notoginsenoside-r1 and Inflammation

Panax notoginseng is an ancient Chinese medicinal plant that has great clinical value in regulating cardiovascular disease in China. As a single component of panax notoginosides, notoginsenoside R1 (NGR1) belongs to the panaxatriol group. Many reports have demonstrated that NGR1 exerts multiple pharmacological effects in ischemic stroke, myocardial infarction, acute renal injury, and intestinal injury. Here, we outline the available reports on the pharmacological effects of NGR1 in ischemia-reperfusion (I/R) injury. We also discuss the chemistry, composition and molecular mechanism underlying the anti-I/R injury effects of NGR1. NGR1 had significant effects on reducing cerebral infarct size and neurological deficits in cerebral I/R injury, ameliorating the impaired mitochondrial morphology in myocardial I/R injury, decreasing kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in renal I/R injury and attenuating jejunal mucosal epithelium injury in intestinal I/R injury. The various organ anti-I/R injury effects of NGR1 are mainly through the suppression of oxidative stress, apoptosis, inflammation, endoplasmic reticulum stress and promotion of angiogenesis and neurogenesis. These findings provide a reference basis for future research of NGR1 on I/R injury.

Topics: Apoptosis; China; Humans; Inflammation; Reperfusion Injury

Topics: Anti-Inflammatory Agents; Chromatography, High Pressure Liquid; Chromatography, Liquid; Cyclooxygenase 2; Flowers; Ginsenosides; Humans; Inflammation; Panax; Panax notoginseng; Saponins; Tandem Mass Spectrometry

High-altitude pulmonary edema (HAPE) is a potentially fatal disease. Notoginsenoside R1 is a novel phytoestrogen with anti-inflammatory, antioxidant and anti-apoptosis properties. However, its effects and underlying mechanisms in the protection of hypobaric hypoxia-induced HAPE rats remains unclear. This study aimed to explore the protective effects and underlying mechanisms of Notoginsenoside R1 in hypobaric hypoxia-induced HAPE. We found that Notoginsenoside R1 alleviated the lung tissue injury, decreased lung wet/dry ratio, and reduced inflammation and oxidative stress. Additionally, Notoginsenoside R1 ameliorated the changes in arterial blood gas, decreased the total protein concentration in bronchoalveolar lavage fluid, and inhibited the occurrence of apoptosis caused by HAPE. In the process of further exploration of the mechanism, it was found that Notoginsenoside R1 could promote the activation of ERK1/2-P90rsk-BAD signaling pathway, and the effect of Notoginsenoside R1 was attenuated after the use of ERK1/2 inhibitor U0126. Our study indicated that the protective effects of Notoginsenoside R1 against HAPE were mainly related to the inhibition of inflammation, oxidative stress, and apoptosis. Notoginsenoside R1 may be a potential candidate for preventing HAPE.

Topics: Altitude; Animals; Hypoxia; Inflammation; MAP Kinase Signaling System; Pulmonary Edema; Rats

The secondary injury plays a vital role in the development of spinal cord injury (SCI), which is characterized by the occurrence of oxidative stress, neuronal apoptosis, and inflammatory response. Notoginsenoside R1 (NGR1) has been involved in the modulation of antioxidative stress and anti-inflammatory response. However, its roles in SCI-induced injury are still unknown. We explored the therapeutic effect of NGR1 and its underlying mechanism after SCI by using behavioral, biochemical, and immunohistochemical techniques. The administration of NGR1 after SCI enhanced the neurological function, and mitigated tissue damage and motor neuron loss than those in SCI + vehicle group. Meanwhile, significantly increased expression of Nrf2 protein and HO-1 protein was found in the SCI + NGR1 group compared with those in the SCI + vehicle group. In addition, the inhibitory effects of oxidative stress, apoptotic neuron ratio, and neuronal inflammation in the SCI + NGR1 group can be partially reversed when the Nrf2/HO-1 signaling pathway was inhibited by ML385. Our results indicate that the administration of NGR1 can attenuate oxidative stress, neuronal apoptosis, and inflammation by activating the Nrf2/HO-1 signaling pathway after SCI, thereby improving neurological function.

