Hee-Seung Lee

Inha University, Seoul, Seoul, South Korea

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Publications (18)68.46 Total impact

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    ABSTRACT: Pulsatilla koreana has been used as a traditional medicine for the treatment of various diseases. The purpose of this study was to determine whether SB365, Pulsatilla saponin D isolated from the root of Pulsatilla koreana inhibits the progression of pancreatic cancer. We found that SB365 strongly suppressed the growth and proliferation of 5 human pancreatic cancer cell lines (MIAPaCa-2, BXPC-3, PANC-1, AsPC-1 and HPAC). The apoptotic effect of SB365 was demonstrated by increased levels of cleaved caspase-3 and decreased Bcl-2 expression via mitochondrial membrane potential, as well as elevated numbers of terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL)-positive apoptotic cells. SB365 was also found to exert an anti-angiogenic effect by decreasing the expression of HIF-1α and VEGF, major factors of angiogenesis, which was confirmed by the suppression of tumor sphere formation of pancreatic cancer cells. An in vivo mouse xenograft study showed that SB365 significantly inhibited tumor growth through the induction of apoptosis and inhibition of angiogenesis with strong anticancer activity. Therefore, SB365 is a good candidate as a natural product for use in the treatment of pancreatic cancer.
    Oncology Reports 06/2013; · 2.30 Impact Factor
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    ABSTRACT: SB 365, Pulsatilla saponin D isolated from the root of Pulsatilla koreana has exhibited potential beneficial effects as a chemopreventive agent for critical health conditions including cancer. However, the molecular mechanisms underlying the activity of SB365 remain unknown. Here, we examined anticancer efficacy of SB365 against gastric cancer and its mechanism of action. SB365 effectively inhibited the growth of gastric cancer cells. Its apoptotic effect was accompanied by increased evidence of cleaved caspase-3 and PARP. To elucidate the anticancer mechanism of SB365, we used an array of 42 different receptor tyrosine kinase (RTKs). Of the 42 different phospho-RTKs, SB365 strongly inhibited expression of activated c-Met in gastric cancer cells. Also, the activation of the c-Met signal cascade components, including Akt and mTOR, were inhibited by SB365 in a dose-dependent manner. In angiogenesis studies, SB365 inhibited tube formation in hepatocyte growth factor (HGF)-induced human umbilical vein endothelial cells, and suppressed microvessel sprouting from the rat aortic ring, ex vivo, and blood vessel formation in the Matrigel plug assay in mice. In xenograft animal models, SB365 significantly delayed tumor growth in a dose-dependent manner. In tumor tissue, SB365 suppressed c-Met signaling, proliferation, and angiogenesis, and induced apoptosis. These findings suggest that SB365 docks at an allosteric site on c-Met, and thereby targets c-Met signaling pathway, cell growth/angiogenesis inhibition, and apoptosis induction. Therefore, SB365 may be a novel drug candidate for the treatment of gastric cancer.
    Carcinogenesis 05/2013; · 5.64 Impact Factor
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    ABSTRACT: Peyronie's disease (PD) is fibrosis localized in the tunica albuginea that is characterized by penile deformity and curvature. The pathogenesis of this disease remains unclear even though transforming growth factor‑β (TGF-β)/smad signalling has been reported to be associated with PD. Recent studies have shown that phosphoinositide 3-kinase (PI3K)/Akt signalling regulates fibrotic responses including collagen synthesis and cell proliferation. Thus, we synthesized HS-173, a novel PI3K inhibitor, and determined whether this compound has anti-fibrotic effects on PD-derived primary fibroblasts. In this study, we found that HS-173 inhibited the growth of fibroblasts in a dose-dependent manner and induced apoptosis. In addition, HS-173 reduced the expression of α-smooth muscle actin (α-SMA), vimentin, PAI-1, fibronectin, collagen type I, collagen IV and TGF-β-activated smad2/3 in PD-derived primary fibroblasts. HS-173 blocked the PI3K/Akt signalling pathway by decreasing the activation of Akt, mTOR and P70S6K. Our results showed that HS-173 suppressed fibrotic responses such as cell proliferation and collagen synthesis by blocking PI3K/Akt signalling in PD-derived primary fibroblasts. Our findings provide molecular insights into the potential therapeutic action of HS-173 through targeting the PI3K/Akt pathway in PD-derived fibroblasts and demonstrated that HS-173 could be used as a pharmacological agent for treating other fibrotic diseases.
