Publications by authors named "Weijie Xie"

46 Publications

A Novel α-Globin Chain Variant, Hb Nanchang [: c.46G>A, Codon 15 (GT>GT) (Gly→Ser)], Detected by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

Hemoglobin 2021 Jul 26:1-4. Epub 2021 Jul 26.

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, People's Republic of China.

Here we report a new α chain variant accidentally discovered during Hb A measurement by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) that revealed the presence of a variant α chain with a mass of 15155 Da. However, this hemoglobin (Hb) variant cannot be detected by the first-line methods such as cation exchange high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Sanger sequencing confirmed the presence of a heterozygous missense mutation [: c.46G>A, codon 15 (GT>GT), (Gly→Ser)]. The theoretical mass difference (30 Da) due to the substitution of amino acid glycine to serine matched the actual measured mass difference (29 Da). As this is the first report of the mutation, we named it Hb Nanchang after the place of residence of the proband.
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http://dx.doi.org/10.1080/03630269.2021.1956946DOI Listing
July 2021

Protective Effects and Network Analysis of Ginsenoside Rb1 Against Cerebral Ischemia Injury: A Pharmacological Review.

Front Pharmacol 2021 2;12:604811. Epub 2021 Jul 2.

Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Ischemic stroke is a leading cause of death and disability worldwide. Currently, only a limited number of drugs are available for treating ischemic stroke. Hence, studies aiming to explore and develop other potential strategies and agents for preventing and treating ischemic stroke are urgently needed. Ginseng Rb1 (GRb1), a saponin from natural active ingredients derived from traditional Chinese medicine (TCM), exerts neuroprotective effects on the central nervous system (CNS). We conducted this review to explore and summarize the protective effects and mechanisms of GRb1 on cerebral ischemic injury, providing a valuable reference and insights for developing new agents to treat ischemic stroke. Our summarized results indicate that GRb1 exerts significant neuroprotective effects on cerebral ischemic injury both and , and these network actions and underlying mechanisms are mediated by antioxidant, anti-inflammatory, and antiapoptotic activities and involve the inhibition of excitotoxicity and Ca2 influx, preservation of blood-brain barrier (BBB) integrity, and maintenance of energy metabolism. These findings indicate the potential of GRb1 as a candidate drug for treating ischemic stroke. Further studies, in particular clinical trials, will be important to confirm its therapeutic value in a clinical setting.
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http://dx.doi.org/10.3389/fphar.2021.604811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283782PMC
July 2021

Comprehensive Analysis of the Relationship Between Metabolic Reprogramming and Immune Function in Prostate Cancer.

Onco Targets Ther 2021 18;14:3251-3266. Epub 2021 May 18.

Department of Urology & Carson International Cancer Center, Shenzhen University General Hospital & Shenzhen University Clinical Medical Academy Center, Shenzhen University, Shenzhen, People's Republic of China.

Purpose: Prostate cancer is the most common malignant urinary tumor among men. Treatments are currently unsatisfactory for advanced prostate cancer. Cancer biology remains the basis for developing new antitumor drugs. Therefore, it is crucial to study the metabolic reprogramming, immune microenvironment, and immune evasion of tumors. This study aimed to clarify the relationship between tumor glycolysis and immune function in prostate cancer.

Materials And Methods: We downloaded the gene expression matrix and clinical data of prostate cancer from The Cancer Genome Atlas. We studied the expression profiles and prognostic significance of glycolysis-related genes and used CIBERSORT to identify the proportion of tumor-infiltrating immune cells. Through differential gene expression analysis, gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, gene set enrichment analysis, and correlation analysis, we further explored the relationship between glycolytic activity and immune function. We also performed immunohistochemistry, Western blot and RT-qPCR experiments using human prostate cancer tissue and cell lines to verify the expression of some glycolytic genes, macrophage infiltration and polarization.

Results: Among glycolysis-related genes, the expression of SLC16A3 in prostate cancer tissues was lower than that in normal tissues, but its high expression was associated with poor prognosis. In the high SLC16A3 expression group, several glycolysis-related genes also showed high expression, which was confirmed by immunohistochemistry experiments and Western blot. In high-glycolysis group, the expression of immune-related genes and the interleukin-17 (IL-17) signaling pathway were upregulated. CD8 T cells, regulatory T cells, macrophages, and other immune cells were highly enriched. Among them, M2 macrophage infiltration was associated with poor prognosis.

Conclusion: The enhanced glycolytic activity of prostate cancer may contribute to the formation of a pro-tumor immune microenvironment. The IL-17 signaling pathway may play an important mediating role in the interaction between tumor glycolysis and immune function.
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http://dx.doi.org/10.2147/OTT.S304298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140915PMC
May 2021

Notoginsenoside R1 Improves Cerebral Ischemia/Reperfusion Injury by Promoting Neurogenesis via the BDNF/Akt/CREB Pathway.

Front Pharmacol 2021 7;12:615998. Epub 2021 May 7.

Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Notoginsenoside R1 (R1), a major component isolated from , is a phytoestrogen that exerts many neuroprotective effects in a rat model of ischemic stroke. However, its long-term effects on neurogenesis and neurological restoration after ischemic stroke have not been investigated. The aim of this study was to evaluate the effects of R1 on neurogenesis and long-term functional recovery after ischemic stroke. We used male Sprague-Dawley rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). R1 was administered by intraperitoneal (i.p.) injection immediately postischemia. We showed that R1 significantly decreased infarct volume and neuronal loss, restored neurological function, and stimulated neurogenesis and oligodendrogenesis in rats subjected to MCAO/R. More importantly, R1 promoted neuronal proliferation in PC12 cells . The proneurogenic effects of R1 were associated with the activation of Akt/cAMP responsive element-binding protein, as shown by the R1-induced increase in brain-derived neurotrophic factor (BDNF) expression, and with the activation of neurological function, which was partially eliminated by selective inhibitors of BDNF and PI3K. We demonstrated that R1 is a promising compound that exerts neuroprotective and proneurogenic effects, possibly via the activation of BDNF/Akt/CREB signaling. These findings offer insight into exploring new mechanisms in long-term functional recovery after R1 treatment of ischemic stroke.
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http://dx.doi.org/10.3389/fphar.2021.615998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138209PMC
May 2021

Comparative Evaluation of the Transdermal Permeation Effectiveness of Fu's Cupping Therapy on Eight Different Types of Model Drugs.

