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1.
Acta Pharmaceutica Sinica ; (12): 2528-2535, 2021.
Article in Chinese | WPRIM | ID: wpr-886936

ABSTRACT

Modern pharmacological studies have shown that Cistanche deserticola (C. deserticola) has a protective effect on the liver, but its active fraction and mechanism are not clear. In order to identify the effective fraction of C. deserticola Y. C. Ma, an acute alcoholic liver injury model in mice was established with 56-proof Erguotou and different fractional extracts of C. deserticola Y. C. Ma (total glycosides, polysaccharides, and oligosaccharides) were administered. After 14 days of oral administration, liver pathology and lipid deposition were measured and the expression of nuclear factor E2-related factor (Nrf-2), kelch-like ECH-associated protein-1 (Keap-1), and plasmalemma vesicle-associated protein-1 (PV1) were measured by immunofluorescence. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), endotoxin (ET), diamine oxidase (DAO), and D-lactic acid (D-LA) in serum, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) in liver were measured by ELISA. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Peking University Health Science Center. The results show that the total glycosides of C. deserticola Y. C. Ma (400 mg·kg-1) could decrease liver pathology, decrease serum endotoxin, diamine oxidase, and D-lactic acid, and reduce hepatic lipid deposition. Total glycosides also promoted Nrf-2 transfer into the nucleus and decreased the expression of Keap-1 and PV1. In summary, the total glycosides of C. deserticola Y. C. Ma had a protective effect in acute alcoholic liver injury and the mechanism may be related to the activation of the Nrf-2/Keap-1 pathway, improvement of intestinal wall integrity, and inhibition of the transport of harmful substances into the liver.

2.
Article in Chinese | WPRIM | ID: wpr-878875

ABSTRACT

Mechanism study was performed to explore how Shouhui Tongbian Capsules promotes energy metabolism of gastrointestinal stromal cells. In this study, gastrointestinal stromal cells line GIST-882 was used as the model to explore energy metabolism regulation effects of Shouhui Tongbian Capsules extract(10, 20, 50 and 100 μg·mL~(-1)) by measuring the cell proliferation, ATP level, mitochondrial membrane potential, and mitochondrial isocitrate dehydrogenase activity. Meanwhile, Western blot was used to detect the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Our results showed that Shouhui Tongbian Capsules promoted cell proliferation and increased ATP level of gastrointestinal stromal cells. In addition, Shouhui Tongbian Capsules obviously improved mitochondrial structural integrity, and increased mitochondrial membrane potential in GIST-882 cells. Mechanism study revealed that Shouhui Tongbian Capsules increased mitochondrial isocitrate dehydrogenase activity and up-regulated the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Collectively, our study indicated that Shouhui Tongbian Capsules promoted the energy metabolism for gastrointestinal stromal cells proliferation by activating mitochondrial isocitrate dehydrogenase to induce ATP production, as well as activating SCF/c-Kit and CDK2/cyclin A signaling pathways.


Subject(s)
Capsules , Cell Line, Tumor , Energy Metabolism , Gastrointestinal Stromal Tumors , Humans , Proto-Oncogene Proteins c-kit/metabolism , Stromal Cells/metabolism
3.
Article in Chinese | WPRIM | ID: wpr-878874