    International Journal of Oncology 04/2013; · 2.66 Impact Factor
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    ABSTRACT: Among many cancer therapeutic targets, c-Met receptor tyrosine kinase has recently given particular attention. This kinase and its ligand, hepatocyte growth factor (HGF), play a central role in cell proliferation and the survival of several human cancers. Thus, we developed KRC-408 as a novel c-Met inhibitor and investigated its anti-cancer effects on human gastric cancer. KRC-408 inhibited the phosphorylation of c-Met and its constitutive downstream effectors such as phosphatidylinositol 3-kinase (PI3K), Akt, Mek, and Erk. This compound was found to exert anti-cancer effects stronger than those of 5-fluorouracil (5-FU) on gastric cancer cells, especially cell lines that overexpressed c-Met. Interestingly, cytotoxicity of KRC-408 was lower than that of 5-FU in normal gastric cells. Apoptosis induced by KRC-408 was accompanied by increased levels of cleaved caspase-3 and PARP as well as DNA condensation and fragmentation. Flow cytometry analysis showed an accumulation of gastric cancer cells in the G2/M phase with concomitant loss of cells in the S phase following treatment with this drug. In the angiogenesis studies, KRC-408 inhibited tube formation and migration of human umbilical vein endothelial cells (HUVECs), and suppressed microvessel sprouting from rat aortic rings ex vivo along with blood vessel formation in a Matrigel plug assay in mice. Results of an in vivo mouse xenograft experiment showed that the administration of KRC-408 significantly delayed tumor growth in a dose-dependent manner, and suppressed Akt and Erk phosphorylation as well CD34 expression in tumor tissues. These findings indicate that KCR-408 may exert antitumor effects by directly affecting tumor cell growth or survival via the c-Met receptor tyrosine kinase pathway. We therefore suggest that KRC-408 is a novel therapeutic candidate effective against gastric cancers that overexpress c-Met.
    Cancer letters 01/2013; · 4.86 Impact Factor
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    ABSTRACT: Background: A metabolomic study of biomarkers associated with dimethylnitrosamine (DMN)-induced hepatic fibrosis in Sprague-Dawley rats was performed using GC-MS. The clinical chemistry of the collected blood and the histopathology of excised liver samples were examined, and urine samples were prepared by solvent extraction. Results: Through pattern analysis, the DMN-treated group was divided into two subgroups based on the aspartate aminotransferase (AST) levels compared with the control, a moderately higher group (DMN subgroup A) and a significantly higher group (DMN subgroup B). Uric acid, orotic acid, N-phenylacetylglycine and glutaric acid were biomarkers for DMN subgroup A, aminomalonic acid was a biomarker for DMN subgroup B, and arabitol level distinguished control versus DMN treatment regardless of AST level. Conclusion: This study suggests that the identification and profiling of AST level-related metabolites may be useful as a diagnostic tool and for the study of the mechanism of liver fibrosis induced by DMN.
    Bioanalysis 01/2013; 5(1):41-51. · 3.25 Impact Factor
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    ABSTRACT: Pulsatilla koreana has been used as a traditional medicine for the treatment of several diseases. The purpose of this study was to determine if SB365, Pulsatilla saponin D isolated from the root of P. koreana inhibits the progression of colon cancer. We found that SB365 strongly suppressed the growth and proliferation of colon cancer cells and induced their apoptosis. Also, SB365 showed anti-angiogenic activity by decreasing the expression of HIF-1α and VEGF. These results were confirmed by an in vivo study showing that SB365 significantly inhibited tumor growth by the induction of apoptosis and inhibition of angiogenesis with stronger anticancer activity than 5-FU. When further examined for its anticancer mechanism, SB365 effectively suppressed the AKT/mTOR pathway both in vitro and in vivo. Taken together, our study demonstrated that SB365 inhibits the AKT/mTOR pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis. Therefore, SB365 is a good candidate as a natural product for use in the treatment of colon cancer.