Curr Drug Deliv 2021 ;18(4):446-459

School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550002, China.

Background: Overcoming the skin barrier to achieve the transdermal penetration of drugs across the Stratum Corneum (SC) remains a significant challenge. Our previous study showed that Fu's Cupping Therapy (FCT) contributes to the transdermal enhancement and percutaneous absorption rate of representative drugs and improves their clinical effects. This work evaluated the transdermal enhancement effect of FCT on drugs with different Molecular Weights (MW).

Methods: We investigated the enhancements in the transdermal penetration of eight types of model drugs through the skin of BALB/c-nu mice and Sprague Dawley rats using Franz diffusion devices. In addition, 3% azone, 5% azone, 3% peppermint oil, and 5% peppermint oil were used as penetration enhancers to study the transdermal behaviour of these drugs.

Results: Our results showed that the BALB/c-nu mouse skin was the best transdermal media, and the optimal time for FCT was 10 min. Compared with other penetration enhancers, FCT exerted a significantly improved effect on enhancing the percutaneous penetration of the selected log(P)- model drugs in addition to the two large MW drugs (ginsenoside Rg1 and notoginsenoside R1). Statistical analysis revealed that the relationship between the log(P) of various model drugs and the permeability coefficient [log(Pcm)] of the FCT group was log(Pcm)=0.080(log(P))2-0.136 (log(P))-0.282.

Conclusion: FCT may be used as a novel method for enhancing physical penetration and thus effectively promoting the transdermal absorption of drugs and might lay a foundation for future research on drug transdermal technology.
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http://dx.doi.org/10.2174/1567201817999201116192238DOI Listing
January 2021

Corrigendum: Ginsenoside Re Attenuates High Glucose-Induced RF/6A Injury Regulating PI3K/AKT Inhibited HIF-1a/VEGF Signaling Pathway.

Front Pharmacol 2020 23;11:1312. Epub 2020 Oct 23.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

[This corrects the article DOI: 10.3389/fphar.2020.00695.].
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http://dx.doi.org/10.3389/fphar.2020.01312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645230PMC
October 2020

Notoginseng Leaf Triterpenes Ameliorates OGD/R-Induced Neuronal Injury via SIRT1/2/3-Foxo3a-MnSOD/PGC-1 Signaling Pathways Mediated by the NAMPT-NAD Pathway.

Oxid Med Cell Longev 2020 23;2020:7308386. Epub 2020 Oct 23.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.

Background: Cerebral ischemic stroke (CIS) is a common cerebrovascular disease whose main risks include necrosis, apoptosis, and cerebral infarction. But few therapeutic advances and prominent drugs seem to be of value for ischemic stroke in the clinic yet. In the previous study, notoginseng leaf triterpenes (PNGL) from notoginseng stem and leaf have been confirmed to have neuroprotective effects against mitochondrial damages caused by cerebral ischemia . However, the potential mechanisms of mitochondrial protection have not been fully elaborated yet.

Methods: The oxygen and glucose deprivation and reperfusion (OGD/R)-induced SH-SY5Y cells were adopted to explore the neuroprotective effects and the potential mechanisms of PNGL . Cellular cytotoxicity was measured by MTT, viable mitochondrial staining, and antioxidant marker detection .Mitochondrial functions were analyzed by ATP content measurement, MMP determination, ROS, NAD, and NADH kit . And the inhibitor FK866 was adopted to verify the regulation of PNGL on the target NAMPT and its key downstream.

Results: In OGD/R models, treatment with PNGL strikingly alleviated ischemia injury, obviously preserved redox balance and excessive oxidative stress, inhibited mitochondrial damage, markedly alleviated energy metabolism dysfunction, improved neuronal mitochondrial functions, obviously reduced neuronal loss and apoptosis , and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL markedly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions and OGD/R-induced SH-SY5Y cells and regulated the downstream SIRT1/2-Foxo3a and SIRT1/3-MnSOD/PGC-1 pathways. And FK866 further verified that the protective effects of PNGL might be mediated by the NAMPT .

Conclusions: The mitochondrial protective effects of PNGL are, at least partly, mediated via the NAMPT-NAD+ and its downstream SIRT1/2/3-Foxo3a-MnSOD/PGC-1 signaling pathways. PNGL, as a new drug candidate, has a pivotal role in mitochondrial homeostasis and energy metabolism therapy via NAMPT against OGD-induced SH-SY5Y cell injury.
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http://dx.doi.org/10.1155/2020/7308386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603631PMC
May 2021

Corrigendum to "Ginsenoside Rb1 and mitochondria: A short review of the literature" [Mol. Cell. Probe (43) 2019 1-5].

Mol Cell Probes 2020 Dec 2;54:101626. Epub 2020 Sep 2.

Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100193, China. Electronic address:

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http://dx.doi.org/10.1016/j.mcp.2020.101626DOI Listing
December 2020

Broad-Band Excited and Tunable Luminescence of CaTbAlO:RE (RE = Ce and/or Eu) Nanocrystalline Phosphors for Near-UV WLEDs.

Inorg Chem 2020 Sep 14;59(17):12348-12361. Epub 2020 Aug 14.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.

Here, we demonstrate a novel donor-intermediate-receptor energy transfer model through a Ce → Tb → Eu scheme in a CaTbAlO:Ce,Eu nanocrystalline phosphor. A new type of CaTbAlO and CaTbAlO:RE (RE = Ce and/or Eu) nanocrystalline phosphors were prepared by a simple sol-gel method. There exist efficient energy transfers of Ce → Tb, Tb → Eu, and Ce → Tb → Eu in CaTbAlO:RE (RE = Ce and/or Eu) nanocrystalline phosphors. With near-UV or UV light excitation, the as-prepared CaTbAlO:RE (RE = Ce and/or Eu) nanocrystalline phosphors' luminous color can be regulated from green to green-yellow, yellow, orange, and orange-red by adjusting the doping concentration, categories, and different proportions of codoping Ce to Eu ions in the CaTbAlO matrix. The luminescence mechanism with respect to the CaTbAlO:RE (RE = Ce and/or Eu) nanocrystalline phosphors has been tentatively proposed. Due to their excellent luminescence properties, the as-prepared CaTbAlO, CaTbAlO:Ce, CaTbAlO:Eu, and CaTbAlO:Ce,Eu nanocrystalline phosphors exhibit bright prospects in NUV-LEDs and other photoelectric field.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01440DOI Listing
September 2020

Hemoglobin variants in southern China: results obtained during the measurement of glycated hemoglobin in a large population.

