Ginseng total saponin attenuates myocardial injury via anti-oxidative and anti-inflammatory properties

AbstractBackgroundGinseng total saponin (GTS) contains various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The aim of this study was to study the effects of GTS on cardiac injury after global ischemia and reperfusion (I/R) in isolated guinea pig hearts.MethodsAnimals were subjected to normothermic ischemia for 60 minutes, followed by 120 minutes of reperfusion. GTS significantly increased aortic flow, coronary flow, and cardiac output. Moreover, GTS significantly increased left ventricular systolic pressure and the maximal rate of contraction (+dP/dtmax) and relaxation (−dP/dtmax). In addition, GTS has been shown to ameliorate electrocardiographic changes such as the QRS complex, QT interval, and RR interval.ResultsGTS significantly suppressed the biochemical parameters (i.e., lactate dehydrogenase, creatine kinase-MB fraction, and cardiac troponin I levels) and normalized the oxidative stress markers (i.e., malondialdehyde, glutathione, and nitrite). In addition, GTS also markedly inhibits the expression of interleukin-1β (IL-1β), IL-6, and nuclear factor-κB, and improves the expression of IL-10 in cardiac tissue.ConclusionThese data indicate that GTS mitigates myocardial damage by modulating the biochemical and oxidative stress related to cardiac I/R injury

Anticancer Efficacy of Cordyceps militaris

Cordyceps militaris is used widely as a traditional medicine in East Asia. Although a few studies have attempted to elucidate the anticancer activities of C. militaris, the precise mechanism of C. militaris therapeutic effects is not fully understood. We examined the anticancer activities of C. militaris ethanolic extract (Cm-EE) and its cellular and molecular mechanisms. For this purpose, a xenograft mouse model bearing murine T cell lymphoma (RMA) cell-derived cancers was established to investigate in vivo anticancer mechanisms. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, immunoblotting analysis, and flow cytometric assay were employed to check in vitro cytotoxicity, molecular targets, and proapoptotic action of Cm-EE. Interestingly, cancer sizes and mass were reduced in a C. militaris-administered group. Levels of the phosphorylated forms of p85 and AKT were clearly decreased in the group administered with Cm-EE. This result indicated that levels of phosphoglycogen synthase kinase 3β (p-GSK3β) and cleaved caspase-3 were increased with orally administered Cm-EE. In addition, Cm-EE directly inhibited the viability of cultured RMA cells and C6 glioma cells. The number of proapoptotic cells was significantly increased in a Cm-EE treated group compared with a control group. Our results suggested that C. militaris might be able to inhibit cancer growth through regulation of p85/AKT-dependent or GSK3β-related caspase-3-dependent apoptosis

Anti-Inflammatory Effect of Piper attenuatum

Piper attenuatum is used as a traditional medicinal plant in India. One of the substances in P. attenuatum has been suggested to have anti-inflammatory effects. However, there is insufficient research about the anti-inflammatory mechanisms of action of P. attenuatum. The effects of P. attenuatum methanol extract (Pa-ME) on the production of inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE2), the expression of proinflammatory genes, the translocation level of transcription factors, and intracellular signaling activities were investigated using macrophages. Pa-ME suppressed the production of NO and PGE2 in lipopolysaccharide- (LPS-), pam3CSK4-, and poly(I:C)-stimulated RAW264.7 cells without displaying cytotoxicity. The mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) were decreased by Pa-ME. P-ME reduced the translocation of p50/NF-κB and AP-1 (c-Jun and c-Fos), as well as the activity of their upstream enzymes Src, Syk, and TAK1. Immunoprecipitation analysis showed failure of binding between their substrates, phospho- (p-) p85 and p-MKK3/6. p-p85 and p-MKK3/6, which were induced by overexpression of Src, Syk, and TAK1, were also reduced by Pa-ME. Therefore, these results suggest that Pa-ME exerts its anti-inflammatory effects by targeting Src and Syk in the NF-κB signaling pathway and TAK1 in the AP-1 signaling pathway

Magnetic Hydroxyapatite Composite Nanoparticles for Augmented Differentiation of MC3T3-E1 Cells for Bone Tissue Engineering

