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In vitro cytotoxicity and in vivo acute toxicity of selected polysaccharide hydrogels as pharmaceutical excipients

  • Kulkarni GT;Gowthanarajan K;Raghu C;Ashok G;Vijayan P
    • Advances in Traditional Medicine
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    • v.5 no.1
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    • pp.29-36
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    • 2005
  • Polysaccharide hydrogels constitute a structurally diverse class of biological macromolecules with a wide range of physicochemical properties. They also constitute important members of the family of industrial water-soluble polymers. They find application in Pharmacy as binders, disintegrants, suspending, emulsifying and sustaining agents. According to the International Pharmaceutical Excipients Council (IPEC), an excipient must have an established safety profile. Hence, in the present study, in vitro cytotoxicity on Vero and HEp-2 cell lines, and in vivo acute toxicity in rats were carried out to establish the safety of polysaccharide hydrogels from the seeds of Plantago ovata and Ocimum basilicum. The in vitro cytotoxicity was determined by MTT and SRB assays. In the in vivo acute toxicity, the effects of three different doses of hydrogels (100, 200 and 400 mg/kg body weight) on food and water intake, body weight, biochemical and hematological parameters were studied. The results of in vitro did not show any cytotoxicity on both the cell lines used. In the in vivo acute toxicity, the hydrogels did not show any toxic symptoms in all three dose levels. This establishes the safety of the selected hydrogels. Hence, they can be used as excipients in pharmaceutical dosage forms.

Effects of Paljintanggagambang extract on antitumoral immunological response and the side effect induced by antitumoral Agents (팔진탕가감방(八珍湯加減方)이 항종양(抗腫瘍) 면역반응(免疫反應)과 항암제(抗癌劑)로 유발(誘發)한 부작용(副作用)에 미치는 영향(影響))

  • Oh Jeung-Jean;Won Jin-Hee;Lee Eon-Jeong;Moon Seok-Jae
    • The Journal of Internal Korean Medicine
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    • v.19 no.2
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    • pp.219-232
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    • 1998
  • Paljintanggagmbang has been used for cure of tumor as a traditional medicine without any experimental evidence to support the rational basis for its clinical use. This study was carried out to evaluate. the possible therapeutic or antitumoral effects of Paljintanggagmbang extract against tumor, and to carry out some mechanisms responsible for its effect. Experimental studis were performed for measurement of Humoral and Cellular Immune Response and Phagocytosis in Mice treated with mitomytion C(MMC) and Paljintanggagmbang alone and combination. The results obtained in this study were as follows 1. The adminstration of Paljintanggagmbang extract decresed size of tumors cell which MCA induced. 2. The adminstration of Paljintanggagmbang extract decresed growth of the tumors which S 180 transplant. 3. The adminstration of Paljintanggagmbang extract decresed reproduction of A549, Hep3b, 3LL cell and S 180 in vivo. 4. The adminstration of Paljintanggagmbang extract incresed activity of the NK cell. These results also suggested that effect of Paljintanggagmbang might be chiefly due to nonspecific enhancement of Humoral and Cellular Immune Response and Phagocytosis in Mice treated with MMC and Paljintanggagmbang alone and combination.

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Antimutagenic and Anticancer Effects of Ramaria botrytis(Fr.) Rick Extracts (싸리버섯 추출물의 항돌연변이성 및 암세포 성장 억제 효과)

  • 이갑랑;김현정;이인선
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.28 no.6
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    • pp.1321-1325
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    • 1999
  • The inhibitory effect of Ramaria botrytis on the mutagenicity in Salmonella assay and cytotoxicity on cancer cell were studied. Ramaria botrytis methanol extracts showed antimutagenic effects of 60~90% on B(a)P and AFB1 in S. typhimurium TA98 and TA100. These extracts showed 73~85% antimutagenicity on TA100 against MNNG. The methanol extracts with strong antimutagenic activities were further fractionated by ethylacetate and water, the ethylacetate fraction were found to be stronger antimutagen icity against MNNG than water fraction. Ramaria botrytis methanol extracts and ethylacetate fraction revealed the highest cytoxicity against HT 29 human colon adenocarcinoma cells in which cell growth was inhibited by 57~88% and 69~94% at 0.25~1.0mg/ml, respectively. These methanol extract and ethyl acetate fraction exhibited 53~79% and 66~87% inhibition against HepG2 human hepatocarcinoma cells, respectively. But water fraction showed only 10~24% inhibition. However, these extract and fractions did not show cytotoxic effect against human chang liver cells. From these results, it is considered that Ramaria botrytis has stronger antimutagenic and anticancer effects in vitro.