Clin Chem Lab Med 2020 07 20;59(1):227-232. Epub 2020 Jul 20.

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, P.R. China.

Objectives: Hemoglobin (Hb) variant is one of the most common monogenic inherited disorders. We aimed to explore the prevalence and hematological and molecular characteristics of Hb variants in southern China.

Methods: We collected blood samples from all patients with suspected variants found during HbA1c measurement via a cation-exchange high-performance liquid chromatography system (Bio-Rad Variant II Turbo 2.0) or a capillary electrophoresis method (Sebia Capillarys). Hematological analysis, Sanger sequencing, and gap-PCR were performed for these samples.

Results: Among the 311,024 patients tested, we found 1,074 Hb variant carriers, including 823 identified using Capillarys and 251 using Variant II Turbo 2.0, with a total carrier rate of 0.35%. We discovered 117 types of Hb variants (52 HBB, 47 HBA, and 18 HBD mutations) containing 18 new mutations. The most common variant found was Hb E, followed by Hb New York, Hb J-Bangkok, Hb Q-Thailand, Hb G-Coushatta, Hb G-Honolulu, Hb G-Taipei, and Hb Broomhill. Most heterozygotes for the Hb variant exhibited normal hematological parameters. However, most patients with compound heterozygotes for the Hb variant and thalassemia showed varied degrees of microcytic hypochromic anemia.

Conclusions: The prevalence of hemoglobin variants remains high and exhibits genetic diversity and widespread distribution in the population of southern China.
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http://dx.doi.org/10.1515/cclm-2020-0767DOI Listing
July 2020

Potential of MALDI-TOF mass spectrometry to overcome the interference of hemoglobin variants on HbA1c measurement.

Clin Chem Lab Med 2020 07 17;59(1):233-239. Epub 2020 Jul 17.

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, PR China.

Objectives: Hemoglobin (Hb) variants remain an important cause of erroneous HbA1c results. We present an approach to overcome the interference of Hb variants on HbA1c measurements using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Methods: Samples containing or not containing Hb variants were analyzed for HbA1c using an MALDI-TOF MS system (QuanTOF) and a boronate affinity comparative method (Ultra2). For QuanTOF, two sets of HbA1c values were obtained through α- and β-chain glycation.

Results: A robust correlation between the glycation degrees of the α- and β-chains was found, and HbA1c values derived from α- and β-chain glycation correlated well with the Ultra2 results. Statistically significant differences (p<0.01) were found for all the Hb variants tested. When using the conventional β-chain glycation to determine HbA1c, clinically significant differences were only found among samples containing β-chain variants detected by QuanTOF (i.e., Hb J-Bangkok, Hb G-Coushatta, and Hb G-Taipei). In contrast, based on α-chain glycation, no clinically significant differences were found for these three variants.

Conclusions: In addition to conventional β-chain glycation, α-chain glycation can be used to calculate HbA1c values. The interference of Hb variants on HbA1c quantification can be overcome by employing the glycation of the globin chain without a genetic variant to estimate HbA1c values.
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http://dx.doi.org/10.1515/cclm-2020-0724DOI Listing
July 2020

Identification of a new hemoglobin variant Hb Liuzhou [:C.182A→G] by MALDI-TOF mass spectrometry during HbA measurement.

Scand J Clin Lab Invest 2020 Oct 28;80(6):479-483. Epub 2020 Jun 28.

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.

Structural hemoglobin (Hb) variant is generally caused by a point mutation in the globin gene that produces one amino acid substitution. Here, we describe a new -chain variant found during HbA measurement. HbA procedures based on both ion-exchange high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) techniques failed to identify its presence. In contrast, MALDI-TOF mass spectrometry (MS) revealed the existence of a variant -chain with a mass of 15155 Da. In addition, the Hb variant interfered with HbA determined by Bio-Rad D100. DNA sequencing confirmed the occurrence of a new heterozygous mutation [:C.182A→G] at codon 60, resulting in a coding change from lysine to arginine. We named it Hb Liuzhou for thde birthplace of the patient. This case exemplified that MALDI-TOF mass spectrometry can serve as the method of choice to identify and quantify the Hb variant.
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http://dx.doi.org/10.1080/00365513.2020.1783698DOI Listing
October 2020

Ginsenoside Re Attenuates High Glucose-Induced RF/6A Injury Regulating PI3K/AKT Inhibited HIF-1α/VEGF Signaling Pathway.

Front Pharmacol 2020 21;11:695. Epub 2020 May 21.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Hyperglycaemia-induced retinal microvascular endothelial cell apoptosis is a critical and principle event in diabetic retinopathy (DR), which involves a series of complex processes such as mitochondrial dysfunction and oxidative stress. Ginsenoside Re (Re), a key ingredients of ginseng, is considered to have various pharmacologic functions, such as antioxidative, inhibition of inflammation and anti-apoptotic properties. However, the effects of Re in DR and the related mechanisms of endothelial cell injury induced by high glucose (HG) exposure remain unclear. The present study was designed to investigate and evaluate the ability of Re to ameliorate HG-induced retinal endothelial RF/6A cell injury and the potential mechanisms involved in the hypoxia-inducible factor-1-alpha (HIF-1α)/vascular endothelial growth factor (VEGF) signaling regulated by phosphoinositide 3-kinase (PI3K)/AKT pathway. Our results showed that preincubation with Re exerted cytoprotective effects by reversing the HG-induced decrease in RF/6A cell viability, downregulation of apoptosis rate and inhibition of oxidative-related enzymes, thereby reducing the excess intracellular reactive oxygen species (ROS) and HG-triggered RF/6A cell injury. In addition, Western blot analysis results showed ginsenoside Re significantly increased HIF-1α expression in the cytoplasm but decreased its expression in the nucleus, suggesting that it reduced the translocation of HIF-1α from the cytoplasm to the nucleus, and downregulated VEGF level. Moreover, this effect is involved in the activation of the PI3K/Akt pathway. LY294002, a PI3K inhibitor, was used to block the Akt pathway. Afterwards, the effects of Re on the regulation of apoptotic related proteins, VEGF and HIF-1α nuclear transcription was partially reversed. These findings suggested the exerting protective effects of ginsenoside Re were associated with regulating of PI3K/AKT and HIF-1α/VEGF signaling pathway, which indicates that ginsenoside Re may ameliorates HG-induced retinal angiogenesis and suggests the potential for the development of Re as a therapeutic for DR.
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http://dx.doi.org/10.3389/fphar.2020.00695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253708PMC
May 2020

A New α Chain Variant, Hb Heilongjiang (: c.49A>C), Found During Hb A Measurement.

