Macrod1 suppresses diabetic cardiomyopathy via regulating PARP1-NAD+-SIRT3 pathway.

Diabetic cardiomyopathy (DCM), one of the most serious long-term consequences of diabetes, is closely associated with oxidative stress, inflammation and apoptosis in the heart. MACRO domain containing 1 (Macrod1) is an ADP-ribosylhydrolase 1 that is highly enriched in mitochondria, participating in the pathogenesis of cardiovascular diseases. In this study, we investigated the role of Macrod1 in DCM. A mice model was established by feeding a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). We showed that Macrod1 expression levels were significantly downregulated in cardiac tissue of DCM mice. Reduced expression of Macrod1 was also observed in neonatal rat cardiomyocytes (NRCMs) treated with palmitic acid (PA, 400 µM) in vitro. Knockout of Macrod1 in DCM mice not only worsened glycemic control, but also aggravated cardiac remodeling, mitochondrial dysfunction, NAD+ consumption and oxidative stress, whereas cardiac-specific overexpression of Macrod1 partially reversed these pathological processes. In PA-treated NRCMs, overexpression of Macrod1 significantly inhibited PARP1 expression and restored NAD+ levels, activating SIRT3 to resist oxidative stress. Supplementation with the NAD+ precursor Niacin (50 µM) alleviated oxidative stress in PA-stimulated cardiomyocytes. We revealed that Macrod1 reduced NAD+ consumption by inhibiting PARP1 expression, thereby activating SIRT3 and anti-oxidative stress signaling. This study identifies Macrod1 as a novel target for DCM treatment. Targeting the PARP1-NAD+-SIRT3 axis may open a novel avenue to development of new intervention strategies in DCM. Schematic illustration of macrod1 ameliorating diabetic cardiomyopathy oxidative stress via PARP1-NAD+-SIRT3 axis.

Dietary Se deficiency dysregulates metabolic and cell death signaling in aggravating the AFB1 hepatotoxicity of chicks.

The objective of this study was to use isobaric tags for relative and absolute quantitation (iTRAQ) proteomic technology to systematically analyze the hepatotoxic mechanism of aflatoxin B1 (AFB1) and its prevention by Se in broilers. Four groups of day-old broilers were allocated into a 2 × 2 factorial design trial that fed a Se-deficient based diet (BD) or the BD + 1.0 mg AFB1/kg, 0.3 mg Se/kg, or 1.0 mg AFB1/kg plus 0.3 mg Se/kg for 3 wk. Dietary AFB1 increased serum ALT and decreased total protein and albumin concentrations, and induced hepatic histopathological lesions in Se adequate groups. Notably, Se deficiency exacerbated these AFB1-induced changes. Furthermore, Se deficiency reduced hepatic glutathione peroxidase but increased thioredoxin reductase and glutathione S-transferase activities and 8-hydroxydeoxyguanosine concentration in AFB1 administrated groups. Moreover, AFB1 dysregulated 261 co-differentially expressed proteins (DEPs) in both Se adequate and deficiency diets, and Se deficiency dysregulated 64 DEPs in AFB1 administrated diets. These DEPs are mainly related to phase I and II metabolizing enzymes, heat shock proteins, DNA repair, fatty acid metabolism and apoptosis. The in vitro study has verified that aldo-keto reductase family1, member10 plays an important role in AFB1-induced hepatotoxicity and Se-mediated detoxification of AFB1 in a chicken leghorn male hepatoma cells. Conclusively, this study has analyzed the hepatic proteome response to dietary AFB1 and Se, and thus shed new light on the mechanisms of hepatotoxicity of AFB1 and its detoxification by Se in broilers.

Aconitine disrupts serotonin neurotransmission via 5-hydroxytryptamine receptor in zebrafish embryo.

