Evelyn Saba

A Novel Korean Red Ginseng Compound Gintonin Inhibited Inflammation by MAPK and NF-κB Pathways and Recovered the Levels of mir-34a and mir-93 in RAW 264.7 Cells

The beneficial health promoting effects of ginseng from vitalizing the body to enhancing long life have been well explored very rapidly in the past few years. Up till now many ginsenosides have been discovered for their marvelous therapeutic effects. However during past three years, a novel ginseng compound has been discovered, called gintonin, that differs from other ginsenosides on the basis of its signal transduction and chemical nature. Gintonin has been widely studied for its anti-Alzheimers disease activities and other neuropathies. However, its anti-inflammatory activity remained unexplored. In our study we have reported for the first time the anti-inflammatory activity of gintonin on RAW 264.7 cells. We found that gintonin potently suppresses the nitric oxide production without any cytotoxicity at given doses and also efficiently suppressed the levels of proinflammatory cytokines. Moreover, it mediaes its signal transduction via MAPK and NF-κB pathways and revives the levels of mir-34a and mir-93. These findings are valuable for the anti-inflammatory effects of this new compound with particular reference to microRNA involvement in the ginseng family.

Black ginseng extract ameliorates hypercholesterolemia in rats

Background Ginseng (Panax ginseng Meyer) is a well-characterized medicinal herb listed in the classic oriental herbal dictionary as “Shin-nong-bon-cho-kyung.” Ginseng has diverse pharmacologic and therapeutic properties. Black ginseng (BG, Ginseng Radix nigra) is produced by repeatedly steaming fresh ginseng nine times. Studies of BG have shown that prolonged heat treatment enhances the antioxidant activity with increased radical scavenging activity. Several recent studies have showed the effects of BG on increased lipid profiles in mice. In this study report the effects of water and ethanol extracts of BG on hypercholesterolemia in rats. To our knowledge, this is the first time such an effect has been reported. Methods Experiments were conducted on male Sprague Dawley rats fed with a high-cholesterol diet supplemented with the water and ethanol extracts of BG (200 mg/kg). Their blood cholesterol levels, serum white blood cell levels, and cholesterol-metabolizing marker genes messenger RNA (mRNA) expression were determined. Liver and adipose tissues were histologically analyzed. Results We found that BG extracts efficiently reduced the total serum cholesterol levels, low-density lipoprotein (LDL) levels with increased food efficiency ratio and increased number of neutrophil cells. It also attenuated the key genes responsible for lipogenesis, that is, acetyl-coenzyme A (CoA) acetyltransferase 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and sterol regulatory element-binding protein 2, at the mRNA level inside liver cells. Furthermore, the BG extract also reduced the accumulation of fat in adipose tissues, and inhibited the neutral fat content in liver cells stained with hematoxylin and eosin and oil red O. Conclusion Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BGs cardioprotective effects.

Acetyl Eburicoic Acid from Laetiporus sulphureus var. miniatus Suppresses Inflammation in Murine Macrophage RAW 264.7 Cells.

Abstract The basidiomycete Laetiporus sulphureus var. miniatus belongs to the Aphyllophorales, Polyporaceae, and grows on the needleleaf tree. The fruiting bodies of Laetiporus species are known to produce N-methylated tyramine derivatives, polysaccharides, and various lanostane triterpenoids. As part of our ongoing effort to discover biologically active compounds from wood-rotting fungi, an anti-inflammatory triterpene, LSM-H7, has been isolated from the fruiting body of L. sulphureus var. miniatus and identified as acetyl eburicoic acid. LSM-H7 dose-dependently inhibited the NO production in RAW 264.7 cells without any cytotoxicity at the tested concentrations. Furthermore it suppressed the production of proinflammatory cytokines, mainly inducible nitric oxide synthase, cyclooxygenase-2, interleukin (IL)-1β, IL-6 and tumor necrosis factor α, when compared with glyceraldehyde 3-phosphate dehydrogenase. These data suggest that LSM-H7 is a crucial component for the antiinflammatory activity of L. sulphureus var. miniatus.

