's extract(CSME) on microcirculation and oxidative stress of wounds in rats with deep second-degree burn. METHODS: One hundred and eighty rats were randomly divided into normal saline group(NS), white petroleum group(WPL), silver sulfadiazine group (SSD), Coriariasinica Maxim's extract group which were divided into low dose(CSME-L),middle dose(CSME-M) and high dose(CSME-H). After anesthesia with burn instrument to burn the hair removal area of rats, these wounds were confirmed by pathological results with deep second degree burns.And then,those drugs were applied respectively on the wounds,such as NS、WPL、SSD and different concentrations of CSME. After injury at 48 h, 7 d, 14 d and 21 d,the healing rate(HR) of wound was measured, and the microvessel density (MVD), tissue moisture (TM), vascular endothelial growth factor (VEGF), model driven architecture (MDA), superoxide dismutase(SOD) and hydroxyproline(HYP) were detected, too. All pathological sections of the wound tissue were observed. RESULTS: The HR of CSME groups were obviously increased with a dose-dependent manner, which was significantly higher than that of NS and WPL (P<0.05); On the 21st day, the diameter, number, distribution of the vessels and and the TM were less than other groups with a dose-dependent manner; On the 7th and 14th day after injury, CSME groups were significantly higher than the NS, WPL and SSD with a dose-dependent manner (P<0.05), but, on the 21st day after injury, they were lower than NS, WPL and SSD with a dose-dependent (P<0.05) manner. The levels of SOD, HYP, NO and ET in CSME groups were higher than those in other groups with dose-dependent on SOD activity, HYP, NO and ET content (P<0.05), while MDA activity was weaker than other groups (P<0.05). Similarly, pathological findings were also shown that CSME groups were better than other groups with a dose-dependent manner in decrease decreasing of wound repair time and hyperplasia of scar tissue. CONCLUSIONS: CSME can relieve tissue edema, promote wound contraction, speed up the formation of eschar and accelerate the proliferation of granulation tissue, which are beneficial to the wound healing in the early stages. But, it can inhibit the hyperplasia of granulation tissue to prevent the excessive scar hyperplasia of burn wound in the later stages. Its mechanism is related to regulation what microcirculation, oxidativestress, NO and VEGF.


Assuntos
Queimaduras/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Microcirculação , Estresse Oxidativo , Cicatrização/efeitos dos fármacos , Animais , Hidroxiprolina/metabolismo , Malondialdeído/metabolismo , Distribuição Aleatória , Ratos , Superóxido Dismutase/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Artigo em Chinês | WPRIM | ID: wpr-773804

RESUMO

OBJECTIVE@#To investigate the effects of Coriaria Sinica Maxim's extract(CSME) on microcirculation and oxidative stress of wounds in rats with deep second-degree burn.@*METHODS@#One hundred and eighty rats were randomly divided into normal saline group(NS), white petroleum group(WPL), silver sulfadiazine group (SSD), Coriariasinica Maxim's extract group which were divided into low dose(CSME-L),middle dose(CSME-M) and high dose(CSME-H). After anesthesia with burn instrument to burn the hair removal area of rats, these wounds were confirmed by pathological results with deep second degree burns.And then,those drugs were applied respectively on the wounds,such as NS、WPL、SSD and different concentrations of CSME. After injury at 48 h, 7 d, 14 d and 21 d,the healing rate(HR) of wound was measured, and the microvessel density (MVD), tissue moisture (TM), vascular endothelial growth factor (VEGF), model driven architecture (MDA), superoxide dismutase(SOD) and hydroxyproline(HYP) were detected, too. All pathological sections of the wound tissue were observed.@*RESULTS@#The HR of CSME groups were obviously increased with a dose-dependent manner, which was significantly higher than that of NS and WPL (<0.05); On the 21 day, the diameter, number, distribution of the vessels and and the TM were less than other groups with a dose-dependent manner; On the 7 and 14 day after injury, CSME groups were significantly higher than the NS, WPL and SSD with a dose-dependent manner (<0.05), but, on the 21 day after injury, they were lower than NS, WPL and SSD with a dose-dependent (<0.05) manner. The levels of SOD, HYP, NO and ET in CSME groups were higher than those in other groups with dose-dependent on SOD activity, HYP, NO and ET content (<0.05), while MDA activity was weaker than other groups (<0.05). Similarly, pathological findings were also shown that CSME groups were better than other groups with a dose-dependent manner in decrease decreasing of wound repair time and hyperplasia of scar tissue.@*CONCLUSIONS@#CSME can relieve tissue edema, promote wound contraction, speed up the formation of eschar and accelerate the proliferation of granulation tissue, which are beneficial to the wound healing in the early stages. But, it can inhibit the hyperplasia of granulation tissue to prevent the excessive scar hyperplasia of burn wound in the later stages. Its mechanism is related to regulation what microcirculation, oxidativestress, NO and VEGF.


