Publications by authors named "Guibo Sun"

135 Publications

Anti-hyperlipidemic effects of the compound Danshen tablet: roles of antioxidation, anti-inflammation, anticoagulation, and anti-apoptosis.

Ann Transl Med 2021 May;9(9):744

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

Background: Hyperlipidemia could cause some serious harm to human health diseases, such as atherosclerosis, coronary heart disease. This study sought to investigate the effects of the compound Danshen tablet (CDT) on hyperlipidemia induced by a high-fat diet in ApoE mice and related antioxidation, anti-inflammation, anticoagulation, and anti-apoptosis mechanisms.

Methods: The control group (Group 1) comprised 15 male C57BL/6N mice, and the other 5 groups (Groups 2-6) comprised 75 male ApoE mice. These 75 mice were randomly divided into 1 of the following 5 groups: Group 2, a model group; Groups 3-5, the CDT groups, each of which was administered 375, 750, or 1,500 mg/kg of CDT; and Group 6, an atorvastatin group, which was administered 5.2 mg/kg of atorvastatin. All the mice were fed a high-fat diet for 16 weeks and intragastrically administered with CDT or atorvastatin once a day according to their body weight. After 16 weeks, serum was collected, the aorta was isolated, and blood lipid levels were detected. An enzyme-linked immunosorbent assay was used to detect the serum levels of 4-hydroxynonenal (4-HNE), 8-hydroxy-2'-deoxyguanosine (8-OHdG), intercellular adhesion molecule 1 (ICAM-1), monocyte chemoattractant protein 1 (MCP-1), thromboxane B2 (TXB2), tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1). The thickness of the aortic wall was measured by ultrasonography. Atherosclerotic plaque and endothelial cell apoptosis in the aortic root were evaluated using oil red O staining and terminal dUTP nick-end labeling (TUNEL) assays, respectively.

Results: A comparison of mice in the CDT group and mice in the model group showed that CDT significantly inhibited mice's weight gain. CDT reduced the levels of the inflammatory factor ICAM-1 and the oxidative damage molecule 4-HNE. In the coagulation system, CDT significantly increased tPA levels and reduced TXB2 and PAI-1 levels. Ultrasonography showed that CDT increased the thickness of the aortic wall. The oil red O staining results revealed that CDT significantly ameliorated lipid accumulation in the aortic valve. TUNEL assays indicated that CDT reduced the number of TUNEL-positive cells in the aortic valve.

Conclusions: CDT has a certain protective effect on hyperlipidemia. The mechanism of CDT may be related to antioxidation, anti-inflammation, anticoagulation, and anti-apoptosis.
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http://dx.doi.org/10.21037/atm-20-7915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246178PMC
May 2021

Peroxiredomin-4 ameliorates lipotoxicity-induced oxidative stress and apoptosis in diabetic cardiomyopathy.

Biomed Pharmacother 2021 Jun 12;141:111780. Epub 2021 Jun 12.

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

Diabetic cardiomyopathy (DCM), one severe complication in the diabetes, leads to high mortality in the diabetic patients. However, the understanding of molecular mechanisms underlying DCM is far from completion. Herein, we investigated the disease-related differences in the proteomes of DCM based on db/db mice and verified the protective roles of peroxiredoxin-4 (Prdx4) in H9c2 cardiomyocytes treated by palmitic acid (PA). Fasting blood glucose (FBG) and cardiac function was detected in the 6-month-old control and diabetic mice. The hearts were then collected and analyzed by a coupled label-free and mass spectrometry approach. In vivo investigation indicated that body weight and FBG of db/db mice markedly increased, and diabetic heart exhibited obvious cardiac hypertrophy and lipid droplet accumulation, and cardiac dysfunction as is indicated by the increases of left ventricle posterior wall thickness in systole (LVPWd) and diastole (LVPWs), and reduction of fractional shortening (FS). We used proteomic analysis and then detected a grand total of 2636 proteins. 175 differentially expressed proteins (DEPs) were markedly detected in the diabetic heart. Thereinto, Prdx4 was markedly down-regulated in the diabetic heart. In vitro experiments revealed that 250 μM PA significantly inhibited viability of H9c2 cell. PA induced much accumulation of lipid droplet in cardiomyocytes and resulted in an increase of mRNA expressions of lipogenic genes (FASN and SCD1) and cardiac hypertrophic genes. Additionally, protein level of Prdx4 evidently reduced in the PA-treated H9c2 cell. It was further found that shRNA-mediated Prdx4 knockdown exacerbated PA-induced oxidative stress and cardiomyocyte apoptosis, whereas overexpressing Prdx4 in the H9c2 cells noteworthily limited PA-induced ROS generation and cardiomyocytes apoptosis. These data collectively reveal the essential role of abnormal Prdx4 in pathological alteration of DCM, and provide potentially therapeutic target for the prevention of DCM.
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http://dx.doi.org/10.1016/j.biopha.2021.111780DOI Listing
June 2021

Hydroxysafflor Yellow A Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Calcium Overload and Apoptosis.

Oxid Med Cell Longev 2021 21;2021:6643615. Epub 2021 May 21.

