• Biomolecules & Therapeutics
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• v.23 no.6
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• pp.549-556
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• 2015

Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key "late" proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKC${\alpha}$). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKC${\alpha}$ signaling pathway.

• Journal of Gastric Cancer
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• v.21 no.4
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• pp.439-456
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• 2021

Purpose: Gastric cancer (GC) has high morbidity and mortality and is a serious threat to public health. The flavonoid compound vitexin is known to exhibit anti-tumor activity. In this study, we explored the therapeutic potential of vitexin in GC and its underlying mechanism. Materials and Methods: The viability, migration, and invasion of GC cells were determined using MTT, scratch wound healing, and transwell assays, respectively. Target molecule expression was determined by western blotting. Tumor growth and liver metastasis were evaluated in vivo using nude mice. Protein expression in the tumor tissues was examined by immunohistochemistry. Results: Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner. Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing HMGB1 expression. Vitexin-mediated inhibition in proliferation, migration, invasion and EMT of GC cells were counteracted by hyper-activation of PI3K/AKT/HIF-1α pathway or HMGB1 overexpression. Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression. Conclusions: Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway. Thus, vitexin may serve as a promising therapeutic agent for the treatment of GC.

• IMMUNE NETWORK
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• v.8 no.2
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• pp.39-45
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• 2008

Background: Down regulation of major histocompatibility complex class II transactivator (CIITA) has been identified as a major factor of immunosuppression in sepsis and the level of CIITA expression inversely correlates with the degree of severity. However, it has not been fully elucidated whether the lower expression of CIITA is a cause of disease process or a just associated sign. Here we determined whether the CIITA deficiency decreased survival rate using murine sepsis model. Methods: Major histocompatibility complex class II (MHC-II) deficient, CIITA deficient and wild type B6 mice were subjected to cecal ligation puncture (CLP) surgery. CIITA and recombination activation gene (RAG)-1 double deficient mice were generated to test the role of lymphocytes in CIITA-associated sepsis progression. Results: Sepsis mortality was enhanced in CIITA deficient mice, not by impaired bacterial clearance resulted from CD4 T cell depletion, but hyper-inflammatory response such as excessive release of a pro-inflammatory cytokine, high-mobility group box 1 (HMGB1). Conclusion: Our results demonstrate that CIITA deficiency affects the course of sepsis via the unexpected function of CIITA, regulation of cytokine release.

• Genomics & Informatics
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• v.11 no.4
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• pp.224-229
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• 2013

Receptor for advanced glycation endproducts (RAGE) is a multi-ligand receptor that is able to bind several different ligands, including advanced glycation endproducts, high-mobility group protein (B)1 (HMGB1), S-100 calcium-binding protein, amyloid-${\beta}$-protein, Mac-1, and phosphatidylserine. Its interaction is engaged in critical cellular processes, such as inflammation, proliferation, apoptosis, autophagy, and migration, and dysregulation of RAGE and its ligands leads to the development of numerous human diseases. In this review, we summarize the signaling pathways regulated by RAGE and its ligands identified up to date and demonstrate the effects of hyper-activation of RAGE signals on human diseases, focused mainly on renal disorders. Finally, we propose that RAGE and its ligands are the potential targets for the diagnosis, monitoring, and treatment of numerous renal diseases.

• Journal of Veterinary Science
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• v.24 no.1
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• pp.2.1-2.14
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• 2023

Background: Hypothermia is a crucial environmental factor that elevates the risk of cardiovascular disease, but the underlying effect is unclear. Objectives: This study examined the role of cold stress (CS) in cardiac injury and its underlying mechanisms. Methods: In this study, a chronic CS-induced myocardial injury model was used; mice were subjected to chronic CS (4℃) for three hours per day for three weeks. Results: CS could result in myocardial injury by inducing the levels of heat shock proteins 70 (HSP70), enhancing the generation of creatine phosphokinase-isoenzyme (CKMB) and malondialdehyde (MDA), increasing the contents of tumor necrosis factor-α (TNF-α), high mobility group box 1 (HMGB1) interleukin1b (IL-1β), IL-18, IL-6, and triggering the depletion of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Multiple signaling pathways were activated by cold exposure, including pyroptosis-associated NOD-like receptor 3 (NLRP3)-regulated caspase-1-dependent/Gasdermin D (GSDMD), inflammation-related toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK), as well as oxidative stressinvolved thioredoxin-1/thioredoxin-interacting protein (Txnip) signaling pathways, which play a pivotal role in myocardial injury resulting from hypothermia. Conclusions: These findings provide new insights into the increased risk of cardiovascular disease at extremely low temperatures.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.4
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• pp.1-11
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• 2021

Objectives: Nephrotic syndrome is a kidney disorder, which is characterized by proteinuria, edema (swelling), and hyperlipidemia. Maydis Stigma (Corn silk) has been widely used in Asia as a traditional medicine and is known to have a diuretic effect and is used for the treatment of edema and indigestion. Methods: The aim of this study is to investigate the improvement effect of Maydis Stigma in treating nephrotic syndrome induced by puromycin aminonucleoside. Sprague-Dawley rats were intravenously injected with 75 mg/kg/day puromycin aminonucleoside, then treated with either Losartan or 200 mg/kg/day Maydis Stigma for seven days. Results: Maydis Stigma significantly decreased ascites and proteinuria level. Plasma levels of blood urea nitrogen (BUN) and plasma creatinine reduced significantly by Maydis Stigma. In addition, treatment with Maydis Stigma attenuated histological damage. Treatment with Maydis Stigma also restored podocin expression and reduced inflammation markers such as intracellular adhesion molecules (ICAM-1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α) and high-mobility group box-1 (HMGB1). Conclusions: Maydis Stigma ameliorates kidney injury in nephrotic syndrome rat models. Maydis Stigma exerts a renoprotective effect owing to its anti-inflammatory effects and reductions of ascites and proteinuria. Thus, these results indicate that Maydis Stigma is likely to be a promising agent in the treatment of nephrotic syndrome.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.228-236
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• 2023

Background: QiShen YiQi pills (QSYQ) is a Traditional Chinese Medicine (TCM) formula, which has a significant effect on the treatment of patients with myocardial infarction (MI) in clinical practice. However, the molecular mechanism of QSYQ regulation pyroptosis after MI is still not fully known. Hence, this study was designed to reveal the mechanism of the active ingredient in QSYQ. Methods: Integrated approach of network pharmacology and molecular docking, were conducted to screen active components and corresponding common target genes of QSYQ in intervening pyroptosis after MI. Subsequently, STRING and Cytoscape were applied to construct a PPI network, and obtain candidate active compounds. Molecular docking was performed to verify the binding ability of candidate components to pyroptosis proteins and oxygen-glucose deprivation (OGD) induced cardiomyocytes injuries were applied to explore the protective effect and mechanism of the candidate drug. Results: Two drug-likeness compounds were preliminarily selected, and the binding capacity between Ginsenoside Rh2 (Rh2) and key target High Mobility Group Box 1 (HMGB1)was validated in the form of hydrogen bonding. 2 μM Rh2 prevented OGD-induced H9c2 death and reduced IL-18 and IL-1β levels, possibly by decreasing the activation of the NLRP3 inflammasome, inhibiting the expression of p12-caspase1, and attenuating the level of pyroptosis executive protein GSDMD-N. Conclusions: We propose that Rh2 of QSYQ can protect myocardial cells partially by ameliorating pyroptosis, which seems to have a new insight regarding the therapeutic potential for MI.