Assuntos
Animais , Ratos , Queimaduras , Tratamento Farmacológico , Medicamentos de Ervas Chinesas , Farmacologia , Hidroxiprolina , Metabolismo , Malondialdeído , Metabolismo , Microcirculação , Estresse Oxidativo , Distribuição Aleatória , Superóxido Dismutase , Metabolismo , Fator A de Crescimento do Endotélio Vascular , Metabolismo , Cicatrização
8.
Chin Med J (Engl) ; 130(10): 1218-1225, 2017 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-28485323

RESUMO

BACKGROUND: Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan failure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins. METHODS: Healthy male Sprague-Dawley rats (weighing 230-250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned to eight groups (n = 6 or 8 each group): sham group (Group A: normal saline gavage); sepsis group (Group B: normal saline gavage); Group C (intraperitoneally, dexamethasone 0.5 mg/kg) immediately after CLP surgery; and rhubarb monomer (100 mg/kg in normal saline)-treated groups (Group D: rhein; Group E: emodin; Group F: 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid; Group G: 1-O-caffeoyl-2-(4-hydroxy-O-cinnamoyl)-D-glucose; and Group H: daucosterol linoleate). Animals were sacrificed after 24 h. Intestinal histology, lactulose, mannitol concentrations were measured, and zonula occludens (ZO)-1, occludin and claudin-5 transcription (polymerase chain reaction), translation (by Western blot analysis), and expression (by immunohistochemistry) were also measured. RESULTS: Intestinal histology revealed injury to intestinal mucosal villi induced by sepsis in Group B, compared with Group A. Compared with Group A (0.17 ± 0.41), the pathological scores in Groups B (2.83 ± 0.41, P < 0.001), C (1.83 ± 0.41, P < 0.001), D (2.00 ± 0.63, P < 0.001), E (1.83 ± 0.41, P < 0.001), F (1.83 ± 0.75, P < 0.001), G (2.17 ± 0.41, P < 0.001),and H (1.83 ± 0.41, P < 0.001) were significantly increased. Lactulose/mannitol (L/M) ratio in Group B (0.046 ± 0.003) was significantly higher than in Group A (0.013 ± 0.001, P< 0.001) while L/M ratios in Groups C (0.028 ± 0.002, P< 0.001), D (0.029 ± 0.003, P< 0.001), E (0.026 ± 0.003, P< 0.001), F (0.027 ± 0.003, P< 0.001), G (0.030 ± 0.005, P< 0.001), and H (0.026 ± 0.002, P< 0.001) were significantly lower than that in Group B. ZO-1, occludin and claudin-5 transcription, translation, and expression in Group B were significantly lower than that in Group A (P < 0.001), but they were significantly higher in Groups C, D, E, F, G, and H than those in Group B (P < 0.05). CONCLUSION: Rhubarb monomer treatment ameliorated mucosal damage in sepsis via enhanced transcription, translation, and expression of junction proteins.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Extratos Vegetais/uso terapêutico , Rheum/química , Sepse/tratamento farmacológico , Sepse/metabolismo , Animais , Claudina-5/metabolismo , Lactulose/metabolismo , Masculino , Manitol/metabolismo , Ocludina/metabolismo , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Proteína da Zônula de Oclusão-1/metabolismo
9.
Chinese Medical Journal ; (24): 1218-1225, 2017.
Artigo em Inglês | WPRIM | ID: wpr-330640

