Publications by authors named "Kiwon Jung"

34 Publications

Identification of gallic acid as a active ingredient of Syzygium aromaticum against tacrolimus-induced damage in renal epithelial LLC-PK1 cells and rat kidney.

Bioorg Med Chem Lett 2021 Jun 8;41:128012. Epub 2021 Apr 8.

College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea. Electronic address:

Tacrolimus (FK506), a calcineurin inhibitor, is an effective immunosuppressive agent mainly used to lower the risk of organ rejection after allogeneic organ transplant. However, FK506-associated adverse effects, such as nephrotoxicity, may limit its therapeutic use. In this study, we confirmed that epigallocatechin-3-gallate (EGCG), sanguiin H-6, and gallic acid increased cell survival following FK506-induced cytotoxicity in renal epithelial LLC-PK1. Among these compounds, gallic acid exerted the strongest protective effect, further confirmed in the FK506-induced nephrotoxicity rat model. Additionally, we identified supporting evidence for the nephroprotective function of gallic acid using molecular docking and bioavailability investigations.
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http://dx.doi.org/10.1016/j.bmcl.2021.128012DOI Listing
June 2021

Discovery of novel potent migrastatic Thiazolo[5,4-b]pyridines targeting Lysyl-tRNA synthetase (KRS) for treatment of Cancer metastasis.

Eur J Med Chem 2021 Jun 30;218:113405. Epub 2021 Mar 30.

College of Pharmacy, CHA University, Gyeonggi-do, 11160, Republic of Korea; College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address:

Recently, non-canonical roles of Lysyl-tRNA Synthetase (KRS), which is associated with cell migration and cancer metastasis, have been reported. Therefore, KRS has emerged as a promising target for the treatment of cell migration-related diseases, especially cancer metastasis, although the satisfying chemical inhibitors targeting KRS have not yet been identified. Here, we report the discovery of novel, mechanistically unique, and potent cell migration inhibitors targeting KRS, including the chemical and biological studies on the most effective N,N-dialkylthiazolo [5,4-b]pyridin-2-amine (SL-1910). SL-1910 exhibited highly potent migration inhibition (EC = 81 nM against the mutant KRS-overexpressed MDA-MB-231 cells) and was superior to the previously reported KRS inhibitor (migration inhibitory EC = 8.5 μM against H226 cells). The KRS protein binding study via fluorescence-based binding titration and KRS protein 2D-NMR mapping study, in vitro concentration-dependent cell migration inhibition, and in vivo anti-metastatic activity of SL-1910, which consists of a new scaffold, have been reported in this study. In addition, in vitro absorption, distribution, metabolism, and excretion studies and mouse pharmacokinetics experiments for SL-1910 were conducted.
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http://dx.doi.org/10.1016/j.ejmech.2021.113405DOI Listing
June 2021

Facile and Rapid Isolation of Oxypeucedanin Hydrate and Byakangelicin from by Using [Bmim]TfN Ionic Liquid.

Molecules 2021 Feb 5;26(4). Epub 2021 Feb 5.

Institute of Pharmaceutical Sciences, College of Pharmacy, CHA University, Sungnam 13844, Korea.

Ionic liquids (ILs) have sparked much interest as alternative solvents for plant materials as they provide distinctive properties. Therefore, in this study, the capacity of ILs to extract oxypeucedanin hydrate and byakangelicin from the roots of () was investigated. The back-extraction method was examined to recover target components from the IL solution as well. Herein, [Bmim]TfN demonstrated outstanding performance for extracting oxypeucedanin hydrate and byakangelicin. Moreover, factors including solvent/solid ratio, extraction temperature and time were investigated and optimized using a statistical approach. Under optimum extraction conditions (solvent/solid ratio 8:1, temperature 60 °C and time 180 min), the yields of oxypeucedanin hydrate and byakangelicin were 98.06% and 99.52%, respectively. In addition, 0.01 N HCl showed the most significant ability to back-extract target components from the [Bmim]TfN solution. The total content of both oxypeucedanin hydrate (36.99%) and byakangelicin (45.12%) in the final product exceeded 80%. Based on the data, the proposed approach demonstrated satisfactory extraction ability, recovery and enrichment of target compounds in record time. Therefore, the developed approach is assumed essential to considerably reduce drawbacks encountered during the separation of oxypeucedanin hydrate and byakangelicin from the roots of
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http://dx.doi.org/10.3390/molecules26040830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915976PMC
February 2021

Protective Effect of γ-mangostin Isolated from the Peel of against Glutamate-Induced Cytotoxicity in HT22 Hippocampal Neuronal Cells.

Biomolecules 2021 01 27;11(2). Epub 2021 Jan 27.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-lo, Gwanak-gu, Seoul 08826, Korea.

The aim of the present study was to examine the protective effect of γ-mangostin, a component of the mangosteen shell, against oxidative damage to nerve cells induced by excessive glutamate, a known excitatory neurotransmitter. To investigate the effect of γ-mangostin on apoptosis, 5 mM of glutamate was used to induce apoptotic cell death in mouse hippocampal HT22 cells. In this study, γ-mangostin was found to exert a stronger protection than N-acetyl cysteine against glutamate-induced cell damage. γ-Mangostin showed prevented glutamate-induced apoptosis in HT22 cells by reducing the production of reactive oxygen species and stimulating the expression of heme oxygenase-1 protein. In addition, glutamate significantly induced the accumulation of intracellular calcium ions, whereas treatment with γ-mangostin markedly reduced it. Hoechst 33342 staining showed an improvement in glutamate-induced nuclear condensation following γ-mangostin treatment. Furthermore, the number of annexin V-positive cells was significantly reduced following treatment with γ-mangostin. Western blot analysis showed the inhibition of glutamate-induced mitogen-activated protein kinase phosphorylation by γ-mangostin. γ-mangostin also inhibited the regulation of the intrinsic mitochondrial apoptotic pathway. Thus, the results of this study suggest that γ-mangostin is an active ingredient of mangosteen and exerts neuroprotective activities in HT22 cells.
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http://dx.doi.org/10.3390/biom11020170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910862PMC
January 2021

The Effects of Triterpenoid Saponins from the Seeds of on Adipocyte Differentiation and Mature Adipocyte Inflammation.

