Publications by authors named "Jialin Duan"

42 Publications

and the Volatile of Attenuate Chronic Myocardial Ischemia Injury in a Pig Model: A Metabonomic Approach for the Mechanism Study.

Oxid Med Cell Longev 2021 28;2021:8840896. Epub 2021 Apr 28.

National Drug Clinical Trial Institute, The Second Affiliated Hospital, Shaanxi University of Chinese Medicine, Xianyang 712000, China.

(SM) coupled with (DO) has been used to relieve cardiovascular diseases in China for many years. Our previous studies have integrated that SM-the volatile oil of DO (SM-DOO)-has a cardioprotective effect on chronic myocardial ischemia based on a pharmacological method, but the cardioprotective mechanism has not been elucidated completely in the metabonomic method. In the present study, a metabonomic method based on high-performance liquid chromatography time-of-flight mass spectrometry (HPLC-Q-TOF-MS) was performed to evaluate the effects of SM-DOO on chronic myocardial ischemia induced by an ameroid constrictor, which was placed on the left anterior descending coronary artery (LAD) of pigs. Pigs were divided into three groups: sham, model, and SM-DOO group. With multivariate analysis, a clear cluster among the different groups was obtained and the potential biomarkers were recognized. These biomarkers were mainly related to energy metabolism, glucose metabolism, and fatty acid metabolism. Furthermore, the protein expressions of phosphorylated AMP-activated protein kinase (p-AMPK) and glucose transporter-4 (GLUT4) were significantly upregulated by SM-DOO. The result indicated that SM-DOO could regulate the above biomarkers and metabolic pathways, especially energy metabolism and glucose metabolism. By analyzing and verifying the biomarkers and metabolic pathways, further understanding of the cardioprotective effect of SM-DOO with its mechanism was evaluated. Metabonomic is a reliable system biology approach for understanding the cardioprotective effects of SM-DOO on chronic myocardial ischemia and elucidating the mechanism underlying this protective effect.
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http://dx.doi.org/10.1155/2021/8840896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099511PMC
April 2021

A Network Pharmacology Approach to Predict the Proangiogenesis Mechanism of Huangqi-Honghua Herb Pair after Cerebral Ischemia.

Evid Based Complement Alternat Med 2021 14;2021:9834856. Epub 2021 Apr 14.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

Objective: Huangqi-Honghua herb pair is known for its medicinal value to treat Qi deficiency and blood stasis syndrome with a long history in clinical practice. To understand its possible mechanism in a systematic study, a network pharmacological method was addressed.

Methods: Detailed information on the HH compounds was obtained from two public databases, and oral bioavailability (OB) and drug-like (DL) of the compounds were evaluated. A correlation between HH compounds, its potential targets, and known targets was extrapolated, and the herb-compound-target-disease (H-C-T-D) network was established. Next, the pathway enrichment and essential genes were analyzed. Then, three key genes (VEGFA, VEGFR2, and eNOS), highly associated with angiogenesis, were screened and verified through western blot assay.

Results: Out of 276 compounds, 21 HH compounds and 78 target genes regulating the major pathways associated with CI in the network are analyzed. The bioactive compounds in HH were active in various signal transduction pathways such as the toll-like receptor signaling pathway, VEGF signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway are important pathways that may regulate anti-inflammatory, antiapoptotic, immune correlation, and antioxidative effects. The core genes are PTGS2, TNF, NOS2, IL6, BCL2, IL1B, SOD2, NOS3, SOD1, MMP9, and VEGFA. The in vitro results suggested that HH treatment could significantly elevate the expression of proangiogenic genes such as VEGFA, VEGFR2, and eNOS compared with OGD groups.

Conclusions: Our results predict that HH may regulate the expression of VEGFA, VEGFR2, and eNOS via the VEGF and HIF-1 signaling pathway to promote angiogenesis and alleviate cerebral ischemia injury.
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http://dx.doi.org/10.1155/2021/9834856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064780PMC
April 2021

Effects of Shuanghuanglian oral liquids on patients with COVID-19: a randomized, open-label, parallel-controlled, multicenter clinical trial.

Front Med 2021 Apr 28. Epub 2021 Apr 28.

Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
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http://dx.doi.org/10.1007/s11684-021-0853-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079840PMC
April 2021

High expression of ISG20 predicts a poor prognosis in acute myeloid leukemia.

Cancer Biomark 2021 ;31(3):255-261

Background: Acute myeloid leukemia (AML) is one of the most malignant hematopoietic system diseases. Interferon stimulated exonuclease gene 20 (ISG20) is a protein induced by interferons or double-stranded RNA, which is associated with poor prognosis in several malignant tumors. However its expression in AML is unknown.

Objective: To explore the expression of ISG20 in AML and its prognostic significance.

Methods: The expression of ISG20 in AML patients was analyzed by GEPIA database, detected by qRT-PCR and their prognosis was followed-up. Chi-square test was used to identify the association between ISG20 expression and clinical characteristics of the patients. Kaplan-Meier analysis was performed to draw survival curves and Cox regression analysis to confirm the independent prognostic factors of AML patients.

Results: Kaplan-Meier analysis revealed that whether to receive treatment, karyotype, and ISG20 expression were related to overall survival time of AML patients (P< 0.05). Cox regression analysis showed that whether to receive treatment (HR = 0.248, 95% CI = 0.076-0.808, P= 0.021) and high expression of ISG20 (HR = 4.266, 95% CI = 1.118-16.285, P= 0.034) were independent unfavorable prognostic factors for AML patients.

Conclusion: The high expression of ISG20 acts as a poor prognosis indicator in AML patients.
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http://dx.doi.org/10.3233/CBM-210061DOI Listing
January 2021

IRS-2/Akt/GSK-3/Nrf2 Pathway Contributes to the Protective Effects of Chikusetsu Saponin IVa against Lipotoxicity.

Oxid Med Cell Longev 2021 3;2021:8832318. Epub 2021 Apr 3.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an Shaanxi 710032, China.