RESUMO

<p><b>BACKGROUND</b>Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan failure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins.</p><p><b>METHODS</b>Healthy male Sprague-Dawley rats (weighing 230-250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned to eight groups (n = 6 or 8 each group): sham group (Group A: normal saline gavage); sepsis group (Group B: normal saline gavage); Group C (intraperitoneally, dexamethasone 0.5 mg/kg) immediately after CLP surgery; and rhubarb monomer (100 mg/kg in normal saline)-treated groups (Group D: rhein; Group E: emodin; Group F: 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid; Group G: 1-O-caffeoyl-2-(4-hydroxy-O-cinnamoyl)-D-glucose; and Group H: daucosterol linoleate). Animals were sacrificed after 24 h. Intestinal histology, lactulose, mannitol concentrations were measured, and zonula occludens (ZO)-1, occludin and claudin-5 transcription (polymerase chain reaction), translation (by Western blot analysis), and expression (by immunohistochemistry) were also measured.</p><p><b>RESULTS</b>Intestinal histology revealed injury to intestinal mucosal villi induced by sepsis in Group B, compared with Group A. Compared with Group A (0.17 ± 0.41), the pathological scores in Groups B (2.83 ± 0.41, P < 0.001), C (1.83 ± 0.41, P < 0.001), D (2.00 ± 0.63, P < 0.001), E (1.83 ± 0.41, P < 0.001), F (1.83 ± 0.75, P < 0.001), G (2.17 ± 0.41, P < 0.001),and H (1.83 ± 0.41, P < 0.001) were significantly increased. Lactulose/mannitol (L/M) ratio in Group B (0.046 ± 0.003) was significantly higher than in Group A (0.013 ± 0.001, P< 0.001) while L/M ratios in Groups C (0.028 ± 0.002, P< 0.001), D (0.029 ± 0.003, P< 0.001), E (0.026 ± 0.003, P< 0.001), F (0.027 ± 0.003, P< 0.001), G (0.030 ± 0.005, P< 0.001), and H (0.026 ± 0.002, P< 0.001) were significantly lower than that in Group B. ZO-1, occludin and claudin-5 transcription, translation, and expression in Group B were significantly lower than that in Group A (P < 0.001), but they were significantly higher in Groups C, D, E, F, G, and H than those in Group B (P < 0.05).</p><p><b>CONCLUSION</b>Rhubarb monomer treatment ameliorated mucosal damage in sepsis via enhanced transcription, translation, and expression of junction proteins.</p>


Assuntos
Animais , Masculino , Ratos , Claudina-5 , Metabolismo , Mucosa Intestinal , Metabolismo , Lactulose , Metabolismo , Manitol , Metabolismo , Ocludina , Metabolismo , Extratos Vegetais , Química , Usos Terapêuticos , Ratos Sprague-Dawley , Rheum , Química , Sepse , Tratamento Farmacológico , Metabolismo , Proteína da Zônula de Oclusão-1 , Metabolismo
10.
Chin Med J (Engl) ; 129(14): 1737-43, 2016 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-27411464

