• Journal of Applied Biological Chemistry
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• v.55 no.4
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• pp.201-205
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• 2012

The present study was conducted to evaluate of the 1,1-Diphenyl-2-Picrylhydrazyl (DPPH) radical scavenging effect, cytotoxicity and tyrosinase inhibition activities using methanol extracts from different parts of four herb plants. The results showed that whole and root extracts of yarrow the highest total polyphenol and flavonoid contents as well as whole of yarrow revealed the highest DPPH radical scavenging effect. In cytotoxicity test against three cancer cell lines, HeLa (uterus), SK-Hep-1 (liver), and YD-15 (oral), the whole extract of feverfew showed the highest toxicity with $IC_{50}$ values of $102.58-138.68{\mu}g/mL$. Also, mallow root extract ($71.24{\mu}g/mL$) exhibited potent tyrosinase inhibitory activity comparable to arbutin ($69.56{\mu}g/mL$), which was used as the control.

• IMMUNE NETWORK
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• v.15 no.3
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• pp.135-141
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• 2015

Dysfunction of gut immune regulation is involved in mucosal damage in inflammatory bowel disease (IBD). However, there is still no efficacious immune-regulator for the treatment of IBD. Alloferon is a novel immune-modulatory peptide that was originally isolated from infected insects. It shows anti-inflammatory effects by the regulation of cytokine production by immune cells and their activities. Therefore, we investigated the effect of alloferon in a mouse model of colitis using dextran sulfate sodium (DSS). Colitis was induced by administration of DSS in drinking water for 7 consecutive days. It was confirmed by the presence of weight loss, diarrhea, hematochezia, and colon contraction. Alloferon was injected 4 days after DSS administration. We found that alloferon improved the pathogenesis of IBD based on the reduced disease activity index (DAI) and colon contraction. Edema, epithelial erosion, and immune cell infiltration were found in mice administered DSS, but the phenomena were reduced following alloferon treatment. The plasma level of IL-6, a classical pro-inflammatory cytokine in colitis, was also decreased by alloferon. Moreover, alloferon inhibited the TNF-${\alpha}$-induced degradation and phosphorylation of $I{\kappa}B$ in Colo205 colon cancer cells. Taken together, these results show that alloferon has anti-inflammatory effects and attenuates DSS-induced colitis.

• Journal of Ginseng Research
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• v.48 no.4
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• pp.373-383
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• 2024

Background: Network pharmacology has emerged as a powerful tool to understand the therapeutic effects and mechanisms of natural products. However, there is a lack of comprehensive evaluations of network-based approaches for natural products on identifying therapeutic effects and key mechanisms. Purpose: We systematically explore the capabilities of network-based approaches on natural products, using Panax ginseng as a case study. P. ginseng is a widely used herb with a variety of therapeutic benefits, but its active ingredients and mechanisms of action on chronic diseases are not yet fully understood. Methods: Our study compiled and constructed a network focusing on P. ginseng by collecting and integrating data on ingredients, protein targets, and known indications. We then evaluated the performance of different network-based methods for summarizing known and unknown disease associations. The predicted results were validated in the hepatic stellate cell model. Results: We find that our multiscale interaction-based approach achieved an AUROC of 0.697 and an AUPR of 0.026, which outperforms other network-based approaches. As a case study, we further tested the ability of multiscale interactome-based approaches to identify active ingredients and their plausible mechanisms for breast cancer and liver cirrhosis. We also validated the beneficial effects of unreported and top-predicted ingredients, in cases of liver cirrhosis and gastrointestinal neoplasms. Conclusion: our study provides a promising framework to systematically explore the therapeutic effects and key mechanisms of natural products, and highlights the potential of network-based approaches in natural product research.

• Korean Journal of Medicinal Crop Science
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• v.18 no.3
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• pp.143-150
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• 2010

This study showed the increase of antitumor activities of water soluble E. sinica extract by nano-encapsulation process with lecithin. Five groups of lecithin only group (LO), lecithin nano-encapsulated E. sinica group (LE), E. sinica only group (EO), one negative control group (NCO) and positive control group (PCO) were set for several anticancer experiment and fed into Sarcoma-180 injected mice. The cytotoxicity of LE on the human normal kidney cell (HEK293) showed 14.8% lower than 19.2% of EO and 18.4% of LO. Growth of human liver carcinoma cell and human stomach carcinoma cell as representative of digestive system in vitro was inhibited up to about 85.1% and 87.3%, in adding 1.0 mg/$m{\ell}$ of LE, which values 15% higher than that from conventional EO. The survival rates of each mice group were 40%, 63%, 48%, 33% and 100%, respectively after 40 days of injecting Sarcoma-180. The increment of their body weights of the extract feeding groups was suppressed down to 10~15%, compared to the negative control. The nano-particles also reduced the hypertrophy of the internal organs such as spleen and liver down to 15~20%, compared to those as the other groups. Among them, LE effectively reduced the size of tumor form to 20%. From these results, in vitro and in vivo antitumor activities of E. sinica could be enhanced by using nano-encapsulation process with lecithin because of better permeation into the cancer cells by confocal observations.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.11
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• pp.1371-1376
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• 2007

