Magnesium lithospermate B mediates anti-inflammation targeting activator protein-1 and nuclear factor-kappa B signaling pathways in human peripheral T lymphocytes

Cheng, Cheng-Chung; Yang, Shih-Ping; Lin, Wei‐Shiang; Ho, Ling‐Jun; Lai, Jenn‐Haung; Cheng, Shu‐Meng; Lin, Wea‐Lung

doi:10.1016/j.intimp.2012.04.011

Cited by 15 publications

(11 citation statements)

References 67 publications

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“…It possesses strong anti-oxidative, anti-apoptotic, and antiinflammatory effects, which are mediated through multiple signaling pathways including the NF-jB cascade. Cheng et al [13] reported that in human peripheral T lymphocytes, MLB suppresses IjBa degradation and nuclear translocation of p65 and p50 subunits, as well as it reduces IKK activity, thus inhibiting activation of T lymphocytes upon exposure to PMA plus ionomycin. Jung et al [31] found that MLB has anti-wrinkle effect and is able to reverse both age-and ultraviolet B-related skin pro-collagen reduction by suppressing the expression and activities of NF-jB and AP-1-dependent matrix-metalloproteinases (MMPs).…”

Section: Discussionmentioning

confidence: 99%

“…After being cultured for 10 days, neurons were preincubated with varying concentrations of MLB (0, 5, 10, 20, and 50 lg/ml) for 4 h, and then exposed to 10 lM oligomeric Ab (1-42) for 24 h. The doses of MLB were chosen based on the studies described previously [12,13].…”

Section: Culture Of Primary Neuronsmentioning

confidence: 99%

“…MLB has been reported to suppress the NF-jB pathway in activated T cells [13]. To test whether MLB is able to prevent Ab (1-42)-induced activation of the NF-jB pathway in primary neurons, we measured this pathway using an NF-jB luciferase reporter construct and detected the levels of cytoplasmic and nuclear NF-jB p65 subunit by Western blot.…”

Section: Mlb Suppresses Ab (1-42)-induced Activation Of the Nf-jb Patmentioning

confidence: 99%

“…Prior research has demonstrated a role for MLB in protecting primary neurons against N-methyl-Daspartic acid (NMDA) injury and attenuating kainic acid (KA)-induced neurodegeneration in the brain of FVB mice [12]. Additionally, MLB is able to reduce the production of cytokines and the activation of the NF-jB and octamer binding transcription factor (Oct-1) signaling pathways in human peripheral T cells treated by phorbol 12-myristate 13-acetate (PMA) and ionomycin [13]. Based on these findings, we hypothesize that MLB has a protective effect against Ab-induced neurotoxicity through the NF-jB pathway.…”

Section: Introductionmentioning

confidence: 99%

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Magnesium Lithospermate B Protects Neurons Against Amyloid β (1–42)-Induced Neurotoxicity Through the NF-κB Pathway

et al. 2015

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Magnesium lithospermate B (MLB) is one of the major bioactive components of Radix Salviae miltiorrhizae, a Chinese traditional herbal medicine colloquially known as Dan Shen. In this study, we investigated the neuroprotective effect of MLB against oligomeric amyloid β (Aβ) (1-42)-induced neurotoxicity in cultured FVB mouse hippocampal neurons. We found that pretreatment with MLB not only prevents a loss in neuronal cell viability following exposure to Aβ (1-42), but also attenuates Aβ (1-42)-induced release of pro-inflammatory cytokines and neuronal apoptosis in a dose-dependent manner. Mechanistic studies show that MLB counteracts Aβ (1-42)-induced activation of the nuclear factor kappa B (NF-κB) pathway, evidenced by the suppression of NF-κB luciferase reporters, decreased expression of phosphorylated Inhibitor κB α and IκB kinase α, and reduced nuclear translocation of p65 in response to pre-treatment with 50 μg/ml MLB prior to Aβ (1-42) exposure. MLB was able to reverse the increase in phosphorylated c-Jun N-terminal kinase (JNK) levels as well as the decrease in phosphorylated Akt levels that are induced by Aβ (1-42), although this finding did not extend to extracellular signal-regulated kinase or p38 kinases. Furthermore, combining MLB with the JNK inhibitor SP600125 synergistically counteracts the Aβ (1-42)-induced reduction in cell viability and neurite growth, and the neuroprotective effects of MLB could be attenuated by the Akt inhibitor triciribine. In conclusion, these results suggest that MLB can protect against Aβ (1-42)-induced neuronal damage, which is most likely to be mediated by the NK-κB pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Culture Of Primary Neuronsmentioning