RESUMO

BACKGROUND: Intact endothelial structure and function are critical for maintaining microcirculatory homeostasis. Dysfunction of the latter is an underlying cause of various organ pathologies. In a previous study, we showed that rhubarb, a traditional Chinese medicine, protected intestinal mucosal microvascular endothelial cells in rats with metastasizing septicemia. In this study, we investigated the effects and mechanisms of rhubarb on matrix metalloproteinase-9 (MMP9)-induced vascular endothelial (VE) permeability. METHODS: Rhubarb monomers were extracted and purified by a series of chromatography approaches. The identity of these monomers was analyzed by hydrogen-1 nuclear magnetic resonance (NMR), carbon-13 NMR, and distortionless enhancement by polarization transfer magnetic resonance spectroscopy. We established a human umbilical vein endothelial cell (HUVEC) monolayer on a Transwell insert. We measured the HUVEC permeability, proliferation, and the secretion of VE-cadherin into culture medium using fluorescein isothiocyanate-dextran assay, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, and enzyme-linked immunosorbent assay, respectively, in response to treatment with MMP9 and/or rhubarb monomers. RESULTS: A total of 21 rhubarb monomers were extracted and identified. MMP9 significantly increased the permeability of the HUVEC monolayer, which was significantly reduced by five individual rhubarb monomer (emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-ß-D-glucose, daucosterol linoleate, and rhein) or a combination of all five monomers (1 µmol/L for each monomer). Mechanistically, the five-monomer mixture at 1 µmol/L promoted HUVEC proliferation. In addition, MMP9 stimulated the secretion of VE-cadherin into the culture medium, which was significantly inhibited by the five-monomer mixture. CONCLUSIONS: The rhubarb mixture of emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-ß-D-glucose, daucosterol linoleate, and rhein, at a low concentration, antagonized the MMP9-induced HUVEC monolayer permeability by promoting HUVEC proliferation and reducing extracellular VE-cadherin concentrations.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Rheum/química , Caderinas/metabolismo , Permeabilidade Capilar/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos
11.
Chinese Medical Journal ; (24): 1737-1743, 2016.
Artigo em Inglês | WPRIM | ID: wpr-251313

RESUMO

<p><b>BACKGROUND</b>Intact endothelial structure and function are critical for maintaining microcirculatory homeostasis. Dysfunction of the latter is an underlying cause of various organ pathologies. In a previous study, we showed that rhubarb, a traditional Chinese medicine, protected intestinal mucosal microvascular endothelial cells in rats with metastasizing septicemia. In this study, we investigated the effects and mechanisms of rhubarb on matrix metalloproteinase-9 (MMP9)-induced vascular endothelial (VE) permeability.</p><p><b>METHODS</b>Rhubarb monomers were extracted and purified by a series of chromatography approaches. The identity of these monomers was analyzed by hydrogen-1 nuclear magnetic resonance (NMR), carbon-13 NMR, and distortionless enhancement by polarization transfer magnetic resonance spectroscopy. We established a human umbilical vein endothelial cell (HUVEC) monolayer on a Transwell insert. We measured the HUVEC permeability, proliferation, and the secretion of VE-cadherin into culture medium using fluorescein isothiocyanate-dextran assay, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, and enzyme-linked immunosorbent assay, respectively, in response to treatment with MMP9 and/or rhubarb monomers.</p><p><b>RESULTS</b>A total of 21 rhubarb monomers were extracted and identified. MMP9 significantly increased the permeability of the HUVEC monolayer, which was significantly reduced by five individual rhubarb monomer (emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-β-D-glucose, daucosterol linoleate, and rhein) or a combination of all five monomers (1 μmol/L for each monomer). Mechanistically, the five-monomer mixture at 1 μmol/L promoted HUVEC proliferation. In addition, MMP9 stimulated the secretion of VE-cadherin into the culture medium, which was significantly inhibited by the five-monomer mixture.</p><p><b>CONCLUSIONS</b>The rhubarb mixture of emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-β-D-glucose, daucosterol linoleate, and rhein, at a low concentration, antagonized the MMP9-induced HUVEC monolayer permeability by promoting HUVEC proliferation and reducing extracellular VE-cadherin concentrations.</p>


Assuntos
Humanos , Caderinas , Metabolismo , Permeabilidade Capilar , Linhagem Celular , Proliferação de Células , Medicamentos de Ervas Chinesas , Química , Farmacologia , Células Endoteliais da Veia Umbilical Humana , Biologia Celular , Metaloproteinase 9 da Matriz , Metabolismo , Rheum , Química
12.
Am J Chin Med ; 42(5): 1215-27, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25176604