ABSTRACT

Shouhui Tongbian Capsules was used to explore the therapeutic effect and potential mechanism on slow transit constipation model mice induced by loperamide hydrochloride. In the experiment, loperamide hydrochloride-induced ICR mice were used as the model of slow transit constipation. Fifty ICR mice were divided into the blank group, model group and high, medium and low dose groups of Shouhui Tongbian Capsules extract(100, 200 and 400 mg·kg~(-1)). The model group and the administration groups were then modeled using loperamide hydrochloride intragastrically to obtain slow transit constipation. After successful modeling, high, medium and low doses of drugs were given to each drug group by intragastric administration. After 14 days of administration, the first defecation time, 6 h defecation grain number, 6 h defecation wet weight and dry weight, black feces discharged within 6 h and the fecal water content were measured. Intestinal tissues were taken for c-Kit and SCF immunohistochemical sections to detect the expression of c-Kit and SCF in the blank group, model group and high, medium and low dose groups of the medicinal extract of Shouhui Tongbian Capsules. The tissue changes in the intestinal wall of mice were detected by HE staining. At the same time, partial intestinal tissues were taken to test the activity of ATP synthase and isocitrate dehydrogenase in intestinal tissues of mice. RESULTS:: showed that Shouhui Tongbian Capsules effectively improved the symptoms of slow transit constipation in ICR mice and promoted intestinal movement. Shouhui Tongbian Capsules obviously shortened the time of discharging black stool for the first time, improved the intestinal propulsion rate, increased the water content and amount of feces, and improved the constipation symptoms. Mechanism study revealed that Shouhui Tongbian Capsules increased ATP synthase activity and mitochondrial isocitrate dehydrogenase activity in intestinal tissue, and up-regulated c-Kit/SCF signaling pathway to promote interstitial Cajal cells proliferation, intestinal nerve transmission, intestinal motility and transport capacity.


Subject(s)
Animals , Capsules , Constipation/drug therapy , Gastrointestinal Transit , Loperamide , Mice , Mice, Inbred ICR
4.
Article in Chinese | WPRIM | ID: wpr-878872

ABSTRACT

"Target fishing" strategy was used to investigate the direct targets and mechanism of Shouhui Tongbian Capsules on relaxing bowel. Magnetic beads cross-linked with the chemical constituents from Shouhui Tongbian Capsules were prepared. The potential target proteins were captured from the total protein lysates of rat intestine using the beads. The captured proteins were further identified by LC-MS/MS, and the associated pathways were analyzed by Cytoscape. RESULTS:: showed that 138 potential target proteins were identified, which were involved in eight signaling pathways, including tricarboxylic acid cycle, pyrimidine metabolism, sulfur metabolism, fatty acid degradation, alanine/aspartate/glutamate metabolism, arginine/proline metabolism, valine/leucine/isoleucine degradation, and β-alanine metabolism. Taken together, Shouhui Tongbian Capsules may exert relaxing bowel effect by acting on multiple signaling pathways to promote intestinal gurgling, inhibit inflammation, as well as improve intestinal barrier function, intestinal water secretion, and intestinal flora.


Subject(s)
Animals , Capsules , Chromatography, Liquid , Intestines , Leucine , Rats , Tandem Mass Spectrometry
5.
Article in English | WPRIM | ID: wpr-888790

ABSTRACT

Three new coumarins, integmarins A-C (1-3), and a new coumarin glycoside, integmaside A (4) were isolated from the leaves and stems of Micromelum integerrimum. Their structures were elucidated on the basis of 1D and 2D NMR and MS data, and their absolute configurations were assigned according to the ECD data of the in situ formed transition metal complexes and comparison of experimental and calculated ECD data. Compounds 1 and 2 are two rare coumarins with butyl and propyl moieties at the C-6 position; compound 3 is a novel coumarin with a highly oxidized prenyl group, and compound 4 is a rare bisdihydrofuranocoumarin glycoside.


Subject(s)
Coumarins/isolation & purification , Glycosides/isolation & purification , Molecular Structure , Plant Leaves/chemistry , Plant Stems/chemistry , Rutaceae/chemistry
6.
Article in English | WPRIM | ID: wpr-880521

ABSTRACT

OBJECTIVE@#To test the effect of Banxia Xiexin Decoction (, BXD) on the contraction and relaxation of gastric smooth muscle (SM) in diabetic gastroparesis (DGP) model rats, and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro.@*METHODS@#Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table: control group, model group, high-, medium- and low-dose BXD groups (9.2, 4.6 and 1.8 g/(kg·d), respectively), and domperidone group (10 mg/(kg·d)), 10 rats per group. DGP model was established initially by a single intraperitoneal injection of streptozotocin (STZ), and was confirmed by recording gastric emptying, intestinal transport velocity and gastric myoelectric activity of rats after 2 months. Each group was treated with a corresponding drug for 4 weeks. The mRNA and protein expressions of phospholipase C (PLC), inositol triphosphate (IP@*RESULTS@#Compared with the model group, high- and medium-dose BXD and domperidone significantly increased the expressions of PLC, IP@*CONCLUSIONS@#Treatment with high- and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats. The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP

7.
Article in Chinese | WPRIM | ID: wpr-771496

ABSTRACT

Traditional Chinese medicine(TCM) is a research area with highly original innovation features,and is also a Chinese name card to the world. However,TCM owns a unique theoretical system which is quite different from western modern medicine,leading to an awkward situation of deficient modern social identity as well as poor international spread. Therefore,how to establish a research strategy in line with the characteristics of TCM itself to systematically interpret the unique scientific connotation of TCM is always a public hot topic. Based on persistent practical exploration and scientific consideration in TCM,our group firstly promoted the concept of traditional Chinese medicine chemical biology(TCM chemical biology,TCMCB). The major idea of TCMCB is to clarify the nature of TCM regulating life progress to link TCM to modern medicine by using TCM components as chemical tools. Notably,TCMCB mainly focuses on TCM target identification and TCM-guided disease molecular mechanism exploration,further to clarify the basic law of TCM mediating disease process. Finally,TCMCB-guided scientific studies can help explain TCM theory and promote the developmentof modern innovative drugs based on identified targets using TCM active components. Moreover,TCMCB is of vital importance for investigating the scientific nature of biological progress and the pattern of disease occurrence and development,indicating a key significance for modern life science and medicine. This review introduces the definition of TCMCB as well as its academic thought,research method,technology system and scientific significance,for providing new research ideas and scientific thoughts for TCM development.


Subject(s)
Biology , Chemistry , Interdisciplinary Research , Medicine , Medicine, Chinese Traditional , Research Design
8.
Article in Chinese | WPRIM | ID: wpr-773277

ABSTRACT

Target identification is an important prerequisite for the study of medicine action mechanism. Currently,drug target identification is mostly based on various cell models in vitro. However,the growth microenvironment,nutrition metabolism,biological properties as well as functions are quite different between in vitro cell culture and physiological environment in vivo; wherefore,it is a challenging scientific issue to establish an effective method for identifying drug targets in vivo condition. In this study,we successfully prepared a kind of magnetic nanoparticles( MNPs) which can be chemically modified by the hydroxyl structure of natural bioactive compound echinacoside( ECH) via the epoxy group label on the surface of MNPs. Therefore,organ-selective and recoverable nanoscale target-recognizing particles were prepared. We then intravenously injected the ECH-binding MNPs into rats and distributed them to specific organs in vivo. After cell endocytosis,ECH-binding MNPs captured target proteins in situ for further analysis. Based on this method,we discovered several potential target proteins in the spleen lysates for ECH,and preliminarily clarified the immuno-regulation mechanism of ECH. Collectively,our strategy developed a proof-of-concept technology using nanoparticles for in vivo target identification,and also provided a feasible approach for drug target prediction and pharmacological mechanism exploration.


Subject(s)
Animals , Drug Delivery Systems , Endocytosis , Glycosides , Magnetics , Magnetite Nanoparticles , Medicine, Chinese Traditional , Proof of Concept Study , Rats
9.
Article in Chinese | WPRIM | ID: wpr-773272

ABSTRACT

To investigate the inhibitory effects and mechanism of Cistanche tubulosa ethanol extract( CTEE) against oxygen-glucose deprivation/reperfusion( OGD/R)-induced PC12 cells neuronal injury. In this study,OGD/R-induced PC12 cells were used to explore the neuroprotective effects of CTEE( 12. 5,25,50 mg·L-1) by detecting cell viability with MTT assay,apoptosis with AO/EB and Hoechst 33258,mitochondrial membrane potential changes with JC-1 staining,mitochondrial oxidative stress with MitoSOX staining,as well as the apoptosis-related protein expression( PARP,cleaved PARP,caspase-3,cleaved caspase-3,Bax,Bcl-2) with Western blot. RESULTS:: showed that CTEE effectively protected OGD/R-induced neuronal injury and increased the survival rate of PC12 cells.AO/EB and Hoechst 33258 staining showed that CTEE could effectively inhibit apoptosis. Moreover,JC-1 and MitoSOX staining results showed that CTEE decreased mitochondrial stress and mitochondrial membrane potential imbalance in PC12 cells in a concentration-dependent manner. Meanwhile,CTEE could obviously suppress the activation of key proteins in mitochondrial apoptosis pathway such as caspase-3 and PARP,and significantly inhibit the rise of Bax and down-regulation of Bcl-2. In conclusion,CTEE has obvious protective effects on OGD/R-induced PC12 cells neuronal injury,potentially via inhibiting mitochondrial oxidative stress and apoptosis-related signaling pathway.