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Biological Activities of Water and Ethanol Extracts from Two Varieties of Rubus coreanus Miquel Fruits

  • Yin, Yu;Wang, Myeong-Hyeon
    • Preventive Nutrition and Food Science
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    • v.16 no.1
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    • pp.89-94
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    • 2011
  • The potential biological activities of water and ethanol extracts from two varieties of Rubus coreanus Miquel fruits produced in the Gochang-gun (GR) and Hoengseong-gun (HR) regions of Korea were examined. The hydroxyl radical ($\cdot$OH) scavenging activity, reducing power, lipid peroxidation inhibitory activity, and antiproliferative activity on cancer cells by these extracts were examined, and $\alpha$-amylase and $\alpha$-glucosidase inhibition assays were also performed. The EtOH extract from GR showed high hydroxyl radical scavenging activity ($EC_{50}=119.47{\pm}5.13\;{\mu}g/mL$), lipid peroxidation inhibitory activity ($EC_{50}=213.45{\pm}3.14\;{\mu}g/mL$) and a concentration dependence, with OD values ranging from 0.15 to 0.56 (50 to 200 ${\mu}g/mL$), for reducing power. The EtOH extract from GR has the highest antiproliferative activities on MDA-MB-231 and HepG2 cancer cells among four extracts. Meanwhile, all extracts showed certain $\alpha$-amylase and $\alpha$-glucosidase inhibition activities. These results indicate that extracts from two varieties of R. coreanus fruits have significant antioxidant, anti-diabetic and anti-tumorigenic activities, which suggest these extracts could be a potential source for pharmaceutical.

Anti-Inflammatory and PPAR Transactivational Effects of Oleanane-Type Triterpenoid Saponins from the Roots of Pulsatilla koreana

  • Li, Wei;Yan, Xi Tao;Sun, Ya Nan;Ngan, Thi Thanh;Shim, Sang Hee;Kim, Young Ho
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.334-340
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    • 2014
  • In this study, 23 oleanane-type triterpenoid saponins were isolated from a methanol extract of the roots of Pulsatilla koreana. The NF-${\kappa}B$ inhibitory activity of the isolated compounds was measured in $TNF{\alpha}$-treated HepG2 cells using a luciferase reporter system. Compounds 19-23 inhibited $TNF{\alpha}$-stimulated NF-${\kappa}B$ activation in a dose-dependent manner, with $IC_{50}$ values ranging from $0.75-8.30{\mu}M$. Compounds 19 and 20 also inhibited the $TNF{\alpha}$-induced expression of iNOS and ICAM-1 mRNA. Moreover, effect of the isolated compounds on PPARs transcriptional activity was assessed. Compounds 7-11 and 19-23 activated PPARs the transcriptional activity significantly in a dose-dependent manner, with $EC_{50}$ values ranging from $0.9-10.8{\mu}M$. These results suggest the presence of potent anti-inflammatory components in P. koreana, and will facilitate the development of novel anti-inflammatory agents.

NF-${\kappa}B$ Inhibitory Activities of Phenolic and Lignan Components from the Stems of Acanthopanax divaricatus var. albeofructus

  • Sun, Ya Nan;Li, Wei;Song, Seok Bean;Yan, Xi Tao;Yang, Seo Young;Kim, Young Ho
    • Natural Product Sciences
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    • v.20 no.4
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    • pp.232-236
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    • 2014
  • Acanthopanax divaricatus var. albeofructus (ADA) is commonly ingested as a traditional medicine or as a component of a health drink in Korea. In this phytochemical study, nine phenolics (1 - 9) and three lignans (10 - 12) were isolated from the MeOH extract of the stems of ADA. Chemical structures were elucidated by comparing spectroscopic data with reported values. Nuclear factor kappa B ($NF-{\kappa}B$) inhibitory activity of the isolated compounds was evaluated using an $NF-{\kappa}B$ luciferase assay in HepG2 cells. Among them, compounds 1, 3 - 8, and 11 showed significant inhibitory effects on $TNF{\alpha}$-induced $NF-{\kappa}B$ transcriptional activity in a dosedependent manner, with $IC_{50}$ values ranging from 13.25 to $37.36{\mu}M$. Further studies on potential anti-inflammatory effects and the benefits of phenolic and lignan components from ADA are warranted.