The effect of Hovenia dulcis Thumb leaves on the mutagenicity in salmonella assay and inhibitory effects on the growth of cancer cells were studied. On antimutagenicity as evaluated by Ames test, the extract and fractions of Hovenia dulcis Thumb leaves had no effect on the mutagenicity by themselves. However, methanol extract and fractions from Hovenia dulcis Thumb showed strong inhibitory effect on the mutagenesis induced by N-methyl-N#-nitro-N-nitroso-guanidine (MNNG) and benzo(a)pyrene (B(a)P). Among the solvent fractions of methanol extract, the hexane, chloroform and butanol fraction exhibited stronger inhibitory activity against MNNG and B(a)P induced mutagenesis than water fraction. For anticancer effects, Hovenia dulcis Thumb loaves extract and fractions against cancer cell lines including HepG2 and HT29 were investigated. The methanol extract, the hexane fraction and the chloroform fraction of Hovenia dulcis Thumb leaves inhibited growth of cancer cells but they had no effect on the cytotoxicity of normal human liver cells under the same conditions.

• Journal of Food Hygiene and Safety
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• v.26 no.4
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• pp.388-397
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• 2011

Selenium (Se) is known to prevent from several cancers, while iron (Fe) is known to be associated with high risk of cancers. The role of Se on colon carcinogenesis was investigated in an animal model induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) in low Fe mice. Six-week old ICR mice fed on a low Fe diet (4.5 ppm Fe; generally 10 times lower than normal Fe) with three different Se (0.02, 0.1 or 0.5 ppm) levels for 24 weeks. The animals received weekly three ($0{\sim}2^{nd}$ weeks) i.p. injections of AOM (10 mg/kg RW), followed by 2% DSS with drinking water for 1 week to induce the colon cancer. There were five experimental groups including vehicle, positive control (normal Fe level, AOM/DSS), Low Fe (LFe) + AOM/DSS+Low Se (LSe), LFe + AOM/DSS + medium Se (MSe) and LFe + AOM/DSS + high Se (HSe) groups. HSe group showed a 66.7% colonic tumor incidence, MSe group showed a 69.2% tumor incidence, and LSe group showed a 80.0% tumor incidence. The tumor incidence was negatively associated with Se levels of diets. Tumor multiplicity in Hse group was significantly low compared to the other groups (p < 0.05). With increasing Se levels of diets, the primary anti-proliferating cell nuclear antigen (PCNA)-positive cells were decreased and apoptotic bodies were increased in a dose-dependent manner. Se-dependent glutathione peroxidase activity and its protein level were dependent on the levels of Se of diets. Malondialdehyde level in liver was lowest in Hse group among experimental groups. These findings indicate that dietary Se is chemopreventive for colon cancer by increasing antioxidant activity and decreasing cell proliferation in Fe-deficient mice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.3
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• pp.480-486
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• 2004

Despite many therapeutic advances in the understanding of the processes in carcinogenesis, overall mortality statistics are unlikely to change until there is reorientation of the concepts for the use of natural products as new anticarcinogenic agents. In this study, we investigated the anticarcinogenic activity, antioxidant and DPPH scavenging activity of Sargassum fulvellum (SF). SF was extracted with methanol, which was further fractionated into five different types: hexane (SFMH), ethylether (SFMEE), ethyl acetate (SFMEA), butanol (SFMB) and aqueous (SFMA) partition layers. We determined the cytotoxic effect of these layers on human cancer cells by MTT assay. Among various partition layers of SF, at starting concentration of 100 $\mu\textrm{g}$/mL, SFMEE showed very high cytotoxicity which were 92, 90 and 84% and kept high throughout 5 concentration levels sparsed by 100 $\mu\textrm{g}$/mL against all three human cancer cell lines: HepG2, HT-29 and HeLa. SFMEA showed a low cytotoxicity at the beginning concentration level, but as the concentration became denser, growth inhibition effect of cancer cell lines started to increase and at 500 $\mu\textrm{g}$/mL, it hit the highest, which were 91, 96 and 98% against the same three cell lines as above. We observed QR induced effect in all fraction layers of SF. SFMEE showed similar tendensy of QR induced effect as did against cytotoxicity. The QR induced effect of SFMEE on HepG2 cells at 25 $\mu\textrm{g}$/mL concentration indicated 3 times higher than the control value of 1.0 and SFMH tended to be concentration-dependent on HepG2 cells. At 100 $\mu\textrm{g}$/mL, the QR induced effects resulted a ratio, which was 2.5 times higher than the control value. In search for antioxidation effects of SF extract and partition layer, the reducing activity on the 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging potential was sequentially screened. The SFM has similar antioxidant activity as to BHT and vitamin C groups.