Topics: Apoptosis; Ginsenosides; Heme Oxygenase-1; Humans; Inflammation; Motor Neurons; NF-E2-Related Factor 2; Oxidative Stress; Signal Transduction; Spinal Cord; Spinal Cord Injuries

Intervertebral disc degeneration (IVDD) is the main cause of low back pain. Notoginsenoside R1 (NR1) is widely applied in the treatment of bone disorders, including IVDD. The present study aimed to investigate the effects of NR1 on the development of IVDD and the potential mechanisms. AF puncture was performed to establish IVDD rat model. Histology changes were analyzed by hematoxylin and eosin (H&E) staining. mRNA expressions were determined using qRT-PCR. Protein expressions were detected with western blot. Cellular functions were detected by MTT, EdU, flow cytometry, and TUNEL assays. The results showed that NR1 suppressed AF puncture induced IVDD, restored intervertebral disc (IVD) function, and suppressed mechanical hyperalgesia and thermal hyperalgesia. Moreover, NR1 promoted the release of extracellular matrix (ECM) in vivo and in vitro, and decreased the mRNA expressions of proinflammation cytokines. Additionally, NR1 inactivated NF-κB/NLRP3 pathways, improved cellular functions of nucleus pulposus cells (NPCs), and suppressed cell pyroptosis, which was reversed by NLRP3 activation. Taken together, NR1 may protect against IVDD via suppressing NF-κB/NLRP3 pathways. This may provide a novel therapy for IVDD.

Topics: Animals; Cells, Cultured; Gene Expression Regulation; Ginsenosides; Inflammation; Male; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Nucleus Pulposus; Pyroptosis; Rats; Rats, Sprague-Dawley; Signal Transduction; Tumor Necrosis Factor-alpha

Endothelial dysfunction in atherosclerotic cardiovascular diseases has become one of the main characteristics in patients with diabetes mellitus, which is usually caused by abnormal inflammation and oxidative stress response. Presently, we focused on the role of Notoginsenoside R1 (NR1), a major component isolated from Panax notoginseng, in endothelial dysfunction caused by high glucose (HG). Human umbilical vein endothelial cells (HUVECs) were treated with HG and then dealt with NR1. Cell counting kit-8 assay and 5-bromo-2'-dexoyuridine assay were conducted to examine cell proliferation and viability. Flow cytometry was used to measure apoptosis. The angiogenesis of HUVECs was determined by tube formation assay. Moreover, the expressions of miR-147a, inflammatory cytokines (TNF-α, IL-6, and IL-10) and oxidative stress markers malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured. The protein levels of MyD88/TRAF6/NF-κB axis, Bax, Bcl2, and Caspase3 were detected by Western blot. Furthermore, gain and loss of functional assays of miR-147a were performed to verify the role of miR-147a in NR1-mediated effects. Our data confirmed that NR1 (at 10-40 μM) reduces HG-induced HUVECs proliferation and viability inhibition, mitigates apoptosis, and enhances tube formation ability. Meanwhile, NR1 inhibited oxidative stress and inflammatory response and blocked the activation of the MyD88/TRAF6/NF-κB pathway induced by HG. In addition, NR1 promoted the expression of miR-147a, which targeted MyD88. Overexpression of miR-147a markedly inactivated MyD88/TRAF6/NF-κB pathway, while the miR-147a inhibitors reversed NR1-mediated protective effect in HG-induced HUVECs through activating MyD88/TRAF6/NF-κB pathway. In conclusion, NR1 relieves HG-induced endothelial cell injury by downregulating the MyD88/TRAF6/NF-κB pathway via upregulating miR-147a.

Topics: Cells, Cultured; Ginsenosides; Glucose; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Intracellular Signaling Peptides and Proteins; MicroRNAs; Myeloid Differentiation Factor 88; Neovascularization, Physiologic; NF-kappa B; Oxidative Stress; Signal Transduction

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).\ \ This article has been retracted at the request of the Editor-in-Chief.\ \ The journal was initially contacted by the corresponding author to request the retraction of the article as the data were not reliable. Given the comments of Dr Elisabeth Bik regarding this article " … the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.