Plants (Basel) 2020 Aug 3;9(8). Epub 2020 Aug 3.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.

Obesity is a medical condition in which abnormal or excessive fat accumulates to an extent that is associated with various diseases. In our ongoing research to figure out natural products with anti-obesity effects, a phytochemical investigation of the EtOH extract of the seeds of was carried out, which resulted in the isolation of two major triterpenoid saponins: gypsogenin 3---d-galactopyranosyl(1→2)-[-l-rhamnopyranosyl (1→3)]--d-glucuronopyranoside () and quillaic acid 3---d-galactopyranosyl(1→2)-[-l-rhamnopyranosyl(1→3)]--d-glucuronopyranoside (). Then, the effects of the isolated triterpenoid saponins ( and ) on adipocyte differentiation were evaluated, and it was demonstrated that the isolated saponin () showed inhibitory effects on adipogenesis. In mature adipocytes, the isolated saponin () reversed tumor necrosis factor α (TNFα)-induced proinflammatory cytokine gene expression. Additionally, the isolated saponin () reduced lipolytic gene expression leading to decreased basal lipolysis activity. Collectively, these findings suggest that saponin () of exerts beneficial effects in the regulation of adipogenesis and adipocyte inflammation and could be a potential therapeutic alternative in the treatment of obesity-induced metabolic diseases.
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http://dx.doi.org/10.3390/plants9080984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466054PMC
August 2020

Cyanidin Chloride Induces Apoptosis by Inhibiting NF-κB Signaling through Activation of Nrf2 in Colorectal Cancer Cells.

Antioxidants (Basel) 2020 Mar 27;9(4). Epub 2020 Mar 27.

College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam, 13488, Korea.

Colorectal cancer (CRC) is the third most common cancer worldwide and a leading cause of cancer-related deaths in developed countries. Anthocyanins are a class of flavonoids, widely distributed in food, exhibiting important biological effects. Cyanidin chloride (CyCl) is the common type of anthocyanin with antioxidative and anti-inflammatory potential. The present study aimed to investigate the molecular mechanisms underlying the chemotherapeutic effects of CyCl in colorectal cancer cells. We found that CyCl treatment induced apoptosis as well as a significant inhibition of cellular proliferation and colony formation in three colon cancer HCT116, HT29, and SW620 cells. In addition, CyCl suppressed nuclear factor-kappa B (NF-κB) signaling and induced the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in tumor necrosis factor-alpha (TNF-α)-stimulated colon cancer cells. Nrf2 and NF-κB are two key transcription factors regulating antioxidative responses and cellular proliferation, respectively. In this study, knockdown of Nrf2 by small interfering RNA (siRNA) transfection inhibited the effect of CyCl on NF-κB signaling and apoptosis, suggesting that there is functional crosstalk between Nrf2 and NF-κB. Our findings demonstrate the important role of Nrf2 in inducing apoptosis through the involvement of NF-κB signaling in colorectal cancer cells, suggesting that CyCl may be used as a potential therapeutic agent for CRC.
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http://dx.doi.org/10.3390/antiox9040285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222181PMC
March 2020

The Inhibitory Effect of Cordycepin on the Proliferation of MCF-7 Breast Cancer Cells, and its Mechanism: An Investigation Using Network Pharmacology-Based Analysis.

Biomolecules 2019 08 26;9(9). Epub 2019 Aug 26.

College of Korean Medicine, Gachon University, Seongnam 13120, Korea.

is a well-known medicinal mushroom. It is non-toxic and has clinical health benefits including cancer inhibition. However, the anticancer effects of cultured in brown rice on breast cancer have not yet been reported. In this study, we simultaneously investigated the anticancer effects of cordycepin and an extract of cultured in brown rice on MCF-7 human breast cancer cells using a cell viability assay, cell staining with Hoechst 33342, and an image-based cytometric assay. The concentrate exhibited significant MCF-7 cell inhibitory effects, and its IC value was 73.48 µg/mL. Cordycepin also exhibited significant MCF-7 cell inhibitory effects, and its IC value was 9.58 µM. We applied network pharmacological analysis to predict potential targets and pathways of cordycepin. The gene set enrichment analysis showed that the targets of cordycepin are mainly associated with the hedgehog signaling, apoptosis, p53 signaling, and estrogen signaling pathways. We further verified the predicted targets related to the apoptosis pathway using western blot analysis. The concentrate and cordycepin exhibited the ability to induce apoptotic cell death by increasing the cleavage of caspase-7 -8, and -9, increasing the Bcl-2-associated X protein/ B-cell lymphoma 2 (Bax/Bcl-2) protein expression ratio, and decreasing the protein expression of X-linked inhibitor of apoptosis protein (XIAP) in MCF-7 cells. Consequently, the concentrate and cordycepin exhibited significant anticancer effects through their ability to induce apoptosis in breast cancer cells.
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http://dx.doi.org/10.3390/biom9090414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770402PMC
August 2019

The Inhibitory Effect of Cordycepin on the Proliferation of MCF-7 Breast Cancer Cells, and its Mechanism: An Investigation Using Network Pharmacology-Based Analysis.

Biomolecules 2019 08 23;9(9). Epub 2019 Aug 23.

College of Korean Medicine, Gachon University, Seongnam 13120, Korea.

is a well-known medicinal mushroom. It is non-toxic and has clinical health benefits including cancer inhibition. However, the anticancer effects of cultured in brown rice on breast cancer have not yet been reported. In this study, we simultaneously investigated the anticancer effects of cordycepin and an extract of cultured in brown rice on MCF-7 human breast cancer cells using a cell viability assay, cell staining with Hoechst 33342, and an image-based cytometric assay. The concentrate exhibited significant MCF-7 cell inhibitory effects, and its IC value was 73.48 µg/mL. Cordycepin also exhibited significant MCF-7 cell inhibitory effects, and its IC value was 9.58 µM. We applied network pharmacological analysis to predict potential targets and pathways of cordycepin. The gene set enrichment analysis showed that the targets of cordycepin are mainly associated with the hedgehog signaling, apoptosis, p53 signaling, and estrogen signaling pathways. We further verified the predicted targets related to the apoptosis pathway using western blot analysis. The concentrate and cordycepin exhibited the ability to induce apoptotic cell death by increasing the cleavage of caspase-7 -8, and -9, increasing the Bax/Bcl-2 protein expression ratio, and decreasing the protein expression of XIAP in MCF-7 cells. Consequently, the concentrate and cordycepin exhibited significant anticancer effects through their ability to induce apoptosis in breast cancer cells.
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http://dx.doi.org/10.3390/biom9090407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770084PMC
August 2019

Rapid and Efficient Separation of Decursin and Decursinol Angelate from Nakai using Ionic Liquid, (BMIm)BF, Combined with Crystallization.