Chronic hyperlipidemia leads to pancreatic -cell apoptosis and dysfunction through inducing oxidative stress. Chikusetsu saponin IVa (CHS) showed antioxidant and antidiabetic properties in our previous studies; however, its protective effects against lipotoxicity-induced -cell oxidative stress and dysfunction are not clear. This study was designed to investigate the effects of CHS against lipotoxicity-induced -cell injuries and its possible mechanism involved. High-fat (HF) diet and a low dose of streptozotocin- (STZ-) induced type 2 diabetes mellitus (T2DM) model and TC3 cells subjected to 0.5 mM palmitate (PA) to imitate the lipotoxic model were performed. Pancreatic functions, ROS, and antioxidant protein measurements were performed to evaluate the effects of CHS on cell injuries. Protein expression levels were measured by Western blotting. Furthermore, siRNA-targeted Nrf2, PI3K/Akt inhibitor (LY294002), or GSK-3 inhibitor (LiCl) was used to investigate the crosstalk relationships between proteins. As the results showed, CHS treatment inhibited apoptosis, promoted insulin release, and reduced oxidative stress. CHS treatment significantly increased the expression of Nrf2 in the cytoplasm and nuclear protein. The antioxidative and benefit effects of CHS were inhibited by siNrf2. The phosphorylation of IRS-2, PI3K, Akt, and GSK-3 was markedly increased by CHS which were inhibited by PA. In addition, inhibition of PI3K/Akt or GSK-3 with specific inhibitors dramatically abrogated the protective effects of CHS, revealing that the IRS-2/Akt/GSK-3 signaling axis was involved in the protective effects of CHS. These results demonstrate that CHS protected TC3 cells against PA-induced oxidative stress and cell dysfunction through Nrf2 by the IRS-2/Akt/GSK-3-mediated pathway.
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http://dx.doi.org/10.1155/2021/8832318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041533PMC
May 2021

A splicing LMNA mutation causing laminopathies accompanied by aortic valve malformation.

J Clin Lab Anal 2021 Apr 24;35(4):e23736. Epub 2021 Feb 24.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Laminopathies caused by LMNA gene mutations are characterized by different clinical manifestations. Among them, cardiac involvement is one of the most severe phenotypes.

Case Presentation: A 30-year-old man visited the hospital because of palpitations, shortness of breath, and fatigue. He also had muscular dystrophy, joint contractures, scoliosis, and mild dysphagia. A novel de novo heterozygous LMNA splice variant (c.810+1G>T) with dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy, and progressive cardiac conduction defect was identified by genetic analysis. The patient also presented with congenital aortic valve malformation, which has never been reported in laminopathies.

Conclusions: The LMNA mutation (c.810+1G>T) was identified for the first time, enriching the mutation spectrum of the LMNA gene. The correlation between an LMNA mutation and congenital aortic valve malformation deserves further study.
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http://dx.doi.org/10.1002/jcla.23736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059745PMC
April 2021

Astragaloside and/or Hydroxysafflor Yellow A Attenuates Oxygen-Glucose Deprivation-Induced Cultured Brain Microvessel Endothelial Cell Death through Downregulation of PHLPP-1.

Evid Based Complement Alternat Med 2020 15;2020:3597527. Epub 2020 Dec 15.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

The incidence of ischemic stroke, a life-threatening condition in humans, amongst Asians is high and the prognosis is poor. In the absence of effective therapeutics, traditional Chinese medicines have been used that have shown promising results. It is crucial to identify traditional Chinese medicine formulas that protect the blood-brain barrier, which is damaged by an ischemic stroke. In this study, we aimed to elucidate such formulas. Brain microvascular endothelial cells (BMECs) were used to establish an ischemia-reperfusion model for oxygen-glucose deprivation (OGD) experiments to evaluate the function of two traditional Chinese medicines, namely, astragaloside (AS-IV) and hydroxysafflor yellow A (HSYA), in protecting against BMEC. Our results revealed that AS-IV and HSYA attenuated the cell loss caused by OGD by increasing cell proliferation and inhibiting cell apoptosis. In addition, these compounds promoted the migration and invasion of BMECs . Furthermore, we found that BMECs rescued by AS-IV and HSYA could be functionally activated , with AS-IV and HSYA showing synergetic effects in rescuing BMECs survival by reducing the expression of PHLPP-1 and activating Akt signaling. Our results elucidated the potential of AS-IV and HSYA in the prevention and treatment of stroke by protecting against cerebral ischemia-reperfusion injury.
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http://dx.doi.org/10.1155/2020/3597527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755473PMC
December 2020

Chrysophanol ameliorates renal interstitial fibrosis by inhibiting the TGF-β/Smad signaling pathway.

Biochem Pharmacol 2020 10 6;180:114079. Epub 2020 Jun 6.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, No. 127, West Changle Road, Xi'an, Shaanxi 710032, China. Electronic address:

Renal interstitial fibrosis (RIF) is a major pathological feature of chronic kidney disease at middle and end stages. Chrysophanol (CP), 1,8-dihydroxy-3-methyl-9,10-anthraquinone, is an anthraquinone isolated from Rheum palmatum L. with a variety of pharmacological activities including the suppression of RIF. However, the effect of CP on renal fibrosis and its potential mechanism have not been elucidated. We conducted a comprehensive study by determining the expression levels of fibrotic markers and proteins including TGF-β1, α-SMA, and Smad3 related to transforming growth factor-beta/Smad (TGF-β/Smad) pathway in unilateral ureteral obstruction (UUO) mice and TGF-β1-stimulated HK-2 cells with the treatment of CP using western blotting and RT-qPCR analyses. Using small interfering RNA and co-immunoprecipitation, we evaluated the influences of CP on the interactions between Smad3 and Smad7 proteins and also on TGF-β RI and TGF-βR II. We found that CP administration significantly ameliorated UUO-induced kidney damage by reversing abnormal serum and urine biochemical parameters and decreasing the production of fibrotic markers including collagen I, collagen III, fibronectin, and α-SMA. Our results showed that TGF-β1 and phospho-Smad3 (p-Smad3) expression was significantly down-regulated and Smad7 expression was up-regulated by CP in UUO mice compared to the model group; however, the expression of Smad2, Smad4, and TGF-β receptors was not affected. Furthermore, CP modulated these fibrotic markers as well as p-Smad3 and Smad7 in TGF-β1-induced HK-2 cells. The inhibitory effect of CP was markedly reduced in TGF-β1-treated HK-2 cells transfected with Smad3 siRNA. Additionally, co-immunoprecipitation analysis indicated that CP blocked the interaction between Smad3 and TGF-β receptor I to suppress p-Smad3 expression. These findings demonstrated that CP alleviated RIF by inhibiting Smad3 phosphorylation, which provides a molecular basis for a new drug candidate for the treatment of RIF.
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http://dx.doi.org/10.1016/j.bcp.2020.114079DOI Listing
October 2020

Renal protection of rhein against 5/6 nephrectomied-induced chronic kidney disease: role of SIRT3-FOXO3α signalling pathway.

J Pharm Pharmacol 2020 May 20;72(5):699-708. Epub 2020 Mar 20.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Objectives: The purpose of this study is to investigate the antifibrosis and anti-oxidation of rhein in vivo and in vitro, and to evaluate potential mechanisms involved in the treatment of chronic kidney disease (CKD).

Methods: In experimental animal studies, CKD was established by 5/6 nephrectomy (5/6Nx). Serum creatinine (Scr) and blood urea nitrogen (BUN) were determined. Histopathologic tests were performed by HE and Masson trichrome stained. The level of ROS was investigated by fluorescence microplate with the probe 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The protein expressions of p47phox and gp91phox were measured in 5/6Nx rats. In HK-2 cells, the expression of SIRT3 and Foxo3α was measured in SIRT3 knockdown conditions. The indicators of oxidation and fibrosisi were measured in SIRT3 knockdown conditions.

