• Biomedical Science Letters
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• v.25 no.1
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• pp.92-98
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• 2019

Metformin is a drug used for the treatment of diabetes and is associated with anti-inflammatory reaction, but the underlying mechanism is unclear. In this study, we investigated the effect of metformin on the inflammatory response in BV-2 microglial cells induced by lipopolysaccharide (LPS) and S100 calcium-binding protein A8 (S100A8). The results revealed that metformin significantly attenuated several inflammatory responses in BV-2 microglial cells, including the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin (IL)-6, involved in the activation of Beclin-1, a crucial regulator of autophagy. In addition, metformin inhibited the LPS-induced phosphorylation of ERK. Metformin also suppressed the activation of NOD-like receptor pyrin domain containing 3 inflammasomes composed of NLRP3, caspase-1, and apoptosis-associated speck like protein containing a caspase recruitment domain, which are involved in the innate immune response. Notably, metformin decreased the secretion of S100A8-induced IL-6 production. These findings suggest that metformin alleviates the neuroinflammatory response via autophagy activation.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.20-20
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• 2022

Herein, we demonstrate that butein (1) can prevent swelling in a murine lymphedema model by suppressing tumor necrosis factor α (TNF-α) production. Butein derivatives were synthesized and evaluated to identify compounds with in vitro anti-inflammatory activity. Among them, 20 µM of compounds 7j, 7m, and 14a showed 50% suppression of TNF-α production in mouse peritoneal macrophages after lipopolysaccharide stimulation. Compound 14a, exhibited the strongest potency with an in vitro IC₅₀ of 14.6 µM and suppressed limb volume by 70% in a murine lymphedema model. The prodrug strategy enabled a six-fold increase in kinetic solubility of compound 1 and five-fold higher levels of active metabolite in the blood for compound 14a via oral administration in the pharmacokinetics study. We suggest that the compound 14a could be developed as a potential therapeutic agent targeting anti-inflammatory activity to alleviate lymphedema progression.

• Preventive Nutrition and Food Science
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• v.16 no.3
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• pp.242-247
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• 2011

The methanolic extract of Rosa davurica Pall. roots exhibited strong antioxidant activity in a 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay and was found to be a dose-dependent inhibitor of non-enzymatic formation of advanced glycation end products (AGEs), which are relevant to diabetes complications. HPLC-diode array detector (DAD) analysis of the R. davurica Pall. root extract led to the identification of four compounds: hydrocaffeic acid, catechin, epicatechin, and ellagic acid. Catechin was present in the largest amount and exhibited high antiglycation activity. A CYP3A4 assay was used to investigate potential interactions between drugs and the extract, and results suggest that the R. davurica Pall. root extract had moderate potential for interfering with drug metabolism. The R. davurica Pall. extract did not display anti-inflammatory activity on the level of that for tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in a lipopolysaccharide (LPS)-stimulated macrophage assay; however, the extract did exhibit low to moderate immunostimulatory activity in a pro-inflammatory macrophage assay. Therefore, we conclude that R. davurica Pall. root is a promising anti-AGE agent with low to moderate risks of associated inflammation or drug interaction.

• The Journal of Korean Obstetrics and Gynecology
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• v.26 no.3
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• pp.44-58
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• 2013

Objectives: Breast cancer is the most common cancer among women and has rapidly increasing rate annually. At present, western cancer therapies by surgery, radiation, and anticancer drug have not been fully effective. So many interests are given to herbal medicine on cancer treatment recently. This study was designed to investigate the effects of Curcuma longa L. (CL) on MDA-MB-231 human breast cancer cells and DMBA-induced breast cancer in rats. Methods: In this experiment, MDA-MB-231 cells were cultured in cell culture plates. 0.0625, 0.125, 0.25, 0.5, 1.0 mg/ml of CL extract were tested for their anti-proliferative effects on MDA-MB-231 cells by MMT assay. And we induced breast cancer in rats. The changes in tumor's weight, and the effects on proliferations of splenocyte and thymocyte were investigated. Results: CL showed anti-proliferative effects on MDA-MB-231 cells in proportion to concentration of the CL. DMBA-induced breast cancer in rats, tumor's weight of the rat was not statistically significant, but showed a tendency to be reduced in the groups treated with CL. Proliferation rate of the rat's splenocyte and thymocyte increased in proportion to CL. In breast cancer tissue, expression of ER-${\alpha}$ was weakened proportionately to the concentration of the CL. Conclusions: These data suggest that CL can prevent the proliferation of breast cancer, then CL is useful to treat patient with breast cancer.