Medicinal plants of the genus Aconitum are one of the most commonly used herbs in traditional medicine in East Asia to treat conditions related to the heart, pain, or inflammation. However, these herbs are also dangerous as accidental poisoning due to misuse is a recurring issue. These plants contain a number of diester-diterpenoid alkaloid compounds and aconitine is the most abundant and active one. This study investigated neurotoxicity of aconitine to zebrafish embryos in early development in relation to serotonin regulation. Experimental results showed that aconitine exposure (1, 10, and 100 µM) increased frequency of coiling behavior in zebrafish embryos in a dose-dependent manner and this effect can be triggered by either exposure to 5-hydroxytryptamine 1A (5-HT1A) receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) or overexpression of serotonin receptor 5-htr1ab. At the same time, coiling behavior caused by aconitine exposure could be rescued by co-exposure to 5-HT1A receptor antagonist WAY-100635 Maleate (WAY100635) and knockdown of 5-htr1ab using morpholino. Exposure to aconitine also significantly increased serotonin receptor 5-htr1ab and 5-htr1bd gene expression at 24 h post fertilization (hpf), but decreased their expression and protein expression of the serotonin receptor at 96 hpf with the high dose. These results suggest that neurotoxicity caused by aconitine is mediated through the 5-HT receptor.

Ginsenoside Rg1 prevents vascular intimal hyperplasia involved by SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes in a rat balloon injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C. A. Mey. is a traditional tonic that has been used for thousands of years, and has positive effects on vascular diseases. Ginsenoside Rg1 (GS-Rg1) is one of the active ingredients of Panax ginseng C. A. Mey. and has been shown to have beneficial effects against ischemia/reperfusion injury. Our previously study has found that GS-Rg1 can mobilize bone marrow stem cells and inhibit vascular smooth muscle proliferation and phenotype transformation. However, pharmacological effects and mechanism of GS-Rg1 in inhibiting intimal hyperplasia is still unknown. AIM OF THE STUDY: This study was aimed to investigate whether GS-Rg1 prevented vascular intimal hyperplasia, and the involvement of stromal cell-derived factor-1α (SDF-1α)/CXCR4, stem cell factor (SCF)/c-kit and fractalkine (FKN)/CX3CR1 axes. MATERIALS AND METHODS: Rats were operated with carotid artery balloon injury. The treatment groups were injected with 4, 8 and 16 mg/kg of GS-Rg1 for 14 days. The degree of intimal hyperplasia was evaluated by histopathological examination. The expression of α-SMA (α-smooth muscle actin) and CD133 were detected by double-label immunofluorescence. Serum levels of SDF-1α, SCF and soluble FKN (sFKN) were detected by enzyme linked immunosorbent assay (ELISA). The protein expressions of SCF, SDF-1α and FKN, as well as the receptors c-kit, CXC chemokine receptor type 4 (CXCR4) and CX3C chemokine receptor type 1 (CX3CR1) were detected by immunochemistry. RESULTS: GS-Rg1 reduced intimal hyperplasia by evidence of the values of NIA, the ratio of NIA/MA, and the ratio of NIA/IELA and the ratio of NIA/LA, especially in 16 mg/kg group. Furthermore, GS-Rg1 8 mg/kg group and 16 mg/kg group decreased the protein expressions of the SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes in neointima, meanwhile GS-Rg1 8 mg/kg group and 16 mg/kg group also attenuated the expressions of SDF-1α, SCF and sFKN in serum. In addition, the expression of α-SMA and CD133 marked smooth muscle progenitor cells (SMPCs) was decreased after GS-Rg1 treatment. CONCLUSIONS: GS-Rg1 has a positive effect on inhibiting vascular intimal hyperplasia, and the underlying mechanism is related to inhibitory expression of SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes.

Pyruvate Protects Against Intestinal Injury by Inhibiting the JAK/STAT Signaling Pathway in Rats With Hemorrhagic Shock.