RESUMO

The intestine plays a vital role in the pathophysiology of sepsis development. The objective of the present study was to explore the effects of rhubarb on intestinal microcirculation in septic rats. We used moorFLPI laser speckle imaging to detect the blood flow of the intestinal mucosa and wall. Using an ELISA, we assayed the concentration of lactate (L) and pyruvic acid (P) in the intestinal tissue to calculate the ratio of lactate to pyruvic acid (L/P ratio). To observe the intestinal mucosal capillaries, gelatin and ink were perfused into the intestine and subsequently stained with hematoxylin and eosin (HE) to measure the ratio of the vessel area. We then used immunohistochemistry to measure CD31 expression. Using an MTT assay, the effect of the rhubarb extract on the proliferation of human umbilical vein endothelial cells (HUVECs) was analyzed. The blood flow in the intestinal wall and mucosa of the control, sham and rhubarb-treated groups was significantly higher, while the sepsis group had relatively low blood flow. The L/P ratio in the intestinal tissue was larger in the sepsis group than in the other three groups. The microvascular area (MVA) in the sepsis group was smaller than in the control group, sham group or rhubarb group. Positive expression for CD31 was observed in the cytoplasm of vascular endothelial cells. The intestinal mucosal capillaries were reduced in septic rats as compared to the other three groups. HUVEC proliferation was enhanced by the rhubarb extract monomers at 1 µmol/L, but suppressed at higher concentrations of 10 to 100 µmol/L. These results suggest that pre-treatment with rhubarb prior to sepsis induction promotes the expansion of the intestinal mucosal capillaries, protects intestinal mucosal capillary endothelial cells and increases the number of functional intestinal capillaries.


Assuntos
Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/metabolismo , Microcirculação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rheum , Sepse/metabolismo , Sepse/fisiopatologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Dobutamina , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Humanos , Ácido Láctico/metabolismo , Masculino , Oxigênio/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ácido Pirúvico/metabolismo , Ratos Sprague-Dawley , Veias Umbilicais/citologia
13.
Acta Pharmacol Sin ; 34(4): 496-500, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23524570

RESUMO

AIM: To investigate the effects of salvianolate, a water-soluble active compound from Salvia miltiorrhiza Bunge, on reactive oxygen species (ROS) production in mouse cardiomyocytes in vitro. METHODS: Primary ventricular cardiomyocytes were prepared from neonatal mouse. The cell viability was determined using MTT assay. Culture medium for each treatment was collected for measuring the levels of NO, iNOS, total antioxidant capacity (TAOC) and transforming growth factor ß1 (TGFß1). TGFß1 and Smad2/3 expression in the cells was detected with Western blotting. RESULTS: H2O2 (1.25 mmol/L) did not significantly affect the cell viability, whereas the high concentration of salvianolate (5 g/L) alone dramatically suppressed the cell viability. Treatment of the cells with H2O2 (1.25 mmol/L) markedly increased ROS and iNOS production, and decreased the levels of NO, TAOC and TGFß1 in the culture medium. Furthermore, the H2O2 treatment significantly increased TGFß1 and Smad2/3 expression in the cells. Addition of salvianolate (0.05, 0.1, and 0.5 g/L) concentration-dependently reversed the H2O2-induced alterations in the culture medium; addition of salvianolate (0.05 g/L) reversed the H2O2-induced increases of TGFß1 and Smad2/3 expression in the cells. Blockage of TGFß1 with its antibody (1 mg/L) abolished the above mentioned effects of salvianolate. CONCLUSION: Salvianolate inhibits ROS and iNOS production and increases TAOC and NO levels in H2O2-treated cardiomyocytes in vitro via downregulation of Smad2/3 and TGFß1 expression. High concentration of salvianolate causes cytotoxicity in mouse cardiomyocytes.


