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Dive into the research topics where Pengyuan Sun is active.

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Featured researches published by Pengyuan Sun.


Cancer Biology & Therapy | 2015

Dasatinib reverses the multidrug resistance of breast cancer MCF-7 cells to doxorubicin by downregulating P-gp expression via inhibiting the activation of ERK signaling pathway.

Ting Chen; Changyuan Wang; Qi Liu; Qiang Meng; Huijun Sun; Xiaokui Huo; Pengyuan Sun; Jinyong Peng; Zhihao Liu; Xiaobo Yang; Kexin Liu

Multidrug resistance (MDR) is one of the major obstacles to the efficiency of cancer chemotherapy, which often results from the overexpression of drug efflux transporters such as P-glycoprotein (P-gp). In the present study, we determined the effect of dasatinib which was approved for imatinib resistant chronic myelogenous leukemia (CML) and (Ph+) acute lymphoblastic leukemia (ALL) treatment on P-gp-mediated MDR. Our results showed that dasatinib significantly increased the sensitivity of P-gp-overexpressing MCF-7/Adr cells to doxorubicin in MTT assays; thus lead to an enhanced cytotoxicity of doxorubicin in MCF-7/Adr cells. Additionally, dasatinib increased the intracellular accumulation, inhibited the efflux of doxorubicin in MCF-7/Adr cells, and significantly enhanced doxorubicin-induced apoptosis in MCF-7/Adr cells. Further studies showed that dasatinib altered the expression levels of mRNA, protein levels of P-gp, and the phosphorylation of signal–regulated kinase (ERK) both in time-dependent (before 24 h) and dose-dependent manners at concentrations that produced MDR reversals. In conclusion, dasatinib reverses P-gp-mediated MDR by downregulating P-gp expression, which may be partly attributed to the inhibition of ERK pathway. Dasatinib may play an important role in circumventing MDR when combined with other conventional antineoplastic drugs.


European Journal of Pharmacology | 2011

Histamine H3 receptor-mediated modulation of perivascular nerve transmission in rat mesenteric arteries

Pengyuan Sun; Shingo Takatori; Xin Jin; Toshihiro Koyama; Panot Tangsucharit; Simin Li; Yoshito Zamami; Yoshihisa Kitamura; Hiromu Kawasaki

The rat mesenteric artery has been shown to be innervated by adrenergic vasoconstrictor nerves and calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves. The present study was designed to investigate the involvement of histamine H(3) receptors in the neurotransmission of perivascular adrenergic and CGRPergic nerves. The mesenteric vascular beds without an endothelium isolated from male Wistar rats were perfused with Krebs solution and perfusion pressure was measured. In preparations with resting tension, the selective H(3) receptor agonist (R)-α-methylhistamine (α-methylhistamine; 10-100nM) significantly reduced periarterial nerve stimulation (2-8Hz)-induced vasoconstriction and noradrenaline release in the perfusate without an effect on the vasoconstriction induced by exogenously injected noradrenaline (0.5, 1.0nmol). In preparations with active tone produced by methoxamine (2μM) and in the presence of guanethidine (5μM), the periarterial nerve stimulation (1, 2Hz)-induced vasodilator response was inhibited by α-methylhistamine (0.1-1μM) perfusion without affecting vasodilation induced by exogenously injected CGRP (5pmol). Clobenpropit (histamine H(3) receptor antagonist, 1μM) canceled the α-methylhistamine-induced decrease in the periarterial nerve stimulation-induced vasoconstriction and noradrenaline release and periarterial nerve stimulation-induced vasodilation. These results suggest that the stimulation of H(3) receptors located in rat perivascular nerves inhibits presynaptically the neurotransmission of not only adrenergic nerves, but also CGRP nerves, by decreasing neurotransmitters.


European Journal of Pharmacology | 2017

Protective effects of glycyrrhizic acid against non-alcoholic fatty liver disease in mice

Xue Sun; Xingping Duan; Changyuan Wang; Zhihao Liu; Pengyuan Sun; Xiaokui Huo; Xiaodong Ma; Huijun Sun; Kexin Liu; Qiang Meng

Abstract Non‐alcoholic fatty liver disease (NAFLD) has become a predictive factor of death from many diseases. The purpose of the present study is to investigate the protective effect of glycyrrhizic acid (GA), a natural triterpene glycoside, on NAFLD induced by a high‐fat diet (HFD) in mice, and further to elucidate the mechanisms underlying GA protection. GA treatment significantly reduced the relative liver weight, serum ALT, AST activities, levels of serum lipid, blood glucose and insulin. GA suppressed lipid accumulation in liver. Further mechanism investigation indicated that GA reduced hepatic lipogenesis via downregulating SREBP‐1c, FAS and SCD1 expression, increased fatty acids &bgr;‐oxidation via an increase in PPAR&agr;, CPT1&agr; and ACADS, and promoted triglyceride metabolism through inducing LPL activity. Furthermore, GA reduced gluconeogenesis through repressing PEPCK and G6Pase, and increased glycogen synthesis through an induction in gene expression of PDase and GSK3&bgr;. In addition, GA increased insulin sensitivity through upregulating phosphorylation of IRS‐1 and IRS‐2. In conclusion, GA produces protective effect against NAFLD, due to regulation of genes involved in lipid, glucose homeostasis and insulin sensitivity.


Phytomedicine | 2017

Calycosin attenuates triglyceride accumulation and hepatic fibrosis in murine model of non-alcoholic steatohepatitis via activating farnesoid X receptor

Xingping Duan; Qiang Meng; Changyuan Wang; Zhihao Liu; Qi Liu; Huijun Sun; Pengyuan Sun; Xiaobo Yang; Xiaokui Huo; Jinyong Peng; Kexin Liu

BACKGROUND Non-alcoholic steatohepatitis (NASH) represents the more severe end of hepatic steatosis and is associated with progressive liver disease. Calycosin, derived from the root of Radix Astragali, has been demonstrated to have favorable efficacy on acute liver injury. PURPOSE The present study was to investigate the hepatoprotective effect of calycosin on attenuating triglyceride accumulation and hepatic fibrosis, as well as explore the potential mechanism in murine model of NASH. STUDY DESIGN The C57BL/6 male mice were fed with methionine choline deficient (MCD) diet for 4 weeks to induce NASH and treated with or without calycosin by oral gavage for 4 weeks. METHODS The body weight, liver weight and the liver to body weight ratios were measured. Serum ALT, AST, TG, TC, FFA, MCP-1 and mKC levels were accessed by biochemical methods. H&E staining and Oil red O staining were used to identify the amelioration of liver histopathology. Immunohistochemistry of a-SMA, Masson trichrome staining and Sirius red staining were used to identify the amelioration of hepatic fibrosis. The quantitative real-time-PCR and Western blot were applied to observe the expression changes of key factors involved in triglyceride synthesis, free fatty acid β-oxidation and hepatic fibrosis. RESULTS Calycosin significantly inhibited body weight loss induced by MCD diet, decreased the ALT and AST activities, MCP-1 and mKC in a dose-dependent manner. The H&E and Oil red O staining indicated calycosin effectively improved hepatic steatosis, improved the degree of triglyceride accumulation. Masson trichrome and Sirius red staining indicated that calycosin treatment remarkably attenuated the degree of hepatic fibrosis. Immunohistochemistry of a-SMA demonstrated that calycosin attenuated hepatic fibrosis by inhibiting hepatic stellate cell activation. Further, calycosin inhibited the expression of SREBP-1c, FASN, ACC and SCD1 involved in triglyceride synthesis, promoted the expression of PPARa, CPT1, Syndecan-1 and LPL involved in free fatty acid β-oxidation. The above effects of calycosin were attributed to FXR activation. CONCLUSION Calycosin attenuates triglyceride accumulation and hepatic fibrosis to protect against NASH via FXR activation.


European Journal of Pharmacology | 2012

Involvement of perivascular nerves and transient receptor potential vanilloid 1 (TRPV1) in vascular responses to histamine in rat mesenteric resistance arteries

Honghua Jin; Pengyuan Sun; Shingo Takatori; Toshihiro Koyama; Yoshito Zamami; Panot Tangsucharit; Yoshihisa Kitamura; Hiromu Kawasaki

A previous report showed that histamine in denuded mesenteric vascular beds produced a triphasic response; an initial small histamine H(2) receptor-mediated vasodilation, a transient histamine H(1) receptor-mediated vasoconstriction, and finally a long-lasting vasodilation. We further investigated the vascular effect of histamine in mesenteric preparations without an endothelium to clarify the possible involvement of perivascular nerves. Male Wistar rat mesenteric vascular beds without an endothelium were perfused with Krebs solution containing methoxamine to produce active tone and lafutidine to block histamine H(2) receptor-mediated vasodilation. Histamine (1-100μM) was perfused for 1min and perfusion pressure was measured with a pressure transducer. Histamine caused a biphasic vascular response; initial vasoconstriction followed vasodilation. Tetrodotoxin (a neurotoxin, 1μM) and procaine (a local anesthetic, 100μM) significantly inhibited the vasoconstriction and vasodilation. Ruthenium red (a transient receptor potential vanilloid 1 (TRPV1) antagonist, 1μM) also significantly inhibited both phases of the response. Pretreatment with capsaicin (a depletor of calcitonin gene-related peptide (CGRP)-containing nerves, 5μM) significantly inhibited the vasodilation without affecting the initial vasoconstriction. Both indomethacin (a cyclooxygenase inhibitor, 0.5μM) and seratrodast (a thromboxane A(2) receptor antagonist, 0.1μM) abolished the histamine-induced vasoconstriction and subsequent vasodilation. These results suggest that histamine-induced vasoconstriction and long-lasting vasodilation are mediated by activation of TRPV1 on capsaicin-sensitive and capsaicin-insensitive nerves. They also suggest that perivascular nerves and prostanoids, probably thromboxane A(2), are responsible for the vascular response to histamine.


American Journal of Physiology-regulatory Integrative and Comparative Physiology | 2012

Do cholinergic nerves innervating rat mesenteric arteries regulate vascular tone

Panot Tangsucharit; Shingo Takatori; Pengyuan Sun; Yoshito Zamami; Mitsuhiro Goda; Poungrat Pakdeechote; Fusako Takayama; Hiromu Kawasaki

Vascular blood vessels have various types of cholinergic acetylcholine receptors (AChR), but the source of ACh has not been confirmed. Perivascular adrenergic nerves and nonadrenergic calcitonin gene-related peptide (CGRP)-containing (CGRPergic) nerves innervate rat mesenteric arteries and regulate vascular tone. However, function of cholinergic innervation remains unknown. The present study investigated cholinergic innervation by examining effects of cholinesterase inhibitor (neostigmine), a muscarinic AChR antagonist (atropine), and a nicotinic AChR antagonist (hexamethonium) on adrenergic nerve-mediated vasoconstriction and CGRPergic nerve-mediated vasodilation in rat mesenteric vascular beds without endothelium. In preparations treated with capsaicin (CGRP depletor) or in the presence of N(ω)-nitro-l-arginine methyl ester (nonselective nitric oxide synthase inhibitor), perivascular nerve stimulation (PNS; 2-12 Hz) evoked a frequency-dependent vasoconstriction. In the same preparations, exogenous norepinephrine induced a concentration-dependent vasoconstriction. Atropine, hexamethonium, and neostigmine had no effect on vasoconstrictor responses to PNS and norepinephrine injections. In denuded preparations, these cholinergic agents did not affect the PNS (12 Hz)-evoked release of norepinephrine in perfusate. In preconstricted preparations without endothelium in the presence of guanethidine (adrenergic neuron blocker), PNS (1-4 Hz) induced a frequency-dependent vasodilation, which was not affected by atropine, hexamethonium, and neostigmine. In denuded preparations treated with capsaicin and guanethidine, PNS did not induce vascular responses, and atropine, neostigmine, and physostigmine had no effect on PNS. Immunohistochemistry study showed choline acetyltransferase-immunopositive fibers, which were resistant to capsaicin and 6-hydroxydopamine (adrenergic toxin). These results suggest that rat mesenteric arteries have cholinergic innervation, which is different from adrenergic and capsaicin-sensitive nerves and not associated with vascular tone regulation.


Journal of Cellular Physiology | 2018

Targeting P-glycoprotein and SORCIN: Dihydromyricetin strengthens anti-proliferative efficiency of adriamycin via MAPK/ERK and Ca2+ -mediated apoptosis pathways in MCF-7/ADR and K562/ADR

Yaoting Sun; Changyuan Wang; Qiang Meng; Zhihao Liu; Xiaokui Huo; Pengyuan Sun; Huijun Sun; Xiaodong Ma; Jinyong Peng; Kexin Liu

Recently, a new target Ca2+‐binding protein SORCIN was reported to participate in multidrug resistance (MDR) in cancer. Here we aim to investigate whether dihydromyricetin (DMY), a dihydroflavonol compound with anti‐inflamatory, anti‐oxidant, anti‐bacterial and anti‐tumor actions, reverses MDR in MCF‐7/ADR and K562/ADR and to elucidate its potential molecular mechanism. DMY enhanced cytotoxicity of adriamycin (ADR) by downregulating MDR1 mRNA and P‐gp expression through MAPK/ERK pathway and also inhibiting the function of P‐gp significantly. Meanwhile, DMY decreased mRNA and protein expression of SORCIN, which resulted in elevating intracellular free Ca2+. Finally, we investigated co‐administration ADR with DMY remarkably increased ADR‐induced apoptosis. Further study showed DMY elevated ROS levels and caspase‐12 protein expression, which signal apoptosis in endoplasmic reticulum. At the same time, proteins related to mitochondrial apoptosis were also changed such as Bcl‐2, Bax, caspase‐3, caspase‐9, and PARP. Finally, nude mice model also demonstrated that DMY strengthened anti‐tumor activity of ADR in vivo. In conclusion, DMY reverses MDR by downregulating P‐gp, SORCIN expression and increasing free Ca2+, as well as, inducing apoptosis in MCF‐7/ADR and K562/ADR. These fundamental findings provide evidence for further clinical research in application of DMY as an assistant agent in the treatment of cancer.


Regulatory Toxicology and Pharmacology | 2018

Ginsenoside Rg1 protects against acetaminophen-induced liver injury via activating Nrf2 signaling pathway in vivo and in vitro

Chenqing Ning; Xiaoguang Gao; Changyuan Wang; Yulong Kong; Zhihao Liu; Huijun Sun; Pengyuan Sun; Xiaokui Huo; Xiaodong Ma; Qiang Meng; Kexin Liu

