Korean Red Ginseng has been used for several decades to treat many diseases, enhancing both immunity and physical strength. Previous studies have documented the therapeutic effects of ginseng, including its anticancer, antiaging, and anti-inflammatory activities. These activities are mediated by ginsenosides present in the ginseng plant. Ginsenoside Rg3, an effective compound from red ginseng, has been shown to have antiplatelet activity in addition to its anticancer and anti-inflammatory activities. Platelets are important for both primary hemostasis and the repair of the vessels after injury; however, they also play a crucial role in the development of acute coronary diseases. We prepared ginsenoside Rg3-enriched red ginseng extract (Rg3-RGE) to examine its role in platelet physiology. To examine the effect of Rg3-RGE on platelet activation in vitro, platelet aggregation, granule secretion, intracellular calcium ([Ca2+]i) mobilization, flow cytometry, and immunoblot analysis were carried out using rat platelets. To examine the effect of Rg3-RGE on platelet activation in vivo, a collagen plus epinephrine-induced acute pulmonary thromboembolism mouse model was used. We found that Rg3-RGE significantly inhibited collagen-induced platelet aggregation and [Ca2+]i mobilization in a dose-dependent manner in addition to reducing ATP release from collagen-stimulated platelets. Furthermore, using immunoblot analysis, we found that Rg3-RGE markedly suppressed mitogen-activated protein kinase phosphorylation (i.e., extracellular stimuli-responsive kinase, Jun N-terminal kinase, p38) as well as the PI3K (phosphatidylinositol 3 kinase)/Akt pathway. Moreover, Rg3-RGE effectively reduced collagen plus epinephrine-induced mortality in mice. These data suggest that ginsenoside Rg3-RGE could be potentially be used as an antiplatelet therapeutic agent against platelet-mediated cardiovascular disorders.

Ginseng has therapeutic effects on various bodily disorders ranging from minor inflammation to major cardiovascular diseases. In our study, we explored the anti‐inflammatory effects of Rg3‐enriched red ginseng extract (Rg3‐RGE), a ginsenoside belonging to the panaxadiol group. We employed nitric oxide assay (NO) and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR), western blot, and hematoxylin and eosin staining (H&E) to elucidate the anti‐inflammatory activity of Rg3‐RGE. Rg3‐RGE potently suppressed NO production in the murine macrophage cell line, RAW 264.7 cells, without any cytotoxicity across dosages. Additionally, it inhibited the mRNA expression of proinflammatory mediators and cytokines like iNOS, COX‐2, IL‐1β, IL‐6, and TNF‐α. Moreover it also inhibited the levels of malondialdehyde levels in serum of septic shock mice. Immunoblot analysis showed that Rg3‐RGE induced anti‐inflammatory signal transduction via the NF‐κB and MAPK pathways. A remarkable attenuation of inflammation by oral treatment with Rg3‐RGE in mice was observed in the survival study. The in vivo study using a septic shock mouse model also showed similar results as the in vitro study. Our findings suggest that Rg3‐RGE can potentially be a potent anti‐inflammatory agent that likely mediates its anti‐inflammatory effects via the NF‐κB and MAPK pathways.

The odontoblastic differentiation of dental pulp stem cells (DPSCs) associated with caries injury happens in an inflammatory context. We recently demonstrated that there is a link between inflammation and dental tissue regeneration, identified via enhanced DPSC-mediated dentinogenesis in vitro. Brain-derived neurotrophic factor (BDNF) is a nerve growth factor-related gene family molecule which functions through tropomyosin receptor kinase B (TrkB). While the roles of BDNF in neural tissue repair and other regeneration processes are well identified, its role in dentinogenesis has not been explored. Furthermore, the role of BDNF receptor-TrkB in inflammation-induced dentinogenesis remains unknown. The role of BDNF/TrkB was examined during a 17-day odontogenic differentiation of DPSCs. Human DPSCs were subjected to odontogenic differentiation in dentinogenic media treated with inflammation inducers (LTA or TNFα), BDNF, and a TrkB agonist (LM22A-4) and/or antagonist (CTX-B). Our data show that BDNF and TrkB receptors affect the early and late stages of the odontogenic differentiation of DPSCs. Immunofluorescent data confirmed the expression of BDNF and TrkB in DPSCs. Our ELISA and qPCR data demonstrate that TrkB agonist treatment increased the expression of dentin matrix protein-1 (DMP-1) during early DPSC odontoblastic differentiation. Coherently, the expression levels of runt-related transcription factor 2 (RUNX-2) and osteocalcin (OCN) were increased. TNFα, which is responsible for a diverse range of inflammation signaling, increased the levels of expression of dentin sialophosphoprotein (DSPP) and DMP1. Furthermore, BDNF significantly potentiated its effect. The application of CTX-B reversed this effect, suggesting TrkB`s critical role in TNFα-mediated dentinogenesis. Our studies provide novel findings on the role of BDNF-TrkB in the inflammation-induced odontoblastic differentiation of DPSCs. This finding will address a novel regulatory pathway and a therapeutic approach in dentin tissue engineering using DPSCs.

Background: Studies on the associations of the adenosine triphosphate-binding cassette transporter A1 gene (ABCA1) rs2230806, rs2230808, and rs2066714 polymorphisms with plasma lipid levels have reported apparently conflicting findings. This meta-analysis aimed to clarify the relationships between the 3 polymorphisms and fasting lipid levels. Methods: A comprehensive search of the literature was carried out by using the databases including Medline, Google Scholar, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, and VIP. The studies that presented mean lipids and standard deviations or standard errors according to the rs2230806, rs2230808, and/or rs2066714 genotypes were examined and included. The random effects model was used. Standardized mean difference and 95% confidence interval were used to assess the differences in lipid levels between the genotypes. Heterogeneity among studies was tested by Cochran's χ²-based Q-statistic, and Galbraith plots were used to detect the potential sources of heterogeneity. Publication bias was assessed by Begg's rank correlation test as well as funnel plots. Results: Sixty-two studies (48,452 subjects), 12 studies (9853 subjects) and 14 studies (10,727 subjects) were identified for the rs2230806, rs2230808, and rs2066714 polymorphisms, respectively. A dominant model was used for all the polymorphisms in this meta-analysis. The A allele carriers of the rs2230806 polymorphism had higher levels of high-density lipoprotein cholesterol (HDL-C) (P <.001), and lower levels of low-density lipoprotein cholesterol (LDL-C) (P =.03) and triglycerides (TG) (P <.01) than the non-carriers. The A allele carriers of the rs2230808 polymorphism had higher levels of total cholesterol (TC) (P <.001) than the non-carriers. The G allele carriers of the rs2066714 polymorphism had higher levels of TC (P <.01) and HDL-C (P = .02) than the non-carriers. Conclusion: The ABCA1 rs2230806, rs2230808, and rs2066714 polymorphisms are significantly associated with plasma lipid levels in the present meta-analysis.