Subject(s)
Animals , Apoptosis , Caspase 3 , Metabolism , Cistanche , Chemistry , Ethanol , Glucose , Neuroprotective Agents , Pharmacology , Oxidative Stress , Oxygen , PC12 Cells , Plant Extracts , Pharmacology , Poly (ADP-Ribose) Polymerase-1 , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Rats , bcl-2-Associated X Protein , Metabolism
10.
Article in English | WPRIM | ID: wpr-776646

ABSTRACT

OBJECTIVE@#To investigate the anti-neuroinflammation effect of extract of Fructus Schisandrae chinensis (EFSC) on lipopolysaccharide (LPS)-induced BV-2 cells and the possible involved mechanisms.@*METHODS@#Primary cortical neurons were isolated from embryonic (E17-18) cortices of Institute of Cancer Research (ICR) mouse fetuses. Primary microglia and astroglia were isolated from the frontal cortices of newborn ICR mouse. Different cells were cultured in specific culture medium. Cells were divided into 5 groups: control group, LPS group (treated with 1 μg/mL LPS only) and EFSC groups (treated with 1 μg/mL LPS and 100, 200 or 400 mg/mL EFSC, respectively). The effect of EFSC on cells viability was tested by methylthiazolyldiphenyltetrazolium bromide (MTT) colorimetric assay. EFSC-mediated inhibition of LPS-induced production of pro-inflammatory mediators, such as nitrite oxide (NO) and interleukin-6 (IL-6) were quantified and neuron-protection effect against microglia-mediated inflammation injury was tested by hoechst 33258 apoptosis assay and crystal violet staining assay. The expression of pro-inflammatory marker proteins was evaluated by Western blot analysis or immunofluorescence.@*RESULTS@#EFSC (200 and 400 mg/mL) reduced NO, IL-6, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression in LPS-induced BV-2 cells (P<0.01 or P<0.05). EFSC (200 and 400 mg/mL) reduced the expression of NO in LPS-induced primary microglia and astroglia (P<0.01). In addition, EFSC alleviated cell apoptosis and inflammation injury in neurons exposed to microglia-conditioned medium (P<0.01). The mechanistic studies indicated EFSC could suppress nuclear factor (NF)-?B phosphorylation and its nuclear translocation (P<0.01). The anti-inflammatory effect of EFSC occurred through suppressed activation of mitogen-activated protein kinase (MAPK) pathway (P<0.01 or P<0.05).@*CONCLUSION@#EFSC acted as an anti-inflammatory agent in LPS-induced glia cells. These effects might be realized through blocking of NF-κB activity and inhibition of MAPK signaling pathways.


Subject(s)
Animals , Astrocytes , Metabolism , Pathology , Cell Line , Cell Nucleus , Metabolism , Chromatography, High Pressure Liquid , Down-Regulation , Inflammation , Pathology , Inflammation Mediators , Metabolism , Lipopolysaccharides , MAP Kinase Signaling System , Mice, Inbred ICR , Microglia , Metabolism , Pathology , NF-kappa B , Metabolism , Nervous System , Pathology , Neurons , Metabolism , Pathology , Neuroprotective Agents , Pharmacology , Plant Extracts , Pharmacology , Schisandra , Chemistry , Spectrometry, Mass, Electrospray Ionization
11.
Article in Chinese | WPRIM | ID: wpr-852290