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

Myocardial ischemia/reperfusion injury (MI/RI) is an urgent problem with a great impact on health globally. However, its pathological mechanisms have not been fully elucidated. Hydroxysafflor yellow A (HSYA) has a protective effect against MI/RI. This study is aimed at further clarifying the relationship between HSYA cardioprotection and calcium overload as well as the underlying mechanisms. We verified the protective effect of HSYA on neonatal rat primary cardiomyocytes (NPCMs) and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from hypoxia-reoxygenation (HR) injury. To explore the cardioprotective mechanism of HSYA, we employed calcium fluorescence, TUNEL assay, JC-1 staining, and western blotting. Finally, cardio-ECR and patch-clamp experiments were used to explain the regulation of L-type calcium channels (LTCC) in cardioprotection mediated by HSYA. The results showed that HSYA reduced the levels of myocardial enzymes and protected NPCMs from HR injury. HSYA also restored the contractile function of hiPSC-CMs and field potential signal abnormalities caused by HR and exerted a protective effect on cardiac function. Further, we demonstrated that HSYA protects cardiomyocytes from HR injury by decreasing mitochondrial membrane potential and inhibiting apoptosis and calcium overload. Patch-clamp results revealed that MI/RI caused a sharp increase in calcium currents, which was inhibited by pretreatment with HSYA. Furthermore, we found that HSYA restored contraction amplitude, beat rate, and field potential duration of hiPSC-CMs, which were disrupted by the LTCC agonist Bay-K8644. Patch-clamp experiments also showed that HSYA inhibits Bay-K8644-induced calcium current, with an effect similar to that of the LTCC inhibitor nisoldipine. Therefore, our data suggest that HSYA targets LTCC to inhibit calcium overload and apoptosis of cardiomyocytes, thereby exerting a cardioprotective effect and reducing MI/RI injury.
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http://dx.doi.org/10.1155/2021/6643615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163549PMC
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

Corrigendum: Hydroxysafflor Yellow A Protects Against Myocardial Ischemia/Reperfusion Injury Suppressing NLRP3 Inflammasome and Activating Autophagy.

Front Pharmacol 2021 22;12:671318. Epub 2021 Apr 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.

[This corrects the article DOI: 10.3389/fphar.2020.01170.].
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http://dx.doi.org/10.3389/fphar.2021.671318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100669PMC
April 2021

Iminostilbene, a novel small-molecule modulator of PKM2, suppresses macrophage inflammation in myocardial ischemia-reperfusion injury.

J Adv Res 2021 03 9;29:83-94. Epub 2020 Sep 9.

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

Introduction: Inflammation is a key factor in myocardial ischemia/reperfusion (MI/R) injury. Targeting leucocyte-mediated inflammation is an important strategy for MI/R therapy. Iminostilbene (ISB), a simple dibenzoazepine small molecule compound, has a strong anti-neurodegenerative effect. However, no study has shown the cardioprotective effect of ISB.

Objectives: This study aimed to investigate the role of ISB against MI/R injury and identify its molecular target.

Methods: To verify the cardiac protection of ISB and , we performed rat MI/R surgery and subjected inflammatory modeling of macrophages. In terms of molecular mechanisms, we designed and synthesized a small molecular probe of ISB and employed it on the click chemistry-activity-based protein profiling technique to fish for ISB targets in macrophages. To identify the target, we applied the competitive inhibition assay, surface-plasmon resonance (SPR), cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay.

Results: , ISB showed robust anti-myocardial injury activity by improving cardiac function, reducing myocardial infarction, and inhibiting macrophage-mediated inflammation. , ISB strongly inhibited the transcription and the expression levels of inflammatory cytokines in macrophages. The pyruvate kinase isozyme type M2 (PKM2) was identified as the potential target of ISB through proteomic analysis and the competitive assay was performed for specific binding verification. Further thermodynamic and kinetic experiments showed that ISB was bound to PKM2 in a dose-dependent manner. Moreover, in terms of the biological function of ISB on PKM2, ISB reduced the expression of PKM2, thereby reducing the expression of HIF1α and the phosphorylation of STAT3.

Conclusion: This study for the first time demonstrated that ISB targeted PKM2 to reduce macrophage inflammation thereby significantly alleviating MI/R injury.
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http://dx.doi.org/10.1016/j.jare.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020153PMC
March 2021

Effect of Saponins and Major Anti-Obesity Components on Weight Loss.

Front Pharmacol 2020 25;11:601751. Epub 2021 Mar 25.

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

The prevalence of individuals who are overweight or obese is rising rapidly globally. Currently, majority of drugs used to treat obesity are ineffective or are accompanied by obvious side effects; hence, the options are very limited. Therefore, it is necessary to find more effective and safer anti-obesity drugs. It has been proven and that the active ingredient notoginsenosides isolated from traditional Chinese medicine (Burk.) F. H. Chen exhibits anti-obesity effects. Notoginsenosides can treat obesity by reducing lipid synthesis, inhibiting adipogenesis, promoting white adipose tissue browning, increasing energy consumption, and improving insulin sensitivity. Although notoginsenosides are potential drugs for the treatment of obesity, their effects and mechanisms have not been analyzed in depth. In this review, the anti-obesity potential and mechanism of action of notoginsenosides were analyzed; thus laying emphasis on the timely prevention and treatment of obesity.
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http://dx.doi.org/10.3389/fphar.2020.601751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027240PMC
March 2021

Classical Active Ingredients and Extracts of Chinese Herbal Medicines: Pharmacokinetics, Pharmacodynamics, and Molecular Mechanisms for Ischemic Stroke.