Molecules 2019 Jun 28;24(13). Epub 2019 Jun 28.

College of Pharmacy, CHA University, Sungnam 13844, Korea.

Ionic liquids (ILs) have gained much attention as alternative solvents to volatile organic solvents due to their attractive properties. This study aimed to develop an efficient method for the selective separation of decursin (D) and decursinol angelate (DA) from Nakai () using ILs and crystallization. The IL 1-butyl-3-methylimidazolium tetrafluoroborate ((BMIm)BF) was the most efficient at extracting D and DA. Parameters including solid-to-liquid ratio, time, and temperature were optimized by response surface methodology (RSM). Under optimal extraction conditions (1 g/6.5 mL solid-to-liquid ratio, 60 °C temperature, and 120 min time), the extraction yields of D and DA were 43.32 mg/g (97.06%) and 17.87 mg/g (97.12%), respectively. Moreover, drowning out crystallization using deionized water (DW) as an anti-solvent offered an excellent ability to recover D and DA from the -(BMIm)BF extraction solution. The rates of recovery and the total purity of D and DA were found to be greater than 97%. Therefore, a rapid and efficient method of combining ILs with crystallization was effectively achieved for the selective separation of D and DA. This approach is assumed to be beneficial in the pharmaceutical industry for the effective obtention of D- and DA-enriched products.
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http://dx.doi.org/10.3390/molecules24132390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651083PMC
June 2019

MD001, a Novel Peroxisome Proliferator-activated Receptor α/γ Agonist, Improves Glucose and Lipid Metabolism.

Sci Rep 2019 02 7;9(1):1656. Epub 2019 Feb 7.

College of Pharmacy, Ajou University, Suwon, Gyeonggi-do, 16499, Korea.

Peroxisome proliferator-activated receptor (PPAR)-α/γ dual agonists have been developed to treat metabolic diseases; however, most of them exhibit side effects such as body weight gain and oedema. Therefore, we developed a novel PPARα/γ dual agonist that modulates glucose and lipid metabolism without adverse effects. We synthesised novel compounds composed of coumarine and chalcone, determined their crystal structures, and then examined their binding affinity toward PPARα/γ. We investigated the expression of PPARα and PPARγ target genes by chemicals in HepG2, differentiated 3T3-L1, and C2C12 cells. We examined the effect of chemicals on glucose and lipid metabolism in db/db mice. Only MD001 functions as a PPARα/γ dual agonist in vitro. MD001 increased the transcriptional activity of PPARα and PPARγ, resulting in enhanced expression of genes related to β-oxidation and fatty acid and glucose uptake. MD001 significantly improved blood metabolic parameters, including triglycerides, free fatty acids, and glucose, in db/db mice. In addition, MD001 ameliorated hepatic steatosis by stimulating β-oxidation in vitro and in vivo. Our results demonstrated the beneficial effects of the novel compound MD001 on glucose and lipid metabolism as a PPARα/γ dual agonist. Consequently, MD001 may show potential as a novel drug candidate for the treatment of metabolic disorders.
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http://dx.doi.org/10.1038/s41598-018-38281-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367362PMC
February 2019

Kinetics of the Solution-Mediated Polymorphic Transformation of the Novel l-Carnitine Orotate Polymorph, Form-II.

Pharmaceutics 2018 Oct 1;10(4). Epub 2018 Oct 1.

Institute of Pharmaceutical Sciences, College of Pharmacy, CHA University, Sungnam 13844, Korea.

Research studies related to the polymorphs of l-Carnitine orotate (CO), a medication used for the treatment and prevention of liver diseases, are insignificant or almost nonexistent. Accordingly, in the present study, l-Carnitine orotate (CO) was prepared for investigating CO polymorphs. Here, a reactive crystallization was induced by reacting 1g of l-Carn (1 equivalent) and 0.97 g of OA (1 equivalent) in methanol (MeOH); as a result, CO form-I and CO form-II polymorphs were obtained after 1 h and 16 h of stirring, respectively. The characterization of CO polymorphs was carried out utilizing Powder X-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and solid-state Nuclear Magnetic Resonance Spectroscopy (solid-state CP/MAS C-NMR). The solution-mediated polymorphic transformation (SMPT) of CO polymorphs was investigated in MeOH at controlled temperature and fixed rotational speed. The results revealed that CO form-I is a metastable polymorph while CO form-II is a stable polymorph. From the same results, it was confirmed that CO form-I was converted to CO form-II during the polymorphic phase transformation process. Moreover, it was assessed that the increase in temperature and supersaturation level significantly promotes the rate of nucleation, as well as the rate of mass transfer of CO form-II. In addition, nucleation and mass transfer equations were employed for the quantitative determination of SMPT experimental results. Lastly, it was suggested that CO form-II was more thermodynamically stable than CO form-I and that both polymorphs belong to the monotropic system.
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http://dx.doi.org/10.3390/pharmaceutics10040171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321437PMC
October 2018

Co-Amorphous Screening for the Solubility Enhancement of Poorly Water-Soluble Mirabegron and Investigation of Their Intermolecular Interactions and Dissolution Behaviors.

Pharmaceutics 2018 Sep 5;10(3). Epub 2018 Sep 5.

Institute of Pharmaceutical Sciences, College of Pharmacy, CHA University, Sungnam 13844, Korea.