• Journal of Food Hygiene and Safety
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• v.28 no.3
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• pp.202-206
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• 2013

High-grade mucoepidermoid carcinomas (MECs) have difficulty in cure and 5-year survival rate is quiet low. Therefore, we need new therapeutic agents and molecular targets. Betulinic acid (BA) is one of the materials which is easily found in the world and shows tumor-suppress effects in various tumor types. In addition, many kinds of normal tissues have a resistance to BA treatment. In this study, we investigated the anti-proliferative activity of BA and its molecular targets in MC-3 human MEC cells using western blot analysis and DAPI staining. BA inhibited cell viability and induced apoptosis in MC-3 cells. It affected Specificity protein 1 (Sp1) and its downstream molecule, survivin whereas it did not affect myeloid cell leukemia-1 (Mcl-1). Therefore, we suggest that BA can be a potential anti-cancer drug candidate regulating Sp 1 and survivin to exert apoptotic cell death.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5703-5707
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• 2015

Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of their antioxidative properties. Melissa officinalis L. (MO), an aromatic and medicinal plant, is well known in thios context. However, toxicity against cancer cells has not been fully studied. Here, we investigated the selective anticancer effects of an MO extract (MOE) in different human cancer cells. Materials and Methods: a hydro-alcoholic extract of MO was prepared and total phenolic content (TPC) and total flavonoid content (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. MTT assays were used to evaluate cytotoxicity of different doses of MOE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) towards A549 (lung non small cell cancer cells), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all cancer cells, MOE reduced the cell viability to values below 33%, even at the lowest doses. In all cases, $IC_{50}$ values were below $5{\mu}g/ml$. The mean growth inhibition was 73.1%, 86.7%, 79.9% and 77.8% in SKOV3, MCF-7 and PC-3 and A549 cells, respectively. Conclusions: Our results indicate that a hydro-alcoholic extract of MO possess a high potency to inhibit proliferation of different tumor cells in a dose independent manner, suggesting that an optimal biological dose is more important than a maximally tolerated one. Moreover, the antiprolifreative effect of MO seems to be tumor type specific, as hormone dependant cancers were more sensitive to antitumoral effects of MOE.

• BMB Reports
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• v.46 no.2
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• pp.97-102
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• 2013

The use of various cancer cell lines can recapitulate known tumor-associated mutations and genetically define cancer subsets. This approach also enables comparative surveys of associations between cancer mutations and drug responses. Here, we analyzed the effects of ~40,000 compounds on cancer cell lines that showed diverse mutation-dependent sensitivity profiles. Over 1,000 compounds exhibited unique sensitivity on cell lines with specific mutational genotypes, and these compounds were clustered into six different classes of mutation-oriented sensitivity. The present analysis provides new insights into the relationship between somatic mutations and selectivity response of chemicals, and these results should have applications related to predicting and optimizing thera-peutic windows for anti-cancer agents.

• Biomedical Science Letters
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• v.18 no.4
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• pp.338-344
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• 2012

Mollugin is the active compound of Rubia cordifolia, a well known herb widely used in alternative medicines for the treatment of various inflammatory diseases including arthritis and uteritis. In the present study, we investigated the anti-inflammatory effects of mollugin in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells. Treatment with mollugin significantly inhibited LPS-induced release of nitric oxide, prostaglandin $E_2$, and inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin-6. In addition, mollugin suppressed LPS-induced nuclear factor-kappa B (NF-${\kappa}B$) transcriptional activity. These results suggest that mollugin inhibits LPS-induced expression of inflammatory molecules via NF-${\kappa}B$, at least in part, and indicate the potential value of mollugin as a valuable new drug candidate for the treatment of various inflammatory diseases.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.19-26
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• 2012

There are many cyclic peptides with diverse biological activities, such as antibacterial activity, immunosuppressive activity, and anti-tumor activity, and so on. Encouraged by natural cyclic peptides with biological activity, efforts have been made to develop cyclic peptides with both genetic and synthetic methods. The genetic methods include phage display, intein-based cyclic peptides, and mRNA display. The synthetic methods involve individual synthesis, parallel synthesis, as well as split-and-pool synthesis. Recent development of cyclic peptide library based on split-and-pool synthesis allows on-bead screening, in-solution screening, and microarray screening of cyclic peptides for biological activity. Cyclic peptides will be useful as receptor agonist/antagonist, RNA binding molecule, enzyme inhibitor and so on, and more cyclic peptides will emerge as therapeutic agents and biochemical tools.

• Bulletin of the Korean Chemical Society
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• v.33 no.1
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• pp.111-114
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• 2012

Androgen receptor (AR) is ligand-inducible nuclear hormone receptor which has been focused on key molecular target in growth and progression of prostate cancer. We synthesized a series of 4-aryl 2-substituted aniline-thiazole analogs and evaluated their anti-cancer activity in AR-dependent human prostate cancer LNCap cells. Among them, the compound 6 inhibited the tumor growth in LNCap-inoculated xenograft model.