Topics: Animals; Cell Survival; Cytokines; Gene Expression Regulation; Ginsenosides; Humans; Inflammation; Lipopolysaccharides; Mice; MicroRNAs; NF-kappa B; Osteoarthritis; Signal Transduction; Spondylitis, Ankylosing

BACKGROUND Notoginsenoside R1 (NR) is a major dynamic constituent of Panax notoginseng found to possess anti-inflammatory activity against various inflammatory diseases. However, its protective effects against renal ischemia-reperfusion (I/R) injury have not been elucidated. In male Wistar rats, we induced I/R under general anesthesia by occluding the renal artery for 60 min, followed by reperfusion and right nephrectomy. MATERIAL AND METHODS Rats were randomized to 4 groups: a sham group, an I/R group, an NR-pretreated (50 mg/kg) before I/R induction group, and an NR control group. All animals were killed at 72 h after I/R induction. Blood and renal tissues were collected, and histological and basic renal function parameters were assessed. In addition, levels of various kidney markers and proinflammatory cytokines were measured using RT-PCR, ELISA, and immunohistochemistry analysis. RESULTS After I/R induction, the onset of renal dysfunction was shown by the elevated levels of serum urea, creatinine levels, and histological evaluation, showing a 2-fold increase in the renal failure markers kim-1 and NGAL compared to control rats. Rats pretreated with NR before I/R induction had significantly better renal functions, with attenuated levels of oxidative markers, restored levels of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), tumor growth factor-ß1 (TGF-ß1), INF-γ, and IL-6, and increased anti-inflammatory cytokine levels (IL-10) compared to I/R-induced rats. CONCLUSIONS NR suppressed I/R-induced inflammatory cytokines production by suppressing oxidative stress and kidney markers, suggesting that NR is a promising drug candidate for prevention, progression, and treatment of renal dysfunction.

Topics: Animals; Anti-Inflammatory Agents; Ginsenosides; Inflammation; Kidney; Male; Nephrectomy; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury; Signal Transduction

Atherosclerosis (AS) is a common vascular disease, which can cause apoptosis of vascular endothelial cells. Notoginsenoside R1 (NGR1) is considered an anti-AS drug. MicroRNAs (miRNAs) are believed to play a vital role in cell apoptosis and angiogenesis. This study aimed to explore the mechanism of NGR1 for treating AS through miRNAs. Flow cytometry was used to detect the apoptosis rate. The levels of inflammatory cytokines interleukin (IL)-6 and IL-1β were detected using ELISA. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels were measured using corresponding assay kits. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to detect miR-221-3p expression. Dual-luciferase reporter and RNA immunoprecipitation assays were carried out to examine the relationship between miR-221-3p and toll-like receptors 4 (TLR4). Also, western blot analysis was performed to determine the levels of TLR4 and nuclear factor kappa B (NF-κB) signaling pathway-related proteins. Oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs) apoptosis, inflammation, and oxidative stress. NGR1 alleviated the negative effect of ox-LDL through promoting the expression of miR-221-3p in HUVECs. TLR4 was a target of miR-221-3p, and its overexpression could reverse the inhibition effects of miR-221-3p on apoptosis, inflammation, and oxidative stress. NGR1 improved miR-221-3p expression to inhibit the activation of the TLR4/NF-κB pathway in ox-LDL-treated HUVECs. NGR1 decreased ox-LDL-induced HUVECs apoptosis, inflammation, and oxidative stress through increasing miR-221-3p expression, thereby inhibiting the activation of the TLR4/NF-κB pathway. This study of the mechanism of NGR1 provided a more theoretical basis for the treatment of AS.