Key Findings: The results showed that, in addition to reducing renal interstitial pathologic injury and collagen fibrils, rhein administration improved renal function. The protective mechanisms were attributed to active SIRT3/FOXO3α signalling pathway and then play the anti-oxidative capacity of rhein, as well as to subsequent antifibrotic effect.

Conclusion: Taken together, rhein protected kidney through SIRT3/FOXO3a involvement. The anti-oxidative capacity of rhein contributed to the protective effects including the subsequent antifibrotic responses.
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http://dx.doi.org/10.1111/jphp.13234DOI Listing
May 2020

Chikusetsu saponin IVa protects pancreatic β cell against intermittent high glucose-induced injury by activating Wnt/β-catenin/TCF7L2 pathway.

Aging (Albany NY) 2020 01 22;12(2):1591-1609. Epub 2020 Jan 22.

Department of Chinese Medicine, School of Life Science, Northwestern University, Xi'an 710032, Shaanxi, China.

Islet β cell mass reduction induced by glucose fluctuation is crucial for the development and progression of T2DM. Chikusetsu saponin IVa (CHS) had protective effects against DM and related injuries. Here we aimed to investigate the role of CHS in β cell injuries and its possible mechanism involved. Isolated rat islets, βTC3 cells and T2DM mice were used in this study. The results showed that CHS restored the secretion activity, promoted β cell survival by increasing β cell proliferation and decreasing apoptosis which induced by intermittent high glucose (IHG). , CHS protected β cell apoptosis to normalize blood glucose and improve insulin sensitivity in DM mice. Further studies showed that CHS activated Wnt3a signaling, inhibited HBP1, promoted β-catenin nuclear translocation, enhanced expressions of TCF7L2, GIPR and GLP-1R, inhibited p53, p27 and p21. The protective effect of CHS was remarkably suppressed by siRNAs against TCF7L2 or XAV-939 (a Wnt/β-catenin antagonist) and in β-catenin mice. In conclusion, we identified a novel role of CHS in protecting β cell survival and regeneration by mechanisms involving the activation of Wnt3a/β-catenin/TCF7L2 signaling. Our results indicated the potential value of CHS as a possible intervention drug for T2DM.
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http://dx.doi.org/10.18632/aging.102702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053639PMC
January 2020

Programmable Assembly of Nano-architectures through Designing Anisotropic DNA Origami Patches.

Angew Chem Int Ed Engl 2020 04 25;59(16):6389-6396. Epub 2020 Feb 25.

College of Engineering and Applied Sciences, National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, 210093, China.

Programmable assembly of nanoparticles (NPs) into well-defined architectures has attracted attention because of tailored properties resulting from coupling effects. However, general and precise approaches to control binding modes between NPs remain a challenge owing to the difficulty in manipulating the accurate positions of the functional patches on the surface of NPs. Here, a strategy is developed to encage spherical NPs into pre-designed octahedral DNA origami frames (DOFs) through DNA base-pairings. The DOFs logically define the arrangements of functional patches in three dimensions, owing to the programmability of DNA hybridization, and thus control the binding modes of the caged nanoparticle with designed anisotropy. Applying the node-and-spacer approach that was widely used in crystal engineering to design coordination polymers, patchy NPs could be rationally designed with lower symmetry encoded to assemble a series of nano-architectures with high-order geometries.
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http://dx.doi.org/10.1002/anie.201913958DOI Listing
April 2020

A network pharmacology approach to reveal the protective mechanism of Salvia miltiorrhiza-Dalbergia odorifera coupled-herbs on coronary heart disease.

Sci Rep 2019 12 18;9(1):19343. Epub 2019 Dec 18.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.

Salvia miltiorrhiza-Dalbergia odorifera coupled-herbs (SMDOCH) has been used to treat coronary heart disease (CHD) for thousands of years, but its unclear bioactive components and mechanisms greatly limit its clinical application. In this study, for the first time, we used network pharmacology to elucidate the mechanisms of action of SMDOCH on CHD. We collected 270 SMDOCH-related targets from 74 bioactive components and 375 CHD-related targets, with 58 overlapping common targets. Next, we performed enrichment analysis for common-target network and protein-protein interaction (PPI) network. The results showed that SMDOCH affected CHD mainly through 10 significant signaling pathways in three biological processes: 'vascular endothelial function regulation', 'inflammatory response', and 'lipid metabolism'. Six pathways belonged to the 'vascular endothelial function regulation' model, which primarily regulated hormone (renin, angiotensin, oestrogen) activity, and included three key upstream pathways that influence vascular endothelial function, namely KEGG:04933, KEGG:05418, and KEGG:04066. Three pathways, namely KEGG:04668, KEGG:04064, and KEGG:04620, belonged to the 'inflammatory response' model. One pathway (KEGG:04920) belonged to the 'lipid metabolism' model. To some extent, this study revealed the potential bioactive components and pharmacological mechanisms of SMDOCH on CHD, and provided a new direction for the development of new drugs for the treatment of CHD.
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http://dx.doi.org/10.1038/s41598-019-56050-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920415PMC
December 2019

Neuroprotective effects of protocatechuic aldehyde through PLK2/p-GSK3β/Nrf2 signaling pathway in both and models of Parkinson's disease.

Aging (Albany NY) 2019 11 6;11(21):9424-9441. Epub 2019 Nov 6.

Nanjing First Hospital, China Pharmaceutical University, Nanjing 211198, China.

Mitochondrial dysfunction and oxidative damage are closely related to the pathogenesis of Parkinson's disease (PD). The pharmacological mechanism of protocatechuic aldehyde (PCA) for PD treatment have retained unclear. The purposes of the present study were to clarify the neuroprotective effects of post-treatment of PCA for PD treatment by mitigating mitochondrial dysfunction and oxidative damage, and to further determine whether its effects were mediated by the polo-like kinase 2/phosphorylated glycogen synthase kinase 3 β/nuclear factor erythroid-2-related factor 2 (PLK2/p-GSK3β/Nrf2) pathways. We found that PCA improved 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced behavioral deficits and dopaminergic cell loss. Moreover, PCA increased the expressions of PLK2, p-GSK3β and Nrf2, following the decrease of α-synuclein (α-Syn) in MPTP-intoxicated mice. Cell viability was increased and the apoptosis rate was reduced by PCA in 1-methyl-4-phenylpyridinium iodide (MPP)-incubated cells. Mitochondrial membrane potential (MMP), mitochondrial complex I activity and reactive oxygen species (ROS) levels in MPP-incubated cells were also ameliorated by treatment with PCA. The neuroprotective effects of PCA were abolished by inhibition or knockdown of PLK2, whereas overexpression of PLK2 strengthened the protection of PCA. Furthermore, GSK3β and Nrf2 were involved in PCA-induced protection. These results indicated that PCA has therapeutic effects on PD by the PLK2/p-GSK3β/Nrf2 pathway.
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http://dx.doi.org/10.18632/aging.102394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874433PMC
November 2019

Protects against I/R-Induced Brain Cell Injury through the Akt/SIRT1/FOXO3a Pathway.