In the present study, the screening of Mirabegron (MBR) co-amorphous was performed to produce water-soluble and thermodynamically stable MBR co-amorphous with the purpose of overcoming the water solubility problem of MBR. MBR is Biopharmaceutics Classification System (BCS) class II drug used for the treatment of an overreactive bladder. The co-amorphous screening was carried out by means of the vacuum evaporation crystallization technique in methanol solvent using three water-soluble carboxylic acids, characterized by a pKa difference greater than 3 with MBR such as fumaric acid (FA), l-pyroglutamic acid (PG), and citric acid (CA). Powder X-ray diffraction (PXRD) results suggested that all solid materials produced at MBR-FA (1 equivalent (eq.)/1 equivalent (eq.)), MBR-PG (1 eq./1 eq.), and MBR-CA (1 eq./1 eq.) conditions were amorphous state solid materials. Furthermore, by means of solution-state nuclear magnetic resonance (NMR) (¹H, C, and 2D) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, we could assess that MBR and carboxylic acid molecules were linked via ionic interactions to produce MBR co-amorphous. Besides, solid-state cross polarization (CP)/magic angle spinning (MAS) C-NMR analysis was conducted for additional assessment of MBR co-amorphous. Afterwards, dissolution tests of MBR co-amorphouses, MBR crystalline solid, and MBR amorphous were carried out for 12 h to evaluate and to compare their solubilities, dissolution rates, and phase transformation phenomenon. Here, the results suggested that MBR co-amorphouses displayed more than 57-fold higher aqueous solubility compared to MBR crystalline solid, and PXRD monitoring result suggested that MBR co-amorphouses were able to maintain their amorphous state for more than 12 h. The same results revealed that MBR amorphous exhibited increased solubility of approximatively 6.7-fold higher compared to MBR crystalline solid. However, the PXRD monitoring result suggested that MBR amorphous undergo rapid phase transformation to crystalline form in just 35 min and that within an hour all MBR amorphous are completely converted to crystalline solid. Accordingly, the increase in MBR co-amorphous' solubility was attributed to the presence of ionic interactions in MBR co-amorphous molecules. Moreover, from the differential scanning calorimetry (DSC) monitoring results, we predicted that the high glass transition temperature () of MBR co-amorphous compared to MBR amorphous was the main factor influencing the phase stability of MBR co-amorphous.
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http://dx.doi.org/10.3390/pharmaceutics10030149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161252PMC
September 2018

Beneficial effects of for the treatment and prevention of neurodegenerative diseases: past findings and future directions.

J Ginseng Res 2018 Jul 15;42(3):239-247. Epub 2017 Apr 15.

College of Korean Medicine, Gachon University, Seongnam, Republic of Korea.

In recent years, several therapeutic drugs have been rationally designed and synthesized based on the novel knowledge gained from investigating the actions of biologically active chemicals derived from foods, plants, and medicinal herbs. One of the major advantages of these naturalistic chemicals is their ability to interact with multiple targets in the body resulting in a combined beneficial effect. Ginseng is a perennial herb (Araliaceae family), a species within the genus , and a highly valued and popular medicinal plant. Evidence for the medicinal and health benefits of and its components in preventing neurodegeneration has increased significantly in the past decade. The beneficial effects of on neurodegenerative diseases have been attributed primarily to the antioxidative and immunomodulatory activities of its ginsenoside components. Mechanistic studies on the neuroprotective effects of ginsenosides revealed that they act not only as antioxidants but also as modulators of intracellular neuronal signaling and metabolism, cell survival/death genes, and mitochondrial function. The goal of the present paper is to provide a brief review of recent knowledge and developments concerning the beneficial effects as well as the mechanism of action of and its components in the treatment and prevention of neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.jgr.2017.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035378PMC
July 2018

Alpha-Mangostin Improves Insulin Secretion and Protects INS-1 Cells from Streptozotocin-Induced Damage.

Int J Mol Sci 2018 May 16;19(5). Epub 2018 May 16.

College of Korean Medicine, Gachon University, Seongnam 13120, Korea.

Alpha (α)-mangostin, a yellow crystalline powder with a xanthone core structure, is isolated from mangosteen (), which is a tropical fruit of great nutritional value. The aim of the present study was to investigate the anti-diabetic effects of α-mangostin and to elucidate the molecular mechanisms underlying its effect on pancreatic beta (β)-cell dysfunction. To assess the effects of α-mangostin on insulin production, rat pancreatic INS-1 cells were treated with non-toxic doses of α-mangostin (1⁻10 μM) and its impact on insulin signaling was examined by Western blotting. In addition, the protective effect of α-mangostin against pancreatic β-cell apoptosis was verified by using the β-cell toxin streptozotocin (STZ). Our results showed that α-mangostin stimulated insulin secretion in INS-1 cells by activating insulin receptor (IR) and pancreatic and duodenal homeobox 1 (Pdx1) followed by phosphorylation of phospho-phosphatidylinositol-3 kinase (PI3K), Akt, and extracellular signal regulated kinase (ERK) signaling cascades, whereas it inhibited the phosphorylation of insulin receptor substrate (IRS-1) (Ser1101). Moreover, α-mangostin was found to restore the STZ-induced decrease in INS-1 cell viability in a dose-dependent manner. In addition, treatment of INS-1 cells with 50 μM STZ resulted in an increase in intracellular reactive oxygen species (ROS) levels, which was represented by the fluorescence intensity of 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). This oxidative stress was decreased by co-treatment with 5 μM α-mangostin. Similarly, marked increases in the phosphorylation of P38, c-Jun N-terminal kinase (JNK), and cleavage of caspase-3 by STZ were decreased significantly by co-treatment with 5 μM α-mangostin. These results suggest that α-mangostin is capable of improving insulin secretion in pancreatic β-cells and protecting cells from apoptotic damage.
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http://dx.doi.org/10.3390/ijms19051484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983655PMC
May 2018

Protective effect of ginsenoside Rb1 against tacrolimus-induced apoptosis in renal proximal tubular LLC-PK1 cells.

J Ginseng Res 2018 Jan 10;42(1):75-80. Epub 2017 Jan 10.

College of Korean Medicine, Gachon University, Seongnam, Republic of Korea.