Oxid Med Cell Longev 2021 13;2021:8868941. Epub 2021 Mar 13.

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.

Stroke is a leading cause of death and disability worldwide, and approximately 87% of cases are attributed to ischemia. The main factors that cause ischemic stroke include excitotoxicity, energy metabolism disorder, Ca overload, oxidative damage, apoptosis, autophagy, and inflammation. However, no effective drug is currently available for the comprehensive treatment of ischemic stroke in clinical applications; thus, there is an urgent need to find and develop comprehensive and effective drugs to treat postischemic stroke. Traditional Chinese medicine (TCM) has unique advantages in treating ischemic stroke, with overall regulatory effects at multiple levels and on multiple targets. Many researchers have studied the effective components of TCMs and have achieved undeniable results. This paper reviews studies on the anticerebral ischemia effects of TCM monomers such as tetramethylpyrazine (TMP), dl-3-n-butylphthalide (NBP), ginsenoside Rg1 (Rg1), tanshinone IIA (TSA), gastrodin (Gas), and baicalin (BA) as well as effective extracts such as extract (EGB). Research on the anticerebral ischemia effects of TCMs has focused mostly on their antioxidative stress, antiapoptotic, anti-inflammatory, proangiogenic, and proneurogenic effects. However, the research on the use of TCM to treat ischemic stroke remains incompletely characterized. Thus, we summarized and considered this topic from the perspective of pharmacokinetics, pharmacological effects, and mechanistic research, and we have provided a reference basis for future research and development on anticerebral ischemia TCM drugs.
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http://dx.doi.org/10.1155/2021/8868941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984881PMC
May 2021

Metro and elderly health in Hong Kong: protocol for a natural experiment study in a high-density city.

BMJ Open 2021 03 17;11(3):e043983. Epub 2021 Mar 17.

Healthy High Density Cities Lab, Faculty of Architecture, The University of Hong Kong, Hong Kong, China.

Introduction: Public transport accessible to older people may offer a transformative solution to achieving healthy ageing. However, the evidence to support such transport infrastructure modifications is unclear. Previous studies on public transport use and elderly health were mostly observational studies using cross-sectional data. Few studies have examined the before-and-after effects of a new metro, for example, to see if it leads to improved elderly health.

Methods And Analysis: We use a new metro line in Hong Kong as a natural experiment to examine the impact of the metro-led public transport intervention on elderly health. In Hong Kong, more than 90% of daily travels are made by public transport. The public transport modifications consist of the new metro line with eight stations and changes in the walking environment and bus services around the stations. We will look at the before-and-after differences in public transport use and health outcomes between elderly participants living in treatment neighbourhoods (400 m walking buffered areas of the new metro stations) and in control groups (living in comparable areas but unaffected by the new metro). Questionnaire-based baseline data were collected in 2019 before the COVID-19 pandemic, while some qualitative interviews are ongoing. Amid the pandemic, we conducted a quick telephone-based survey of COVID-19's potential impact on public transport use behaviours of our elderly cohort in September 2020. Note there is no lockdown in Hong Kong until the writing of the paper (January 2021). After the new metro opens, we will conduct a follow-up survey, tentatively in late 2022. We aim to investigate if the new metro and the associated changes in the built environment have any effects on public transport use behaviours, physical activity and wider health outcomes among the elderly (eg, social inclusion, quality of life, subjective well-being).

Ethics And Dissemination: The Human Research Ethics Committee of the University of Hong Kong reviewed and approved the study procedures and materials (reference number: EA1710040). Results will be communicated through scientific papers and research reports.
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http://dx.doi.org/10.1136/bmjopen-2020-043983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978095PMC
March 2021

Ursodesoxycholic acid alleviates liver fibrosis via proregeneration by activation of the ID1-WNT2/HGF signaling pathway.

Clin Transl Med 2021 02;11(2):e296

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, P. R. China.

Background: The human liver possesses a remarkable capacity for self-repair. However, liver fibrosis remains a serious medical concern, potentially progressing to end-stage liver cirrhosis and even death. Liver fibrosis is characterized by excess accumulation of extracellular matrix in response to chronic injury. Liver regenerative ability, a strong indicator of liver health, is important in resisting fibrosis. In this study, we provide evidence that ursodesoxycholic acid (UDCA) can alleviate liver fibrosis by promoting liver regeneration via activation of the ID1-WNT2/hepatocyte growth factor (HGF) pathway.

Methods: Bile duct ligation (BDL) and partial hepatectomy (PH) mouse models were used to verify the effects of UDCA on liver fibrosis, regeneration, and the ID1-WNT2/HGF pathway. An Id1 knockdown mouse model was also used to assess the role of Id1 in UDCA alleviation of liver fibrosis.

Results: Our results demonstrate that UDCA can alleviate liver fibrosis in the BDL mice and promote liver regeneration via the ID1-WNT2/HGF pathway in PH mice. In addition, Id1 knockdown abolished the protection afforded by UDCA in BDL mice.

Conclusions: We conclude that UDCA protects against liver fibrosis by proregeneration via activation of the ID1-WNT2/HGF pathway.
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http://dx.doi.org/10.1002/ctm2.296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828260PMC
February 2021

Saponins in Chinese Herbal Medicine Exerts Protection in Myocardial Ischemia-Reperfusion Injury: Possible Mechanism and Target Analysis.

Front Pharmacol 2020 14;11:570867. Epub 2021 Jan 14.