Oxid Med Cell Longev 2019 12;2019:7609765. Epub 2019 May 12.

Biomedicine Key Laboratory of Shaanxi Province, College of Life Science, Northwest University, Xi'an 710069, China.

Background: Saponin from Aralia taibaiensis (sAT) showed excellent antioxidative effects in several models; however, its effects on brain cells were unknown to us. The present study was designed to evaluate the protective effects of sAT on ischemia/reperfusion- (I/R-) induced injury and clarify its mechanisms.

Methods: , HT22 cells were pretreated with sAT and then subjected to I/R. Apoptosis rate, mitochondrial function, and antioxidant proteins were measured. To clarify the mechanisms, siRNA were used. , sAT was pretreated through intragastric administration for 7 days and the I/R model was induced. The neurobehavioral scores, infarction volumes, and some cytokines in the brain were measured. Protein levels were investigated by Western blotting.

Results: The results showed that sAT treatment significantly protected cells from I/R-induced cell apoptosis and mitochondrial dysfunction. The antioxidant protein levels were increased in a dose-dependent manner. Further study revealed that sAT induced the deacetylation and phosphorylation of PGC-1 and FOXO3a. sAT treatment also induced the phosphorylation levels of Akt and the expression levels of SIRT1. Using the specific targeted siRNA transfection, the interplay relationship between Akt, SIRT1, PGC-1, and FOXO3a was verified. Furthermore, the same protective effects were also observed in rats subjected to I/R.

Conclusion: sAT protected brain cells from I/R-induced mitochondrial oxidative stress and dysfunction through regulating the Akt/SIRT1/FOXO3a/PGC-1 pathway.
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http://dx.doi.org/10.1155/2019/7609765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535894PMC
December 2019

Neuroprotective effect of Apelin 13 on ischemic stroke by activating AMPK/GSK-3β/Nrf2 signaling.

J Neuroinflammation 2019 Feb 1;16(1):24. Epub 2019 Feb 1.

Department of Pharmacy, Xijing Hospital, Air Force Medical University, No. 127, Changle West Road, Xi'an, 710032, Shaanxi, China.

Background: Previous studies had showed that Apelin 13 could protect against apoptosis induced by ischemic/reperfusion (I/R). However, the mechanisms whereby Apelin 13 protected brain I/R remained to be elucidated. The present study was designed to determine whether Apelin 13 provided protection through AMPK/GSK-3β/Nrf2 pathway.

Methods: In vivo, the I/R model was induced and Apelin 13 was given intracerebroventricularly 15 min before reperfusion. The neurobehavioral scores, infarction volumes, and some cytokines in the brain were measured. For in vitro study, PC12 cells were used. To clarify the mechanisms, proteases inhibitors or siRNA were used. Protein levels were investigated by western blotting.

Results: The results showed that Apelin 13 treatment significantly reduced infarct size, improved neurological outcomes, decreased brain edema, and inhibited cell apoptosis, oxidative stress, and neuroinflammation after I/R. Apelin 13 significantly increased the expression of Nrf2 and the phosphorylation levels of AMPK and GSK-3β. Furthermore, in cultured PC12 cells, the same protective effects were also observed. Silencing Nrf2 gene with its siRNA abolished the Apelin 13's prevention of I/R-induced PC12 cell injury, oxidative stress, and inflammation. Inhibition of AMPK by its siRNA decreased the level of Apelin 13-induced Nrf2 expression and diminished the protective effects of Apelin 13. The interplay relationship between GSK-3β and Nrf2 was also verified with relative overexpression. Using selective inhibitors, we further identified the upstream of AMPK/GSK-3β/Nrf2 is AR/Gα/PLC/IP3/CaMKK.

Conclusions: In conclusion, the previous results showed that Apelin 13 protected against I/R-induced ROS-mediated inflammation and oxidative stress through activating the AMPK/GSK-3β pathway by AR/Gα/PLC/IP3/CaMKK signaling, and further upregulated the expression of Nrf2-regulated antioxidant enzymes.
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http://dx.doi.org/10.1186/s12974-019-1406-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357442PMC
February 2019

A steroid alkaloid derivative 02F04 upregulates thymic stromal lymphopoietin expression slowly and continuously through a novel Gq/11-ROCK-ERK1/2 signaling pathway in mouse keratinocytes.

Cell Signal 2019 05 19;57:58-64. Epub 2019 Jan 19.

Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Miyagi, Japan. Electronic address:

Thymic stromal lymphopoietin (TSLP), a master switch of allergic inflammation, plays an important role in the pathogenesis of allergic diseases. Although many compounds upregulate TSLP expression in vivo or in vitro, most of them are pollutants or toxicants. In the previous study, for the first time, we found that a steroid alkaloid derivative 02F04, which has a unique skeletal structure compared with other TSLP-inducing chemicals, significantly induced TSLP production in mouse keratinocytes. However, it is not investigated thoroughly that how 02F04 produces TSLP and why. In this study, we did a detailed investigation on the inducible effect and underlying molecular mechanism of 02F04 on TSLP production. We found that the peak time of TSLP mRNA level induced by 02F04 at 48 h led to a slow and continuous TSLP production in PAM212 cells. Besides, 02F04-induced TSLP production was significantly suppressed by inhibitors of Rho-associated protein kinase (ROCK), guanine nucleotide-binding protein subunit alpha q/11 (Gq/11) and extracellular signal-regulated kinase 1/2 (ERK1/2) at not only protein but also mRNA levels, and by siRNA-mediated knockdown of Gq or G11. This suggested that ROCK, Gq/11 and ERK1/2 signaling pathways were involved in 02F04-induced TSLP production. Increase in the level of p-ERK1/2 induced by 02F04 was suppressed by both inhibitors of ROCK and Gq/11, indicating that ROCK and Gq/11 molecules were located at the upstream of ERK1/2 to regulate 02F04-induced TSLP production. Gq/11 was located at the upstream of ROCK because the specific Gq/11 inhibitor of YM-254890 significantly reduced 02F04-induced actin stress fiber formation. Taken together, 02F04 upregulates a slow and continuous TSLP production through a novel Gq/11-ROCK-ERK1/2 signaling pathway. The thorough understanding the effect and mechanism of 02F04 on TSLP production is expected to supply it as a novel TSLP-regulating compound and a potential new tool for investigating the role of TSLP in allergic disorders.
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http://dx.doi.org/10.1016/j.cellsig.2019.01.005DOI Listing
May 2019

Bazedoxifene exhibits growth suppressive activity by targeting interleukin-6/glycoprotein 130/signal transducer and activator of transcription 3 signaling in hepatocellular carcinoma.