    Food Chemistry 01/2013; 136(1):26-33. · 3.33 Impact Factor
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    ABSTRACT: Plants or herb extracts have emerged as a novel approach to controling various diseases, including cancers. Among them, Pulsatilla koreana extract (PKE) has been widely used as an anti-inflammatory agent and for treating dysentery in traditional Korean and Chinese medicine. However, the effect of PKE as a cancer drug candidate has been less reported. Thus, we investigated the effect of PKE on cell growth and its mechanism in anaplastic thyroid cancer (ATC) cells. In this study, PKE suppressed the growth of ATC cells in a dose-dependent manner. Additionally, PKE induced apoptosis by increasing expression of cleaved PARP and caspase-3 in ATC cells. The apoptotic effect of PKE was confirmed by diamidino-2-phenylindole (DAPI) and terminal deoxynucleotidyltransferase-mediated nick end labeling (TUNEL) assay, showing apoptotic body and DNA fragmentation. In addition, PKE decreased the expression of hypoxia-inducible factor 1α (HIF‑1α) and vascular endothelial growth factor (VEGF) as well as inhibiting tube formation and migration of human umbilical vein endothelial cells (HUVECs). Furthermore, in vivo studies showed that PKE significantly inhibited tumor growth and weight in a mouse xenograft model. Taken together, the present study demonstrated that PKE induced apoptosis, as well as inhibiting cell growth and angiogenesis in ATC cells. We suggest that PKE is a potent anticancer drug candidate for the treatment of thyroid cancer.
    Molecular Medicine Reports 11/2012; · 1.17 Impact Factor
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    ABSTRACT: The anticancer effect of a new pyrazole derivative, KI-10F (2-(4-(2-(4-(dimethylamino) phenyl)pyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol‑1-yl) acetonitrile)•3.5HCl) was evaluated in human colon cancer cells. KI-10F strongly suppressed the growth of human colon cancer cells and induced apoptosis by increasing the proportion of sub-G1 presenting apoptotic cells as well as causing cell cycle arrest at the G2/M phase. Apoptosis by KI-10F was confirmed by observation of an increase in the expression of cleaved caspase-3, caspase-8, caspase-9 and Bax, and the decrease of Bcl-2. Decreased expression of HIF-1α and VEGF, and the inhibition of HUVEC tube formation and migration showed that KI-10F effectively inhibited the angiogenesis process. Furthermore, in vivo study in a mouse xenograft model showed that KI-10F produced a stronger antitumor activity than 5-FU, a conventional anticancer drug prescribed for the treatment of colon cancer. The effects of KI-10F on tumor proliferation (PCNA), angiogenesis (CD34) and apoptosis (cleaved caspase-3) were evaluated by immunohistochemistry using isolated tumor tissue samples. Taken together, our results demonstrated that KI-10F induces apoptosis and inhibits cell growth and angiogenesis both in vitro and in vivo. We suggest that KI-10F is an effective chemotherapeutic candidate for use against colon cancer.
    International Journal of Oncology 08/2012; 41(5):1715-22. · 2.66 Impact Factor
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    ABSTRACT: Identification of small molecules that safely inhibit cancer progression is critical for cancer therapeutics. Saponins exhibit cytostatic and cytotoxic activity against various cancer cells, but the mechanism is not well understood. Here, we investigated whether saponin D (designated SB365), an active component isolated from Pulsatilla koreana, could inhibit the progression of hepatocellular carcinoma (HCC) and considered its mechanism. SB365 strongly suppressed the growth of HCC cells in a dose-dependent manner and induced apoptosis by increasing the proportion of sub G1 apoptotic cells from 8% to 21% through induction of expression of Bax and cleaved caspase-3. In addition, SB365 exhibited potent anti-angiogenic activity and decreased the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor, a key molecule for angiogenesis. Furthermore, SB365 suppressed the tube formation and migration of HUVEC, as well as in vivo neovascularization in a mouse Matrigel plug assay. In vivo study showed that SB365 significantly inhibited tumor growth in an HCC xenograft model, inducing apoptosis by increasing the expression of the cleaved caspase-3 and DNA fragmentation. The expressions of vascular endothelial growth factor and CD34 in the tumor tissue were decreased by SB365 treatment. In examining its mechanism, SB365 was found to effectively suppress the phosphorylation of PI3K downstream factors, such as Akt, mTOR and p70S6K both in vitro and in vivo. Our study demonstrates that SB365 not only induces apoptosis but also inhibits cell growth and angiogenesis through modulation of the PI3K/Akt/mTOR pathway in human HCC. We suggest that SB365 may be a new chemotherapeutic candidate against HCC.