Hemoglobin 2020 Mar 19;44(2):143-145. Epub 2020 May 19.

Department of Laboratory Medicine, Weifang People's Hospital, Weifang, People's Republic of China.

We here report a new hemoglobin (Hb) variant found in a Chinese woman. The presence of the Hb variant can be easily recognized by HbA procedures based on ion exchange high performance liquid chromatography (HPLC) or capillary electrophoresis (CE) techniques. DNA sequencing revealed a new point mutation (: c.49A>C) at codon 16, resulting in an amino acid substitution from lysine to glutamine. Moreover, the Hb variant affected Hb A determination by VARIANT II Turbo 2.0 and D100. We named the new Hb variant Hb Heilongjiang for the birthplace of the proband.
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http://dx.doi.org/10.1080/03630269.2020.1766487DOI Listing
March 2020

Correction: Zhou, P., et al. Notoginsenoside R1 Ameliorates Diabetic Retinopathy through PINK1-Dependent Activation of Mitophagy. , 2019, , 213.

Cells 2020 Feb 17;9(2). Epub 2020 Feb 17.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.

The authors wish to make the following corrections to this paper [...].
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http://dx.doi.org/10.3390/cells9020450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072801PMC
February 2020

Optimization of the extraction and purification of based on the Q-marker uniform design method.

BMC Chem 2020 Dec 11;14(1). Epub 2020 Feb 11.

College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Huaxi University Town, Dongqing South Road, Guiyang, 550025 Guizhou People's Republic of China.

alkaloids are mainly divided into three categories: protoberberine, prototropine and aporphine alkaloids. Therefore, we have taken into account these three alkaloid contents when extracting and purifying crude drugs, which is essential for the quality control of and its derivative products. Herein, we investigated the feasibility of the Q-marker uniform design method in the optimization of the extraction and purification of . In this study, Q-marker-based comprehensive scoring (CS) and uniform design methods were used to optimize the extraction and purification of . The inspective factors included the solvent concentration, pH, liquid-solid ratio, extraction time and frequency. Then 8 Q-markers, the total alkaloid extraction and the extraction rate were considered as the evaluating indicators during the process. The results indicated that the optimal reflux extraction process of was as follows: a total amount of 20 times 70% ethanol (pH = 10 of diluted ammonia), heating and refluxing twice, and extracting each time for 60 min. The results of nine-resin screening exhibited that NKA-9 macroporous adsorption resin had the best separation and purification effect on 8 kinds of alkaloids with stronger enrichment. During the optimal enrichment process and elution conditions, the water-soluble impurities were washed off with 5 BV distilled water at a volume flow rate of 2 BV/h, and the elution solvent was 70% ethanol with an elution volume flow rate of 1.5 BV/h and an elution dosage of 12 BV. Additionally, the total alkaloids of the obtained product were over 50%, of which eight quality markers were (+)-corydaline 3.55%, tetrahydropalmatine 3.13%, coptisine 2.79%, palmatine hydrochloride 2.24%, dehydrocorydaline 13.11%, (R)-(+)-corypalmine 2.37%, protopine 2.71% and glaucine 14.03%. Our data demonstrated that the optimal extraction and purification process was stable and feasible, which was expected to provide an experimental basis and reference for the industrial production of .
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http://dx.doi.org/10.1186/s13065-020-00666-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011255PMC
December 2020

Central Sensitization-Related Changes in Brain Function Activity in a Rat Endometriosis-Associated Pain Model.

J Pain Res 2020 13;13:95-107. Epub 2020 Jan 13.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.

Background: Pain sensitization processing in the central nervous system may be related to endometriosis-associated pain in patients. The purpose of this study was to understand the alterations in the abnormal pain response in central brain areas and explore the central sensitization mechanism of endometriosis-associated pain.

Methods: An endometriosis model was established in 40 Sprague-Dawley rats, and the rats underwent pain model assessment through behavioral tests. Twenty Sprague-Dawley rats underwent a sham operation as the control group. Thirteen pain rats and 8 control rats received Rs-fMRI examination to explore the brain functional activity areas, and the regional homogeneity (ReHo) method was used to analyze relevant functional signals among the whole brain. The states of neurons and expression of TRPV1 and NMDRA located in the abnormal ReHo signal brain regions were observed using Nissl staining, qRT-PCR and immunohistochemistry.

Results: The rats were divided into a pain group and a control group based on the different syndromes and behavioral assessments. We detected significant enhancement of ReHo signals in the anterior cingulate cortex, hippocampus, and thalamus and a reduction in the ReHo values in the basomedial amygdaloid nucleus (BM) and primary motor cortex (M1) in the pain rat group via Rs-fMRI examination. The number of Nissl bodies and apoptotic neurons was increased; moreover, the volume of neurons increased compensatorily in the cingulate cortex, thalamus and hippocampus in the pain group. TRPV1 and NMDRA were overexpressed in apoptotic neurons in the higher ReHo value brain regions in the endometriosis pain group.

Conclusion: These findings suggest that in rats with endometriosis-associated pain, ReHo signal enhancement was observed in the cingulate cortex, thalamus and hippocampus, which may be due to the increase in the number of apoptotic neurons or the compensatory increase in the volume of overactive neurons.
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http://dx.doi.org/10.2147/JPR.S232313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968808PMC
January 2020

Antidepressant-like effects of the Guanxin Danshen formula via mediation of the CaMK II-CREB-BDNF signalling pathway in chronic unpredictable mild stress-induced depressive rats.

Ann Transl Med 2019 Oct;7(20):564

Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.