Cancer Sci 2019 Mar 16;110(3):950-961. Epub 2019 Feb 16.

Division of Cardiology, Departments of Internal Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The interleukin (IL)-6/glycoprotein (GP)130/signal transducer and activator of transcription (STAT)3 pathway is emerging as a target for the treatment of hepatocellular carcinoma. IL-6 binds to IL-6R, forming a binary complex, which further combines with GP130 to transduce extracellular signaling by activating STAT3. Therefore, blocking the interaction between IL-6 and GP130 may inhibit the IL-6/GP130/STAT3 signaling pathway and its biological effects. It has been reported that bazedoxifene acetate (BAZ), a selective estrogen receptor modulator approved by the US Food and Drug Administration, could inhibit IL-6/GP130 protein-protein interactions. Western blot, immunofluorescence staining, wound healing and colony formation assays were used to detect the effect of BAZ on liver cancer cells. Cell viability was evaluated by MTT assay. Apoptosis of cells was determined using the Annexin V-FITC detection kit. Mouse xenograft tumor models were utilized to evaluate the effect of BAZ in vivo. Our data showed that BAZ inhibited STAT3 phosphorylation (P-STAT3) and expression of STAT3 downstream genes, inducing apoptosis in liver cancer cells. BAZ inhibited P-STAT3 induced by IL-6, but not by leukemia inhibitory factor. BAZ inhibited P-STAT1 and P-STAT6 less significantly as elicited by interferon-α, interferon-γ and IL-4. In addition, pretreatment of BAZ impeded the translocation of STAT3 to nuclei induced by IL-6. BAZ inhibited cell viability, wound healing and colony formation in vitro. Furthermore, tumor growth in HEPG2 mouse xenografts were significantly inhibited by daily intragastric gavage of BAZ. Our results suggest that BAZ inhibited the growth of hepatocellular carcinoma in vitro and in vivo, indicating another potential strategy for HCC prevention and therapy.
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http://dx.doi.org/10.1111/cas.13940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398888PMC
March 2019

Cardioprotective effects and underlying mechanism of Radix Salvia miltiorrhiza and Lignum Dalbergia odorifera in a pig chronic myocardial ischemia model.

Int J Mol Med 2018 Nov 27;42(5):2628-2640. Epub 2018 Aug 27.

Department of Pharmacy, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

Traditional Chinese medicines, including Radix Salvia miltiorrhiza (SM) and Lignum Dalbergia odorifera (DO) extracts, have historically been used to treat myocardial ischemia and other cardiovascular diseases. The volatile oil of DO (DOO) is one of the main components of DO. The aim of the present study was to assess the cardioprotective effects and possible underlying mechanisms of SM‑DOO in pigs with ameroid constriction‑induced chronic myocardial ischemia. An ameroid constrictor was placed around the left anterior descending coronary artery of pigs to induce chronic myocardial ischemia. At weeks 2, 6 and 8, myocardial injury markers and blood gas levels were detected. At week 8, coronary angiography, echocardiography and hemodynamics analysis were performed to evaluate myocardial function. Following sacrifice, myocardial tissue was collected and subjected to morphological, histopathological and apoptosis assays. Western blotting was used to detect the protein expression of Bcl‑2 associated X (Bax), Bcl‑2, Akt, phosphorylated (p)‑Akt, glycogen synthase kinase (GSK)‑3β and p‑GSK‑3β. It was revealed that SM‑DOO treatment following chronic myocardial ischemia significantly downregulated the expression of myocardial injury markers, ameliorated myocardial oxygen consumption, increased collateralization, reduced regional cardiac dysfunction and limited the extent of myocardial damage. Furthermore, the results of an apoptosis assay revealed that the apoptosis rate was decreased, the expression of Bax decreased and Bcl‑2 increased, and the ratio of Bcl‑2/Bax was increased. Further experiments indicated that treatment with SM‑DOO increased the phosphorylation of Akt and GSK‑3β. These findings suggest that SM‑DOO treatment ameliorates myocardial injury in a chronic myocardial ischemia model, and that the underlying mechanisms responsible may be associated with the activation of the Akt/GSK‑3β signal pathway. Thus, experimental evidence that SM‑DOO may be an effective drug for the prevention and treatment of chronic myocardial ischemia in clinical applications has been provided.
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http://dx.doi.org/10.3892/ijmm.2018.3844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192790PMC
November 2018

Anticancer drugs-related QTc prolongation, torsade de pointes and sudden death: current evidence and future research perspectives.

Oncotarget 2018 May 22;9(39):25738-25749. Epub 2018 May 22.

Department of Cardiology, An Zhen Hospital, Capital Medical University, Beijing, P.R. China.

Anticancer drugs may have proarrhythmic effects including drug-induced QT interval prolongation, which is of particular importance because it can lead to a fatal polymorphic ventricular tachycardia termed torsade de pointes (TdP). QT interval prolongation and TdP are rare life-threatening untoward effects of anticancer therapy, particularly with arsenic trioxides and anthracyclines, and even some novel molecular targeted drugs touted as 'tumor specific'. Several factors that affect myocardial repolarization can further increase the risk of TdP. This article reviews the mechanism of QT interval prolongation, risk factors for TdP and the QT toxicity of anticancer drugs as well as its management. Specific attention should be paid to high-risk populations such as patients with underlying heart diseases, electrolyte imbalance and bradycardia. To minimize the occurrence of QT interval prolongation and TdP, it is advisable to conduct a careful risk factor assessment before antitumor therapy. To this end, several new biomarkers have been introduced to predict TdP triggering and recent studies have pointed out the potential clinical relevance of genetic testing.
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http://dx.doi.org/10.18632/oncotarget.25008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986642PMC
May 2018

Ursolic acid prevents angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E-knockout mice.

Atherosclerosis 2018 04 15;271:128-135. Epub 2018 Feb 15.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background And Aims: Abdominal aortic aneurysms (AAA) is a chronic inflammatory disease in which signal transducer and activator of transcription 3 (STAT3), and disintegrin and metalloproteinase 17 (ADAM17) play important roles. However, it remains unclear whether ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, can have an impact on STAT3 and ADAM17 and hence influence the formation of AAA. The objective of this study was to characterize the potential effect of UA on the pathogenesis of AAA and on STAT3 and ADAM17.

Methods: Male ApoE mice were infused with angiotensin II (AngII) (1000 ng/kg/min) for 4 weeks to induce AAAs. Daily intragastric gavage with 100 mg/kg UA or tap water containing Tween 80 as controls was provided. Immunohistochemistry, cell viability assay, colony formation, wound healing assay, and Western blot were used to explore the potential effect of UA on AAA.

Results: UA decreased the incidence of AngII-induced AAA in mice. UA alleviated the degradation of elastin fibers and inflammation and decreased the expression of MMP2, MMP9, ADAM17 and phospho-STAT3 (pSTAT3) in aorta of mice induced with AngII. UA inhibited the constitutive and stimuli-induced (AngII and tumor necrosis factor-α) expression of MMP2, MMP9, ADAM17 and pSTAT3 in vascular smooth muscle cells (VSMCs). Furthermore, UA decreased cell viability, and suppressed colony formation and wound healing in vitro.

Conclusions: We demonstrated that UA ameliorated the severity of AAA and exhibited an inhibitory effect on the expression of pSTAT3 and ADAM17. UA might emerge as a promising agent contributing to the prevention or treatment of AAA.
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http://dx.doi.org/10.1016/j.atherosclerosis.2018.02.022DOI Listing
April 2018

Beneficial effects of extracts from Lucilia sericata maggots on burn wounds in rats.

Mol Med Rep 2017 Nov 20;16(5):7213-7220. Epub 2017 Sep 20.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

Lucilia sericata maggots have beneficial properties; however, their protective effects on burn wounds have yet to be fully elucidated. In the present study, a deep second‑degree burn rat model was used to investigate the burn wound healing properties of aqueous extract of maggots (MAE). The anti‑inflammatory, antioxidative and antibacterial activities were examined. In addition, the protein expression levels of Akt, vascular endothelial growth factor A (VEGFA) and nuclear factor‑κB (NF‑κB) were detected by western blotting. The findings of the present study revealed that MAE treatment increased burn wound healing and hydroxyproline content in the burn‑treated rats. A total of seven compounds (MAE‑P1‑P7) were separated from MAE and a comparative study was performed to identify the major active component. The results demonstrated that MAE‑P6 exerted greater antibacterial activity compared with the other compounds. MAE‑P6 treatment reduced tissue levels of malondialdehyde, tumor necrosis factor‑α and interleukin‑6, and increased superoxide dismutase activity. Furthermore, MAE‑P6 increased the expression levels of VEGFA and reduced NF‑κB expression through Akt, which was verified by treatment with the Akt‑specific inhibitor, LY294002. In conclusion, the present study demonstrated that the beneficial effects of MAE on burn wound healing were due to its antibacterial, antioxidative and anti‑inflammatory activities. MAE‑P6 reduced the release of inflammatory cytokines via the Akt/NF‑κB signaling pathway, and regulated angiogenesis and vasopermeability via the Akt/VEGFA pathway.
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http://dx.doi.org/10.3892/mmr.2017.7566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865848PMC
November 2017

Danshensu accelerates angiogenesis after myocardial infarction in rats and promotes the functions of endothelial progenitor cells through SDF-1α/CXCR4 axis.

Eur J Pharmacol 2017 Nov 31;814:274-282. Epub 2017 Aug 31.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an 710032, Shaanxi, PR China. Electronic address:

The present study was performed to investigate the potential role of Danshensu in therapeutic angiogenesis in ischemic myocardium and endothelial progenitor cells (EPCs) function. The rat model of myocardial infarction (MI) injury was induced by left anterior descending coronary artery ligation for 14 days. Danshensu significantly alleviated myocardial ischemia injury by ameliorating left ventricular function and reducing infarct size. Furthermore, Danshensu potentiated post-ischemia neovascularization as evidenced by increased microvessel density in infarction boundary zone, as well as the expression of marker proteins vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Moreover, Danshensu notably promoted stromal cell-derived factor-1α (SDF-1α) level in plasma and C-X-C chemokine receptor type 4 (CXCR4) expression in peri-infarction myocardium, and AMD3100 (CXCR4 antagonist) could reverse the angiogenic and cardioprotective effects of Danshensu. For in vitro study, EPCs were isolated from bone marrow of rats. On the one hand, Danshensu provided significant cytoprotection against hypoxia insult by boosting EPCs viability and inhibiting apoptosis, and upregulated Akt phosphorylation. On the other hand, Danshensu enhanced proangiogenic functions of EPCs on cell migration and tube formation, and increased SDF-1α and CXCR4 expression. Likewise, the cytoprotection and proangiogenic functions of Danshensu on EPCs were partly negated by LY294002 (PI3K antagonist) and CXCR4 siRNA, respectively. Taken together, our results suggested that the cardioprotection of Danshensu in MI rats may be related to promoting myocardial neovascularization. The possible mechanisms may involve improving EPCs survival in hypoxia condition through Akt phosphorylation, and accelerating EPCs proangiogenic functions through SDF-1α/CXCR4 axis.
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http://dx.doi.org/10.1016/j.ejphar.2017.08.035DOI Listing
November 2017

Inhibition of STAT3 signaling pathway by ursolic acid suppresses growth of hepatocellular carcinoma.

Int J Oncol 2017 Aug 8;51(2):555-562. Epub 2017 Jun 8.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.

The signal transducer and activator of transcription 3 (STAT3) has been found to be constitutively active in liver cancer. There is no STAT3 inhibitors approved to be used clinically for the treatment or prevention of liver cancer. Some dietary compounds including ursolic acid (UA) have been reported to inhibit the growth of cancer cells. However, whether UA could inhibit STAT3 phosphorylation in hepatocellular carcinoma has not been reported. The inhibitory effects of UA on STAT3 phosphorylation, along with cell viability, migration, colony formation in vitro, as well as tumor growth in vivo were examined in human liver cancer cell lines. Our data showed that UA inhibited the P-STAT3 induced by interleukin-6 (IL-6) in Hep3B liver cancer cells which express very low basal level of P-STAT3. The constitutive STAT3 phosphorylation was also inhibited by UA in HEPG2, 7721 and Huh7 human liver cancer cell lines. UA decreased the expression of downstream target genes of STAT3, such as Bcl-2, Bcl-xl and survivin in general, with difference in these cell lines. UA also suppressed cell viability, cell migration and colony formation in liver cancer cells. Furthermore, UA suppressed STAT3 phosphorylation and HEPG2 tumor growth by oral daily treatment in vivo. UA, which exists widely in fruits and herbs, could inhibit STAT3 activation and the growth of human liver cancer cells in vitro and in vivo. It might be a potential health care product that could be used daily for prevention, as well as a promising candidate for chemotherapy of liver cancer.
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http://dx.doi.org/10.3892/ijo.2017.4035DOI Listing
August 2017

Cardioprotective effects and mechanism of Radix Salviae miltiorrhizae and Lignum Dalbergiae odoriferae on rat myocardial ischemia/reperfusion injury.