BACKGROUND: This study aimed to investigate the role of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in protection by peritoneal resuscitation (PR) using pyruvate-peritoneal dialysis solution (PY-PDS) against intestinal injury from hemorrhagic shock (HS) in rats. MATERIALS AND METHODS: Sixty-four rats were assigned to eight groups: group SHAM; group intravenous resuscitation (VR); groups NS, LA, and PY in which the rats were subjected to HS and PR with normal saline (NS), lactate-peritoneal dialysis solution (LA-PDS), and PY-PDS, respectively, combined with VR; and groups DMSO, RPM, and AG490 in which the rats were subjected to HS and VR with pretreatment of dimethyl sulfoxide (DMSO), rapamycin (RPM), and tyrphostin B42 (AG490). RESULTS: At 2 h after HS and resuscitation, the levels of diamine oxidase, 15-F2t-isoprostane, thromboxane B2, and endothelin-1, in the blood and the intestinal mucosal apoptotic index and caspase-3 were lower in groups PY, RPM, and AG490 than in groups VR, NS, LA, and DMSO. Group PY showed lower levels of malondialdehyde and myeloperoxidase and a higher level of superoxide dismutase than groups VR, NS, and LA. Phosphorylated JAK2 and phosphorylated STAT3 levels were lower in groups PY, RPM, AG490, and LA than in groups VR, NS, and DMSO. CONCLUSIONS: The protection mechanism of PR with PY-PDS combined with VR was related to the inhibition of the JAK/STAT signaling pathway during HS and resuscitation. The process might include suppression of oxidative stress, reduction of neutrophil infiltration, regulation of microcirculation, and inhibition of apoptosis.

Selenium Deficiency Aggravates Aflatoxin B1-Induced Immunotoxicity in Chick Spleen by Regulating 6 Selenoprotein Genes and Redox/Inflammation/Apoptotic Signaling.

BACKGROUND: Selenium (Se) plays a protective role in aflatoxin B1 (AFB1)-induced splenic immunotoxicity in chicks. OBJECTIVE: This study was designed to reveal the underlying mechanism of Se-mediated protection against AFB1-induced splenic injury in broilers. METHODS: Four groups of 1-d-old Cobb male broilers (n = 5 cages/diet, 6 chicks/cage) were arranged in a 3-wk 2 × 2 factorial design trial whereby they were fed an Se-deficient, corn- and soy-based diet [base diet (BD), 36 µg Se/kg], BD plus 1.0 mg AFB1/kg, BD plus 0.3 mg Se/kg, or BD plus 1.0 mg AFB1/kg and 0.3 mg Se/kg (as 2-hydroxy-4-methylselenobutanoic acid). Serum and spleen were collected at week 3 to assay for cytokines, histology, redox status, selected inflammation- and apoptosis-related genes and proteins, and the selenogenome. RESULTS: Dietary AFB1 induced growth retardation and spleen injury, decreasing (P < 0.05) body weight gain, feed intake, feed conversion efficiency, and serum interleukin-1ß by 17.8-98.1% and increasing (P < 0.05) the spleen index and serum interleukin-6 by 37.6-113%. It also reduced the splenic lymphocyte number, the white pulp region, and histiocyte proliferation in Se-adequate groups. However, Se deficiency aggravated (P < 0.05) these AFB1-induced alterations by 16.2-103%. Moreover, Se deficiency decreased (P < 0.05) splenic glutathione peroxidase (GPX) activity and glutathione-S transferase and glutathione concentrations by 35.6-89.4% in AFB1-exposed groups. Furthermore, Se deficiency upregulated (P < 0.05) the apoptotic (Caspase 3 and Caspase 9) and antimicrobial (ß defensin 1 and 2) genes, but downregulated (P < 0.05) antiapoptotic (B-cell lymphoma 2) and inflammatory (E3 ubiquitin-protein ligase CBL-B) genes at the mRNA and/or protein level in AFB1 supplementation groups. Additionally, Se deficiency downregulated (P < 0.05) GPX3, thioredoxin reductase 1 (TXNRD 1), GPX4, and selenoprotein (SELENO) S, and upregulated (P < 0.05) SELENOT and SELENOU in spleen in AFB1 administered groups. CONCLUSIONS: Dietary Se deficiency exacerbated AFB1-induced spleen injury in chicks, partially through the regulation of oxidative stress, inflammatory and apoptotic signaling, and 6 selenoproteins.

Avian selenogenome: response to dietary Se and vitamin E deficiency and supplementation.