Cancer Cell Growth Inhibition of Lanostane-type Triterpenoids Isolated from Ganoderma gibbosum (칠황버섯으로부터 분리한 Lanostane-type Triterpenoid의 암세포성장 억제효과)

  • Kim, Donghwa;Lee, Sang Kook;Park, Hee-Juhn
    • Korean Journal of Pharmacognosy
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    • v.51 no.1
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    • pp.36-40
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    • 2020
  • The CHCl3 fraction of the MeOH extract of Ganoderma gibbosum (Ganodermataceae) exhibited cytotoxic activity on five cancer cell lines (MDA-MB-231, SK-hep1, A549, HCT116, and SNU638). Six highly oxygenated lanostane-type triterpenoids (lanostanoids) were isolated by column chromatography to test cytotoxicity on cancer cells. The five known lanostanoids were identified as gibbosic acids A, B, D, G, and H by comparison of molecular ion peaks with the literature data. The structure of a new lanostanoid, gibbosic acids I, was identified to be 3β,8β,15β,20S-tetrahydroxy-7,12,23-trioxolanost-9(11)-en-26-oic acid on the basis of NMR and MS spectroscopy. The three lanostanoids of gibbosic acids A, H, and I of the six isolates significantly suppressed the growth of cancer cells. In particular, the IC50 of gibbosic acid H was prominently low ranging from 2.64-6.56 μM.

SENP2 Regulates Hepatocellular Carcinoma Cell Growth by Modulating the Stability of β-catenin

  • Shen, Huo-Jian;Zhu, Hong-Yi;Yang, Chao;Ji, Fu
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3583-3587
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    • 2012
  • SUMOylation has emerged as an important post-translational modification that modulates the localization, stability and activity of a broad spectrum of proteins. A dynamic process, it can be reversed by a family of SUMO-specific proteases (SENPs). However, the biological roles of SENPs in mammalian development and pathogenesis remain largely elusive. Here, we demonstrated that SENP2 plays a critical role in the control of hepatocellular carcinoma cell growth. SENP2 was found to be down-regulated in hepatocellular carcinoma (HCC) tissues and over-expression suppressed the growth and colony formation of HCC cells. In contrast, silencing of SENP2 by siRNAs promoted cancer cell growth. We further found that stability of ${\beta}$-catenin was markedly decreased when SENP2 was over-expressed. Interestingly, the decrease was dependent on the de-SUMOylation activity of SENP2, because over-expression of a SENP2 catalytic mutant form had no obviously effects on ${\beta}$-catenin. Our results suggest that SENP2 might play a role in hepatocellular carcinoma cell growth control by modulating the stability of ${\beta}$-catenin.

In vitro cytotoxic evaluation of some essential oils

  • P., Vijayan;Godavarthi, Ashok;Chandrashekhar, Raghu;Badami, Shrishilappa;SA, Dhanaraj;B., Suresh
    • Advances in Traditional Medicine
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    • v.3 no.4
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    • pp.187-190
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    • 2003
  • Seven essential oils were tested for in vitro cytotoxicity against the cancerous cell lines A-549, HEp-2 and DLA and normal BRL-3A, NRK-49F and Vero cell lines using standard MTT, SRB and dye exclusion techniques. The A-549 cell line was found to be the most susceptible to all the essential oils. The essential oils of A. nilagirica, A. calamus and O. sanctum were found to be the more active against these cells with mean $CTC_{50}$ values of 17.75, 19.00 and $24.37\;{\mu}g/ml$, respectively. The essential oil of Acorus calamus was found to be the most potent with low $CTC_{50}$ values against the cancerous and comparatively higher $CTC_{50}$ values against the normal cell lines. Artemisia pellens and Pelargonium graveolens oils also showed potent activity. These oils merit further investigation to identify the active principles and nature of the anti tumor activity in animal models.

Cytotoxic Constituents of the Leaves of Ixeris sonchifolia

  • Suh, Ji-Young;Jo, Young-Mi;Kim, Nam-Deuk;Bae, Song-Ja;Jung, Jee-H.;Im, Kwang-Sik
    • Archives of Pharmacal Research
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    • v.25 no.3
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    • pp.289-292
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    • 2002
  • The ethyl acetate extract of the leaves of Ixeris sonchifolia afforded two new and two known sesquiterpene lactone glucosides of the guaiane-type, together with a known alkenol glucoside. The known compounds were identified as ixerin Z (1), ixerin Z-6'-p-hydroxyphenylace-tate (2), and (Z)-3-hexen-1-ol-$\beta$-D-glucopyranoside (3), respectively. The structures of the new compounds were elucidated as 11, 13a-dihydroixerin Z [4, 3-hydroxy-2-oxo-guaia-1 (10), $3-dien-5{\alpha},6{\beta},7{\alpha},11{\beta}H-12,6-olide-3-O-{\beta}-D-glucopyranoside],{\;}and{\;}3,10{\$beta}-dihydroxy-2-oxo-guaia-3,11(13)-dien-1{\alpha},5{\alpha},6{\alpha},7aH-12,6-olide-10-O-{\beta}-D-glucopyranoside$ (5), respectively. The cytotoxicity of these compounds against human hepatocellular carcinoma cell (HepG2) and human melanoma cell (SK-MEL-2) was evaluated.