    Cancer Science 08/2012; · 3.48 Impact Factor
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    ABSTRACT: Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway frequently instigates tumorigenesis leading to hepatocellular carcinoma (HCC). We synthesized N-(5-(3-(3-methyl-1,2,4-oxadiazol-3-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (HS-104), a novel PI3K inhibitor, and investigated its in vitro anticancer effect and in vivo capacity in an animal xenograft model. The inhibition of cell growth by HS-104 revealed that it was effective against HCC cell lines. Also, the activation of the AKT/mTOR signal cascade was inhibited by HS-104 treatment in a dose dependent manner. Flow cytometry analysis showed an accumulation of HCC cells in the G2/M phase with concomitant loss of cells in the S phase. The apoptotic effect of HS-104 was accompanied by increased evidence of cleaved caspase-3 and PARP, as well as DNA fragmentation. In angiogenesis studies, HS-104 inhibited the tube formation of vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cells (HUVECs), and suppressed microvessel sprouting from a rat aortic ring, ex vivo, and blood vessel formation in the Matrigel plug assay in mice. HS-104 inhibited the expression of the downstream proteins of PI3K including p-AKT, p-mTOR and p-p70S6K in VEGF-induced HUVECs. In the xenograft animal model, HS-104 significantly delayed tumor growth in a dose dependent manner and suppressed the expression of PCNA, CD34 and cleaved caspase-3 in tumor tissue. These studies show that HS-104 inhibited the PI3K/AKT/mTOR signaling pathway resulting in cell growth/angiogenesis inhibition and apoptosis induction. Therefore, HS-104 is considered as a novel drug candidate for the treatment of HCC.
    Cancer letters 08/2012; · 4.86 Impact Factor
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    ABSTRACT: Fucoidan, a sulfated polysaccharide extracted from various brown seaweeds, possesses a wide range of pharmacological properties. In this study, we investigated the protective effect of fucoidan on acetaminophen-induced acute liver injury in rats. Liver injury was induced by administration of acetaminophen (800 mg/kg, i.p.) and fucoidan was administered (100 mg kg, p.o.) 2 h before and after acetaminophen administration. After 24 h, co-treatment of fucoidan ameliorated liver damage and cell death induced by acetaminophen. Acetaminophen induced the overexpression of CYP2E1, one of the metabolizing enzymes of acetaminophen, but cotreatment with fucoidan suppressed its increased expression of CYP2E1. Fucoidan also reduced the hepatic apoptosis induced by acetaminophen exposure as shown in the protein expression of Bax, Bcl-2, and cleaved caspase-3. The anti-oxidative effect of fucoidan was observed from the increase of the production and expression of glutathione, superoxide dismutase, and glutathione peroxidase, both of which were decreased by acetaminophen. Also, fucoidan decreased the expression of inflammatory mediators, including tumor necrosis factoralpha, interleukin 1 beta, and inducible nitric oxide synthase. Taken together, the data demonstrate the hepato-protective effects of fucoidan against acetaminophen-induced liver injury via anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms.
    Archives of Pharmacal Research 06/2012; 35(6):1099-105. · 1.54 Impact Factor
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    ABSTRACT: The phosphatidylinositol 3-kinase (PI3K) pathway plays a central role in cell proliferation and survival of human cancers. As PI3K is active in many cancer patients, resulting in cancer development and progression, we developed an azaindole derivative, HS-116 as a novel PI3K inhibitor. This study aimed to clarify the anticancer effect of HS-116 in human hepatocellular carcinoma (HCC). To identify the effect of HS-116 on HCC cells, a PI3K assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blotting were conducted. IC(50) of HS-116 for PI3Kα was 31nM, and it effectively suppressed the phosphorylation of PI3K downstream factors such as AKT, mTOR, p70S6K, and 4EBP1. Also, HS-116 induced apoptosis by increasing the proportion of sub-G1 apoptotic cells from 1.8% to 35% and increasing the expressions of Bax, cleaved-caspase-3, and cleaved-PARP as well as decreasing the expression of Bcl-2. In addition, chromatin condensation and apoptotic bodies were detected in HS-116-treated HCC cells. Furthermore, HS-116 decreased protein expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), and inhibited the tube formation and migration of human umbilical vein endothelial cells (HUVECs). In vivo, the ability of mice to vascularize subcutaneously implanted Matrigel plugs was diminished when the mice were treated with HS-116. These results show that HS-116 inhibits the PI3K/AKT/mTOR pathway via apoptosis and anti-angiogenesis in HCC cells. We suggest that HS-116 may be an effective novel therapeutic candidate against HCC.