confidence: 99%

Section: Mlb Suppresses Ab (1-42)-induced Activation Of the Nf-jb Patmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Magnesium Lithospermate B Protects Neurons Against Amyloid β (1–42)-Induced Neurotoxicity Through the NF-κB Pathway

et al. 2015

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“…Immunosuppressive methotrexate for treatment of atherosclerosis is currently under investigation [28] . One study found that MLB effectively suppressed maturation of human monocyte-derived dendritic cells (h-monDC) induced by ox-LDL through activation of PPARγ [45] and inhibition of IL-2, IL-4, TNF-α, and IFN-γ production from activated T cells [46] ; MLB also effectively reduced the expression of T cell activation markers CD25 and CD69 [46] . With molecular modeling, MLB was found to act as an inhibitor of protein-protein interactions between the SH2 domains of the Src-family kinases, Src and Lck.…”

Section: Potential Immunomodulatorsmentioning

confidence: 99%

Pharmacological actions and therapeutic applications of Salvia miltiorrhiza depside salt and its active components

Wang

2012

Acta Pharmacol Sin

108

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Salvia miltiorrhiza, a traditional medical herb known as danshen, has been widely used in China to improve blood circulation, relieve blood stasis, and treat coronary heart disease. S miltiorrhiza depside salt is a novel drug recently developed at the Shanghai Institute of Materia Medica; it contains magnesium lithospermate B (MLB) and its analogs, rosmarinic acid (RA) and lithospermic acid (LA), as active components. The drug has been used in the clinic to improve blood circulation and treat coronary heart disease. The pharmacological effects of the depside salt from S miltiorrhiza and its components have been extensively investigated. Experimental studies have demonstrated that magnesium lithospermate B possesses a variety of biological activities, especially protective effects in the cardiovascular system such as attenuation of atherosclerosis and protection against myocardial ischemia-reperfusion injury. Rosmarinic acid and lithospermic acid also show beneficial effects on the cardiovascular system. This paper reviews the recent findings regarding the mechanisms underlying the pharmacological actions of the active components of S miltiorrhiza depside salt, based on published works and our own observations.

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Impact of Methimazole Treatment on Magnesium Concentration and Lymphocytes Activation in Adolescents with Graves’ Disease

Klatka

Grywalska

Partyka

et al. 2013

Biol Trace Elem Res

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The aim of this research was to assess plasma magnesium (Mg) concentration, the frequencies of activated T CD4+ and T CD8+ lymphocytes and B lymphocytes in adolescents with hyperthyroidism due to Graves’ disease (GD), and to assess changes in the above-mentioned parameters during methimazole (MMI) treatment. The frequencies of activated T and B cells were measured by flow cytometry method and plasma Mg concentration was determined by spectrophotometry method in 60 adolescents at the time of GD diagnosis and after receiving the normalisation of the thyroid hormones levels. The control group consisted of 20 healthy volunteers. We observed lower plasma Mg concentration, and higher frequencies of activated T and B lymphocytes in the study group before the treatment in comparison with healthy controls, and with study group in MMI-induced euthyreosis (p < 0.01).Statistically significant negative correlations between the percentages of activated T CD3+, T CD4+, T CD8+ and B CD19+ lymphocytes, and plasma Mg concentration before the treatment were found (r < −0.335, p < 0.002). After the treatment no vital differences in plasma Mg concentration, and in percentages of activated cells between GD patients and controls were found, except CD8+CD25+ cells (p = 0.03). The present study demonstrates that both activated T and B cells might play an important role in the pathogenesis of GD, and activation is related to Mg plasma level. The use of MMI in treatment of hyperthyroidism due to GD leads to decrease the frequencies of activated lymphocytes and normalisation of Mg levels.

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Magnesium lithospermate B mediates anti-inflammation targeting activator protein-1 and nuclear factor-kappa B signaling pathways in human peripheral T lymphocytes

Cited by 15 publications

References 67 publications

Magnesium Lithospermate B Protects Neurons Against Amyloid β (1–42)-Induced Neurotoxicity Through the NF-κB Pathway

Magnesium Lithospermate B Protects Neurons Against Amyloid β (1–42)-Induced Neurotoxicity Through the NF-κB Pathway

Pharmacological actions and therapeutic applications of Salvia miltiorrhiza depside salt and its active components

Impact of Methimazole Treatment on Magnesium Concentration and Lymphocytes Activation in Adolescents with Graves’ Disease

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