Topics: Apoptosis; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Ginsenosides; Human Umbilical Vein Endothelial Cells; Humans; Immunoprecipitation; Inflammation; Lipoproteins, LDL; MicroRNAs; NF-kappa B; Oxidative Stress; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Signal Transduction; Toll-Like Receptor 4; Transcriptional Activation; Up-Regulation

Atherosclerosis is a common reason for acute cardio-cerebral vascular diseases. The purpose of this study was to clarify the functional effects of Notoginsenoside R1 (NGR1) on atherosclerosis.. HUVECS were exposed to oxidized low-density lipoprotein (ox-LDL) in the current study. The proliferation ability of HUVECS was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT). Flow cytometry assays were performed to evaluate the apoptosis of HUVECS. Ox-LDL caused inflammatory response and oxidative stress were assessed by checking pro-inflammatory cytokines and intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). The regulatory roles of NGR1 in HUVECs were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The interaction relationship between miR-221-3p and X-inactive specific transcript (XIST) or TNF-receptor-associated factor 6 (TRAF6) was predicted by bioinformatics tools. Dual-luciferase reporter and RNA pull-down assays were used to confirm the interaction relationship.. Currently, ox-LDL inhibited proliferation and induced apoptosis, inflammatory response, and oxidative stress in HUVECs, which were alleviated by treatment with NGR1. Importantly, the increase of XIST in ox-LDL-induced HUVECs was abolished by NGR1. In addition, the gain-of-functional experiment suggested that the upregulation of XIST neutralized the protection effects of NGR1 in HUVECs treated with ox-LDL. In addition, miR-221-3p was a target of XIST in HUVECs as confirmed by dual-luciferase reporter and RNA pull-down assays. Furthermore, miR-221-3p interacted with TRAF6, and NGR1 regulated proliferation, apoptosis, inflammatory response, and oxidative stress in HUVECs exposed to ox-LDL by regulation of the XIST/miR-221-3p/TRAF6 axis through Nuclear Factor Kappa B (NF-κB) pathway.. NGR1 could exert regulatory functions in ox-LDL-induced HUVECS by regulation of XIST/miR-221-3p/TRAF6 axis, which provided valuable insights into the development of potential therapeutic strategy for atherosclerosis.

Topics: Anti-Inflammatory Agents; Apoptosis; Atherosclerosis; Ginsenosides; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Intracellular Signaling Peptides and Proteins; MicroRNAs; Oxidative Stress; RNA, Long Noncoding

Alveolar bone is vital for dental implantation and periodontal treatment. Notoginsenoside R1 (NTR1) may promote the differentiation of human alveolar osteoblasts (HAOBs), but the underlying molecular mechanisms remain unclear. The present study investigated the pro‑differentiation function of NTR1 on HAOBs in order to find new methods of dental treatment. HAOBs were surgically obtained from dental patients and the cells were isolated, cultured and identified under an inverted phase contrast microscope. The cells were treated with different concentrations of NTR1 alone or further stimulated by TNF‑α. An alkaline phosphate (ALP) activity assay and alizarin red staining were performed to detect ALP activity and mineralization of the cells, respectively. Cell viability was assayed using an MTT assay. The expressions of osteogenic‑related factors and the factors associated with the NF‑κB and Wnt/β‑catenin pathways were examined by reverse transcription‑quantitative PCR or western blot analysis. Successfully passaged HAOBs presented blue granules and red calcium deposits after staining. The viability of HAOBs was unchanged following treatment with NTR1 at ≤20 µmol/l and/or TNF‑α, but slightly reduced by 40 µmol/l NTR1. TNF‑α‑induced decreases of calcium nodules and ALP activity were decreased by NTR1 in HAOBs. TNF‑α also regulated the expressions of runt‑related transcription factor 2, osteopontin (OPN), osteocalcin (OCN), p50, phosphorylated p65, AXIN2, Dickkopf‑related protein 1 and β‑catenin, while the regulatory effect was reversed by NTR1. NTR1 promoted the differentiation of HAOBs in the TNF‑α‑induced inflammatory microenvironment through inhibiting the NF‑κB pathway and activating the Wnt/β‑catenin pathway.