Selenium (Se) is an essential nutrient for humans and all food-producing animal species. Nutritional deficiencies of Se and (or) vitamin E induce exudative diathesis, nutritional pancreatic atrophy, and nutritional muscular dystrophy in chicks. Although these diseases are presumably associated with the need of Se for the synthesis of the 21st amino acid, selenocysteine (Sec, U) in selenoproteins, metabolic functions of the 25 selenoproteins identified in avian species remain largely unknown. This paper reviews regulations of the whole selenogenome and selected selenoproteins by different concentrations and chemical forms of dietary Se and (or) vitamin E in various affected tissues. The avian selenogenome may be divided into 2 groups: responders and non-responders, based on its response to dietary Se and vitamin E changes. Mechanisms for the gene-, tissue-, and age-dependent responses and the correlation with the stress and cell death signaling are explored. Overall, this review intends to link the novel regulation and function of avian selenogenome to the protection by Se against oxidative insults associated with the classical Se/vitamin E deficiency diseases in chicks.

Ginsenoside Re inhibits vascular neointimal hyperplasia in balloon-injured carotid arteries through activating the eNOS/NO/cGMP pathway in rats.

Ginsenoside Re (GS-Re) is one of the main ingredients of ginseng, a widely known Chinese traditional medicine, and has a variety of beneficial effects, including vasorelaxation, antioxidative, anti-inflammatory, and anticancer properties. The aims of the present study were to observe the effect of GS-Re on balloon injury-induced neointimal hyperplasia in the arteries and to investigate the mechanisms underlying this effect. A rat vascular neointimal hyperplasia model was generated by rubbing the endothelium of the common carotid artery (CCA) with a balloon, and GS-Re (12.5, 25 or 50 mg/kg/d) were subsequently continuously administered to the rats by gavage for 14 days. After GS-Re treatment, the vessel lumen of injured vessels showed significant increases in the GS-Re 25.0 and 50.0 mg/kg/d (intermediate- and high-dose) groups according to H.E. staining. Additionally, a reduced percentage of proliferating cell nuclear antigen (PCNA)-positive cells and an increased number of SM α-actin-positive cells were detected, and the levels of NO, cyclic guanosine monophosphate (cGMP), and eNOS mRNA as well as the phos-eNOSser1177/eNOS protein ratio were obviously upregulated in the intermediate- and high-dose groups. Moreover, the promotive effects of GS-Re on NO and eNOS expression were blocked by L-NAME treatment to different degrees. These results suggested that GS-Re can suppress balloon injury-induced vascular neointimal hyperplasia by inhibiting VSMC proliferation, which is closely related to the activation of the eNOS/NO/cGMP pathway.

Hydrogen Peroxide Induce Human Cytomegalovirus Replication through the Activation of p38-MAPK Signaling Pathway.

Human cytomegalovirus (HCMV) is a major risk factor in transplantation and AIDS patients, which induces high morbidity and mortality. These patients infected with HCMV experience an imbalance of redox homeostasis that cause accumulation of reactive oxygen species (ROS) at the cellular level. H2O2, the most common reactive oxygen species, is the main byproduct of oxidative metabolism. However, the function of H2O2 on HCMV infection is not yet fully understood and the effect and mechanism of N-acetylcysteine (NAC) on H2O2-stimulated HCMV replication is unclear. We, therefore, examined the effect of NAC on H2O2-induced HCMV production in human foreskin fibroblast cells. In the present study, we found that H2O2 enhanced HCMV lytic replication through promoting major immediate early (MIE) promoter activity and immediate early (IE) gene transcription. Conversely, NAC inhibited H2O2-upregulated viral IE gene expression and viral replication. The suppressive effect of NAC on CMV in an acute CMV-infected mouse model also showed a relationship between antioxidants and viral lytic replication. Intriguingly, the enhancement of HCMV replication via supplementation with H2O2 was accompanied with the activation of the p38 mitogen-activated protein kinase pathway. Similar to NAC, the p38 inhibitor SB203580 inhibited H2O2-induced p38 phosphorylation and HCMV upregulation, while upregulation of inducible ROS was unaffected. These results directly relate HCMV replication to H2O2, suggesting that treatment with antioxidants may be an attractive preventive and therapeutic strategy for HCMV.