Black ginseng-enriched Chong-Myung-Tang extracts improve spatial learning behavior in rats and elicit anti-inflammatory effects in vitro

Background Chong-Myung-Tang (CMT) extract is widely used in Korea as a traditional herbal tonic for increasing memory capacity in high-school students and also for numerous body ailments since centuries. The use of CMT to improve the learning capacity has been attributed to various plant constituents, especially black ginseng, in it. Therefore, in this study, we have first investigated whether black ginseng-enriched CMT extracts affected spatial learning using the Morris water maze (MWM) test. Their molecular mechanism of action underlying improvement of learning and memory was examined in vitro. Methods We used two types of black ginseng-enriched CMT extracts, designated as CM-1 and CM-2, and evaluated their efficacy in the MWM test for spatial learning behavior and their anti-inflammatory effects in BV2 microglial cells. Results Our results show that both black ginseng-enriched CMT extracts improved the learning behavior in scopolamine-induced impairment in the water maze test. Moreover, these extracts also inhibited nitric oxide production in BV2 cells, with significant suppression of expression of proinflammatory cytokines, especially inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1β. The protein expression of mitogen-activated protein kinase and nuclear factor-κB pathway factors was also diminished by black ginseng-enriched CMT extracts, indicating that it not only improves the memory impairment, but also acts a potent anti-inflammatory agent for neuroinflammatory diseases. Conclusion Our research for the first time provides the scientific evidence that consumption of black ginseng-enriched CMT extract as a brain tonic improves memory impairment. Thus, our study results can be taken as a reference for future neurobehavioral studies.

Alleviation of diabetic complications by ginsenoside Rg3-enriched red ginseng extract in western diet-fed LDL–/– mice

In this study, we precisely showed how the Rg3-enriched red ginseng extract (Rg3-RGE) lowers glucose, triglyceride, and low-density lipoprotein (LDL) levels in LDL–/– mice. Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase), alanine aminotransferase /serum glutamate-pyruvate transaminase, and steatohepatitis were found to be reduced, and atheroma formation was inhibited by Rg3-enriched red ginseng extract.

Fermented rice bran prevents atopic dermatitis in DNCB-treated NC/Nga mice

Abstract The fermentation of natural plants has a favorable effect on the functional and biological activities of living systems. These include anti-oxidative, anti-inflammatory, and anti-platelet aggregation activities. This is attributed to the chemical conversion of the parent plants to functional constituents, which show more potent biological activity. In our study, rice bran along with oriental medicinal plants (Angelicae gigantis, Cnidium officinale, Artemisia princeps, and Camellia sinensis) was fermented by Lactobacillus rhamnosus and Pichia deserticola (FRBE). We evaluated the effects of oral administration of FRBE on atopic dermatitis in 1-chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. FRBE significantly ameliorated the macroscopic and microscopic appearance of skin lesions in DNCB-induced atopic dermatitis and reduced levels of serum immunoglobulin E and the differential white blood cell count. In addition, it reduced skin thickness compared to that of atopic dermatitis-affected skin. FRBE treatment also reduced mast cell incorporation in skin lesions of atopic dermatitis. The total cell number in dorsal skin tissue and the axillary lymph node increased following DNCB application, and this was normalized by FRBE treatment. Moreover, it decreased the levels of CD8+ helper T cells and Gr-1+/CD11b+ B cells in peripheral blood mononuclear cells and skin lesions in DNCB-induced atopic dermatitis. Using real-time polymerase chain reaction analysis, we demonstrated that FRBE significantly inhibited mRNA expression of cytokines (e.g., interleukin-5 and interleukin-13) and cyclooxygenase-2 in AD skin lesions. These results suggest that FRBE could be a valuable herbal remedy for the treatment of atopic dermatitis.

Gintonin modulates platelet function and inhibits thrombus formation via impaired glycoprotein VI signaling

Panax ginseng (P. ginseng), one of the most valuable medicinal plants, is known for its healing and immunobooster properties and has been widely used in folk medicine against cardiovascular diseases, including stroke and heart attack. In this study, we explored the anti-platelet activity of gintonin (a recently discovered non-saponin fraction of ginseng) against agonist-induced platelet activation. In vitro effects of gintonin on agonist-induced human and rat platelet aggregation, granule secretion, integrin αIIbβ3 activation, and intracellular calcium ion ([Ca2+]i) mobilization were examined. Western blot analysis and immunoprecipitation techniques were used to estimate the expression of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and interaction of glycoprotein VI (GPVI) signaling pathway molecules such as Src family kinases (SFK), tyrosine kinase Syk, and PLCγ2. In vivo effects were studied using acute pulmonary thromboembolism model in mice. Gintonin remarkably inhibited collagen-induced platelet aggregation and suppressed granule secretion, [Ca2+]i mobilization, and fibrinogen binding to integrin αIIbβ3 in a dose-dependent manner and clot retraction. Gintonin attenuated the activation of MAPK molecules and PI3K/Akt pathway. It also inhibited SFK, Syk, and PLCγ2 activation and protected mice from thrombosis. Gintonin inhibited agonist-induced platelet activation and thrombus formation through impairment in GPVI signaling molecules, including activation of SFK, Syk, PLCγ2, MAPK, and PI3K/Akt; suggesting its therapeutic potential against platelet related CVD.