ABSTRACT

Objective Cistanches Herba is a kind of tonic traditional Chinese medicine with several therapy effects including tonifying kidney-yin, anti-dementia, anti-aging and relaxing bowel. Phenylethanoid glycosides (PhGs) are the major effective components in C. tubulosa. However, there were no further studies on molecular pharmacologic mechanisms due to its complex components and mechanism diversity of action in PhGs till to now. The aim of this study was to investigate the target protein groups and related mechanisms associated with PhGs in anticerebral ischemia-reperfusion injury. Methods The middle cerebral artery occlusion (MCAO) model was established in rats, and the protective effects of PhGs on cerebral ischemia-induced injuries were determined. A kind of solid bead whose surface was cross-linked with PhGs was prepared to capture the target proteins from brain tissue lysates. The target proteins were further identified with LC-MS/MS. Results PhGs significantly inhibited cerebral ischemia-induced injuries by reducing ischemia size and rat behavioral scores and elevated the SOD levels in rat brain tissues. Eighteen target proteins were identified based on “target fishing” strategy and divided into 9 kinds according to their biological functions, including anti-oxidation, ion channel, immunoregulation, cell survival and cytoskeleton, etc. Conclusion These findings reveal the potential pharmacological mechanisms of PhGs in anti-dementia, fatigability alleviating, anti-tumor, immunoloregulation, etc, and also present a promising technology for investigating the complicated pharmacological mechanisms of traditional Chinese medicine.

12.
Article in Chinese | WPRIM | ID: wpr-705364

ABSTRACT

OBJECTIVE Our group mainly focuses on the target identification and pharmacological mechanism study of TCM.We deeply identified the direct targets of the active ingredients in TCM using molecule probe-'Target Fishing' technology in chemical biology, and explored the related signaling pathways to explain the traditional efficiency of TCM. METHODS We synthesized biotin-tagged mole-cule probe by connecting biotin tag to TCM active molecule using PGE as a linker. Then, the biotin-tagged molecule probe was bound to the surface of solid beads by strong biotin-avidin interaction. Thus, the molecule probe-bound beads were mixed with cell lysates to capture the potential targets and identified by MS.RESULTS Our study found that SA which was an anti-inflammatory compound-could selectively bind to IMPDH2 in microglial cells,and SA showed weaker anti-inflammatory effect on IMPDH2-knock down microglial cells,suggesting IMPDH2 as a key anti-inflammatory target for SA.Ad-ditionally,handelin was a key anti-inflammatory compound.We identified the target protein of handelin as Hsp70 from microglial cells using target pull-down technology. Moreover, handelin showed weaker anti-inflammatory effect on Hsp70-knock down microglial cells,revealing that Hsp70 was the direct anti-inflammatory target of handelin. CONCLUSION Our study provided methodology references for TCM target identification in the future, and also showed a new insight for exploring the pharmacological mechanism of TCM active ingredients.More importantly,we can perform scientific annotation for TCM efficiency by clarifying the biological functions of each target protein,showing important significance on modernization and internationalization of TCM.

13.
Article in Chinese | WPRIM | ID: wpr-335806

ABSTRACT

Traditional Chinese medicine(TCM) is a complex system with multiple chemical compositions. The most significant character of TCM is that the chemical compositions interact with each other by multi-target synergism to treat diseases. Previous reports mainly focused on the investigation of single signaling pathway detection or the phenotypic analysis of proteomics difference; however, no studies have been conducted on the identification of direct targets of TCM. Therefore, it is difficult to analyze the molecular mechanism of traditional Chinese medicine from the target source, and it is difficult to explain its traditional efficacy scientifically, thus seriously affecting its clinical application and internationalization. In this article, we discussed the methodology for the identification of direct TCM targets(groups), and presented the strategy for preparation of TCM chemical composition solid coupling beads, as well as of enrichment and identification strategy of target proteins based on photosensitive coupling technique. We also discussed the advantages and limitations of this strategy, and put forward some new ideas for the future developments. We hope this article can provide some guidance and reference significance for the researchers on TCM pharmacology study, especially on target identification.