• Journal of Life Science
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• v.21 no.11
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• pp.1558-1564
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• 2011

Cytochrome P450 2J2 (CYP2J2) plays important roles in the metabolism of endogenous metabolites such as arachidonic acid as well as therapeutic drugs. CYP2J2 is overexpressed in human cancer tissues and cancer cell lines, as well as in epoxyeicosatrienoic acids (EETs) and CYP2J2-mediated metabolites, and prevent apoptosis of cancer cells. This study aimed to screen marketed drugs for inhibitory potential on CYP2J2 isoforms using human liver microsomes. The initial screen isolated 4 compounds, from 120 marketed drugs, that inhibited the CYP2J2-mediated astemizole O-demethylation more than 50% in the following the order: haloperidol (75%) > terfenadine (56%) > aripiprazole (55%) > miconazole (52%). Miconazole strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}$=11.2 ${\mu}M$) and terfenadine hydroxylation ($IC_{50}$=2.2 ${\mu}M$), and terfenadine also inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}$=13.6 ${\mu}M$) in a dose dependent manner. The present data suggest that these drugs are potential candidates for further evaluation for their anti-cancer activities.

• Journal of Veterinary Clinics
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• v.28 no.6
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• pp.549-554
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• 2011

FK506 is a widespread immunosuppressive drug after liver transplantion in patients with advanced-stage hepatocellular carcinoma. Dexamethasone is frequently used as co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons. Our aim was to investigate antitumor effects of FK506 in Hep3B cells, one of differentiated human hepatocellular carcinoma cell lines and inhibitory effects of dexamethsone on FK506- induced antitumor effects. Cell injury was evaluated by biochemical assays as cell viability, lactate dehydrogenase (LDH) and reactive oxygen species (ROS) in Hep3B cells. Intracellular calcium concentration ([$Ca^{2+}$]i) and the level of activation of the c-Jun-N-terminal kinase (JNK) and the Bax protein in cultured Hep3B cells was measured. Exposure of 0.1 ${\mu}M$ FK506 to Hep3B cells led to cell death accompanied by a decrease in cell viability and an increase in LDH, ROS and [$Ca^{2+}$]i. FK506 induced an increase in activity of Bax and JNK protein but inhibited the activity of Bcl-2 protein. Treatment of dexamethsone, per se, had no effects on cell viability, LDH and ROS. However, co-treatment of FK506 and dexamethasone diminished the FK506-induced LDH release, ROS generation and JNK activation. These results demonstrate that FK506 has antitumor effect in Hep3B cells but the combination of FK506 and dexamethasone antagonizes the FK506-induced antitumor effects.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.4
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• pp.391-398
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• 2018

Mesenchymal stem cells (MSCs) are an attractive resource for refractory patients because of their anti-inflammatory/immunomodulatory capability and multi-lineage differentiation potential. The transplantation of MSCs has led to positive results in preclinical and clinical application to various diseases, including autoimmune disease, cardiovascular disease, cancer, liver cirrhosis, and ischemic stroke. On the other hand, studies have shown that paracrine factors, not direct cell replacement for damaged cells or tissue, are the main contributors in MSC-based therapy. More recently, evidence has indicated that MSC-derived exosomes play crucial roles in regulating the paracrine factors that can mediate tissue regeneration via transferring nucleic acids, proteins, and lipids to the local microenvironment and cell-to-cell communication. The use of these exosomes is likely to be beneficial for the therapeutic application of MSCs because their use can avoid harmful effects, such as tumor formation involved in cell transplantation. Therefore, therapeutic applications using MSC-derived exosomes might be safe and efficient strategies for regenerative medicine and tissue engineering. This review summarizes the recent advances and provides a comprehensive understanding of the role of MSC-derived exosomes as a therapeutic agent.