• 한방안이비인후피부과학회지
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• 제32권3호
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• pp.13-22
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• 2019

Objectives : Armeniacae semen is the seed of Prunus armenica L. var. ansu MAXIM, and this is classified into Rosaceae. Armeniacae semen has been used for centuries in traditional oriental medicine for the treatment of pain and inflammatory diseases. Amygdalin is the major compound of Armeniacae semen, and it is now being used for the treatment of pain and cancer. Methods : In the present study, we compared the effects of an aqueous extract of Armeniacae semen and a solution of amygdalin extracted from Armeniacae semen on lipopolysaccharide(LPS)-stimulated prostaglandin E2 synthesis and nitric oxide production in mouse BV-2 microglial cells. For this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, reverse transcription-polymerase chain reaction(RT-PCR), prostaglandin E2 immunoassay and nitric oxide detection were performed on mouse BV-2 microglial cells. Results : In the present study, an aqueous extract of Armeniacae semen and an amygdalin solution extracted from Armeniacae semen suppressed prostaglandin E2 synthesis and nitric oxide production by inhibiting the LPS-induced enhancement of cyclooxygenase-2(COX-2) mRNA and the inducible nitric oxide synthase mRNA in mouse BV-2 cells. For the cyclooxygenase-1(COX-1) expression, an aqueous extract of Armeniacae semen showed a more potent suppression effect compared to the amygdalin solution. However, the amygdalin solution more potently suppressed the LPS-induced COX-2 mRNA expression compared to the aqueous extract of Armeniacae semen. Conclusions : As a result, aqueous extract of Armeniacae semen and amygdalin exert anti-inflammatory and analgesic effects.

• 대한약침학회지
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• 제22권2호
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• pp.102-108
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• 2019

Objectives: Esophageal squamous cell carcinoma (ESCC) is considered as a deadly medical condition that affects a growing number of people worldwide. Targeted therapy of ESCC has been suggested recently and required extensive research. With cyclin D1 as a therapeutic target, the present study aimed at evaluating the anticancer effects of doxorubicin (Dox) or Hypericum perforatum L. (HP) extract encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on the ESCC cell line KYSE30. Methods: Nanoparticles were prepared using double emulsion method. Cytotoxicity assay was carried out to measure the anti-proliferation activity of Dox-loaded (Dox NPs) and HP-loaded nanoparticles (HP NPs) against both cancer and normal cell lines. The mRNA gene expression of cyclin D1 was evaluated to validate the cytotoxicity studies at molecular level. Results: Free drugs and nanoparticles significantly inhibited KYSE30 cells by 55-73% and slightly affected normal cells up to 29%. The IC50 of Dox NPs and HP NPs was ~ 0.04-0.06 mg/mL and ~ 0.6-0.7 mg/mL, respectively. Significant decrease occurred in cyclin D1 expression by Dox NPs and HP NPs (P < 0.05). Exposure of KYSE-30 cells to combined treatments including both Dox and HP extract significantly increased the level of cyclin D1 expression as compared to those with individual treatments (P < 0.05). Conclusion: Dox NPs and HP NPs can successfully and specifically target ESCC cells through downregulation of cyclin D1. The simultaneous use of Dox and HP extract should be avoided for the treatment of ESCC.

• 동의생리병리학회지
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• 제34권4호
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• pp.177-183
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• 2020

The Hippo-YAP signaling pathway is critical for cell proliferation, survival, and self-renewal in both Drosophila and mammals. Disorder of Hippo-YAP pathway leads to tumor development, progression and poor prognosis in various cancers. YAP/TAZ are the key downstream effectors of the Hippo pathway and they can be inhibited through LATS1/2, core kinases in the Hippo pathway, mediated phosphorylation. In this study, we investigated the effect of Angelica gigas Nakai extract (AGNE) on Hippo-YAP/TAZ pathway. First, ANGE induced YAP/TAZ phosphorylation and dissociation of the YAP/TAZ-TEAD transcription complex. By qRT-PCR, we found that ANGE inhibits the expression of YAP/TAZ-TEAD target gene, CTGF and CYR61. In addition, the transcriptional activity of YAP/TAZ was not suppressed significantly in LATS1/2 double-knockout (DKO) cells by ANGE compared to LATS1/2 wild-type (WT) cells, which means AGNE inhibits YAP/TAZ signaling through direct action on LATS1/2. Further, it was confirmed that AGNE-induced activation of LATS1/2 inhibited the migration potential of the vector-expressing cells by suppressing YAP/TAZ activity. The reduced migration potential was restored in active YAP-TEAD expressing cells. Taken together, the results of this study indicate that ANGE downregulates YAP/TAZ signaling in cells through the activation of LATS1/2.