Mol Med Rep 2017 Aug 20;16(2):1759-1770. Epub 2017 Jun 20.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

Radix Salviae miltiorrhizae (SM) and Lignum Dalbergiae odoriferae (DO) are traditional Chinese medicinal herbs used to treat ischemic heart disease and other cardiovascular diseases; however, to the best of our knowledge, there are currently few studies regarding their effects. The present study aimed to investigate the cardioprotective effects of SM and DO during myocardial ischemia/reperfusion (MI/R) injury in rats, and explore the molecular mechanisms that underlie their actions. In the present study, Sprague‑Dawley rats were pretreated with SM, the aqueous extract of DO (DOA) and the volatile oil of DO (DOO), either as a monotherapy or in combination for 7 days. Subsequently, the rats were subjected to 30 min of ischemia followed by 180 min of reperfusion. Traditional pharmacodynamic evaluation and metabonomics based on gas chromatography/time‑of‑flight mass spectrometry were used to identify the therapeutic effects of these traditional Chinese medicines. The results revealed that SM, DOA and DOO monotherapies ameliorated cardiac function, and this effect was strengthened further when used in combined therapies. Among the combined treatments, SM + DOO exhibited the greatest potential (P<0.05) to improve electrocardiogram results and heart rate, reduce the heart weight index and myocardial infarct size, and decrease the levels of creatine kinase‑MB and lactate dehydrogenase. In addition, metabonomics‑based findings, including the principal component analysis and partial least squares discriminant analysis score plot of the metabolic state in rat serum, provided confirmation for the aforementioned results, verifying that SM + DOO exerted synergistic therapeutic efficacies to exhibit a greater effect on rats with MI/R injury when compared with the other pretreatment groups. Furthermore, the most effective duration of SM + DOO treatment was 30 min and the least effective duration was 180 min. Treatment with SM + DOO also significantly (P<0.01) reduced the number of terminal deoxynucleotidyl transferase‑mediated dUTP nick end‑labeling‑positive cells, tumor necrosis factor‑α andinterleukin‑6 expression, and malondialdehyde content, and increased the serum and tissue activity of superoxide dismutase. These results indicated that the combined effects of SM + DOO may be more effective compared with the single pretreatments against MI/R injury in rats. This effect may be achieved partly through anti‑apoptotic, antioxidant and anti‑inflammatory activities. Therefore, SM + DOO may be considered an effective and promising novel strategy for the prophylaxis and treatment of ischemic heart disease.
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http://dx.doi.org/10.3892/mmr.2017.6821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562082PMC
August 2017

The Role of TRPC6 in the Neuroprotection of Calycosin Against Cerebral Ischemic Injury.

Sci Rep 2017 06 8;7(1):3039. Epub 2017 Jun 8.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P.R. China.

Our previous studies have provided evidences that calycosin can protect the brain from ischemia/reperfusion injury, but its mechanisms is not fully understand. Transient receptor potential canonical 6 (TRPC6) has a critical role in promoting neuronal survival against cerebral ischemic injury. The aim of the present study is to test whether calycosin protects against cerebral ischemic injury through TRPC6-CREB pathway. In vivo, rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h and then treated with different doses of calycosin at the onset of reperfusion. In vitro, primary cultured neurons were treated by calycosin, then exposed to 2 h oxygen glucose deprivation (OGD) followed by 24 h reoxygenation. Our results showed that treatment with calycosin protected against ischemia-induced damages by increasing TRPC6 and P-CREB expression and inhibiting calpain activation. The neuroprotection effect of calycosin was diminished by inhibition or knockdown of TRPC6 and CREB. These findings indicated that the potential neuroprotection mechanism of calycosin was involved with TRPC6-CREB pathway.
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http://dx.doi.org/10.1038/s41598-017-03404-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465205PMC
June 2017

Clinical analysis of the effect of anti-allergy treatment on pocket-related complications following pacemaker implantation.

Exp Ther Med 2017 Jun 20;13(6):2876-2882. Epub 2017 Apr 20.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

A total number of 339 patients who received a pacemaker implantation between June 2012 and June 2014 at Tongji Hospital of Tongji Medical College (Wuhan, China) were investigated in the present study. The aims of the present study were to explore the risk factors of pocket hematoma following pacemaker implantation, and to analyze the effect of anti-allergy treatment on pocket-related complications following pacemaker implantation. Predictors of hematoma occurrence were determined and analyzed via a Chi-square test. Patients suffering from pocket hematoma, which were indicated to be partially caused by an allergic reaction to the pacemaker component, were distinguished by routine blood parameters. Furthermore, the pacemaker component was distinguished by histopathological examinations in one patient. Promethazine (25 mg/day) was used to treat allergic patients. The results demonstrated that in patients with a history of allergies, the rate of pocket hematoma was significantly higher when compared with patients without a history of allergies (22.00 vs. 7.61%; P=0.027). A significantly increased incidence of hematoma was indicated in patients with a lower body mass index when compared with patients of normal weight (15.79 vs. 7.38%; P=0.042). Furthermore, implantation of larger-sized devices, such as an implantable cardioverter-defibrillator and cardiac resynchronization therapy, were significantly predictive of hematoma development (29.63 vs. 8.01%; P=0.015). Patients with diabetes were also identified to exhibit a significantly high incidence of hematoma (22.22 vs. 8.25%; P=0.023). Promethazine administration significantly decreased the incidence of re-operating (P=0.017) and the duration of hospital stay (P=0.038) in patients whose pocket hematoma was caused by an allergy. In conclusion, promethazine may be a beneficial agent to treat pocket hematoma caused by allergic reactions following pacemaker surgery.
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http://dx.doi.org/10.3892/etm.2017.4366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450729PMC
June 2017

Protective effect of butin against ischemia/reperfusion-induced myocardial injury in diabetic mice: involvement of the AMPK/GSK-3β/Nrf2 signaling pathway.

Sci Rep 2017 01 27;7:41491. Epub 2017 Jan 27.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.

Hyperglycemia-induced reactive oxygen species (ROS) generation contributes to development of diabetic cardiomyopathy (DCM). This study was designed to determine the effect of an antioxidant butin (BUT) on ischemia/reperfusion-induced myocardial injury in diabetic mice. Myocardial ischemia/reperfusion (MI/R) was induced in C57/BL6J diabetes mice. Infarct size and cardiac function were detected. For in vitro study, H9c2 cells were used. To clarify the mechanisms, proteases inhibitors or siRNA were used. Proteins levels were investigated by Western blotting. In diabetes MI/R model, BUT significantly alleviated myocardial infarction and improved heart function, together with prevented diabetes-induced cardiac oxidative damage. The expression of Nrf2, AMPK, AKT and GSK-3β were significantly increased by BUT. Furthermore, in cultured H9c2 cardiac cells silencing Nrf2 gene with its siRNA abolished the BUT's prevention of I/R-induced myocardial injury. Inhibition of AMPK and AKT signaling by relative inhibitor or specific siRNA decreased the level of BUT-induced Nrf2 expression, and diminished the protective effects of BUT. The interplay relationship between GSK-3β and Nrf2 was also verified with relative overexpression and inhibitors. Our findings indicated that BUT protected against I/R-induced ROS-mediated apoptosis by upregulating the AMPK/Akt/GSK-3β pathway, which further activated Nrf2-regulated antioxidant enzymes in diabetic cardiomyocytes exposed to I/R.
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http://dx.doi.org/10.1038/srep41491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269748PMC
January 2017

Hydroxysafflor yellow A promotes neovascularization and cardiac function recovery through HO-1/VEGF-A/SDF-1α cascade.