Anticancer Effect of Ursodeoxycholic Acid in Human Oral Squamous Carcinoma HSC-3 Cells through the Caspases.

Bear bile was used as a traditional medicine or tonic in East Asia, and ursodeoxycholic acid (UDCA) is the most important compound in bear bile. Further, synthetic UDCA is also used in modern medicine and nutrition; therefore, its further functional effects warrant research, in vitro methods could be used for the fundamental research of its anticancer effects. In this study, the apoptotic effects of UDCA in human oral squamous carcinoma HSC-3 cells through the activation of caspases were observed by the experimental methods of MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, DAPI (4',6-diamidino-2-phenylindole) staining, flow cytometry analysis, RT-PCR (reverse transcription-polymerase chain reaction) assay and Western blot assay after HSC-3 cells were treated by different concentrations of UDCA. With 0 to 400 µg/mL UDCA treatment, UDCA had strong growth inhibitory effects in HSC-3 cells, but had almost no effect in HOK normal oral cells. At concentrations of 100, 200 and 400 µg/mL, UDCA could induce apoptosis compared to untreated control HSC-3 cells. Treatment of 400 µg/mL UDCA could induce more apoptotic cancer cells than 100 and 200 µg/mL treatment; the sub-G1 DNA content of 400 µg/mL UDCA treated cancer cells was 41.3% versus 10.6% (100 µg/mL) and 22.4% (200 µg/mL). After different concentrations of UDCA treatment, the mRNA and protein expressions of caspase-3, caspase-8, caspase-9, Bax, Fas/FasL (Fas ligand), TRAIL (TNF-related apoptosis-inducing ligand), DR4 (death receptor 4) and DR5 (death receptor 5) were increased in HSC-3 cells, and mRNA and protein expressions of Bcl-2 (B-cell lymphoma 2), Bcl-xL (B-cell lymphoma-extra large), XIAP (X-linked inhibitor of apoptosis protein), cIAP-1 (cellular inhibitor of apoptosis 1), cIAP-2 (cellular inhibitor of apoptosis 2) and survival were decreased. Meanwhile, at the highest concentration of 400 µg/mL, caspase-3, caspase-8, caspase-9, Bax, Fas/FasL, TRAIL, DR4, DR5, and IκB-α expression levels were the highest, and Bcl-2, Bcl-xL, XIAP, cIAP-1, cIAP-2, survival, and NF-κB expression levels were the lowest. These results proved that UDCA could induce apoptosis of HSC-3 cancer cells through caspase activation, and the higher concentration of UDCA had stronger effects in vitro. UDCA might be a good nutrient for oral cancer prevention.

Study of the interaction between sodium salts of (2E)-3-(4'-halophenyl)prop-2-enoyl sulfachloropyrazine and bovine serum albumin by fluorescence spectroscopy.

Three sodium salts of (2E)-3-(4'-halophenyl)prop-2-enoyl sulfachloropyrazine (CCSCP) were synthesized and their structures were determined by (1)H and (13)C NMR, LC-MS and IR. The binding properties between CCSCPs and bovine serum albumin (BSA) were studied using fluorescence spectroscopy in combination with UV-vis absorbance spectroscopy. The results indicate that the fluorescence quenching mechanisms between BSA and CCSCPs were static quenching at low concentrations of CCSCPs or combined quenching (static and dynamic) at higher CCSCP concentrations of 298, 303 and 308 K. The binding constants, binding sites and corresponding thermodynamic parameters (ΔH, ΔS, ΔG) were calculated at different temperatures. All ΔG values were negative, which revealed that the binding processes were spontaneous. Although all CCSCPs had negative ΔH and positive ΔS, the contributions of ΔH and ΔS to ΔG values were different. When the 4'-substituent was fluorine or chlorine, van der Waals interactions and hydrogen bonds were the main interaction forces. However, when the halogen was bromine, ionic interaction and proton transfer controlled the overall energetics. The binding distances between CCSCPs and BSA were determined using the Förster non-radiation energy transfer theory and the effects of CCSCPs on the conformation of BSA were analyzed by synchronous fluorescence spectroscopy.