Mediation of antiinflammatory effects of Rg3-enriched red ginseng extract from Korean red ginseng via retinoid X receptor α–peroxisome-proliferating receptor γ nuclear receptors

Background Ginseng has a wide range of beneficial effects on health, such as the mitigation of minor and major inflammatory diseases, cancer, and cardiovascular diseases. There are abundant data regarding the health-enhancing properties of whole ginseng extracts and single ginsenosides; however, no study to date has determined the receptors that mediate the effects of ginseng extracts. In this study, for the first time, we explored whether the antiinflammatory effects of Rg3-enriched red ginseng extract (Rg3-RGE) are mediated by retinoid X receptor α–peroxisome-proliferating receptor γ (RXRα-PPARγ) heterodimer nuclear receptors. Methods Nitric oxide assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, quantitative reverse transcription polymerase chain reaction, nuclear hormone receptor–binding assay, and molecular docking analyses were used for this study. Results Rg3-RGE exerted antiinflammatory effects via nuclear receptor heterodimers between RXRα and PPARγ agonists and antagonists. Conclusion These findings indicate that Rg3-RGE can be considered a potent antiinflammatory agent, and these effects are likely mediated by the nuclear receptor RXRα-PPARγ heterodimer.

Luteolin attenuates airway inflammation by inducing the transition of CD4+CD25– to CD4+CD25+ regulatory T cells

ABSTRACT Regulatory T cells play an important role in autoimmunity and have been shown to exert anti‐inflammatory effects in allergic asthma. Mouse model of airway inflammation was used to examine the suppressive activity of luteolin‐induced CD4+CD25+ regulatory T cells (Tregs) in vivo. In this study, BALB/c mice were sensitized with ovalbumin antigen (OVA) by aerosol challenge. Then, various biological processes were examined, including airway eosinophilia; mucus hypersecretion; elevation of OVA‐specific IgE, expression of Th2 cytokines and chemokine levels; expression of eotaxin 2 and CCR3; and airway hyper responsiveness (AHR). Luteolin significantly inhibited OVA‐induced increase in immune cell and eosinophil counts as well as IL‐4, IL‐5, IL‐13, and eotaxin levels in bronchoalveolar lavage fluid (BAL Fluid). Luteolin and cyclosporine A (CsA) which was a positive control also substantially reduced OVA‐specific IgE levels, eotaxin 2 levels, and CCR3 expression in BAL Fluid. In contrast, luteolin significantly increased IL‐10 and IFN‐&ggr; protein levels, as well as IL‐10 and TGF‐&bgr;1 mRNA expression in the lung. In vitro studies showed that the number of luteolin‐induced CD4+CD25+ Treg (iTreg) cells was higher, with elevated levels of TGF‐&bgr;1 and foxp3 mRNA expression in lungs tissue. Transfer of iTreg cells into OVA‐sensitized mice reduced AHR, eosinophil recruitment, eotaxin, IgE, and Th2 cytokine expressions, and increased IFN‐&ggr; production in BAL Fluid after allergen challenge. Furthermore, adoptive transfer of iTreg cells prevented disease in a CD25‐depleted mouse asthma model. Luteolin via induction of foxp3 and CD4+CD25+ Treg cells may represent a new strategy in the development of therapies for managing asthma.

Anti-Inflammatory Activity of Crude Venom Isolated from Parasitoid Wasp, Bracon hebetor Say

Pest control in the agricultural fields, a major concern globally, is currently achieved through chemical or biological methods. Chemical methods, which leave toxic residue in the produce, are less preferred than biological methods. Venoms injected by stings of various wasps that kill the pest is considered as the examples of the biological method. Although several studies have investigated the biological control of pests through these venoms, very few studies have reported the effects of these venoms on mammalian cells. Bracon hebetor, an ectoparasitoid of the order Hymenoptera, is having a paramount importance in parasitizing various lepidopterous larvae including Plodia interpunctella also called as Indianmeal moth (IMM). Since it is biologically controlled by B. hebetor venom, therefore in our study, herein for the first time, we report the anti-inflammatory activities of the venom from B. hebetor (BHV). We developed a septic shock mice model for in vivo anti-inflammatory studies and RAW 264.7 cells for in vitro studies. Our results clearly demonstrate that BHV can dose dependently abrogate the nitric oxide (NO) production and suppress the levels of proinflammatory mediators and cytokines without posing any cytotoxicity via the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways.