PMID: 

J Ginseng Res. 2019 Oct ;43(4):499-507. Epub 2017 Jul 25. PMID: 31695559

Abstract Title: 

Ginsenoside Rb1 ameliorates cisplatin-induced learning and memory impairments.

Abstract: 

Background: Ginsenoside Rb1 (Rb1), a dominant component from the extract ofroot, exhibits neuroprotective functions in many neurological diseases. This study was intended to investigate whether Rb1 can attenuate cisplatin-induced memory impairments and explore the potential mechanisms.Methods: Cisplatin was injected intraperitoneally with a dose of 5 mg/kg/wk, and Rb1 was administered in drinking water at the dose of 2 mg/kg/d to rats for 5 consecutive wk. The novel objects recognition task and Morris water maze were used to detect the memory of rats. Nissl staining was used to examine the neuron numbers in the hippocampus. The activities ofsuperoxide dismutase, glutathione peroxidase, cholineacetyltransferase, acetylcholinesterase, and the levels of malondialdehyde, reactive oxygen species, acetylcholine, tumor necrosis factor-α, interleukin-1β, and interleukin-10 were measured by ELISA to assay the oxidative stress, cholinergic function, and neuroinflammation in the hippocampus.Results: Rb1 administration effectively ameliorates the memory impairments caused by cisplatin in both novel objects recognition task and Morris water maze task. Rb1 also attenuates the neuronal loss induced by cisplatin in the different regions (CA1, CA3, and dentate gyrus) of the hippocampus. Meanwhile, Rb1 is able to rescue the cholinergic neuron function, inhibit the oxidative stress and neuroinflammation in cisplatin-induced rat brain.Conclusion: Rb1 rescues the cisplatin-induced memory impairment via restoring the neuronal loss by reducing oxidative stress and neuroinflammation and recovering the cholinergic neuron functions.

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PMID: 

Brain Res Bull. 2020 Jan ;154:51-60. Epub 2019 Nov 9. PMID: 31715311

Abstract Title: 

Ginsenoside Rb1 Promotes Motor Functional Recovery and Axonal Regeneration in Post-stroke Mice through cAMP/PKA/CREB Signaling Pathway.

Abstract: 

The central nervous system (CNS) has a poor self-repairing capability after injury because of the inhibition of axonal regeneration by many myelin-associated inhibitory factors. Therefore, ischemic stroke usually leads to disability. Previous studies reported that Ginsenoside Rb1 (GRb1) plays a role in neuronal protection in acute phase after ischemic stroke, but its efficacy in post-stroke and the underlying mechanism are not clear. Recent evidences demonstrated GRb1 promotes neurotransmitter release through the cAMP-depend protein kinase A (PKA) pathway, which is related to axonal regeneration. The present study aimed to determine whether GRb1 improves long-term motor functional recovery and promotes cortical axon regeneration in post-stroke. Adult male C57BL/6 mice were subjected to distal middle cerebral artery occlusion (dMCAO). GRb1 solution (5 mg/ml) or equal volume of normal saline was injected intraperitoneally for the first time at 24 h after surgery, and then daily injected until day 14. Day 3, 7, 14 and 28 after dMCAO were used as observation time points. Motor functional recovery was assessed with Rota-rod test and grid walkingtask. The expression of growth-associated protein 43 (GAP43) and biotinylated dextran amine (BDA) was measured to evaluate axonal regeneration. The levels of cyclic AMP (cAMP) and PKA were measured by Elisa, PKAc and phosphorylated cAMP response element protein (pCREB) were determined by western blot. Our results shown that GRb1 treatment improved motor function and increased the expression of GAP43 and BDA in ipsilesional and contralateral cortex. GRb1 significantly elevated cAMP and PKA, increased the protein expression of PKAc and pCREB. However, the effects of GRb1 were eliminated by H89intervention (a PKA inhibitor). These results suggested that GRb1 improved functional recovery in post-stroke by stimulating axonal regeneration and brain repair. The underlying mechanism might be up-regulating the expression of cAMP/PKA/CREB pathway.