Progressive aging harms bone tissue structure and function and, thus, requires effective therapies focusing on permanent tissue regeneration rather than partial cure, beginning with regenerative medicine. Due to advances in tissue engineering, stimulating osteogenesis with biomimetic nanoparticles to create a regenerative niche has gained attention for its efficacy and cost-effectiveness. In particular, hydroxyapatite (HAP, Ca10(PO4)6(OH)2) has gained significant interest in orthopedic applications as a major inorganic mineral of native bone. Recently, magnetic nanoparticles (MNPs) have also been noted for their multifunctional potential for hyperthermia, MRI contrast agents, drug delivery, and mechanosensitive receptor manipulation to induce cell differentiation, etc. Thus, the present study synthesizes HAP-decorated MNPs (MHAP NPs) via the wet chemical co-precipitation method. Synthesized MHAP NPs were evaluated against the preosteoblast MC3T3-E1 cells towards concentration-dependent cytotoxicity, proliferation, morphology staining, ROS generation, and osteogenic differentiation. The result evidenced that MHAP NPs concentration up to 10 µg/mL was non-toxic even with the time-dependent proliferation studies. As nanoparticle concentration increased, FACS apoptosis assay and ROS data showed a significant rise in apoptosis and ROS generation. The MC3T3-E1 cells cocultured with 5 µg/mL MHAP NPs showed significant osteogenic differentiation potential. Thus, MHAP NPs synthesized with simple wet chemistry could be employed in bone regenerative therapy

Korean Red Ginseng water extract arrests growth of xenografted lymphoma cells

Background: Although numerous studies of the anticancer activities of Korean Red Ginseng (KRG) have been performed, the therapeutic effect of KRG on leukemia has not been fully elucidated. In this study, we investigated the antileukemia activities of KRG and its cellular and molecular mechanisms. Methods: An established leukemia tumor model induced by xenografted T cell lymphoma (RMA cells) was used to test the therapeutic activity of KRG water extract (KRG-WE). Direct cytotoxic activity of KRG-WE was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The immunomodulatory activities of KRG-WE were verified by immunohistochemistry, nitric oxide production assay. The inhibitory effect of KRG-WE on cell survival signaling was also examined. Results: Orally administered KRG-WE reduced the sizes of tumor masses. Levels of apoptosis regulatory enzymes and cleaved forms of caspases-3 and -8 were increased by this extract. In addition, expression of matrix metalloproteinase-9, a metastasis regulatory enzyme, was decreased by KRG-WE treatment. The proportion of CD11c+ cells was remarkably increased in the KRG-treated group compared to the control group. However, KRG-WE did not show significant direct cytotoxicity against RMA cells. Conclusion: Our results strongly suggest that the KRG might have antileukemia activity through CD11c+ cell-mediated antitumor immunity

Fermented ginseng, GBCK25, ameliorates hemodynamic function on experimentally induced myocardial injury

In the present study, we investigated whether treatment with GBCK25 facilitated the recovery of hemodynamic parameters, left ventricle systolic pressure, left ventricular developed pressure, and electrocardiographic changes. GBCK25 significantly prevented the decrease in hemodynamic parameters and ameliorated the electrocardiographic abnormality. These results indicate that GBCK25 has distinct cardioprotective effects in rat heart

Endothelial and mural laminin-α5 contributes to neurovascular integrity maintenance