Topics: Adult; Alkaline Phosphatase; Alveolar Process; Axin Protein; beta Catenin; Cell Differentiation; Cell Proliferation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Female; Ginsenosides; Humans; I-kappa B Proteins; Inflammation; Male; NF-kappa B; Osteoblasts; Osteocalcin; Osteogenesis; Wnt Signaling Pathway

Topics: Animals; Cell Death; Diabetic Retinopathy; Ependymoglial Cells; Eye Proteins; Ginsenosides; Glucose; Inflammation; Mice; Mitochondria; Mitophagy; Nerve Growth Factors; Oxidative Stress; Protein Kinases; Rats; Serpins; Vascular Endothelial Growth Factor A

Delayed inflammatory response is closely associated with the severity of Spinal cord injury (SCI). Herein, the function and molecular mechanism of notoginsenoside R1 (NGR1) in the in vitro model of SCI inflammation injury were explored.. PC-12 neuronal cells were subjected with LPS to construct a cell-based model of SCI inflammatory injury. NGR1 was applied in this cell model. miR-132 was silenced by transfection with miR-132 inhibitor. Cell viability and apoptosis were assessed, respectively. Then, the expression changes of pro-inflammatory cytokines and JNK pathway were examined.. In this model, LPS was neurotoxic, with inhibiting PC-12 cell viability, inducing apoptosis, and enhancing concentrations of IL-6, IL-8 and TNF-α. However, NGR1 weakened the influence of LPS on PC-12 cells via elevating cell viability, decreasing apoptosis, decreasing pro-inflammatory cytokines expression, and suppressing activation of JNK signalling pathway. miR-132 was up-regulated by NGR1 treatment. Silence of miR-132 eliminated the influence of NGR1 on LPS-stimulated PC-12 cells.. NGR1 relieved PC-12 cells from LPS-triggered inflammatory damage via elevating miR-132 and hereafter suppressing JNK pathway.

Topics: Animals; Apoptosis; Ginsenosides; Inflammation; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; MAP Kinase Signaling System; MicroRNAs; PC12 Cells; Rats

Notoginsenoside R1 (NG-R1), a unique and main active ingredient of Panax notoginseng, has been described to exhibit anti-inflammatory activity. However, its protective effects against oxidized low-density lipoprotein (oxLDL)-induced inflammatory injury in vascular endothelial cells have not been clarified. In the present study, we have evaluated the anti-inflammatory effects of NG-R1 on oxLDL-induced endothelial cells and its possible molecular mechanism of action. Our results showed that NG-R1 treatment significantly attenuated oxLDL-induced expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. These effects were accompanied with suppression of oxLDL-induced activation of NF-κB and Mitogen-activated protein kinases (MAPK). Moreover, NG-R1 also increased in Peroxisome proliferator-activated receptor γ (PPARγ) protein expression and transcription levels, and attenuated oxLDL-induced suppression of PPARγ expression. The inhibition of NG-R1 on oxLDL-induced TNF-α and IL-1β productions can be reversed by PPARγ antagonist GW9662. In conclusion, these data suggested that NG-R1 could suppress oxLDL-induced inflammatory cytokines production via activating PPARγ, which subsequently inhibiting oxLDL-induced NF-κB and MAPK activation.

Topics: Anti-Inflammatory Agents; Cell Line, Tumor; Cell Survival; Cytokines; Endothelial Cells; Enzyme Activation; Ginsenosides; Humans; Inflammation; Lipoproteins, LDL; Mitogen-Activated Protein Kinases; NF-kappa B; PPAR gamma

The present study was designed to examine the protective effect of notoginsenoside R1 (NR1) on podocytes in a rat model of streptozotocin (STZ)‑induced diabetic nephropathy (DN), and to explore the mechanism responsible for NR1-induced renal protection. Diabetes was induced by a single injection of STZ, and NR1 was administered daily at a dose of 5 mg/kg (low dose), 10 mg/kg (medium) and 20 mg/kg (high) for 16 weeks in Sprague-Dawley rats. Blood glucose levels, body weight and proteinuria were measured every 4 weeks, starting on the day that the rats received NR1. Furthermore, on the day of sacrifice, blood, urine and kidneys were collected in order to assess renal function according to general parameters. Pathological staining was performed to evaluate the renal protective effect of NR1, and the expression of the key slit diaphragm proteins, namely neprhin, podocin and desmin, were evaluated. In addition, the serum levels of inflammatory cytokines [tumor necrosis factor-α (TNF-α), tumor growth factor-β1 (TGF-β1), interleukin (IL)-1 and IL-6] as well as an anti-inflammatory cytokine (IL-10) were assessed, and the apoptosis of podocytes was quantified. Finally, the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway and the involvement of nuclear factor-κB (NF-κB) inactivation was further analyzed. In this study, NR1 improved renal function by ameliorating histological alterations, increasing the expression of nephrin and podocin, decreasing the expression of desmin, and inhibiting both the inflammatory response as well as the apoptosis of podocytes. Furthermore, NR1 treatment increased the phosphorylation of both PI3K (p85) and Akt, indicating that activation of the PI3K/Akt signaling pathway was involved. Moreover, NR1 treatment decreased the phosphorylation of NF-κB (p65), suggesting the downregulation of NF-κB. This is the first study to the best of our knowledge, to clearly demonstrate that NR1 treatment ameliorates podocyte injury by inhibiting both inflammation and apoptosis through the PI3K/Akt signaling pathway.