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PMID: 

Sci Rep. 2019 Dec 31 ;9(1):20425. Epub 2019 Dec 31. PMID: 31892729

Abstract Title: 

Ginsenoside Rb1 exerts antiarrhythmic effects by inhibiting Iand Iin rabbit ventricular myocytes.

Abstract: 

Ginsenoside Rb1 exerts its pharmacological action by regulating sodium, potassium and calcium ion channels in the membranes of nerve cells. These ion channels are also present in cardiomyocytes, but no studies have been reported to date regarding the effects of Rb1 on cardiac sodium currents (I), L-type calcium currents (I) and action potentials (APs). Additionally, the antiarrhythmic potential of Rb1 has not been assessed. In this study, we used a whole-cell patch clamp technique to assess the effect of Rb1 on these ion channels. The results showed that Rb1 inhibited Iand I, reduced the action potential amplitude (APA) and maximum upstroke velocity (V), and shortened the action potential duration (APD) in a concentration-dependent manner but had no effect on the inward rectifier potassium current (I), delayed rectifier potassium current (I) or resting membrane potential (RMP). We also designed a pathological model at the cellular and organ level to verify the role of Rb1. The results showed that Rb1 abolished high calcium-induced delayed afterdepolarizations (DADs), depressed the increase in intracellular calcium ([Ca]), relieved calcium overload and protected cardiomyocytes. Rb1 can also reduce the occurrence of ventricular premature beats (VPBs) and ventricular tachycardia (VT) in ischemia-reperfusion (I-R) injury.

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PMID: 

J Agric Food Chem. 2019 Dec 26 ;67(51):14074-14085. Epub 2019 Dec 16. PMID: 31793297

Abstract Title: 

Ginsenoside-Rb1 Improved Diabetic Cardiomyopathy through Regulating Calcium Signaling by Alleviating Protein O-GlcNAcylation.

Abstract: 

Ginsenoside-Rb1 (Rb1), a major active component of ginseng, has many benefits for cardiovascular disease and diabetes mellitus (DM), but the effect and mechanism on diabetic cardiomyopathy are not clear. In the present study, we found that Rb1-feeding significantly improved cardiac dysfunction and abnormal cardiomyocytes calcium signaling caused by diabetes. This improved calcium signaling was because Rb1 reduced Caleakage caused by overactivated ryanodine receptor 2 (RyR2) and increased Cauptake by sarcoplasmic reticulum Ca-ATPase 2a (SERCA 2a). Furthermore, we found that Rb1 not only enhanced energy metabolism like metformin and eliminated O-GlcNAcylation of calcium handling proteins to regulate calcium signaling but also directly inhibited RyR2 activity to regulate calcium signaling. The present study indicated that as a health supplement or drug, Rb1 was a relatively effective auxiliary therapeutic substance for diabetic cardiomyopathy.

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PMID: 

Nutrients. 2019 Nov 12 ;11(11). Epub 2019 Nov 12. PMID: 31726767

Abstract Title: 

Black Ginseng and Ginsenoside Rb1 Promote Browning by Inducing UCP1 Expression in 3T3-L1 and Primary White Adipocytes.

Abstract: 

In this study, we investigated the effects of black ginseng (BG) and ginsenoside Rb1, which induced browning effects in 3T3-L1 and primary white adipocytes (PWATs) isolated from C57BL/6 mice. BG and Rb1 suppressed the expressions of CCAAT/enhancer-binding protein alpha (C/EBPα) and sterol regulatory element-binding transcription factor-1c (SREBP-1c), whereas the expression level of peroxisome proliferator-activated receptor gamma (PPARγ) was increased. Furthermore, BG and Rb1 enhanced the protein expressions of the brown-adipocyte-specific markers PR domain containing16 (PRDM16), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and uncoupling protein 1 (UCP1). These results were further supported by immunofluorescence images of mitochondrial biogenesis. In addition, BG and Rb1 induced expressions of brown-adipocyte-specific markerproteins by AMP-activated protein kinase (AMPK) activation. BG and Rb1 exert antiobesity effects by inducing browning in 3T3-L1 cells and PWATs through AMPK-mediated pathway activation. We suggest that BG and Rb1 act as potential functional antiobesity food agents.

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PMID: 

Am J Chin Med. 2019 ;47(6):1237-1251. Epub 2019 Sep 9. PMID: 31495180

Abstract Title: 

Inhibitory Effects of Black Ginseng on Particulate Matter-Induced Pulmonary Injury.

Abstract: 

Inhalation of fine particulate matter () is associated with elevated pulmonary injury caused by the loss of vascular barrier integrity. Black ginseng (BG), steamed and dried ginseng nine times, exhibits various pharmacological activities such as antibacterial, antihyperglycemic, anti-atopic, antibacterial, and anti-inflammatory activities. In this study, we investigated the beneficial effects of black ginseng extract (BGE) against PM-induced lung endothelial cell (EC) barrier disruption and pulmonary inflammation. Permeability, leukocyte migration, activation of proinflammatory proteins, generation of reactive oxygen species (ROS), and histology were examined in-treated ECs and mice. BGE significantly scavenged-induced ROS and inhibited the ROS-induced activation of p38 mitogen-activated protein kinase (MAPK). Concurrently, BGE activated Akt, which helped maintain endothelial integrity. Furthermore, BGE reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid in PM-induced lung tissues. These results indicated that BGE may exhibit protective effects against PM-induced inflammatory lung injury and vascular hyperpermeability.

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PMID: 

Chemosphere. 2020 Feb ;240:124836. Epub 2019 Sep 11. PMID: 31561165

Abstract Title: 

Combined effects of ambient air pollution and home environmental factors on low birth weight.

Abstract: 

BACKGROUND: Low birth weight (LBW) remains a major public health problem worldwide, yet its crucial environmental risk factors are still unclear.OBJECTIVE: To examine the association between LBW (term and preterm LBW) and prenatal exposure to ambient air pollution and home environmental factors as well as their combination, in order to identify critical time window for exposure and key outdoor and indoor factors in LBW development.METHODS: A cohort study of 3509 preschool children was performed in Changsha, China during the period 2011-2012. A questionnaire was conducted to survey each child's birth outcome and each mother's exposure to home environmental factors including parental smoking, new furniture, redecoration, mold/damp stains, window pane condensation, and household pets during pregnancy. Maternal exposure to inhalable particulate matter (PM), industrial air pollutant (SO), and traffic air pollutant (NO) was estimated during different time windows of gestation, including conception month, three trimesters, birth month, and whole gestation. Associations of term and preterm LBW with ambient air pollutants and home environmental factors were assessed by multiple logistic regression models in terms of odds ratio (OR) with 95% confidence interval (CI).RESULTS: Term LBW (TLBW) was significantly associated with exposure to ambient PMduring pregnancy, with OR (95% CI) = 1.47 (1.00-2.14) for per IQR increase after adjustment for the covariates and home environmental factors. Specifically, we identified the significant association in early phase of pregnancy including conception month (1.90, 1.09-3.30) and the first trimester (1.72, 1.10-2.69). We further found that TLBW was significantly related with parental smoking at home, OR (95% CI) = 2.17 (1.09-4.33). However, no association was observed for preterm LBW (PLBW). The TLBW risk of ambient air pollution and home environmental factors was independent each other and hence the combined exposure to ambient PMand indoor parental smoking caused the highest risk. Sensitivity analysis suggested that foetus with younger mothers were significantly more susceptible to risk of indoor parental smoking, while those with smaller house and cockroaches were more sensitive to risk of outdoor PMexposure.CONCLUSION: Prenatal exposure to combined outdoor and indoor air pollution, particularly in critical window(s) during early pregnancy, significantly increases the risk of term LBW.

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PMID: 

J Environ Sci (China). 2020 Mar ;89:227-237. Epub 2019 Nov 9. PMID: 31892394

Abstract Title: 

PMexposure induces age-dependent hepatic lipid metabolism disorder in female mice.