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

Myocardial ischemia is a high-risk disease among middle-aged and senior individuals. After thrombolytic therapy, heart tissue can potentially suffer further damage, which is called myocardial ischemia-reperfusion injury (MIRI). At present, the treatment methods and drugs for MIRI are scarce and cannot meet the current clinical needs. The mechanism of MIRI involves the interaction of multiple factors, and the current research hotspots mainly include oxidative stress, inflammation, calcium overload, energy metabolism disorders, pyroptosis, and ferroptosis. Traditional Chinese medicine (TCM) has multiple targets and few toxic side effects; clinical preparations containing C. A. Mey., (Burk.) F. H. Chen, L., cardioprotection, and other Chinese herbal medicines have been used to treat patients with coronary heart disease, angina pectoris, and other cardiovascular diseases. Studies have shown that saponins are the main active substances in TCMs containing C. A. Mey., (Burk.) F. H. Chen, L., and . In the present review, we sorted the saponin components with anti-MIRI effects and their regulatory mechanisms. Each saponin can play a cardioprotective role via multiple mechanisms, and the signaling pathways involved in different saponins are not the same. We found that more active saponins in C. A. Mey. are mainly dammar-type structures and have a strong regulatory effect on energy metabolism. The highly active saponin components of L. are oleanolic acid structures, which have significant regulatory effects on calcium homeostasis. Therefore, saponins in Chinese herbal medicine provide a broad application prospect for the development of highly effective and low-toxicity anti-MIRI drugs.
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http://dx.doi.org/10.3389/fphar.2020.570867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883640PMC
January 2021

Scutellarin protects against diabetic cardiomyopathy via inhibiting oxidative stress and inflammatory response in mice.

Ann Palliat Med 2021 Mar 2;10(3):2481-2493. Epub 2021 Feb 2.

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

Background: Scutellarin (Scu) shows both anti-inflammatory and antioxidant activities. The study investigates cardioprotective effects of Scu in mice with type 1 diabetes and the underlying molecular mechanism.

Methods: Streptozotocin (STZ) was used to induce diabetic cardiomyopathy (DCM) in C57BL/6 mice by intraperitoneal injection (i.p.). Normal and diabetic mice were divided into 6 groups: control, diabetic model group (DM), DM + Scu (5 mg/kg), DM + Scu (10 mg/kg), DM + Scu (20 mg/kg), DM + pioglitazone (Pio) (10 mg/kg). Scu was administered to the mice intraperitoneally and Pio was administrated by oral. Mice in control and DM groups were simply treated normal saline. Four weeks later, myocardial function, myocardial fibrosis, the levels inflammatory factors and oxidative stress were detected.

Results: Scu improved cardiac function and reduced heart injury in diabetic mice, which was indicated by increasing Left ventricular (LV) end-diastolic volume (LVVd), fractional shortening (FS), and ejection fraction (EF) levels and decreased pathological changes of heart. Scu inhibited the level of myocardial fibrosis by reducing the release of inflammatory cytokines and increasing activities of antioxidant enzymes. Further study showed that Scu inhibited the activation of nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) and nuclear factor-kappa B (NF-κB) and activated phospho-protein kinase B (p-AKT), nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase (HO-1).

Conclusions: Scu protects against DCM in STZ-induced diabetic mice by inhibiting oxidative stress and inflammatory responses and might be a potential therapeutic agent to treat DCM.
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http://dx.doi.org/10.21037/apm-19-516DOI Listing
March 2021

Ginsenoside Rb1 ameliorates cardiotoxicity triggered by aconitine via inhibiting calcium overload and pyroptosis.

Phytomedicine 2021 Mar 17;83:153468. Epub 2021 Jan 17.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; 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 & Chinese Academy of Medical Sciences, Beijing 100193, China; Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences, Beijing 100193, China. Electronic address:

Background: Aconitine-induced cardiotoxicity limits the clinical treatment of cardiotonic, cancers and immune-related diseases. Ginsenoside Rb1 (Rb1) is an active ingredient of traditional Chinese medicine with cardioprotective effect.

Purpose: This study aims to study the mechanism of aconitine cardiotoxicity and the detoxification mechanism of Rb1.

Study Design: METHODS: The regulatory effect of Rb1 on aconitine was evaluated in vitro and in vivo by myocardial enzyme indicators, pathological analysis, CardioECR detection, calcium transient analysis, western blotting and immunohistochemistry.

Results: Rb1 (10, 20, 40 mg/kg) alleviated apoptotic myocardial damage caused by aconitine in rats. Furthermore, Rb1 (25, 50, 100 μM) restored the contractile function and field potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) by regulating calcium channels and reduced myocardial cell damage by inhibiting the calcium transients of adult rat ventricular myocytes (ARVMs). Rb1 significantly reduced calcium levels in hiPSC-CMs, directly indicating that aconitine-induced calcium overload was alleviated by Rb1. Further, aconitine caused calcium overload by changing the expression of calcium pathway proteins, while Rb1 effectively restored calcium homeostasis. In addition, Rb1 also had a cardioprotective role by inhibiting cell pyroptosis. These results suggested that the maintenance of calcium homeostasis helped to suppress the inflammatory response related to pyroptosis of the heart.