Topics: Animals; Apoptosis; Blood Glucose; Cell Nucleus; Cytokines; Desmin; Diabetic Nephropathies; Ginsenosides; Inflammation; Intracellular Signaling Peptides and Proteins; Kidney; Male; Membrane Proteins; Phosphatidylinositol 3-Kinases; Phosphorylation; Podocytes; Protective Agents; Proteinuria; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction

Estrogen receptors (ERs) are important for preventing endotoxin-induced myocardial dysfunction. Therefore, plant-derived phytoestrogens, which target ERs may also affect endotoxin-induced toxicity in cardiomyocytes. Our previous study revealed that notoginsenoside-R1 (NG-R1), a predominant phytoestrogen from Panax notoginseng, protects against cardiac dysfunction. However, the effects of NG-R1 on cardiomyocytes and the precise cellular/molecular mechanisms underlying its action remain to be elucidated. In the present study, pretreatment with NG-R1 suppressed the lipopolysaccharide (LPS)-induced degradation of inhibitor of nuclear factor-κB (NF-κB) α, the activation of NF-κB and caspase-3, and the subsequent myocardial inflammatory and apoptotic responses in H9c2 cardiomyocytes. An increase in the mRNA and protein expression of ERα was also observed in the NG-R1-treated cardiomyocytes. However, the expression pattern of ERβ remained unaltered. Furthermore, the cardioprotective properties of NG-R1 against LPS-induced apoptosis and the inflammatory response in cardiomyocytes were attenuated by ICI 182780, a non-selective ERα antagonist, and methyl-piperidino-pyrazole, a selective ERα antagonist. These findings suggested that NG-R1 reduced endotoxin-induced cardiomyocyte apoptosis and the inflammatory response via the activation of ERα. Therefore, NG-R1 exerted direct anti-inflammatory and anti-apoptotic effects on the cardiomyocytes, representing a potent agent for the treatment of myocardial inflammation during septic shock.

Topics: Animals; Apoptosis; Endotoxins; Estrogen Receptor alpha; Gene Expression Regulation; Ginsenosides; Humans; Inflammation; Myocardium; Myocytes, Cardiac; NF-kappa B; Panax notoginseng; Rats; RNA, Messenger; Shock, Septic; Signal Transduction; Tumor Necrosis Factor-alpha