14.
Article in Chinese | WPRIM | ID: wpr-335805

ABSTRACT

Baoyuan decoction (BYD) is a well-known traditional Chinese medicine formula for coronary heart disease with Qi deficiency. However, the detailed pharmacological mechanism of BYD is still unknown because of its complicated chemical compositions. In this study, we synthesized a kind of solid beads with benzophenone groups on its surface. Benzophenone can be activated and chemically cross-linked with the C-H bonds of the chemical compositions in BYD (BYD beads) under UV activation. We thus captured all the target proteins from mouse heart tissue lysates by using BYD beads. Based on proteomics analysis, we discovered totally 46 potential binding target proteins, most of which were located in mitochondria. KEGG analysis revealed that these target proteins were mainly associated with TCA cycle and amino acid metabolism signaling pathways, suggesting that the cardioprotection of BYD might be associated with regulating mitochondrial function and energy production. Moreover, JC-1 staining analysis also confirmed the protective effect of BYD on mitochondrial damage. In summary, our findings elucidated the potential mechanism of BYD on cardioprotection through "target fishing" strategy, and further explained its traditional efficacy in the molecular level. In addition, we also provide an approach for investigating the target group of complicated compositions in Chinese herbal formula. This novel method may provide a methodological reference for exploring the pharmacological mechanism of traditional Chinese formula in the future.

15.
Article in Chinese | WPRIM | ID: wpr-335804

ABSTRACT

Targets group identification in complex Chinese medicine system is a key step for revealing the potential mechanism of Chinese medicine. The solid beads with magnetic core and benzophenone-modified surface were made in our study, and then benzophenone was activated and cross-linked with the C-H bonds of chemical compositions in Chinese medicines under UV excitation. Thus the chemical compositions of modified Wuzi Yanzong pill(MWP) were linked to the solid bead surface, and enriched the neuroprotective targets group of MWP after being co-incubated with nerve cell lysate. We performed proteomics analysis on these targets and discovereda total of 32 potential binding targets. KEGG analysis revealed that these targets were mainly associated with Hippo and Cell cycle signaling pathways, suggesting that MWP might be involved in regulating the proliferation and differentiation of neural stem cells. Our findings elucidate the potential targets and mechanism of MWP on anti-dementia and neuroprotection, and further providean approach for investigating the targets group in complex Chinese medicine system. This novel method may provide methodological references for exploring the pharmacological mechanism of Chinese medicinal formulae in the future.

16.
Article in Chinese | WPRIM | ID: wpr-335803

ABSTRACT

Dried stem bark from Albizia julibrissin(AJ) is a common traditional Chinese herb with several therapy effects including insomnia, anxiety and anti-tumor. Recently, the anti-tumor effect and mechanism studies of AJ have drawn much attention; however, there are still some troubles in chemical composition separation, which leads to the difficulties in pharmacological research of AJ. In this study, we firstly confirmed the proliferation inhibitory effect of total saponins from AJ(TSAJ)on human hepatocarcinoma(HepG2) cells, and also tested the apoptosis induction effect of TSAJ. Then, we successfully captured the potential target proteins from HepG2 lysates by using TSAJ-modified solid beads, and identified the target proteins by LC-MS/MS. Finally, we confirmed 5 target proteins including Exportin-2, Beta-actin-like protein 2, Myosin-9, Protein transport protein Sec61 subunit beta,and Cytochrome c oxidase copper chaperone, which are responsible forcell apoptosis, proliferation, differentiation andmigration. In summary, our findings elucidate the potential anti-tumor mechanism of TSAJ from the direct target proteins, and provide a new insight for exploring the pharmacological mechanism of traditional Chinese medicine.

17.
Article in Chinese | WPRIM | ID: wpr-335802

ABSTRACT

This study aims to investigate the targets and targets-involved mechanism for the macrophage activation of low molecular weight saccharides from Cistanche deserticola (LMSC). The phagocytic activity and NO release of RAW264.7 cells were detected, and results showed that LMSC exerts immune activation effect by significantly increasing the phagocytic activity and NO release. LMSC-conjugated epoxy-activated sepharose beads were prepared as affinity reagent to capture the target proteins. Twenty-four proteins such as Eef2 were identified by LC-MS/MS analysis. Pathway enrichment analysis showed LMSC activated RAW264.7 cells by regulating Fcgamma receptor dependent phagocytosis, TNF-alpha NF-κB signaling pathway, glycolysis/gluconeogenesis and the citric acid cycle and respiratory electron transport pathway.