Background: Depression is a chronic and recurrent syndrome of mood disorder causing immense social and economic burden; thus, treatment should be improved. Guanxin Danshen formula (GXDSF), a natural botanical drug composition prescription, has significant cardiovascular protective effects and is widely used in the clinical treatment of myocardial ischaemic diseases. However, it is still unclear and seldom studied whether GXDSF has neuroprotective effects against depressive disorders. This study explored whether GXDSF has antidepressant-like effects in rats exposed to chronic unpredictable mild stress (CUMS) and analysed the possible underlying neurotrophic expression and psychotropic mechanisms.

Methods: The present study was designed to investigate the antidepressant effects of GXDSF treatment in a CUMS-induced rat model. Based on the clinical doses, the drug-treated group was intragastrically administered GXDSF for 30 days, and rats were simultaneously exposed to CUMS stimulation for 30 days. After induction and drug administration, the depression-like behaviours were determined via the sucrose preference test (SPT), the open field test (OFT), the tail suspension test (TST), and the forced swim test (FST). ELISA kits were used to examine the monoaminergic neurotransmitters, monoamine oxidase (MAO) and Ca levels in the hippocampus. Moreover, we measured and analysed the brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels and the upstream regulation and signal pathways of BDNF and NGF to explore their related mechanisms in this animal model of depression, including calcium-calmodulin dependent protein kinase-II (CaMKII) and cAMP response element-binding (CREB).

Results: The results revealed that GXDSF may possess significant antidepressant-like effects via improving body weight, raising the sucrose preference in the SPT, increasing the total distance, the number of upright stands, and the residence time of the central zone in the open field test (OPF) and reducing the immobility time in the TST and FST. In addition, GXDSF significantly upregulated the relative levels of neurotransmitters, including dopamine (DA), norepinephrine (NE), and serotonin (5-HT), in a dose-dependent manner and inhibited MAO activities in the hippocampus. Moreover, GXDSF reversed the decline in intracellular CREB and p-CREB expression induced by CUMS, downregulated the phosphorylation levels of intracellular CaMKII and its two subunits CaMKIIα and CaMKIIβ in the hippocampus, and thus, clearly upregulated the downstream effector protein expression levels of BDNF, NGF, and synitaxine-1 in the hippocampus. These data suggest that the antidepressant effects of GXDSF have a potential relationship with regulating changes in the CaMKII-CREB-BDNF pathway.

Conclusions: Despite several limitations of this study, the results have suggested that GXDSF administration possesses antidepressant-like effects in CUMS-treated rats and provide the first demonstration of a possible mechanism of GXDSF via regulating changes in the CaMKII-CREB-BDNF signalling pathway. These findings provide a novel potential substrate by which herbal antidepressants may exert therapeutic effects in the treatment of depression.
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http://dx.doi.org/10.21037/atm.2019.09.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861747PMC
October 2019

Detection of Hb Phnom Penh by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry during the measurement of glycated hemoglobin.

Clin Chem Lab Med 2020 09;58(10):e233-e235

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Lianhua Road No. 1120, Futian District, Shenzhen, Guangdong, P.R. China.

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http://dx.doi.org/10.1515/cclm-2019-0934DOI Listing
September 2020

Ginsenoside Rb1 mitigates oxidative stress and apoptosis induced by methylglyoxal in SH-SY5Y cells via the PI3K/Akt pathway.

Mol Cell Probes 2019 12 16;48:101469. Epub 2019 Oct 16.

Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China. Electronic address:

Diabetic encephalopathy is a severe diabetic complication characterized by cognitive dysfunction and neuropsychiatric disability. Methylglyoxal (MGO), a highly reactive metabolite of hyperglycemia, serves as a major precursor of advanced glycation end products that play key roles in diabetic complications. Ginsenoside Rb1 (abbreviated as Rb1) has received extensive attention due to its potential therapeutic effects on diabetes and neurodegeneration. Therefore, this study aimed to investigate the effects of Rb1 on MGO-induced damage in SH-SY5Y cells and the related mechanism. SH-SY5Y cells were pretreated with Rb1 for 8 h and then exposed to MGO (0.5 mM) for 24 h. Cell survival was assessed by the MTT assay. Cell apoptosis was assessed using Hoechst 33342/propidium iodide (PI) staining and an Annexin-V/PI kit. The activities of oxidative stress markers were examined using commercial kits. Reactive oxygen species (ROS) staining and JC-1 staining were used to evaluate mitochondria injury. In addition, protein levels were measured by Western blot analysis. As a result, Rb1 alleviated the injury induced by MGO by increasing the activities of superoxide dismutase, catalase and total glutathione, decreasing the level of malondialdehyde, and alleviating mitochondrial damage and ROS production. Furthermore, Rb1 could enhance the Bcl-2/Bax ratio, inhibit the expression of cleaved caspase-3 and cleaved caspase-9, and enhance the levels of phosphorylated Akt. Moreover, the protective effects of Rb1 against MGO-induced apoptosis were partly abolished by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) phosphorylation. Our results demonstrated that Rb1 ameliorated MGO-induced oxidative stress and apoptosis in SH-SY5Y cells via activating the PI3K/Akt signaling pathway.
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http://dx.doi.org/10.1016/j.mcp.2019.101469DOI Listing
December 2019

HMGB1-triggered inflammation inhibition of notoginseng leaf triterpenes against cerebral ischemia and reperfusion injury via MAPK and NF-κB signaling pathways.

Biomolecules 2019 09 20;9(10). Epub 2019 Sep 20.

Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.

Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by cerebral ischemia and reperfusion (I/R) injury. This process has particular significance for the treatment of stroke patients. Notoginseng leaf triterpenes (PNGL), as a valuable medicine, have been discovered to have neuroprotective effects. However, it was not confirmed that whether PNGL may possess neuroprotective effects against cerebral I/R injury. To explore the neuroprotective effects of PNGL and their underlying mechanisms, a middle cerebral artery occlusion/reperfusion (MCAO/R) model was established. In vivo results suggested that in MCAO/R model rats, PNGL pretreatment (73.0, 146, 292 mg/kg) remarkably decreased infarct volume, reduced brain water content, and improved neurological functions; moreover, PNGL (73.0, 146, 292 mg/kg) significantly alleviated blood-brain barrier (BBB) disruption and inhibited neuronal apoptosis and neuronal loss caused by cerebral I/R injury, while PNGL with a different concertation (146, 292 mg/kg) significantly reduced the concentrations of IL-6, TNF-α, IL-1 β, and HMGB1 in serums in a dose-dependent way, which indicated that inflammation inhibition could be involved in the neuroprotective effects of PNGL. The immunofluorescence and western blot analysis showed PNGL decreased HMGB1 expression, suppressed the HMGB1-triggered inflammation, and inhibited microglia activation (IBA1) in hippocampus and cortex, thus dose-dependently downregulating inflammatory cytokines including VCAM-1, MMP-9, MMP-2, and ICAM-1 concentrations in ischemic brains. Interestingly, PNGL administration (146 mg/kg) significantly downregulated the levels of p-P44/42, p-JNK1/2 and p-P38 MAPK, and also inhibited expressions of the total NF-κB and phosphorylated NF-κB in ischemic brains, which was the downstream pathway triggered by HMGB1. All of these results indicated that the protective effects of PNGL against cerebral I/R injury could be associated with inhibiting HMGB1-triggered inflammation, suppressing the activation of MAPKs and NF-κB, and thus improved cerebral I/R-induced neuropathological changes. This study may offer insight into discovering new active compounds for the treatment of ischemic stroke.
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http://dx.doi.org/10.3390/biom9100512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843331PMC
September 2019

Interspecies Variation in NCMNDemethylation in Liver Microsomes from Various Species.

Molecules 2019 Jul 30;24(15). Epub 2019 Jul 30.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

NCMN (-(3-carboxy propyl)-4-methoxy-1,8-naphthalimide), a newly developed ratiometric two-photon fluorescent probe for human Cytochrome P450 1A (CYP1A), shows the best combination of specificity and reactivity for real-time detection of the enzymatic activities of CYP1A in complex biological systems. This study aimed to investigate the interspecies variation in NCMNdemethylation in commercially available liver microsomes from human, mouse, rat, beagle dog, minipig and cynomolgus monkey. Metabolite profiling demonstrated that NCMN could be -demethylated in liver microsomes from all species but the reaction rate varied considerably. CYP1A was the major isoform involved in NCMNdemethylation in all examined liver microsomes based on the chemical inhibition assays. Furafylline, a specific inhibitor of mammalian CYP1A, displayed differential inhibitory effects on NCMNdemethylation in all tested species. Kinetic analyses demonstrated that NCMNdemethylation in liver microsomes form rat, minipig and cynomolgus monkey followed biphasic kinetics, while in liver microsomes form human, mouse and beagle dog obeyed Michaelis-Menten kinetics, the kinetic parameters from various species are much varied, while NCMNdemethylation in MLM exhibited the highest similarity of specificity, kinetic behavior and intrinsic clearance as that in HLM. These findings will be very helpful for the rational use of NCMN as a practical tool to decipher the functions of mammalian CYP1A or to study CYP1A associated drug-drug interactions .
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http://dx.doi.org/10.3390/molecules24152765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695839PMC
July 2019

Clinical significance of LOXL4 expression and features of LOXL4-associated protein-protein interaction network in esophageal squamous cell carcinoma.

Amino Acids 2019 May 21;51(5):813-828. Epub 2019 Mar 21.

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, 515041, Guangdong, People's Republic of China.

Lysyl oxidase-like 4 (LOXL4), a member of the LOX family proteins, catalyzes oxidative deamination of lysine residues in collagen and elastin, which are responsible for maintaining extracellular matrix homeostasis. In this study, the mRNA expression of LOXL4 in seven esophageal squamous cell carcinoma (ESCC) cell lines and 15 ESCC pairs of clinical samples were examined. Furthermore, LOXL4 protein levels in the ESCC cell lines were determined using western blotting. With the use of immunofluorescence, LOXL4 was observed to be localized primarily in the cytoplasm, but was also present in the nucleus. In addition, the results indicated that the upregulated expression of LOXL4 was associated with poor survival in patients with ESCC even following curative resection (P = 0.010). Similar Kaplan-Meier estimator curves for proteins that interact with LOXL4, SUV39H1 (P = 0.014) and COL2A1 (P = 0.011), were plotted. The analyses based on the protein-protein interaction network depicted the expression of LOXL4 and its associated proteins as well as their functions, suggesting that LOXL4 and its associated proteins may serve a significant role in the development and progression of ESCC. In conclusion, the results of the present study suggest that LOXL4 is a potential biomarker for patients with ESCC, as well as SUV39H1 and COL2A1, and high expression levels of these genes are associated with poor prognosis in patients with ESCC.
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http://dx.doi.org/10.1007/s00726-019-02723-4DOI Listing
May 2019

Notoginsenoside R1 Ameliorates Diabetic Retinopathy through PINK1-Dependent Activation of Mitophagy.

Cells 2019 03 2;8(3). Epub 2019 Mar 2.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.

Accumulating evidence has indicated that inflammation, oxidative stress, apoptosis, and autophagy in retinal Müller cells are involved in diabetic retinopathy (DR). Notoginsenoside R1 (NGR1), a novel saponin extracted from , posesses pharmacological properties, including treating diabetic encephalopathy and improving microcirculatory disorders. Nevertheless, its beneficial effects on DR and the potential mechanism remain to be elucidated. In this study, we found retinal vascular degeneration, reduced retinal thickness, and impaired retinal function in db/db mice were all dramatically attenuated by oral treatment with NGR1 (30 mg/kg) for 12 weeks. NGR1 pretreatment also significantly inhibited apoptosis, markedly suppressed the VEGF expression, markedly increased PEDF expression and markedly inhibited oxidative stress and inflammation in rat retinal Müller cells (rMC-1) subjected to high glucose (HG) and in the retinas of db/db mice. Furthermore, NGR1 pre-treatment upregulated the level of PINK1 and Parkin, increased the LC3-II/LC3-I ratio, and downregulated the level of p62/SQSTM1 in rMC-1 cells induced by HG and in the retinas of db/db mice. Moreover, NGR1 administration enhanced the co-localization of GFP-LC3 puncta and MitoTracker in rMC-1 cells. Importantly, knockdown of PINK1 abolished the protective effects of NGR1. In conclusion, these phenomena suggested that NGR1 prevented DR via PINK1-dependent enhancement of mitophagy.
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http://dx.doi.org/10.3390/cells8030213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468581PMC
March 2019

Ginsenoside Rb1 as an Anti-Diabetic Agent and Its Underlying Mechanism Analysis.