Conclusion: Aconitine-induced cardiotoxicity can be alleviated by Rb1 via restoring calcium homeostasis and inhibiting apoptosis and pyroptosis.
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http://dx.doi.org/10.1016/j.phymed.2021.153468DOI Listing
March 2021

Gypenoside XVII alleviates early diabetic retinopathy by regulating Müller cell apoptosis and autophagy in db/db mice.

Eur J Pharmacol 2021 Mar 22;895:173893. Epub 2021 Jan 22.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China; Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China. Electronic address:

Diabetic retinopathy (DR) is a widespread vision-threatening disease in working people. Müller cells are important glial cells that participate in the blood retinal barrier and promote the maintenance of retinal physiological and structural homeostasis. Müller cell apoptosis and autophagy play an important role in the pathogenesis of DR. Gypenoside XVII (Gyp-17) exerts strong antiapoptotic and autophagic activities. However, the effect of Gyp-17 on DR and its mechanism of action have not been elucidated. This study explored the effect of Gyp-17 on early DR and Müller cell injury in db/db mice. Blood glucose and blood lipids were measured. Optical coherence tomography and fundus fluorescein angiography were applied to detect retinal thickness and vascular leakage, respectively. Hematoxylin eosin staining assessed the pathological changes of the retina. Retinal oxidative environment and cell apoptosis and autophagy were monitored using commercial kits, immunofluorescence, and Western blot assays. Results showed that Gyp-17 exerted no significant effect on blood glucose and lipid levels but maintained normal retinal permeability, physiological structure, high anti-oxidative enzyme expression, and the thickness of the inner nuclear layer compared with the model group. Moreover, Western blot analysis and TUNEL assay indicated that Gyp-17 significantly decreased pro-apoptotic-related protein expression and increased pro-autophagy-related protein expression compared with the model group. Immunofluorescence colocalization exhibited that the regulating action of Gyp-17 may focus on Müller cells. These data strongly demonstrate that Gyp-17 prevents early DR by decreasing apoptosis and increasing autophagy in Müller cells. Gyp-17 may be a candidate drug for early DR therapy.
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http://dx.doi.org/10.1016/j.ejphar.2021.173893DOI Listing
March 2021

Targeting Orphan Nuclear Receptors NR4As for Energy Homeostasis and Diabetes.

Front Pharmacol 2020 27;11:587457. Epub 2020 Nov 27.

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.

Orphan nuclear receptors are important members of the nuclear receptor family and may regulate cell proliferation, metabolism, differentiation, and apoptosis. NR4As, a subfamily of orphan nuclear receptors, have been reported to play key roles in carbohydrate and lipid metabolism and energy homeostasis. Popularity of obesity has resulted in a series of metabolic diseases such as diabetes and its complications. While imbalance of energy intake and expenditure is the main cause of obesity, the concrete mechanism of obesity has not been fully understood. It has been reported that NR4As have significant regulatory effects on energy homeostasis and diabetes and are expected to become new targets for discovering drugs for metabolic syndrome. A number of studies have demonstrated that abnormalities in metabolism induced by altered levels of NR4As may contribute to numerous diseases, such as chronic inflammation, tumorigenesis, diabetes and its complications, atherosclerosis, and other cardiovascular diseases. However, systematic reviews focusing on the roles of NR4As in mediating energy homeostasis and diabetes remain limited. Therefore, this article reviews the structure and regulation of NR4As and their critical function in energy homeostasis and diabetes, as well as small molecules that may regulate NR4As. Our work is aimed at providing valuable support for the research and development of drugs targeting NR4As for the treatment of obesity and related metabolic diseases.
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http://dx.doi.org/10.3389/fphar.2020.587457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728612PMC
November 2020

Mechanism overview and target mining of atherosclerosis: Endothelial cell injury in atherosclerosis is regulated by glycolysis (Review).

Int J Mol Med 2021 01 24;47(1):65-76. Epub 2020 Nov 24.

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

Atherosclerosis (AS) is a chronic disease with a complex pathology that may lead to several cardiovascular and cerebrovascular diseases; however, further research is necessary to fully elucidate its pathogenesis. The main risk factors for AS include lipid metabolism disorders, endothelial cell injury, inflammation and immune dysfunction, among which vascular endothelial cell damage is considered as the main trigger for AS occurrence and development. Endothelial cell damage leads to enhanced intimal permeability and leukocyte adhesion, promoting thrombus formation and accelerating disease progression. The function of endothelial cells is affected by glycolysis regulation, since 80% of ATP in these cells is produced via this pathway. Genes associated with AS and endothelial cell glycolysis, including AKT1, interleukin‑6, vascular endothelial growth factor A, TP53, signal transducer and activator of transcription 3, SRC and mitogen‑activated protein kinase 1, were screened. Through integrated analysis, these genes were found to play a key role in AS by regulating multiple signaling pathways associated with cell signal transduction, energy metabolism, immune function and thrombosis. In conclusion, endothelial cell injury in AS may be alleviated by glycolysis and is a potential clinical treatment strategy for AS.
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http://dx.doi.org/10.3892/ijmm.2020.4798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723681PMC
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

Ginsenoside Compound K Attenuates Ox-LDL-Mediated Macrophage Inflammation and Foam Cell Formation Autophagy Induction and Modulating NF-κB, p38, and JNK MAPK Signaling.

Front Pharmacol 2020 15;11:567238. Epub 2020 Sep 15.