Acetaminophen (APAP) is a worldwide used drug for treating fever and pain. However, APAP overdose is the leading cause of drug-induced liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of ginsenoside Rg1 (Rg1), the main pharmacologically active compounds of Panax ginseng, against APAP-induced acute liver injury, and further to elucidate the involvement of Nrf2 signaling pathway by in vivo and in vitro experiments. Male C57BL/6 mice were treated with Rg1 for 3 days before injection of APAP. Serum and liver tissue samples were collected 6 h later. The results indicated that Rg1 significantly attenuated APAP-induced hepatotoxicity and oxidative stress in a dose-dependent manner. Rg1 effectively enhanced antioxidant and detoxification capacity, which is largely dependent on up-regulating Nrf2 nuclear translocation, reducing Keap1 protein expression and up-regulating Nrf2 target genes including GCLC, GCLM, HO-1, NQO1, Ugt1a1, Ugt1a6, Ugt2b1, Sult2a1, Mrp2, Mrp3 and Mrp4. Furthermore, Rg1 repressed the activities of Cyp2e1, Cyp3a11, Cyp1a2, which are important enzymes in the formation of APAP toxic metabolite N-acetyl-p-benzoquinone imine. However, the changes in transporters and enzymes, as well as ameliorative liver histology induced by Rg1 were abrogated by Nrf2 antagonist all-transretinoic acid in vivo and Nrf2 siRNA in vitro. In conclusion, Rg1 produced hepatoprotective effects against APAP-induced acute liver injury via Nrf2 signaling pathway. Rg1 might be an effective approach for the prevention against acute liver injury.


Journal of Gastroenterology and Hepatology | 2018

Effects of calycosin against high fat diet-induced nonalcoholic fatty liver disease in mice

Xingping Duan; Qiang Meng; Changyuan Wang; Zhihao Liu; Huijun Sun; Xiaokui Huo; Pengyuan Sun; Xiaodong Ma; Jinyong Peng; Kexin Liu

Nonalcoholic fatty liver disease (NAFLD) has become a major health concern worldwide. The present study was designed to investigate the effects of calycosin against high‐fat diet (HFD)‐induced NAFLD in mice.


European Journal of Pharmacology | 2018

Protective effects of yangonin from an edible botanical Kava against lithocholic acid-induced cholestasis and hepatotoxicity

Yulong Kong; Xiaoguang Gao; Changyuan Wang; Chenqing Ning; Kexin Liu; Zhihao Liu; Huijun Sun; Xiaodong Ma; Pengyuan Sun; Qiang Meng

&NA; Accumulation of toxic bile acids in liver could cause cholestasis and liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of yangonin, a product isolated from an edible botanical Kava against lithocholic acid (LCA)‐induced cholestasis, and further to elucidate the involvement of farnesoid X receptor (FXR) in the anticholestatic effect using in vivo and in vitro experiments. The cholestatic liver injury model was established by intraperitoneal injections of LCA in C57BL/6 mice. Serum biomarkers and H&E staining were used to identify the amelioration of cholestasis after yangonin treatment. Mice hepatocytes culture, gene silencing experiment, real‐time PCR and Western blot assay were used to elucidate the mechanisms underlying yangonin hepatoprotection. The results indicated that yangonin promoted bile acid efflux and reduced hepatic uptake via an induction in FXR‐target genes Bsep, Mrp2 expression and an inhibition in Ntcp, all of which are responsible for bile acid transport. Furthermore, yangonin reduced bile acid synthesis through repressing FXR‐target genes Cyp7a1 and Cyp8b1, and increased bile acid metabolism through an induction in gene expression of Sult2a1, which are involved in bile acid synthesis and metabolism. In addition, yangonin suppressed liver inflammation through repressing inflammation‐related gene NF‐&kgr;B, TNF‐&agr; and IL‐1&bgr;. In vitro evidences showed that the changes in transporters and enzymes induced by yangonin were abrogated when FXR was silenced. In conclusions, yangonin produces protective effect against LCA‐induced hepatotoxity and cholestasis due to FXR‐mediated regulation. Yangonin may be an effective approach for the prevention against cholestatic liver diseases.

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Kexin Liu

Dalian Medical University

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Changyuan Wang

Dalian Medical University

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Huijun Sun

Dalian Medical University

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Qiang Meng

Dalian Medical University

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Zhihao Liu

Dalian Medical University

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Xiaodong Ma

Dalian Medical University

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Xiaokui Huo

Dalian Medical University

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Jinyong Peng

Dalian Medical University

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Xiaobo Yang

Dalian Medical University

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