Abstract Background Laminin-α5, a major component of the basal lamina, is predominantly synthesized by endothelial and mural cells (pericytes and vascular smooth muscle cells) in the CNS. Loss of laminin-α5 in either population fails to induce any abnormalities due to functional redundancy. Thus, the functional significance of laminin-α5 in neurovascular integrity remains unknown. Here, we hypothesize that ablation of laminin-α5 in both endothelial and mural cells increases neurovascular permeability. Methods The compound knockout mice were generated by crossing laminin-α5 floxed mice with Tie2-Cre and PDGFRβ-Cre, which target endothelial cells and mural cells, respectively. Neurovascular permeability in these mutants was determined with both exogenous and endogenous tracers. Endothelial paracellular and transcellular permeability was assessed by examining the expression of tight junction proteins and transcytosis-associated proteins. In addition, transmission electron microscopy (TEM) was used to visualize tight junction ultrastructure and endothelial caveolae vesicles. Defects in pericytes and astrocytes were investigated by examining pericyte coverage/contact and astrocyte polarity. Results Elevated neurovascular permeability was observed in the mutants. Subsequent studies found increased Caveolin-1 and decreased major facilitator superfamily domain-containing protein 2a (MFSD2A) expression, but unaltered Claudin-5 or zonula occludens-1 (ZO-1) expression. Consistent with these results, mutant mice exhibited increased endothelial caveolae vesicle number with intact tight junction structure under TEM. Additionally, pericyte coverage and contact were also decreased in the mutant mice, while astrocyte polarity was unaffected. Conclusions These results strongly indicate that endothelial and mural cell-derived laminin-α5 actively maintains neurovascular integrity via the transcellular rather than paracellular mechanism

1-(2,3-Dibenzimidazol-2-ylpropyl)-2-methoxybenzene Is a Syk Inhibitor with Anti-Inflammatory Properties

Inflammation is the protective action of our bodies against external pathogens by recognition of pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). Proper regulation of inflammatory responses is required to maintain our body’s homeostasis, as well as there are demands to develop proper acute or chronic inflammation. In this study, we elucidated the regulatory mechanism of NF-κB-mediated inflammatory responses by a novel compound, 1-(2,3-dibenzimidazol-2-ylpropyl)-2-methoxybenzene (DBMB). We found that DBMB suppressed inflammatory mediators, nitric oxide (NO) and prostaglandin E2 (PGE2), reacted to exposure to a number of toll like receptor (TLR) ligands. Such observations occurred following to decreased mRNA expression of several pro-inflammatory mediators, and such diminished mRNA levels were caused by inhibited transcriptional factor nuclear factor (NF)-κB, as evaluated by luciferase reporter assay and molecular biological approaches. To find the potential targets of DBMB, we screened phosphorylated forms of NF-κB signal molecules: inhibitor of κBα (IκBα), IκB kinase (IKK)α/β, Akt, 3-phosphoinositide dependent protein kinase-1 (PDK1), p85, and spleen tyrosine kinase (Syk). We found that DBMB treatment could suppress signal transduction through these molecules. Additionally, we conducted in vitro kinase assays using immunoprecipitated Syk and its substrate, p85. Consequently, we could say that DBMB clearly suppressed the kinase activity of Syk kinase activity. Together, our results demonstrate that synthetic DBMB has an effect on the inflammatory NF-κB signaling pathway and suggest the potential for clinical use in the treatment of inflammatory diseases

Anticancer effect of joboksansam, Korean wild ginseng germinated from bird feces

Background: Joboksansam, Korean bird wild ginseng, is an artificially cultivated wild ginseng germinated from bird feces. Although numerous pharmacologic activities of wild ginsengs have been reported, the beneficial effect of joboksansam in cancer has not been elucidated. In this study, we investigated the in vivo and in vitro anticancer activities of joboksansam powder. Methods: To evaluate the in vivo anticancer activity of joboksansam, we established a xenograft mouse model bearing RMA cell-derived cancer. Direct cytotoxicity induced by joboksansam powder was also investigated in vitro using (3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) assay. The inhibitory activity of this powder on the activation of cell survival signaling involving Akt and Src was examined with immunoblot analysis. Results: Joboksansam powder displayed strong inhibitory activity against the increased tumor size, increased weight of total body and cancer tissues, and mortality of tumor-bearing mice. Joboksansam powder also suppressed the activation of survival regulatory enzymes Akt and Src, as assessed by phosphorylation levels in the immunoblot analysis of tumor tissues. Interestingly, the viability of RMA cells in vitro was directly decreased by joboksansam treatment. Conclusion: Overall, our results strongly suggest that joboksansam powder has the potential to protect against cancer generation by direct cytotoxic effects on cancer cells resulting from suppression of cell survival signaling