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

Atherosclerosis is a major reason for the high morbidity and mortality of cardiovascular diseases. Macrophage inflammation and foam cell formation are the key pathological processes of atherosclerosis. Ginsenoside compound K (CK) is a metabolite derived from ginseng. CK has anti atherosclerotic effect, but the molecular mechanism remains to be elucidated. We aim to explore the protective effect of CK against ox-LDL-induced inflammatory responses and foam cells formation and explore its potential mechanisms. Through the results of oil red O staining, Western blot, and qPCR, we found that CK significantly inhibited the foam cell formation, reduced the expression of SR-A1 and increased ABCA1 and ABCG1 expression. In addition, CK increased the number of autophagosomes and upregulated the LC3II/LC3I ratio and the expressions of ATG5 and Beclin-1 but decreased p62 expression. Moreover, CK significantly inhibited the NF-κB, p38, and JNK MAPK signaling pathway. Altogether, CK attenuated macrophage inflammation and foam cell formation autophagy induction and by modulating NF-κB, p38, and JNK MAPK signaling. Thus, CK has potential as a therapeutic drug for atherosclerosis.
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http://dx.doi.org/10.3389/fphar.2020.567238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522510PMC
September 2020

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

Hydroxysafflor Yellow A Protects Against Myocardial Ischemia/Reperfusion Injury Suppressing NLRP3 Inflammasome and Activating Autophagy.

Front Pharmacol 2020 30;11:1170. Epub 2020 Jul 30.

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.

Myocardial ischemia/reperfusion (MI/R) injury is a serious threat to human health. Hydroxysafflor yellow A (HSYA), the main water-soluble ingredient extracted from Carthami flos ( L.), has therapeutic potential for treating MI/R injury. However, the mechanisms of HSYA-mediated protection from MI/R injury are incompletely understood. In the present study, we investigated the effects and the underlying mechanisms of HSYA during MI/R. Adult Sprague-Dawley rats were subjected to left anterior descending artery ligation for 30 min followed by 24 h of reperfusion with or without HSYA treatment. The protective effect of HSYA was detected by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin eosin (HE) staining, and myocardial enzymes detections. Serum levels of inflammatory factors such as TNF-α, interleukin (IL)-1β, and IL-18, were detected using ELISA kits. The expression of NLRP3 and other related proteins in the myocardium was detected by western blot and immunohistochemistry. The expression of autophagy-related proteins, including Atg5, BECN1, P62, and LC3B, was detected by western blot to evaluate the effect of HSYA on autophagy. Results showed that HSYA decreased the myocardial infarct size and attenuated the cardiac dysfunction in rats after I/R. In addition, HSYA inhibited myocardial apoptosis compared with the I/R group, decreased the levels of inflammatory cytokines in rat serum, reduced NLRP3 inflammasome expression, and induced autophagy. Mechanistically, our results demonstrated that HSYA can activate AMPK to improve autophagy and inhibit NLRP3 inflammasome by inhibiting the mTOR pathway. This work provides strong data supporting for the clinical applications of HSYA in MI/R injury.
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http://dx.doi.org/10.3389/fphar.2020.01170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406911PMC
July 2020

Bavachinin inhibits cholesterol synthesis enzyme FDFT1 expression via AKT/mTOR/SREBP-2 pathway.

Int Immunopharmacol 2020 Nov 20;88:106865. Epub 2020 Aug 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, PR China; Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, PR China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China; Key Laboratory of Efficacy Evaluation of Chinese Medicine Against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, PR China. Electronic address:

Non-alcoholic fatty liver disease (NAFLD) is a progressive and chronic liver disease. No effective drug is currently approved for the treatment of NAFLD. Traditionally it is thought that pathogenesis of NAFLD develops from some imbalance in lipid control, thereby leading to hepatotoxicity and disease development. Squalene synthase (SQS), encoded by FDFT1, is a key regulator in cholesterol synthesis and thus a potential target for the treatment of NAFLD. Here we could identify bavachinin, a component from traditional Chinese medicine Fructus Psoraleae (FP), which apparently protects HepaRG cells from palmitic acid induced death, suppressing lipid accumulation and cholesterol synthesis through inhibition of FDFT1 through the AKT/mTOR/SREBP-2 pathway. Over-expression of FDFT1 abolished bavachinin (BVC) -induced inhibition of cholesterol synthesis. The data presented here suggest that bavachinin acts as a cholesterol synthesis enzyme inhibitor, and might serve as a drug for treating NAFLD in the future.
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http://dx.doi.org/10.1016/j.intimp.2020.106865DOI Listing
November 2020

Water Extract Ameliorates Hypothalamic-Pituitary-Adrenal Axis Hyperactivity and Inflammation Induced by Chronic Unpredictable Mild Stress in Rats.

Biomed Res Int 2020 10;2020:8374614. Epub 2020 Jun 10.