Inhibitory Effect of Ginsenoside Rg1 on Vascular Smooth Muscle Cell Proliferation Induced by PDGF-BB Is Involved in Nitric Oxide Formation.

Ginsenoside Rg1 (Rg1) has been reported to suppress the proliferation of vascular smooth muscle cells (VSMCs). This study aimed to observe the role of nitric oxide (NO) in Rg1-antiproliferative effect. VSMCs from the thoracic aorta of SD rats were cultured by tissue explant method, and the effect of Rg1 (20 mg·L(-1), 60 mg·L(-1), and 180 mg·L(-1)) on platelet-derived growth factor-BB (PDGF-BB)-induced proliferation was evaluated by MTT assay. The cell cycle was analyzed by flow cytometry. For probing the mechanisms, the content of NO in supernatant and cGMP level in VSMCs was measured by nitric oxide kit and cGMP radio-immunity kit, respectively; the expressions of protooncogene c-fos and endothelial NO synthase (eNOS) mRNA in the VSMCs were detected by real-time RT-PCR; the intracellular free calcium concentration ([Ca2(+)](i)) was detected with Fura-2/AM-loaded VSMCs. Comparing with that in normal group, Rg1 180 mg·L(-1) did not change the absorbance of MTT and cell percent of G(0)/G(1), G(2)/M, and S phase in normal cells (P > 0.05). Contrarily, PDGF-BB could increase the absorbance of MTT (P < 0.01) and the percent of the S phase cells but decrease the G(0)/G(1) phase cell percent in the cell cycle, accompanied with an upregulating c-fos mRNA expression (P < 0.01), which was reversed by additions of Rg1(20 mg·L(-1), 60 mg·L(-1), and 180 mg·L(-1)). Rg1 administration could also significantly increase the NO content in supernatant and the cGMP level in VSMCs, as well as the eNOS mRNA expression in the cells, in comparison of that in the group treated with PDGF-BB alone (P < 0.01). Furthermore, Rg1 caused a further increase in the elevated [Ca(2+)](i) induced by PDGF-BB. It was concluded that Rg1 could inhibit the VSMC proliferation induced by PDGF-BB through restricting the G(0)/G(1) phase to S-phase progression in cell cycle. The mechanisms may be related to the upregulation of eNOS mRNA and the increase of the formation of NO and cGMP.

Ginsenoside Rg1 inhibits vascular intimal hyperplasia in balloon-injured rat carotid artery by down-regulation of extracellular signal-regulated kinase 2.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside Rg1 (Rg1) is one of the main active components of Panax ginseng a well-known herbal medicine. It has been demonstrated to inhibit proliferation of vascular smooth muscle cells (VSMCs) induced by tumor necrosis factor-αin vitro. The present study is aimed to examine the possible effects of Rg1 on vascular neointimal hyperplasia in balloon-injured carotid artery of rats in vivo. MATERIALS AND METHODS: The animal model was established by rubbing the endothelia with a balloon catheter in the common carotid artery (CCA) of male Sprague Dawley rats. Then the rats were intraperitoneally injected with distilled water in model group and sham operation control, or with Rg1 4, 8 and 16mg/kg/d in other balloon injured groups. After consecutive 14 days, the vascular intimal hyperplasia was evidenced by histopathological alterations of the CCA and by changes observed in the marker of the proliferation of VSMCs-the proliferating cell nuclear antigen (PCNA). The protein expressions of PCNA and the phosphorylated extracellular signal-regulated kinase2 (p-ERK2) as well as mitogen-ativated protein kinase phosphatase-1 (MKP-1) were examined by immunohistochemistry; while the expressions of proto-oncogene (c-fos), ERK2 and smooth muscle α-actin (SM α-actin) mRNA were analyzed by Real-Time RT-PCR. RESULTS: Rg1 administration could significantly ameliorate the histopathology of CCA and decrease the protein expression of PCNA induced by endothelia rubbing; and Rg1 medication also significantly decreased the expressions of p-ERK2 protein, ERK2 and c-fos mRNA in vessel wall, but up-regulated the MKP-1 expression, which was reported to inactivate mitogen-ativated protein kinase pathway. Furthermore, Rg1 could elevate the decreased SM α-actin mRNA expression induced by balloon injury. CONCLUSIONS: Rg1 can suppress the vascular neointimal hyperplasia induced by balloon injury, the mechanism may be involved in the inhibition on ERK2 signaling, and related, at least partly, to the increase in MKP-1 expression.