Background: The aim of the present study was to evaluate the potential protective effects of six ginsenosides (Rb1, Rb2, Rc, Rd, Rg1, and Rg3) isolated from against tacrolimus (FK506)-induced apoptosis in renal proximal tubular LLC-PK1 cells.

Methods: LLC-PK1 cells were treated with FK506 and ginsenosides, and cell viability was measured. Protein expressions of mitogen-activated protein kinases, caspase-3, and kidney injury molecule-1 (KIM-1) were evaluated by Western blotting analyses. The number of apoptotic cells was measured using an image-based cytometric assay.

Results: Reduction in cell viability by 60μM FK506 was ameliorated significantly by cotreatment with ginsenosides Rg1 and Rb1. The phosphorylation of p38, extracellular signal-regulated kinases, and KIM-1, and cleavage of caspase-3, increased markedly in LLC-PK1 cells treated with FK506 and significantly decreased after cotreatment with ginsenoside Rb1. The number of apoptotic cells decreased by 6.0% after cotreatment with ginsenoside Rb1 (10μM and 50μM).

Conclusion: The antiapoptotic effects of ginsenoside Rb1 on FK506-induced apoptosis were mediated by the inhibition of mitogen-activated protein kinases and caspase activation.
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http://dx.doi.org/10.1016/j.jgr.2016.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766699PMC
January 2018

Crystal Structure Analysis of the First Discovered Stability-Enhanced Solid State of Tenofovir Disoproxil Free Base Using Single Crystal X-ray Diffraction.

Molecules 2017 Jul 14;22(7). Epub 2017 Jul 14.

College of Pharmacy, CHA University, Sungnam 13844, Korea.

Tenofovir disoproxil (TD), an anti-virus drug, is currently marketed under its most stable form, Form-I of Tenofovir disoproxil fumarate (TDF). However, studies regarding the properties of TD free base crystal as a promising drug as well as its crystal structure have not yet been reported. This assumption was made because TD free base is not directly produced in a solid form during the manufacturing process. TD free base is first obtained in an oil form, and is then synthesized into TDF crystal. In this regard, the present study was conducted to investigate both the potentiality of TD free base to be an active pharmaceutical ingredient (API) and its crystal structure. Here, TD free base solid was produced by means of drowning-out crystallization. Next, single crystal X-ray diffraction (SXD) was employed to determine the crystal structure. Powder X-ray diffraction (PXRD) and a differential scanning calorimetry (DSC) analysis were performed to evaluate the crystal's properties. Furthermore, experiments were carried out at 15%, 35%, 55%, 75%, and 95% relative humidity (RH) for 12 h using a hygroscopic tester to determine and to compare the hygroscopicity and stability of TD free base with TDF crystal. Additionally, experiments were conducted under accelerated (40 °C, RH 75%) and stress storage (60 °C, RH 75%) conditions for 30 days to investigate the changes in purity and the formation of dimer. In this work, we report that TD free base possesses lower hygroscopicity, and thus does not generate dimer impurity from hydrolysis. Primarily, this is attributed to the fact that TD free base is not an easily ionized salt but comprises neutral hydrophobic molecules. According to the structural properties, the improved hygroscopic property of the TD free base crystal was due to the decrease of crystal polarity owing to the intermolecular H-bonds present in TD free base rings. In addition, the solubility investigation study carried out in aqueous solution and at gastrointestinal pH revealed a similarity in TDF and TD free base solubility under the mentioned conditions. Accordingly, we could confirm the potentiality of TD free base as an active pharmaceutical ingredient.
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http://dx.doi.org/10.3390/molecules22071182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152289PMC
July 2017

Anti-inflammatory effects and corresponding mechanisms of cirsimaritin extracted from Cirsium japonicum var. maackii Maxim.

Bioorg Med Chem Lett 2017 07 17;27(14):3076-3080. Epub 2017 May 17.

College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea. Electronic address:

In this study, we investigated the anti-inflammatory effects and mechanisms of cirsimaritin isolated from an ethanol extract of the aerial parts of Cirsium japonicum var. maackii Maxim. using RAW264.7 cells. The extract and its flavonoid cirsimaritin inhibited nitric oxide (NO) production and inducible nitric oxide synthase expression in RAW264.7 cells. Cirsimaritin inhibited interleukin-6, tumor necrosis factor-α, and NO production in a concentration-dependent manner in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. From a western blot study, pretreatment with cirsimaritin inhibited phosphorylation/degradation of IκBα and phosphorylation of Akt in LPS-stimulated RAW264.7 cells. Moreover, cirsimaritin suppressed activation of LPS-induced transcription factors, such as c-fos and signal transducer and activator of transcription 3 (STAT3), in RAW264.7 cells. Collectively, these results show that cirsimaritin possesses anti-inflammatory activity, which is regulated by inhibition of c-fos and STAT3 phosphorylation in RAW264.7 cells.
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http://dx.doi.org/10.1016/j.bmcl.2017.05.051DOI Listing
July 2017

Preventive effect of fermented black ginseng against cisplatin-induced nephrotoxicity in rats.

J Ginseng Res 2017 Apr 8;41(2):188-194. Epub 2016 Mar 8.

Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung, Korea.

Background: Fermented black ginseng (FBG) is processed ginseng by the repeated heat treatment and fermentation of raw ginseng. The protective effect and mechanism of FBG on cisplatin-induced nephrotoxicity was investigated to evaluate its therapeutic potential.

Methods: The free radical scavenging activity of FBG was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH). In addition, the protective effect against cisplatin-induced renal damage was tested in rats. FBG was orally administered every day at a dose of 150 mg/kg body weight for 10 d, and a single dose of cisplatin was administered intraperitoneally (7.5 mg/kg body weight) with 0.9% saline on the 4 d.

Results: The DPPH radical-scavenging activity of FBG (IC = 384 μg/mL) was stronger than that of raw ginseng. The improved DPPH radical-scavenging activity was mediated by the generation phenolic compounds. The decreased cell viability by cisplatin was recovered significantly after treatment with FBG in a dose-dependent manner. Then, the protective effect of FBG on cisplatin-induced oxidative renal damage was investigated in rats. The decreased creatinine clearance levels, which are a reliable marker for renal dysfunction in cisplatin-treated rats, were reduced to the normal level after the administration of FBG. Moreover, FBG showed protective effects against cisplatin-induced oxidative renal damage in rats through the inhibition of NF-κB/p65, COX-2, and caspase-3 activation.