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

is a highly valuable traditional herbal medicine commonly used to treat neurological disorders. The present study is designed to determine the antidepressant-like effect of the water extract (GRWE) on a depression model and the potential mechanisms. The chronic unpredictable mild stress (CUMS) rat model was used to induce depression. The sucrose preference test, open field test, forced swimming test, and tail suspension test were performed to assess the depressive-like behaviors, respectively. Hypothalamic-pituitary-adrenal (HPA) function was measured via plasma corticosterone (CORT), adrenocorticotrophic hormone (ACTH), hypothalamic corticotropin-releasing factor (CRF), and glucocorticoid receptor (GR) concentrations. Plasma concentrations of proinflammatory cytokines including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-) were also evaluated. The results showed that GRWE significantly attenuates the behavioral abnormalities in CUMS rats, as shown by elevated sucrose consumption, raised locomotor activity, and reduced immobility duration. Moreover, GRWE treatment reduced CORT, ACTH, CRF, and GR levels and decreased the plasma IL-1, IL-6, and TNF- concentrations. These findings indicate that GRWE improves depressive behaviors in a chronic stress model of rats; its effect may be ascribed to the modulation of the HPA axis activity and inflammatory response.
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http://dx.doi.org/10.1155/2020/8374614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305529PMC
March 2021

Targeting Calcium Homeostasis in Myocardial Ischemia/Reperfusion Injury: An Overview of Regulatory Mechanisms and Therapeutic Reagents.

Front Pharmacol 2020 9;11:872. Epub 2020 Jun 9.

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

Calcium homeostasis plays an essential role in maintaining excitation-contraction coupling (ECC) in cardiomyocytes, including calcium release, recapture, and storage. Disruption of calcium homeostasis may affect heart function, leading to the development of various heart diseases. Myocardial ischemia/reperfusion (MI/R) injury may occur after revascularization, which is a treatment used in coronary heart disease. MI/R injury is a complex pathological process, and the main cause of increased mortality and disability after treatment of coronary heart disease. However, current methods and drugs for treating MI/R injury are very scarce, not ideal, and have limitations. Studies have shown that MI/R injury can cause calcium overload that can further aggravate MI/R injury. Therefore, we reviewed the effects of critical calcium pathway regulators on MI/R injury and drew an intuitive diagram of the calcium homeostasis pathway. We also summarized and analyzed calcium pathway-related or MI/R drugs under research or marketing by searching Therapeutic Target and PubMed Databases. The data analysis showed that six drugs and corresponding targets are used to treat MI/R injury and involved in calcium signaling pathways. We emphasize the relevance of further detailed investigation of MI/R injury and calcium homeostasis and the therapeutic role of calcium homeostasis in MI/R injury, which bridges basic research and clinical applications of MI/R injury.
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http://dx.doi.org/10.3389/fphar.2020.00872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296066PMC
June 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

Protective Effects of Biscoclaurine Alkaloids on Leukopenia Induced by Co- Radiation.

Evid Based Complement Alternat Med 2020 18;2020:2162915. Epub 2020 May 18.

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, 100193 Beijing, China.

Objective: Leukopenia, a common complication of tumor chemoradiotherapy, contributes serious damage to the hematopoietic, gastrointestinal, and immune systems of the body and can cause delay, discontinuation, or even failure to tumor treatment, thereby greatly threatening human health. The present study aims to investigate the protective effects of biscoclaurine alkaloids (BA) on leukopenia.

Methods: This study was conducted on 60 Kunming mice, which were randomly divided into six groups containing 10 animals each. A hematology analyzer was used to count white blood cells (WBC) in the peripheral blood cell. Mice serum was collected, and the granulocyte-macrophage colony-stimulating factor, vascular cell adhesion molecule 1 (VCAM-1), and interferon- (IFN-) were detected by enzyme-linked immunosorbent assays. Pathological changes were detected through hematoxylin and eosin staining in the liver and spleen of mice. The spleen and liver ultrastructures were observed via electron microscopy.

Results: Results showed that BA ameliorated WBC, PLT reduction in the peripheral blood and significantly increased the levels of IFN- and VCAM-1 in mice serum. BA reduced ionizing radiation-induced injuries to spleen, mitigated the reduction of superoxide dismutase (SOD), and significantly decreased the malonaldehyde (MDA) and xanthine oxidase (XOD) levels in the liver.

Conclusion: BA enhanced the immune and hematopoietic functions and ameliorated the oxidative stress induced by Co- radiation, revealing its therapeutic potential both as a radioprotector and as a radiation mitigator for leukopenia induced by Co- radiation.
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http://dx.doi.org/10.1155/2020/2162915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251465PMC
May 2020

Development of a prognostic index of colon adenocarcinoma based on immunogenomic landscape analysis.

Ann Transl Med 2020 Mar;8(6):284

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

Background: Colon adenocarcinoma (COAD) is one of the most commonly diagnosed cancers, and it is closely related to the immune microenvironment. Considering that immunotherapy is not effective for all COAD patients, it is necessary to identify the effective population before administering treatment. In this study, we established an independent prognostic index based on immune-related genes (IRGs), in order to evaluate the clinical outcome of COAD.

Methods: The gene expression profiles and IRGs taken from The Cancer Genome Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort), respectively, were integrated in order to identify the differentially expressed IRGs. Functional enrichment analysis was conducted and the prognostic value of survival-related IRGs was determined. Based on Cox regression analysis, the IRG-based prognostic index (IRGPI) was established, and the model was evaluated and applied.

Results: A total of 51 differentially expressed survival-related IRGs were identified. The most significant signaling pathway was "cytokine-cytokine receptor interaction". The index established herein was based on 12 survival-related IRGs, and it was highly accurate in monitoring prognosis. Moreover, the IRGPI was significantly correlated with multiple clinicopathologic factors, as well as with the infiltration of immune cells.