Total Ginsenosides suppress the neointimal hyperplasia of rat carotid artery induced by balloon injury.

Ginsenosides, the active components found in Panax ginseng, have been reported to inhibit the cardiac hypertrophy in rats. This study aims to observe the potential effect of total ginsenosides (TG) on the hypertrophic vascular diseases. The model of vascular neointimal hyperplasia was established by rubbing the endothelia of the common carotid artery with a balloon in male Sprague Dawley rats. TG (15 mg/kg/day, 45 mg/kg/day), L-arginine (L-arg) 200 mg/kg/day, and NG-nitro-L-arginine-methyl ester (L-NAME) 100 mg/kg/day used with the same dose of L-arg or TG 45 mg/kg/day were given for 7 and 14 consecutive days after surgery. TG and L-arg administrations significantly ameliorated the histopathology of injured carotid artery, which was abolished or blunted by L-NAME, an NOS inhibitor; TG and L-arg could also remarkably reduce the expression of proliferating cell nuclear antigen (PCNA), a proliferation marker of vascular smooth muscle cells(VSMCs), in neointima of the injured artery wall. Further study indicated that balloon injury caused a decreased superoxide dismutase (SOD) activity and an elevated malondialdehyde (MDA) content in plasma, and reduced the cGMP level in the artery wall, which were reversed by TG. It was concluded that TG suppress the rat carotid artery neointimal hyperplasia induced by balloon injury, which may be involved in its anti-oxidative action and enhancing the inhibition effects of NO/cGMP on VSMC proliferation.

Role of nitric oxide in ginsenoside Rg(1)-induced protection against left ventricular hypertrophy produced by abdominal aorta coarctation in rats.

Ginsenoside Rg(1) (Rg(1)), one of the active components of Panax ginseng, has been reported to promote endogenous nitric oxide (NO) production in some tissues, and to inhibit left ventricular (LV) hypertrophy in rats. This study aimed to investigate whether Rg(1)-induced inhibition of rat LV hypertrophy is mediated by NO-production. Rat LV hypertrophy was induced by abdominal aorta coarctation. Rg(1) 15 mg/kg/d, L-arginine 200 mg/kg/d, and the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME) 100 mg/kg/d used with the same dose of L-arginine or Rg(1) were given starting from 1 d after surgery for 21 consecutive days. LV hypertrophy was evidenced by determining LV weight and mRNA expression of atrial natriuretic peptide, a marker of cardiac hypertrophic response, as well as by histopathology. Rg(1) and L-arginine administration significantly reduced the elevated LV hypertrophic parameters independent of LV systolic pressure changing, and ameliorated the histopathology of LV myocardium and LV diastolic function. All the beneficial effects of Rg(1) and L-arginine were abolished or blunted by L-NAME. Further to examine the role of NO in Rg(1) inhibition on LV hypertrophy, expression of endothelial NOS was determined at the transcript levels. In our experimental conditions endothelial NOS mRNA expression in LV tissue was lowered by abdominal aorta coarctation, and upregulated by Rg(1) administration. These results demonstrate that Rg(1)-induced protection against LV hypertrophy elicited by abdominal aorta coarctation in rats is mediated, at least in part, via endogenous NO production and release.

[Study on the EMF-temperature co-effects on protein conformation by fluorometry].

The bioelectromagnetic effects are wildly concerned for a long time, and related researches are conducted in all kinds of directions in recent years. The EMF-temperature co-effects are more interesting nowadays. By studying the effects of EMF co-operated with temperature on a protein, an irreversible protein denaturation is found under the processing of EMF, and this denaturation is also Arrhenius-rule-obeyed. In addition, a protein denaturation model under the EMF-temperature co-effects is built. In this paper the EMF-temperature co-effects are explained in a way of molecular reacting kinetics, and the athermal effects of EMF are also discussed to some degree.