Assuntos
Peróxido de Hidrogênio/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Antioxidantes/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Camundongos , Miócitos Cardíacos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Salvia miltiorrhiza/química , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo
14.
Zhong Xi Yi Jie He Xue Bao ; 7(9): 827-30, 2009 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-19747437

RESUMO

OBJECTIVE: To explore the cognitive level and the mental status of the patients suffering from perimenopausal syndrome in Shanghai, and to identify the traditional Chinese medicine syndrome distribution feature of perimenopausal syndrome. METHODS: The cognitive level of the perimenopausal women was evaluated by using general living problem questionnaire. The mental status of the perimenopausal women was evaluated by using self-rating depressive scale. The traditional Chinese medicine syndrome distribution feature of perimenopausal syndrome was identified by using traditional Chinese medical symptoms questionnaire. RESULTS: A total of 634 perimenopausal women finished the investigation. There were 74.76% (474/634) patients who knew little about the perimenopausal syndrome; 77.29% (490/634) patients had a depressive tendency; 8.36% (53/634) patients had depressive disorder. There were 72.40% (459/634) patients who had the symptoms such as susceptibility to anger and restlessness, restless sleep at night, thirst with dry throat and bitter taste, and all these symptoms could be classified into hyperactivity of heart and liver fire syndrome. CONCLUSION: Patients suffering from perimenopausal syndrome know little about this disease and mostly have depressive tendency, and the major traditional Chinese medicine syndrome pattern is hyperactivity of heart and liver fire based on the chief clinical manifestations of the patients.


Assuntos
Depressão/epidemiologia , Medicina Tradicional Chinesa , Perimenopausa/psicologia , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome
15.
Zhongguo Zhong Yao Za Zhi ; 30(8): 621-4, 2005 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-16011291

RESUMO

OBJECTIVE: To study the effect of Acanthopanax senticosus injection (ASI) on the activities of human tumor necrosis factor (TNF) and natural killer cell (NKC) in the patients with lung cancer and the underlying mechanism. METHOD: 73 cases with lung cancer were randomly divided into two groups, namely, the treatment group (n = 39) and observation group (n = 34); 61 cases with or without other diseases were respectively divided into control A (n = 30) and B (n = 31) groups. The patients in treatment group were injected with ASI for 21 days. The activities of human TNF and NKC and the levels of IgG, IgA and IgM were detected respectively. RESULT: After injection with ASI the activity of TNF-alpha in treatment group was comparable with that in the two control groups and was significant lower that that in observation group. The activity of TNF-beta and the levels of IgA, IgG and IgM were significantly higher than those in observation group and two control groups (P < 0.01). The activity of NKC was also remarkably higher than observation and two control groups. CONCLUSION: ASI can regulate the cellular immunity and factor, indicating that ASI can be used as an assistant drug to regulate the function of cellular immunity in the patients with lung cancer.


Assuntos
Eleutherococcus , Células Matadoras Naturais/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Polissacarídeos/farmacologia , Adulto , Idoso , Eleutherococcus/química , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Isotipos de Imunoglobulinas/sangue , Infusões Intravenosas , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , Linfotoxina-alfa/metabolismo , Masculino , Pessoa de Meia-Idade , Plantas Medicinais/química , Polissacarídeos/administração & dosagem , Polissacarídeos/isolamento & purificação , Fator de Necrose Tumoral alfa/metabolismo
16.
Artigo em Chinês | WPRIM | ID: wpr-279096

RESUMO

<p><b>OBJECTIVE</b>To study the effect of Acanthopanax senticosus injection (ASI) on the activities of human tumor necrosis factor (TNF) and natural killer cell (NKC) in the patients with lung cancer and the underlying mechanism.</p><p><b>METHOD</b>73 cases with lung cancer were randomly divided into two groups, namely, the treatment group (n = 39) and observation group (n = 34); 61 cases with or without other diseases were respectively divided into control A (n = 30) and B (n = 31) groups. The patients in treatment group were injected with ASI for 21 days. The activities of human TNF and NKC and the levels of IgG, IgA and IgM were detected respectively.</p><p><b>RESULT</b>After injection with ASI the activity of TNF-alpha in treatment group was comparable with that in the two control groups and was significant lower that that in observation group. The activity of TNF-beta and the levels of IgA, IgG and IgM were significantly higher than those in observation group and two control groups (P < 0.01). The activity of NKC was also remarkably higher than observation and two control groups.</p><p><b>CONCLUSION</b>ASI can regulate the cellular immunity and factor, indicating that ASI can be used as an assistant drug to regulate the function of cellular immunity in the patients with lung cancer.</p>


Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Eleutherococcus , Química , Imunidade Celular , Isotipos de Imunoglobulinas , Sangue , Infusões Intravenosas , Células Matadoras Naturais , Neoplasias Pulmonares , Sangue , Alergia e Imunologia , Patologia , Linfotoxina-alfa , Metabolismo , Plantas Medicinais , Química , Polissacarídeos , Farmacologia , Fator de Necrose Tumoral alfa , Metabolismo
17.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 24(3): 216-9, 2004 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-15074088

RESUMO

OBJECTIVE: To observe the therapeutic effect of Modified Banxia Houpu Decoction (MBHD) in treating heroin abusers with protracted abstinence syndrome. METHODS: One hundred and eighty-seven heroin abusers were randomly divided into three groups, the 58 patients in the control group, 62 in the treated group A and 67 in the treated group B. All were detoxified with lofexidine hydrochloride (LFX) tablet for 12 days. MBHD was given to the two treated groups, the medication started from the beginning of detoxification in the group B, and from the end of detoxification in group A for 60 days. To the control group, an imitate preparation was given. The observation was carried out 10 days after withdrawal of medication, and the protracted abstinence related symptoms were observed and scored. And the condition of re-abusing in patients were investigated through urinary examination one year later. RESULTS: The heroin abusers' protracted abstinence symptom score in the treated group was significantly lower than that in the control group (P < 0.01), and comparison of the scores between the two treated groups also showed significant difference (A < B, P < 0.01). The 1-year re-abusing rate in treated group B was significantly lower than that in the control group and in the treated group A (P < 0.05). CONCLUSION: MBHD could improve the heroin abusers' protracted abstinence symptoms after detoxification. In spite of the complexity of various factors, to effectively control the early stage abstinence symptoms and median stage protracted abstinence symptoms is one of the effective measures to prevent drug re-abusing.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Dependência de Heroína/tratamento farmacológico , Fitoterapia , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adolescente , Adulto , Clonidina/análogos & derivados , Clonidina/uso terapêutico , Feminino , Humanos , Masculino , Antagonistas de Entorpecentes/uso terapêutico
18.
Artigo em Chinês | WPRIM | ID: wpr-320209

RESUMO

<p><b>OBJECTIVE</b>To observe the therapeutic effect of Modified Banxia Houpu Decoction (MBHD) in treating heroin abusers with protracted abstinence syndrome.</p><p><b>METHODS</b>One hundred and eighty-seven heroin abusers were randomly divided into three groups, the 58 patients in the control group, 62 in the treated group A and 67 in the treated group B. All were detoxified with lofexidine hydrochloride (LFX) tablet for 12 days. MBHD was given to the two treated groups, the medication started from the beginning of detoxification in the group B, and from the end of detoxification in group A for 60 days. To the control group, an imitate preparation was given. The observation was carried out 10 days after withdrawal of medication, and the protracted abstinence related symptoms were observed and scored. And the condition of re-abusing in patients were investigated through urinary examination one year later.</p><p><b>RESULTS</b>The heroin abusers' protracted abstinence symptom score in the treated group was significantly lower than that in the control group (P < 0.01), and comparison of the scores between the two treated groups also showed significant difference (A < B, P < 0.01). The 1-year re-abusing rate in treated group B was significantly lower than that in the control group and in the treated group A (P < 0.05).</p><p><b>CONCLUSION</b>MBHD could improve the heroin abusers' protracted abstinence symptoms after detoxification. In spite of the complexity of various factors, to effectively control the early stage abstinence symptoms and median stage protracted abstinence symptoms is one of the effective measures to prevent drug re-abusing.</p>


Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Clonidina , Usos Terapêuticos , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Dependência de Heroína , Tratamento Farmacológico , Antagonistas de Entorpecentes , Usos Terapêuticos , Fitoterapia , Síndrome de Abstinência a Substâncias , Tratamento Farmacológico
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