Conclusions: An independent IRGPI was established in order to assess the immune status and tumor prognosis in COAD patients. This index can serve as a robust biomarker in clinical prognosis applications, including cancer immunotherapy.
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http://dx.doi.org/10.21037/atm.2020.03.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186653PMC
March 2020

Ginsenoside Rg1 prevents early diabetic retinopathy reducing retinal ganglion cell layer and inner nuclear layer cell apoptosis in db/db mice.

Ann Transl Med 2020 Mar;8(5):232

College of Pharmacy, Harbin University of Commerce, Harbin 150076, China.

Background: Diabetic retinopathy (DR), a diabetic vascular complication, is prone to developing into blindness. Ginsenoside Rg1 (GRg1), a major saponin in ginseng, exerts high anti-apoptotic activity.

Methods: This study aimed to explore the protective effects of GRg1 against diabetes-induced retinal damage. Measurements of blood glucose, blood lipids and vascular permeability were performed, as well as assessments of pathological changes, and the retinal thickness of each layer. Retinal cell apoptosis related protein expression levels were measured by immunofluorescence and western blot assays.

Results: Our data demonstrated that GRg1 effectively reduced blood glucose and triglyceride levels and maintained normal retinal permeability and physiological structure. GRg1 maintained the thickness of the ganglion cell layer (GCL) and the inner nuclear layer (INL) by reducing cell apoptosis.

Conclusions: These data strongly indicate that GRg1 prevents diabetic retinal changes by decreasing GCL and INL cell apoptosis. GRg1 may be a promising drug for early DR treatment.
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http://dx.doi.org/10.21037/atm.2019.12.155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154486PMC
March 2020

New metro system and active travel: A natural experiment.

Environ Int 2020 05 7;138:105605. Epub 2020 Mar 7.

Key Lab of Poyang Lake Wetland and Watershed Research of Ministry of Education and School of Geography and Environment, Jiangxi Normal University, China.

Background: We used the first metro system in a developing city as a natural experiment to investigate the causal inference in the new metro's impact on modal shift and active travel.

Material And Methods: The treatment group was formed by residents from neighbourhoods located within the 800-m walking distance to new metro stations. The first control group was formed by residents lived 1.6 km away from and outside of walking distance to the nearest station, and the second was 5 km away and outside of cycling distance. The groups were determined by local transit-oriented planning practice and empirical studies on active travel. Of the 5627 participants who had finished a baseline travel behaviour survey before new metro launched, 1770 returned and completed the follow-up survey a year after the metro's operation, which consists of 833 cohort participants in the treatment group and 937 in the two types of control groups. We used a difference-in-difference method to make before and after comparisons of travel behaviour changes between treatment and control groups.

Results: Our longitudinal data analyses revealed diverse travel behaviour changes. In general, people who used to take bus have adopted metro. The average metro usage was 30.9 (28.8-33.3) minutes daily for work trips and 16.6 (14.9-18.7) minutes daily for non-work trips. Walking time decreased 19.7 minutes at most (p < 0.001), and cycling decreased 22.1 minutes daily (p < 0.001). Car and e-bike usages remained largely unchanged before and after new metro, without difference between treatment and control groups.

Conclusion: The natural experiment study provided the first empirical evidence in a developing city context on causal inference in new metro's impact on active travel. A new metro does not necessarily promote active travel increase or car use reduction, calling for caution in making general assumptions about the effects of urban rail transit investments. We suggest local urban and transport planning knowledge could be useful in designing and explaining the complex natural experiments in transport and health.
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http://dx.doi.org/10.1016/j.envint.2020.105605DOI Listing
May 2020

Atorvastatin promotes AMPK signaling to protect against high fat diet-induced non-alcoholic fatty liver in golden hamsters.

Exp Ther Med 2020 Mar 22;19(3):2133-2142. Epub 2020 Jan 22.

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

Non-alcoholic fatty liver disease (NAFLD) is characterized by diffuse fatty acid degeneration and excess fat accumulation in the liver. Notably, the currently available medications used to treat NAFLD remain limited. The aim of the present study was to investigate the protective role of atorvastatin (Ato) against NAFLD in golden hamsters fed a high fat diet (HFD) and in HepG2 cells treated with palmitate, and identify the underlying molecular mechanism. Ato (3 mg/kg) was administered orally every day for 8 weeks to the hamsters during HFD administration. Hamsters in the model group developed hepatic steatosis with high serum levels of triglyceride, cholesterol, insulin and C-reactive protein, which were effectively reduced by treatment with Ato. Additionally, the relative liver weight of hamsters treated with Ato was markedly lower compared with that of the model group. Hematoxylin and eosin, and oil red O staining indicated that the livers of the animals in the model group exhibited large and numerous lipid droplets, which were markedly decreased after Ato treatment. Western blot analysis indicated that Ato inhibited fat accumulation in the liver through the AMP-activated protein kinase (AMPK)-dependent activation of peroxisome proliferator activated receptor α (PPARα), peroxisome proliferator-activated receptor-γ coactivator 1 α and their target genes. Furthermore, , Ato inhibited PA-induced lipid accumulation in HepG2 cells. This inhibitory effect was attenuated following Compound C treatment, indicating that AMPK may be a potential target of Ato. In conclusion, the increase in AMPK-mediated PPARα and its target genes may represent a novel molecular mechanism by which Ato prevents NAFLD.
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http://dx.doi.org/10.3892/etm.2020.8465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027324PMC
March 2020