Abstract: 

Particulate matter exposure has been described to elevate the risk of lung and cardiovascular diseases. An increasing number of recent studies have indicated positive correlations between PM(the fraction of airborne particles with an aerodynamic diameter less than 2.5 μm) exposure and the risk of liver diseases. However, research on the effects of PMexposure on liver fat synthesis, secretion, and clearance mechanisms under normal diet conditions is limited, and whether these effects are age-dependent is largely unknown. Female C57BL/6 mice at different ages (4 weeks (4 w), 4 months (4 m), and 10 months (10 m)) were treated with 3 mg/kg body weight of PMevery other day for 4 weeks. Subsequently, the ultrastructural changes of liver, the expression of genes involved in oxidative damage and lipid metabolism in the liver were examined. Observation of hepatic ultrastructure showed more and larger lipid droplets in the livers of 4-week-old and 10-month-old mice exposed to PM. Further analysis showed that PMexposure increased the expression of genes related to lipid synthesis, but decreased the expression of genes involved in lipid transport and catabolism in the livers of 10-month-old mice. Our findings suggest that exposure to PMdisrupts the normal metabolism of liver lipids and induces lipid accumulation in the liver of female mice in an age-dependent manner, with older mice being more susceptible to PM.

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PMID: 

Environ Geochem Health. 2020 Jan 1. Epub 2020 Jan 1. PMID: 31894453

Abstract Title: 

Effect of long-term particulate matter exposure on Parkinson's risk.

Abstract: 

Environmental pollution is a critical predisposing factor underlying neurodegenerative diseases, but the association between particulate matter (PM) exposure and Parkinson's disease (PD) remains unclear. This study aimed to evaluate the association between long-term PM2.5/PM10 exposure and PD risk. We searched the PubMed, Ovid Medline, EMBASE, Cochrane Library, and Web of Science citation databases to select studies about the relationship between long-term PM exposure and PD risk. The association was assessed using meta-analysis, and subgroup analysis was carried out on the basis of the types of PM (PM2.5 and PM10). Among the 611 articles identified from the databases, we selected six articles, including three cohort studies and three case-control studies, which collectively involved 10,077,029 participants. With every 10 μg/mincrement, the relative risks (RRs) and 95% confidence intervals (CIs) were 1.03 (0.98, 1.07), 1.21 (0.95, 1.54), and 1.01 (0.97, 1.05) for the total PM, PM2.5, and PM10, respectively. In the current study, no statistically substantial association was observed between long-term PM2.5/PM10 exposure and PD incidence. However, further large-scale prospective studies are needed to determine the association.

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PMID: 

Med Sci Monit. 2019 Dec 20 ;25:9794-9800. Epub 2019 Dec 20. PMID: 31860907

Abstract Title: 

Lycium Barbarum Exerts Protection against Glaucoma-Like Injury Via Inhibition of MMP-9 Signaling In Vitro.

Abstract: 

BACKGROUND The phytochemical ingredients of berries have been used in the treatment of various bodily ailments; while their roles in preventing the severity of glaucoma are poorly understood. Hence, the present study was framed to investigate whether ethanolic extracts of Lycium barbarum exerts protection against the onset of glaucoma using cultured PC12 neuronal cells by modulating the expression of extracellular matrix proteins. MATERIAL AND METHODS In order to develop glaucoma like condition in cells, cultured PC12 cells were subjected to 50 and 100 mmHg hydrostatic pressure for 24 hours. The pressure exposed cells were analyzed for the expression of glaucoma markers such as ANGPTL7 and the expressions of extracellular matrix proteins in the presence and absence of L. barbarum, matrix metalloproteinase (MMP)-9 inhibitor, and latanoprost, a current drug for the treatment of glaucoma. RESULTS PC12 cells exposed to hydrostatic pressures (50 and 100 mmHg) increased the expression of glaucoma marker, ANGPTL7. Moreover, results have demonstrated the significant changes in the expression of MMP-2, MMP-9, collagen I, and TGF-ß at the gene level. In contrast, cells pretreated with L. barbarum extracts showed reduced expression of ANGPTL7 and extracellular matrix proteins compared to control. Furthermore, to elucidate the role of MMP-9 in the onset of glaucoma, cells were silenced using MMP-9 inhibitor along with L. barbarum demonstrated a significant reduction in the glaucoma marker ANGPTL7 while improving the expression of caveolin-1 expression in cells subjected to pressure. CONCLUSIONS The extract of L. barbarum protects the cells from intraocular pressure by activating caveolin-1 dependent pathway via inhibition of MMP-9 expression.

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