    Cancer letters 11/2011; 316(2):187-95. · 4.86 Impact Factor
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    ABSTRACT: Chemoprevention through the use of food and plants has emerged as a novel approach to control various malignancies including cancer. Pulsatilla koreana extract (PKE) has been used to treat malaria and dysentery. The functions and effect of PKE in cancer treatment have been reported but with less information. In this study, we investigated the effect of PKE on the progression of hepatocellular carcinoma (HCC) cells and its mechanism. PKE strongly suppressed the growth of HCC cells in a dose-dependent manner. Apoptosis by PKE was observed by DAPI and TUNEL staining and accompanied with increases of cleaved PARP and caspase-3 in Huh-7 cells. Also, PKE decreased the expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF), and inhibited tube formation and migration of human umbilical vein endothelial cells (HUVECs). In addition, PKE potently suppressed in vivo neovascularization in a mouse Matrigel plug assay. Furthermore, in vivo study showed that PKE significantly inhibited tumor growth in a mouse xenograft model, and induced apoptosis by increasing the cleaved PARP and caspase-3. The expressions of Ki-67, VEGF, and CD31 in the tumor tissue were decreased by the treatment of PKE. Taken together, our study demonstrates that PKE not only induced apoptosis but also inhibited cell growth and angiogenesis of human HCC. We suggest that PKE is an effective chemotherapeutic candidate for cancer therapy against HCC.
    International Journal of Oncology 09/2011; 40(2):452-60. · 2.66 Impact Factor
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    ABSTRACT: Fucoidan, a sulfated polysaccharide extracted from various types of brown seaweed, possesses a wide range of pharmacological properties. We investigated the protective effect of fucoidan on dimethylnitrosamine-induced liver fibrogenesis in rats and its mechanism. Liver fibrosis was induced by injecting DMN (10 mg/kg, 3 times per week, I.P.) for 4 weeks, and fucoidan was simultaneously administered (100 mg/kg, 3 times per week, P.O.). The anti-oxidative and anti-inflammatory effects of fucoidan were observed by relative mediators. Fucoidan improved liver fibrosis by inhibiting the expression of transforming growth factor beta 1 (TGF-β(1))/Smad3 and the tissue inhibitor of metalloproteinase 1 (TIMP-1), and increasing the expression of metalloproteinase-9 (MMP-9). Fucoidan also significantly decreased the accumulation of the extracellular matrix (ECM) and collagen. These results suggest that fucoidan had an anti-fibrotic effect, which was exerted by inhibiting the TGF-β/Smad pathway, as well as anti-oxidative and anti-inflammatory effects.
    Bioscience Biotechnology and Biochemistry 05/2011; 75(5):833-40. · 1.27 Impact Factor
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    ABSTRACT: Acute pancreatitis (AP) has a high mortality rate; repetitive AP induces chronic AP and pancreatic adenocarcinoma. Mesenchymal stem cells (MSCs) have immunoregulatory effects and reduce inflammation. We developed a protocol to isolate human bone marrow-derived clonal MSCs (hcMSCs) from bone marrow aspirate and investigated the effects of these cells in rat models of mild and severe AP. Mild AP was induced in Sprague-Dawley rats by 3 intraperitoneal injections of cerulein (100 μg/kg), given at 2-hour intervals; severe AP was induced by intraparenchymal injection of 3% sodium taurocholate solution. hcMSCs were labeled with CM-1,1'-dioctadecyl-3,3,3'-tetramethylindo-carbocyanine perchloride and administered to rats through the tail vein. hcMSCs underwent self-renewal and had multipotent differentiation capacities and immunoregulatory functions. Greater numbers of infused hcMSCs were detected in pancreas of rats with mild and severe AP than of control rats. Infused hcMSCs reduced acinar-cell degeneration, pancreatic edema, and inflammatory cell infiltration in each model of pancreatitis. The hcMSCs reduced expression of inflammation mediators and cytokines in rats with mild and severe AP. hcMSCs suppressed the mixed lymphocyte reaction and increased expression of Foxp3(+) (a marker of regulatory T cells) in cultured rat lymph node cells. Rats with mild or severe AP that were given infusions of hcMSCs had reduced numbers of CD3(+) T cells and increased expression of Foxp3(+) in pancreas tissues. hcMSCs reduced inflammation and damage to pancreatic tissue in a rat model of AP; they reduced levels of cytokines and induced numbers of Foxp3(+) regulatory T cells. hcMSCs might be developed as a cell therapy for pancreatitis.