Conclusion: These results collectively show that the therapeutic evidence for FBG ameliorates the nephrotoxicity via regulating oxidative stress, inflammation, and apoptosis.
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http://dx.doi.org/10.1016/j.jgr.2016.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386130PMC
April 2017

Src/Syk-Targeted Anti-Inflammatory Actions of Triterpenoidal Saponins from Gac (Momordica cochinchinensis) Seeds.

Am J Chin Med 2017 2;45(3):459-473. Epub 2017 Apr 2.

† Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.

Momordica cochinchinensis Spreng (family Cucurbitaceae), also known as gac, or red melon, is an edible Southeast Asian fruit valued for its nutritional and medicinal properties. Specifically, Momordicae Semen, the seeds of the gac fruit, is used in traditional Chinese medicine to treat boils, rheumatic pain, muscle spasm, hemorrhoids, and hemangiomas. In this study, a chemical investigation into a gac seed ethanol (EtOH) extract resulted in the identification of three triterpenoidal saponins (1-3), which were investigated for their anti-inflammatory effects. Among the saponins, momordica saponin I (compound 3) reduced the production of nitric oxide (NO) in LPS-activated RAW264.7 cells without inducing cytotoxicity. The mRNA levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were decreased by momordica saponin I. Additionally, the translocation of p65 and p50 (subunits of the transcription factor NF-[Formula: see text]B) into the nucleus was remarkably inhibited. Furthermore, the phosphorylation levels of inflammatory signaling proteins (I[Formula: see text]B[Formula: see text], Src, and Syk) known to be upstream regulatory molecules of p65 were decreased under momordica saponin I-treated conditions. The molecular targets of momordica saponin I were confirmed in overexpression experiments and through immunoblot analyses with Src and Syk. This study provides evidence that momordica saponin I could be beneficial in treating inflammatory diseases, and should be considered a bioactive immunomodulatory agent with anti-inflammatory properties.
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http://dx.doi.org/10.1142/S0192415X17500288DOI Listing
September 2017

Phenolics and neolignans isolated from the fruits of Juglans mandshurica Maxim. and their effects on lipolysis in adipocytes.

Phytochemistry 2017 May 5;137:87-93. Epub 2017 Feb 5.

College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, South Korea. Electronic address:

Juglans mandshurica Maxim. (Juglandaceae) is a traditional folk medicine used for treatment of dermatosis and to relieve aches in Korea and China. In this study, eight compounds, along with six known compounds, were isolated from the fruit of J. mandshurica. Among the six known compounds, the absolute configuration of two compounds were determined. The structures of compounds were determined on the basis of extensive spectroscopic methods, including 1D and 2D NMR and CD spectroscopic data. All isolated compounds were tested for their lipolytic activities in differentiated adipocytes using C3H10T1/2 mouse embryonic fibroblasts. Among them, 2-(4-formyl-2-methoxyphenoxy)-propan-1,3-diol and 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol exhibited the most potent lipolytic activities.
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http://dx.doi.org/10.1016/j.phytochem.2017.01.019DOI Listing
May 2017

Poloxamer-Based Thermoreversible Gel for Topical Delivery of Emodin: Influence of P407 and P188 on Solubility of Emodin and Its Application in Cellular Activity Screening.

Molecules 2017 Feb 7;22(2). Epub 2017 Feb 7.

College of Pharmacy, CHA University, 521 CHA Bio Complex, 335 Pangyo-ro, Bundang-gu, Seongnam 463-400, Korea.

Emodin is a component in a Chinese herb, Baill, traditionally used for diabetes and anticancer. Its poor solubility is one of the major challenges to pharmaceutical scientists. We previously reported on thermoreversible gel formulations based on poloxamer for the topical delivery of emodin. The present study was to understand the effect of poloxamer type on emodin solubility and its application in cellular activity screening. Various gel formulations composed of poloxamer 407 (P407), poloxamer 188 (P188) and PEG400 were prepared and evaluated. Major evaluation parameters were the gelation temperature (Tgel) and solubility of emodin. The emodin solubility increased with increasing poloxamer concentration and the Tgel was modulated by the proper combination of P407. In particular, this study showed that the amount of P407 in thermoreversible poloxamer gel (PG) was the dominant factor in enhancing solubility and P188 was effective at fixing gelation temperature in the desired range. A thermoreversible emodin PG was selected as the proper composition with the liquid state at room temperature and gel state at body temperature. The gel showed the solubility enhancement of emodin at least 100-fold compared to 10% ethanol or water. The thermoreversible formulation was applied for in vitro cellular activity screening in the human dermal fibroblast cell line and DLD-1 colon cancer cell line after dilution with cell culture media. The thermoreversible gel formulation remained as a clear solution in the microplate, which allowed reliable cellular activity screening. In contrast, emodin solution in ethanol or DMSO showed precipitation at the corresponding emodin concentration, complicating data interpretation. In conclusion, the gel formulation is proposed as a useful prototype topical formulation for testing emodin in vivo as well as in vitro.
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http://dx.doi.org/10.3390/molecules22020246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155703PMC
February 2017

Capillarisin augments anti-oxidative and anti-inflammatory responses by activating Nrf2/HO-1 signaling.

Neurochem Int 2017 May 1;105:11-20. Epub 2017 Feb 1.