Cells 2019 02 28;8(3). Epub 2019 Feb 28.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.

and , two well-known medical plants with economic value, have a long history of use for managing various diseases in Asian countries. Accumulating clinical and experimental evidence suggests that notoginsenosides and ginsenosides, which are the major bioactive components of the plants, have a variety of beneficial effects on several types of disease, including metabolic, vascular, and central nervous system disease. Considerable attention has been focused on ginsenoside Rb1 derived from their common ownership as an anti-diabetic agent that can attenuate insulin resistance and various complications. Particularly, in vitro and in vivo models have suggested that ginsenoside Rb1 exerts various pharmacological effects on metabolic disorders, including attenuation of glycemia, hypertension, and hyperlipidemia, which depend on the modulation of oxidative stress, inflammatory response, autophagy, and anti-apoptosis effects. Regulation of these pathophysiological mechanisms can improve blood glucose and insulin resistance and protect against macrovascular/microvascular related complications. This review summarizes the pharmacological effects and mechanisms of action of ginsenoside Rb1 in the management of diabetes or diabetic complications. Moreover, a multi-target effect and mechanism analysis of its antidiabetic actions were performed to provide a theoretical basis for further pharmacological studies and new drug development for clinical treatment of type 2 diabetes. In conclusion, ginsenoside Rb1 exerts significant anti-obesity, anti-hyperglycemic, and anti-diabetic effects by regulating the effects of glycolipid metabolism and improving insulin and leptin sensitivities. All of these findings suggest ginsenoside Rb1 exerts protective effects on diabetes and diabetic complications by the regulation of mitochondrial energy metabolism, improving insulin resistance and alleviating the occurrence complications, which should be further explored. Hence, ginsenoside Rb1 may be developed as a potential anti-obesity, anti-hyperglycemic, and anti-diabetic agent with multi-target effects.
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http://dx.doi.org/10.3390/cells8030204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468558PMC
February 2019

Protective Effects of Total Saponins of (Miq.) on Endothelial Cell Injury Induced by TNF-α via Modulation of the PI3K/Akt and NF-κB Signalling Pathways.

Int J Mol Sci 2018 Dec 21;20(1). Epub 2018 Dec 21.

Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.

Atherosclerosis is an arterial disease associated with inflammation. Hence, the discovery of novel therapeutic agents for suppressing inflammatory responses is urgent and vital for the treatment of atherosclerosis in cardiovascular diseases. The total saponins of (Miq.) Seem. (TAS) are the main components extracted from the Chinese traditional herb Longya L., a folk medicine used in Asian countries for treating numerous diseases, enhancing energy and boosting immunity. However, the protective effects of TAS against inflammation-triggered vascular endothelial dysfunction, a critical early event during the course of atherosclerosis, and the potential mechanisms of this protection have been not demonstrated. Accordingly, the aim of this study was to investigate the anti-inflammatory and anti-apoptotic effects and the protective mechanisms of TAS, and show how TAS ameliorates human umbilical vein endothelial cell (HUVEC) damage caused by tumour necrosis factor-α (TNF-α). The results indicated that TAS exerted cytoprotective effects by inhibiting TNF-α-triggered HUVEC apoptosis, mitochondrial membrane potential depolarisation, and the regulation of inflammatory factors (IL-6, MCP-1, and VCAM-1) while suppressing NF-κB transcription. Furthermore, this phenomenon was related to activation of the phosphoinositide 3-kinase (PI3K)/Akt signalling pathway. Blocking the Akt pathway with LY294002, a PI3K inhibitor, reversed the cytoprotective effect of TAS against TNF-α-induced endothelial cell death. Moreover, LY294002 partially abolished the effects of TAS on the upregulation of the Bcl-2 family of proteins and the downregulation of Bax protein expression. In conclusion, the results of our study suggest that TAS suppresses the inflammation and apoptosis of HUVECs induced by TNF-α and that PI3K/Akt signalling plays a key role in promoting cell survival and anti-inflammatory reactions during this process.
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http://dx.doi.org/10.3390/ijms20010036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337668PMC
December 2018

Protective Effects and Target Network Analysis of Ginsenoside Rg1 in Cerebral Ischemia and Reperfusion Injury: A Comprehensive Overview of Experimental Studies.

Cells 2018 Dec 12;7(12). Epub 2018 Dec 12.

Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.

Cerebral ischemia-reperfusion is a complicated pathological process. The injury and cascade reactions caused by cerebral ischemia and reperfusion are characterized by high mortality, high recurrence, and high disability. However, only a limited number of antithrombotic drugs, such as recombinant tissue plasminogen activator (r-TPA), aspirin, and heparin, are currently available for ischemic stroke, and its safety concerns is inevitable which associated with reperfusion injury and hemorrhage. Therefore, it is necessary to further explore and examine some potential neuroprotective agents with treatment for cerebral ischemia and reperfusion injury to reduce safety concerns caused by antithrombotic drugs in ischemic stroke. Ginseng Rg1 (G-Rg1) is a saponin composed of natural active ingredients and derived from the roots or stems of and ginseng in traditional Chinese medicine. Its pharmacological effects exert remarkable neurotrophic and neuroprotective effects in the central nervous system. To explore and summarize the protective effects and mechanisms of ginsenoside Rg1 against cerebral ischemia and reperfusion injury, we conducted this review, in which we searched the PubMed database to obtain and organize studies concerning the pharmacological effects and mechanisms of ginsenoside Rg1 against cerebral ischemia and reperfusion injury. This study provides a valuable reference and clues for the development of new agents to combat ischemic stroke. Our summarized review and analysis show that the pharmacological effects of and mechanisms underlying ginsenoside Rg1 activity against cerebral ischemia and reperfusion injury mainly involve 4 sets of mechanisms: anti-oxidant activity and associated apoptosis via the Akt, Nrf2/HO-1, PPARγ/HO-1, extracellular regulated protein kinases (ERK), p38, and c-Jun N-terminal kinase (JNK) pathways (or mitochondrial apoptosis pathway) and the caspase-3/ROCK1/MLC pathway; anti-inflammatory and immune stimulatory-related activities that involve apoptosis or necrosis via MAPK pathways (the JNK1/2 + ERK1/2 and PPARγ/HO-1 pathways), endoplasmic reticulum stress (ERS), high mobility group protein1 (HMGB1)-induced TLR2/4/9 and receptor for advanced glycation end products (RAGE) pathways, and the activation of NF-κB; neurological cell cycle, proliferation, differentiation, and regeneration via the MAPK pathways (JNK1/2 + ERK1/2, PI3K-Akt/mTOR, PKB/Akt and HIF-1α/VEGF pathways); and energy metabolism and the regulation of cellular ATP levels, the blood-brain barrier and other effects via N-methyl-D-aspartic acid (NMDA) receptors, ERS, and AMP/AMPK-GLUT pathways. Collectively, these mechanisms result in significant neuroprotective effects against cerebral ischemic injury. These findings will be valuable in that they should further promote the development of candidate drugs and provide more information to support the application of previous findings in stroke clinical trials.
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http://dx.doi.org/10.3390/cells7120270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316103PMC
December 2018