    Gastroenterology 12/2010; 140(3):998-1008. · 12.82 Impact Factor
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    ABSTRACT: Oxidative stress in liver injury is a major pathogenetic factor in progress of liver fibrosis. Resveratrol, a representative antioxidant derived from grapes, has been reported to show widespread pharmacological properties. In this study, we investigated the protective effects of resveratrol on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Rats were treated with resveratrol daily by oral gavage for seven days after a single intraperitoneal injection of DMN (40 mg/kg). Resveratrol remarkably recovered body and liver weight loss due to DMN-induced liver fibrosis. Liver histology showed that resveratrol alleviated the infiltration of inflammatory cells and fibrosis of liver tissue. Resveratrol decreased the level of malondialdehyde and increased the levels of glutathione peroxidase and superoxide dismutase. Also, resveratrol significantly inhibited the mRNA expression of inflammatory mediators including inducible nitric oxide, tumor necrosis factor-alpha and interleukin-1beta. In addition, resveratrol showed not only reduced mRNA expression of fibrosis-related genes such as transforming growth factor beta 1, collagen type I, and alpha-smooth muscle actin, but also a significant decrease of hydroxyproline in rats with DMN-induced liver fibrosis. Our results suggest that resveratrol could be used to treat liver injury and fibrosis and be useful in preventing the development of liver fibrosis and cirrhosis.
    Archives of Pharmacal Research 04/2010; 33(4):601-9. · 1.54 Impact Factor
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    ABSTRACT: Melatonin exhibits a wide variety of biological effects, including antioxidant and anti-inflammatory functions. Its antioxidant role impedes the etiopathogenesis of pancreatitis, but little is known about the signaling pathway of melatonin in the induction of antioxidant enzymes in acute pancreatitis (AP). The aim of this study was to determine whether melatonin could prevent cerulein-induced AP through nuclear factor erythroid 2-related factor 2 (Nrf2) and curtail inflammation by inhibition of NF-kappaB. AP was induced by two intraperitoneal (i.p.) injections of cerulein at 2 h intervals (50 microg/kg) in Sprague-Dawley rats. Melatonin (10 or 50 mg/kg/daily, i.p.) was administered 24 h before each injection of cerulein. The rats were killed 12 h after the last injection. Acinar cell degeneration, pancreatic edema, and inflammatory infiltration were significantly different in cerulein- and melatonin-treated rats. Melatonin significantly reduced amylase, lipase, MPO, and MDA levels, and increased antioxidant enzyme activities including SOD and GPx, which were decreased in AP (P < 0.05). Melatonin increased the expression of NQO1, HO-1, and SOD2 when compared with the cerulein-induced AP group (P < 0.05). In addition, melatonin increased Nrf2 expression, and reduced expressions of tumor necrosis factor-alpha, IL-1beta, IL-6, IL-8, and iNOS. The elevated nuclear binding of NF-kappaB in the cerulein-induced pancreatitis group was inhibited by melatonin. These results show that melatonin increases antioxidant enzymes and Nrf2 expression, and limits inflammatory mediators in cerulein-induced AP. It is proposed that melatonin may play an important role in oxidative stress via the Nrf2 pathway in parallel with reduction of inflammation by NF-kappaB inhibition.
    Journal of Pineal Research 03/2010; 48(3):239-50. · 7.30 Impact Factor
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    ABSTRACT: Morin, a plant-derived flavonoid, has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the protective effect of morin on hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Oral administration of morin remarkably prevented weight loss in the body and liver from DMN and inhibited the elevation of serum alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin levels. For the evaluation of hepatic fibrosis-related factors, we investigated expressions of collagen type I, transforming growth factor beta(1) (TGF-beta(1)), and alpha-smooth muscle actin (alpha-SMA) in mRNA and protein levels. We observed that morin significantly reduced the expression of collagen type I, TGF-beta(1), and alpha-SMA on hepatic fibrosis induced by DMN. Taken together, this study demonstrated that morin showed hepatoprotective and antifibrogenic effects against DMN-induced hepatic injury. This suggests that morin may be useful in preventing the development of hepatic fibrosis and cirrhosis.
    Digestive Diseases and Sciences 04/2009; 54(4):782-8. · 2.26 Impact Factor