College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam, Gyeonggi-do 13488, Republic of Korea. Electronic address:

Capillarisin is a naturally isolated chromone, which is one of the major bioactive constituents of Artemisia capillaries. Capillarisin has antioxidant, anti-inflammatory, and anti-tumor potential, but the underlying molecular mechanisms remain largely unclear. In the present study, we demonstrate that the transcription factor nuclear factor E2-related factor-2 (Nrf2) is activated by capillarisin in neuroblastoma SH-SY5Y cells and microglial BV2 cells. Capillarisin leads to Nrf2 phosphorylation, subsequent activation of antioxidant response element (ARE)-mediated transcription, and up-regulation of downstream molecules, such as heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1. Capillarisin protects SH-SY5Y cells from 6-hydroxydopamine-induced oxidative stress and attenuates inflammatory responses in lipopolysaccharide-treated BV2 cells. The cytoprotective and anti-inflammatory effects of capillarisin are significantly abolished in cells transfected with specific Nrf2 or HO-1 siRNA, suggesting that these pharmacological properties of capillarisin are primarily due to increased HO-1 activity. Capillarisin induces the activation of c-Jun N-terminal kinase in SH-SY5Y and BV2 cells, which is responsible for Nrf2 phosphorylation and HO-1 upregulation. Together, this study demonstrates that capillarisin is a potential activator of the Nrf2/ARE-dependent pathway and could be an attractive candidate for the regulation of oxidative stress and inflammatory responses in the brain.
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http://dx.doi.org/10.1016/j.neuint.2017.01.018DOI Listing
May 2017

Renoprotective chemical constituents from an edible mushroom, Pleurotus cornucopiae in cisplatin-induced nephrotoxicity.

Bioorg Chem 2017 04 19;71:67-73. Epub 2017 Jan 19.

School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address:

Pleurotus cornucopiae (Pleurotaceae) is an edible and medicinal mushroom widely distributed in Korea, China, and Japan. The MeOH extract of the fruiting bodies of P. cornucopiae showed renoprotective effects against cisplatin-induced kidney cell damage. Chemical investigation of the MeOH extract led to the isolation and identification of 12 compounds including noransine (1), uridine (2), uracil (3), (3β, 5α, 6β, 22E, 24S) -ergosta-7, 22-diene-3, 5, 6, 9-tetrol (4), (22E,24S)-ergosta-7,22-diene-3β,5α,6β-triol (5), (22E,24R)-ergosta-8(14),22-diene-3β,5α,6β,7α-tetrol (6), cerebroside B (7), (2R) -N- [(1S, 2R, 3E, 7E) -1- [(β-d-glucopyranosyloxy) methyl] -2-hydroxy-8-methyl-3, 7-heptadecadien-1-yl] -2-hydroxy-heptadecanamide (8), cerebroside D (9), nicotinamide (10), 1,2-bis(hydroxymethyl)-4,5-dimethoxybenzene (11), and benzoic acid (12). Among them, compounds 1 and 11 were isolated as naturally occurring products for the first time, though they were reported as synthetic products in previous papers. All of the compounds (except 8 and 11) abrogated cisplatin-induced LLC-PK1 cell damage in a dose-dependent manner. Of special note, compounds 2, 5, 6, and 12 ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 10μM. The protective effects of compounds 2, 5, 6, and 12 were mediated via the deactivation of JNK-caspase 3 apoptotic cascade. This study is the first to demonstrate that the chemical constituents of P. cornucopiae display renoprotective effects against anticancer drug-induced damage in kidney cells.
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http://dx.doi.org/10.1016/j.bioorg.2017.01.012DOI Listing
April 2017

Protective effect of α-mangostin against iodixanol-induced apoptotic damage in LLC-PK1 cells.

Bioorg Med Chem Lett 2016 08 12;26(15):3806-9. Epub 2016 May 12.

Institute of Pharmaceutical Sciences, College of Pharmacy, CHA University, Sungnam 13844, Republic of Korea. Electronic address:

Radiographic contrast media facilitate the visibility of internal body structures, but its use to patients with lowered renal function needs to be careful because of severe side effect in kidney. The present study aims to evaluate potential protective effect and mechanism of Alpha mangostin (α-mangostin) against contrast-induced apoptotic damage in LLC-PK1 cells. As a result, α-mangostin in non-toxic concentrations improved the viability of the iodixanol-treated cells up to 90.42% against contrast-induced damage in LLC-PK1 cells. Iodixanol treatment increased the phosphorylation of p38, ERK and cleavage of caspase-3 in LLC-PK1 cells, which were significantly decreased by co-treatment with α-mangostin (2.5 and 5μM). The protective effect of α-mangostin on contrast-induced apoptotic damage was mediated by the inhibition of MAPKs and caspase activation.
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http://dx.doi.org/10.1016/j.bmcl.2016.05.031DOI Listing
August 2016

Application of ionic liquid to polymorphic transformation of anti-viral/HIV drug adefovir dipivoxil.

Arch Pharm Res 2016 May 23;39(5):646-59. Epub 2016 Feb 23.

Institute of Pharmaceutical Sciences, College of Pharmacy, CHA University, Sungnam, 13844, Republic of Korea.

Ionic liquids (ILs) are defined as salts with a melting point below 100 °C. ILs have received increasing attention as new alternative to organic solvents because of their unique physicochemical properties. Therefore, this study was conducted in the purpose to present the efficacy of ILs as new solvents capable to control the Polymorphic transformation phenomenon. Here, the polymorphic transformation phenomenon of adefovir dipivoxil, an efficient antiviral active pharmaceutical ingredient on human immunodeficiency virus, was investigated. The phase transformation phenomenon from the metastable polymorph, new form (NF) to the stable polymorph, Form-X in 1-allyl-3-ethylimidazolium tetrafluoroborate (AEImBF4) and 1-butyl-2,3-dimethylimidazolium tetrafluoroborate (BDMImBF4) ILs solutions was observed utilizing the solvent-mediated phase transformation method The thermodynamic factors, AEImBF4/BDMImBF4 solvent composition ratio of 3:7-6:4 and the temperature in range of 25-100 °C, as well as the dynamic factor, the rational speed in range of 300-1000 rpm were parameters studied in this experiment. The thermodynamic and dynamic equations involving nucleation and mass transfer were applied for the quantitative analysis. The result of the present study confirmed the use of ILs as substitute solvent for volatile organic solvents, and demonstrated the efficacy of ILs as potential solvent-media to control the polymorphic transformation.
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http://dx.doi.org/10.1007/s12272-016-0721-0DOI Listing
May 2016

Protective effect and mechanism of action of saponins isolated from the seeds of gac (Momordica cochinchinensis Spreng.) against cisplatin-induced damage in LLC-PK1 kidney cells.