Gastrodin Ameliorates Cognitive Dysfunction in Diabetes Rat Model via the Suppression of Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation.

Front Pharmacol 2018 22;9:1346. Epub 2018 Nov 22.

Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Patients with diabetes mellitus (DM) are at high risk for cognitive dysfunction. Endoplasmic reticulum stress (ERS) and inflammation play crucial roles in DM. Gastrodin (Gas), the main component of , possesses anti-oxidative stress, anti-inflammatory, and neuroprotective effects. This present study aims to investigate whether Gas could ameliorate cognitive dysfunction in DM and to explore its underlying mechanisms. Rats with streptozotocin-induced type 2 DM were used in this study. After administration of Gas for 5 weeks, the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in serum, TNF-α, IL-1β, MDA and SOD in the hippocampus were measured. Morris water maze, hematoxylin and eosin (HE) and Nissl staining were performed to assess the effects of Gas on cognitive function and hippocampal neuronal apoptosis. Protein levels of GLUT3, brain derived neurotrophic factor (BDNF), GRP78, PERK, P-PERK, TXNIP, ASC, NLRP3, CHOP, Bcl-2 and Bax were measured by using Western blot. The results showed that Gas could improve hyperglycemia and dyslipidemia in DM rats, as the levels of TC, TG LDL-C in serum were decreased. TNF-α, IL-1β, MDA contents in the hippocampus were decreased, and SOD contents was increased in the hippocampus of DM rats. Inflammation, oxidative stress, ERS, and apoptosis were observed in the hippocampus of DM rats, accompanied with decreased expression of BDNF and GLUT3. Gas improved the cognitive deficits caused by diabetes and inhibited inflammation, oxidative stress, ERS, and apoptosis in the hippocampus. Furthermore, Gas substantially increased the expression of GLUT3, and inhibited hippocampal ERS and ERS-mediated apoptosis. Additionally, Gas increased the expression of BDNF and decreased the activation of NLRP3 inflammasome. These results suggested that by inhibiting ERS and NLRP3 inflammasome activation and increasing the expression of BDNF and GLUT3, Gas exhibits neuroprotective effects against cognitive dysfunction in DM.
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http://dx.doi.org/10.3389/fphar.2018.01346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262084PMC
November 2018

Ginsenoside Rb1 and mitochondria: A short review of the literature.

Mol Cell Probes 2019 02 4;43:1-5. Epub 2018 Dec 4.

Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100193, China. Electronic address:

Mitochondria play a central role in various critical cellular processes, including energy synthesis, energy supply and apoptosis. Panax notoginseng, a commonly used traditional Chinese medicine, has various pharmacological effects on the human body. Ginsenosides are representative bioactive components of P. notoginseng. Recently, more attention has focused on ginsenoside Rb1 as an antioxidative and anti-inflammatory agent that can protect the nervous system and the cardiovascular system. Numerous studies have shown that Rb1 exerts these effects by regulating mitochondrial energy metabolism, mitochondrial fission and fusion, apoptosis, oxidative stress and reactive oxygen species release, mitophagy and mitochondrial membrane potential. Thus, the mitochondria are pivotal targets of Rb1. This review summarized the available reports of the effects of ginsenoside Rb1 on the regulation of mitochondria and showed that it has a promising role in treating mitochondrial diseases.
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http://dx.doi.org/10.1016/j.mcp.2018.12.001DOI Listing
February 2019

Inhibitory Effects of Ginsenoside Rb1 on Early Atherosclerosis in ApoE-/- Mice via Inhibition of Apoptosis and Enhancing Autophagy.

Molecules 2018 Nov 8;23(11). Epub 2018 Nov 8.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.

Inflammation is a major contributing factor to the progression of atherosclerosis. Ginsenoside Rb1 (Rb1), an active saponin of , has been found to exert beneficial effects on inflammation and oxidative stress. This study investigated the ability of Rb1 to inhibit the formation of atherosclerotic plaques and the potential mechanisms. In this study, the effects of Rb1 on the development of atherosclerosis were investigated in ApoE-/- deficient mice fed with a western diet. Mice were intragastrically administrated with Rb1 (10 mg/kg) for 8 weeks. This study is that ginsenoside Rb1 exerted an inhibitory effect on early atherosclerosis in ApoE-/- mice via decreasing body weight and food intake daily, upregulating the lipid levels of serum plasma, including those of TC, TG and LDL-C and HDL-C and reducing the atherosclerotic plaque area, suppressing inflammatory cytokines (levels of IL-1β, IL-6 and TNF-α) in the serum of ApoE-/- mice, changing the expression levels of BCL-2, BAX, cleaved caspase-3 and cleaved caspase-9 and weakening apoptosis associated with anti-inflammatory activity. Hence, all these effects against atherosclerosis were tightly associated with regulation of necrosis or apoptosis associated with anti-inflammatory activity. Additionally, the results found that ginsenoside Rb1 increased autophagy flux to inhibit apoptosis via acceleration of autophagy by promoting transformation of LC3 from type I to type II in high-fat diet-induced atherosclerosis in ApoE-/- mice. This finding, along with those of the previous study, provides evidence that Rb1 promotes the process of autophagy to protect against atherosclerosis via regulating BCL-2 family-related apoptosis. These results indicate that Rb1 exhibits therapeutic effects in atherosclerosis by reversing the imbalance between apoptosis and autophagy.
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http://dx.doi.org/10.3390/molecules23112912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278435PMC
November 2018
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