Biomed Pharmacother 2017 Apr 22;88:409-420. Epub 2017 Jan 22.

Department of Pharmacy, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China. Electronic address:

Aim: The present study was to investigate the proangiogenic and cardioprotective effects of hydroxysafflor yellow A (HSYA) against myocardial infarction (MI) injury and the underlying mechanisms.

Methods: MI model was induced by ligation of the left coronary artery in normal and heme oxygenase-1 (HO-1) knockout mice and the ones receiving vascular endothelial growth factor-A (VEGF-A) or stromal cell-derived factor-1α (SDF-1α) antagonists. They were treated with three doses or single dose of HSYA for 28days. The cardiac function, endothelial progenitor cells (EPCs) mobilization, angiogenesis, the expression of HO-1, VEGF-A, SDF-1α and apoptosis or fibrosis related proteins in the peri-infarct area were evaluated at respective times. We further examined the effect of HSYA on EPCs CXC chemokiner receptor 4 (CXCR4) expression and the role of SDF-1α on EPCs function in vitro.

Results: HSYA could dose dependently reduce left ventricular function impairment, myocardial apoptosis and fibrosis, and promote EPCs mobilization and myocardial neovascularization. Further, HO-1 knockout abolished HSYA-induced up-regulation of HO-1, VEGF-A and SDF-1α. VEGF antagonist significantly reduced HSYA-increased VEGF-A and SDF-1α levels and SDF-1 antagonist abolished HSYA-simulated up-regulation of SDF-1α. Meanwhile, HO-1 knockout, administration of VEGF and SDF-1 antibodies abrogated HSYA-promoted expression of the marker proteins of newborn microvessels and cardiac functional recovery. In vitro, HSYA dose dependently promoted (CXCR4) expression on EPCs. SDF-1α significantly accelerated EPCs function which was reversed by CXCR4 antagonist.

Conclusion: HSYA could promote EPCs function through the HO-1/VEGF-A/SDF-1α signaling cascade, which contributed largely to myocardial neovascularization and further improved cardiac function in MI mice.
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http://dx.doi.org/10.1016/j.biopha.2017.01.074DOI Listing
April 2017

Metabonomic Strategy for the Evaluation of Chinese Medicine Salvia miltiorrhiza and Dalbergia odorifera Interfering with Myocardial Ischemia/Reperfusion Injury in Rats.

Rejuvenation Res 2017 Aug 7;20(4):263-277. Epub 2017 Mar 7.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University , Xi'an, China .

Extract of Salvia miltiorrhiza and Dalbergia Odorifera (SM-DOO) has been traditionally used for the prevention and treatment of cardiovascular diseases. However, information regarding the pharmacodyamic material basis and potential mechanism remain unknown. Male Sprague-Dawley rats were divided into four groups: Sham, Model, Diltiazem, and SM-DOO group, n = 6. Rats were pretreated with homologous drugs for 7 days, and then subjected to 30 minutes of ischemia followed by 180 minutes of reperfusion. Cardioprotection effects of SM-DOO on myocardial ischemia/reperfusion (MI/R) injury rats were examined by hemodynamics, infarct area, histopathology, biochemical indicators, and Western blot analysis. Metabonomics technology was further performed to evaluate the endogenous metabolites profiling systematically. According to the results of pattern recognition analysis, a clear separation of MI/R injury in the Model group and Sham group was achieved and SM-DOO pretreatment group was located much closer to the Sham group than the Model group, which was consistent with results of biochemistry and histopathological assay. Moreover, potential biomarkers were identified to elucidate the drug mechanism of SM-DOO, which may be related with pathways of energy metabolism, especially tricarboxylic acid (TCA) cycle (citric acid) and β-oxidation of fatty acids (3-hydroxybutyric, palmitoleic acid, heptadecanoic acid, and arachidonic acid). In addition, the protein expressions of p-AMPK and p-ACC in the SM-DOO group were significantly elevated, while the levels of carnitine palmitoyl-CoA transferase-1 (CPT-1), p-PDK, and p-PDC were dramatically reduced by SM-DOO. In conclusion, SM-DOO pretreatment could ameliorate MI/R injury by intervening with energy metabolism, especially TCA cycle and β-oxidation of fatty acids. This work showed that the metabonomics method combinate with conventional pharmacological methods is a promising tool in the efficacy and mechanism research of traditional Chinese medicines.
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http://dx.doi.org/10.1089/rej.2016.1884DOI Listing
August 2017

Iridoid glycosides from the flowers of Gentiana macrophylla Pall. ameliorate collagen-induced arthritis in rats.

J Ethnopharmacol 2016 Aug 12;189:1-9. Epub 2016 May 12.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Street 127, Xi'an, Shaanxi 710032, PR China. Electronic address:

Background: The flowers of Gentiana macrophylla have been usually applied to cure the joint inflammation and rheumatoid arthritis in Traditional Chinese Medicine.

Hypothesis/purpose: This work aimed to investigate the anti-rheumatoid arthritic effect and possible mechanism of iridoid glycosides from G. macrophylla (GMI) using an animal model of collagen-induced rheumatoid arthritis (CIA) in rats.

Study Design: All rats were randomly divided into five groups: normal control, CIA, dexamethasone, 15mg/kg and 30mg/kg GMI.

Methods: CIA was induced (day 0) in male Sprague-Dawley rats by intradermal injection of complete Bovine CII at the base of the tail. Dexamethasone was chosen as the positive drug. The administration of different drugs started from day 1 and continued for 28 days. Paw swelling, arthritis score and histopathological changes were examined to assess the severity of arthritis. In addition, the serum levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions in joint synovial tissues were detected.

Results: GMI reduced paw edema, arthritis scores and the index of spleen and thymus from day 7 to 21 after CIA compared with those in the CIA group. Our data also demonstrated that GMI inhibited pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6, regulated the expression of iNOS and COX-2 compared with those in the CIA group. We also obtained four major components from GMI, identified as loganic acid, swertamarin, gentiopicroside and sweroside, and the contents of them were also calculated respectively.

Conclusion: Taken together, our results shed light on the therapeutic efficacy of GMI in rats rheumatoid arthritis model by reducing the levels of IL-1β, IL-6 and TNF-α in serum as well as down-regulating the levels of iNOS and COX-2. Therefore, GMI may be an effective therapy for the treatment of rheumatoid arthritis.
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http://dx.doi.org/10.1016/j.jep.2016.05.027DOI Listing
August 2016
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