18.
Article in Chinese | WPRIM | ID: wpr-335720

ABSTRACT

To investigate the immune activation effect and mechanism of low molecular weight saccharides from Cistanche deserticola(LMSC) on mouse peritoneal macrophages, RAW264.7 cells. The RAW264.7 cells were divided into the normal control group, LPS positive control group, and LMSC treatment groups. The RAW264.7 cells were treated with various concentrations of LMSC from 3.91 to 62.5 g•L ⁻¹. The neutral red assay was employed to detect the phagocytic activity of macrophages. NO release was detected by using NO kit, and macrophage activation associated protein expression levels (TNF-α, IL-6, IKKβ, p-IKKβ, IκBα, p-IκBα, NF-κB, and p-NF-κB) were detected by Western blot. Results showed that LMSC had an activation effect on macrophages; it can significantly increase the release of NO in RAW264.7 cells and promote the expression of cytokines TNF-α and IL-6. Moreover, LMSC significantly increased the phosphorylation of IKKβ, IκBα, and NF-κB p65. Furthermore, mannitol's one of the main constituents in LMSC significantly enhanced the phagocytic activity of macrophages. These results showed that LMSC could activate macrophages by up-regulating the NF-κB signaling pathway, and mannitol may be one of the main active components in LMSC.

19.
Article in Chinese | WPRIM | ID: wpr-275141

ABSTRACT

Diabetes mellitus, a kind of chronic metabolic disease, has become one of major threats to human health with an increasing incidence. As a basic pathology of chronic complications related to diabetes mellitus, cerebral microangiopathy is mainly found in patients with Alzheimer's disease and lacunar infarction, and becomes one of the main reasons of death and disability in diabetic patients. The pathogenesis of cerebral microangiopathy is complicated, involving such signal pathways as metabolic abnormalities of polyol, saccharification hyperactivity, oxidative stress, abnormal transport of amyloid-β across blood-brain barrier and protein kinase C activation. Treatment targeting at related pathogenesis may bring a new hope to prevention and delay of the occurrence and development of cerebral microangiopathy of diabetes mellitus. Currently, pathogenesis, diagnosis and therapies for cerebral microangiopathy of diabetes mellitus have become hot topics in medical studies. This article reviews pathogenesis, clinical diagnosis and treatment for cerebral microangiopathy of diabetes mellitus, in order to provide new ideas for the prevention and treatment of cerebral microangiopathy of diabetes mellitus.

20.
Article in English | WPRIM | ID: wpr-812069

ABSTRACT

Microglial activation and resultant neuroinflammatory response are implicated in various brain diseases including Alzheimer's disease and Parkinson's disease. Treatment with anti-neuroinflammatory agents could provide therapeutic benefits for such disorders. Protosappanin A (PTA) is a major bioactive ingredient isolated from Caesalpinia sappan L.. In this work, the anti-neuroinflammatory effects of PTA on LPS-stimulated BV2 cells were investigated and the underlying mechanisms were explored. Results showed that PTA significantly inhibited the production of TNF-α and IL-1β in LPS-activated BV2 microglia. Moreover, the mRNA expressions of IL-6, IL-1β, and MCP-1 were reduced by PTA in a dose-dependent manner. Furthermore, PTA suppressed JAK2/STAT3-dependent inflammation pathway through down-regulating the phosphorylation of JAK2 and STAT3, as well as STAT3 nuclear translocation against LPS treatment. These observations suggested a novel role for PTA in regulating LPS-induced neuroinflammatory injuries.


Subject(s)
Animals , Anti-Inflammatory Agents , Pharmacology , Humans , Inflammation , Drug Therapy , Genetics , Allergy and Immunology , Interleukin-1beta , Genetics , Allergy and Immunology , Lipopolysaccharides , Pharmacology , Mice , Microglia , Allergy and Immunology , Nitric Oxide , Genetics , Allergy and Immunology , Phenols , Pharmacology , STAT3 Transcription Factor , Genetics , Allergy and Immunology , Signal Transduction , Tumor Necrosis Factor-alpha , Genetics , Allergy and Immunology
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