Bioorg Med Chem Lett 2016 Mar 21;26(5):1466-70. Epub 2016 Jan 21.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address:

This study was performed to investigate the renoprotective effect and mechanism of Momordicae Semen, gac seeds, against the cisplatin-induced damage in LLC-PK1 kidney cells. In order to identify the active components, three major saponins were isolated from extract of the gac seed, gypsogenin 3-O-β-d-galactopyranosyl(1→2)-[α-L-rhamnopyranosyl(1→3)]-β-d-glucuronopyranoside (1), quillaic acid 3-O-β-D-galactopyranosyl(1→2)-[α-L-rhamnopyranosyl(1→3)]-β-D-glucuronopyranoside (2), and momordica saponin I (3). Compounds 1 and 2 ameliorated cisplatin-induced nephrotoxicity up to 80% of the control value at both 5 and 25μM. Phosphorylation of MAPKs was decreased along cisplatin treatment after treatment with compounds 1 and 2. These results show that blocking the MAPKs signaling cascade plays a critical role in mediating the renoprotective effect of Momordicae Semen extract and compounds 1 and 2.
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http://dx.doi.org/10.1016/j.bmcl.2016.01.056DOI Listing
March 2016

Protective effect and mechanism of action of lupane triterpenes from Cornus walteri in cisplatin-induced nephrotoxicity.

Bioorg Med Chem Lett 2015 Dec 22;25(23):5613-8. Epub 2015 Oct 22.

School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address:

The present study reports a renoprotective effect and the mechanism of action of lupane triterpenes isolated from Cornus walteri in cisplatin-induced renal toxicity. A phytochemical investigation of the MeOH extract of the stems and stem bark of C. walteri resulted in the isolation and identification of twelve lupane triterpenes. Among these, betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 125 μM. Upregulated phosphorylation of JNK, ERK, and p38 following cisplatin treatment were markedly decreased after co-treatment with betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol. In addition, the protein expression level of cleaved caspase-3 and the percentage of apoptotic cells were also significantly reduced after co-treatment with betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol. These results show that blocking the MAPK signaling cascade plays a critical role in mediating the renoprotective effect of betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol isolated from C. walteri extract.
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http://dx.doi.org/10.1016/j.bmcl.2015.10.035DOI Listing
December 2015

A new cerebroside from the fruiting bodies of Hericium erinaceus and its applicability to cancer treatment.

Bioorg Med Chem Lett 2015 Dec 2;25(24):5712-5. Epub 2015 Nov 2.

School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address:

A new cerebroside, cerebroside E (1) was isolated from the fruiting bodies of Hericium erinaceus (Hericiaceae). The structure of 1 was elucidated by a combination of extensive spectroscopic analyses, including extensive 2D NMR, HR-MS, and chemical reactions. Compound 1 was evaluated for its applicability to medicinal use in several human diseases using cell-based assays. As a result, compound 1 attenuated cisplatin-induced nephrotoxicity in LLC-PK1 cells and exhibited a significant inhibitory effect on angiogenesis in HUVECs. These results collectively reflect the beneficial effects of compound 1 in cancer treatment.
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http://dx.doi.org/10.1016/j.bmcl.2015.10.092DOI Listing
December 2015

Inhibitory effects of SKI3246, the rhizome extract of Atractylodes japonica, on visceral hypersensitivity in experimental irritable bowel syndrome rat models.

Arch Pharm Res 2015 30;38(5):642-9. Epub 2014 Jul 30.

Life Science R&D Center, SK Chemicals, Seongnam, 463-400, Gyeonggi-do, Republic of Korea.

We evaluated the effect of SKI3246, the 50% ethanol extract of the rhizome of Atractylodes japonica, on visceral hypersensitivity, which is a major characteristic feature of IBS. We used various rat models of visceral hypersensitivity to assess the visceral pain responses to colorectal distension (CRD) in comparison with conventional IBS treatments. Oral administration of SKI3246 dose-dependently and significantly attenuated the abdominal withdrawal reflex (AWR) score in a model of acetic acid-induced visceral hypersensitivity. We also found that it reduced the number of abdominal contractions in response to CRD in a model of 2,4,6-trinitrobenzenesulfonic acid-induced visceral hypersensitivity, which was comparable to ramosetron or alosetron. Furthermore, treatment with SKI3246 also increased the pain threshold and abolished the elevated AWR scores to CRD in a rat model of neonatal maternal separation. We presumed that the modulation of the NK2 receptor is involved in the inhibitory activity of SKI3246 on the basis that it significantly inhibited the contraction of the distal colonic muscle induced by neurokinin A, the NK2 receptor agonist. The present results indicate that SKI3246 has the potential to be an effective therapeutic agent for IBS, especially insofar as it can relieve visceral hypersensitivity.
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http://dx.doi.org/10.1007/s12272-014-0454-xDOI Listing
February 2016

Anti-inflammatory properties of a triterpenoidal glycoside from Momordica cochinchinensis in LPS-stimulated macrophages.

Immunopharmacol Immunotoxicol 2013 Feb 23;35(1):8-14. Epub 2012 Aug 23.

College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Shinlim-dong, Kwanak-gu, Seoul 151-742, Republic of Korea.

Two triterpenoidal saponins were isolated from the seeds of Momordica cochinchinensis Sprenger (Cucurbitaceae). Identification of chemical structures has been performed by (1)H- and (13)C-NMR spectroscopy and gas chromatography (GC). One of the saponins is a new gypsogenin glycoside, named as gypsogenin 3-O-β-D-galactopyranosyl(1→2)-[α-L-rhamnopyranosyl(1→3)]-β-D-glucuronopyranoside (compound 1), which is reported for the first time from natural resources. The other saponin is a quillaic acid glycoside (compound 2), which showed anti-inflammatory activities in RAW 264.7 cells. The mechanistic understanding of anti-inflammatory activities demonstrates that compound 2 inhibits lipopolysaccharide-induced expression of nitric oxide and IL-6 via NF-κB pathway.
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http://dx.doi.org/10.3109/08923973.2012.715165DOI Listing
February 2013