Astragalus and Panax notoginseng are commonly used to treat cardio-cerebrovascular diseases in China and are often combined together to promote curative effect. We speculate that the enhancement of the combination on anticerebral ischemia injury may come from the main active components. The purpose of this work was to probe the effects and mechanisms of Astragaloside IV (the active component of Astragalus) combined with Ginsenoside Rg1, Ginsenoside Rb1, and Notoginsenoside R1 (the active components of P. notoginseng) to antagonize ischemia/reperfusion (I/R) injury via inflammation and apoptosis. C57BL/6 mice were randomly divided into sham, model, Astragaloside IV, Ginsenoside Rg1, Ginsenoside Rb1, Notoginsenoside R1, four active components combination, and Edaravone groups. After administration for 3 days, bilateral common carotid arteries (CCA) were occluded with artery clip for 20[Formula: see text]min followed by reperfusion for 24[Formula: see text]h. Our results showed that the survival rate of nerve cell in hippocampal CA1 decreased while the apoptotic rate increased, and the level of caspase-3 protein in brain tissues was elevated, the expressions of TNF-a, IL-1, and ICAM-1 mRNA as well as phosphorylated nuclear factor kappa B (NF-κB) inhibitor protein α (p-IκBa) in brain tissues were up-regulated, and the nuclear translocation rate of NF-κB was raised. Additionally, the protein expressions of phosphorylated tyrosine kinase 1 (p-JAK1), phosphorylated signal transducer and activator of transcription-1 (p-STAT1), glucose regulated protein 78 (GRP78), caspase-12, and phosphorylated c-Jun N-terminal kinases 1/2 (p-JNK1/2) in brain tissues were also significantly strengthened after I/R for 24 h. All drugs could increase neurocyte survival rate in hippocampal CA1, decrease the apoptotic rate, and inhibit caspase-3 protein expression, in contrast, the effects of four active components combination were better than those of active components alone. In addition, Astragaloside IV and Ginsenoside Rg1 could down-regulate the level of TNF-α, and ICAM-1 mRNA, respectively, Notoginsenoside R1 reduced both TNF-α and ICAM-1 mRNA, and the combination of the 4 effective components had inhibitory effects on the expressions of TNF-α, IL-1β, and ICAM-1 mRNA. Astragaloside IV, Ginsenoside Rg1, Notoginsenoside R1, and 4 effective components combination were able to restrain the phosphorylation of IκBα, and relieve the nuclear translocation rate of NF-κB. Moreover, the eff

Topics: Animals; Apoptosis; Astragalus Plant; Brain Ischemia; CA1 Region, Hippocampal; Cell Survival; Disease Models, Animal; Drug Combinations; Endoplasmic Reticulum Chaperone BiP; Ginsenosides; Inflammation; Janus Kinase 1; Male; Mice, Inbred C57BL; Neurons; Neuroprotective Agents; NF-kappa B; Panax notoginseng; Phytotherapy; Reperfusion Injury; Saponins; STAT1 Transcription Factor; Triterpenes

Notoginsenoside R1 (NG-R1), a novel phytoestrogen isolated from Panax notoginseng, is believed to have anti-inflammatory, anti-oxidative and anti-apoptotic properties. However, its cardioprotective properties and underlying mechanisms are largely unknown. Here we have assessed the contribution of the anti-inflammatory effects of NG-R1 to the amelioration of septic cardiac dysfunction and inflammation in mice.. We assessed cardiac function in mice by echocardiography. We studied the protein or mRNA levels of some inflammatory factors, apoptotic factors and oestrogen receptors (ERs) in heart tissues upon stimulation with bacterial LPS, NG-R1 or some pharmacological inhibitors.. Six hours after LPS administration (10 mg·kg(-1) , i.p.) cardiac function was decreased, an effect attenuated by NG-R1 pretreatment (25 mg·kg(-1) ·d(-1) , i.p.). NG-R1 also improved the imbalance between iNOS and eNOS, prevented activation of NF-κB and the subsequent myocardial inflammatory and apoptotic responses in endotoxemic mice. The effects of NG-R1 were closely associated with activation of the oestrogen receptor ERα and of PI3K/PKB (Akt) signalling, as characterized by NG-R1-induced preservation in ERα, phospho-Akt, phospho-GSK3β and I-κBα, and of cardiac function that was partially blocked by selective inhibitors of ERα or PI3K. However, NG-R1 had no effect on LPS-activated TLR-4.. NG-R1 is a promising compound for protecting the heart from septic shock, possibly via the activation of ERα and PI3K/Akt signalling. This mechanism produces blockade of NF-κB activation and attenuation of the pro-inflammatory state and apoptotic stress in the myocardium.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Cytokines; Endotoxemia; Estrogen Receptor alpha; Gene Expression Regulation; Ginsenosides; Heart; Inflammation; Lipopolysaccharides; Male; Mice; Myocardium; NF-kappa B; Nitric Oxide Synthase; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; RNA, Messenger; Signal Transduction