• International Journal of Oral Biology
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• 제46권1호
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• pp.23-29
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• 2021

Demethoxycurcumin (DMC), which is a curcuminoid found in turmeric, has anti-proliferative effects on cancer cells. However, the effect of DMC on osteosarcoma has not been established. The aim of this study was to examine the effects of DMC on cell growth and apoptosis induction in MG-63 human osteosarcoma cells. This study was investigated using 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromid assay, Live/Dead cell assay, 4', 6-diamidino-2-phenylindole staining, and immunoblotting in MG-63 cells. DMC induced MG-63 cell death in a dose-dependent manner, with an estimated IC50 value of 54.4 µM. DMC treatment resulted in nuclear condensation in MG-63 cells. DMC-induced apoptosis in MG-63 cells was mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting results showed that Bcl-2 and Bcl-xL were downregulated, while Bax and Bad were upregulated by DMC in MG-63 cells. These results indicated that DMC inhibits cell proliferation and induces apoptotic cell death in MG-63 human osteosarcoma cells via the death receptor-mediated extrinsic apoptotic pathway and mitochondria-mediated intrinsic apoptotic pathway.

• Journal of Korean Neurosurgical Society
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• 제64권5호
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• pp.716-725
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• 2021

Objective : The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effect of propranolol to human glioblastoma cell lines, and the role of Notch and Hes signaling in this process. Methods : We performed immunohistochemical staining on 31 surgically resected primary human glioblastoma tissues. We also used glioblastoma cell lines of U87-MG, LN229, and neuroblastoma cell line of SH-SY5Y in this study. The effect of propranolol and isoproterenol on cell proliferation was evaluated using the MTT assay (absorbance 570 nm). The impact of propranolol on gene expression (Notch and Hes) was evaluated using real-time polymerase chain reaction (RT-PCR, whereas protein levels of Notch1 and Hes1 were measured using Western blotting (WB), simultaneously. Small interfering RNA (siRNA) was used to suppress the Notch gene to investigate its role in the proliferation of glioblastoma. Results : Propranolol and isoproterenol caused a dose-dependent decrease in cell proliferation (MTT assay). RT-PCR showed an increase in Notch1 and Hes1 expression by propranolol, whereas WB demonstrated increase in Notch1 protein, but a decrease in Hes1 by propranolol. The proliferation of U87-MG and LN229 was not significantly suppressed after transfection with Notch siRNA. Conclusion : These results demonstrated that propranolol suppressed the proliferation of glioblastoma cell lines and neuroblastoma cell line, and Hes1 was more closely involved than Notch1 was in glioblastoma proliferation.

• 한국자원식물학회지
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• 제34권6호
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• pp.555-565
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• 2021

Melon fruits are a year-old plant in the family Cucurbitae and are the most cultivated fruit in tropical countries. Melon flesh is an important source of anti-cancer, antioxidant effects, attracting attention as a functional food. We investigated the morphological properties, β-carotene content, and cucumisin activity of seeds of 58 melon genetic resources. Melon resources have shown various morphological properties. Melons grouped by morphological properties were the five groups. β-carotene content varied between 82.34 mg/kg, 86.75 mg/kg, 25.56 mg/kg, 86.25 mg/kg, and 54.65 mg/kg. Between β-carotene, cucumisin activity and other quantitative fruit morphological properties, the color of the pulp and the firmness of the pulp had a significant amount of correlation between the β-carotene content. However, cucumisin activity and β-carotene content had significant negative correlation, and the color of the fruit and shape of the fruit had significant negative correlation with β-carotene content and activity of cucumisin. Our study vindicated that high diversity in melon morphological characters of genetic sources that provide beneficial baseline data for the future and in the activity of β-carotene and cucumisin, and these results could predict indicators of β-carotene content by the length of leaf, the width of fruit, the length of joint, and the length of seed, and collectively the morphological properties of melons could help predict indicators of β-carotene content and help develop functional sarcoma and farmhouse cultivation.

• Journal of Microbiology and Biotechnology
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• 제31권12호
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• pp.1624-1631
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• 2021

Prodigiosin as a high-valued compound, which is a microbial secondary metabolite, has the potential for antioxidant and anticancer effects. However, the large-scale production of functionally active Hahella chejuensis-derived prodigiosin by fermentation in a cost-effective manner has yet to be achieved. In the present study, we established carbon source-optimized medium conditions, as well as a procedure for producing prodigiosin by fermentation by culturing H. chejuensis using 10 L and 200 L bioreactors. Our results showed that prodigiosin productivity using 250 ml flasks was higher in the presence of glucose than other carbon sources, including mannose, sucrose, galactose, and fructose, and could be scaled up to 10 L and 200 L batches. Productivity in the glucose (2.5 g/l) culture while maintaining the medium at pH 6.89 during 10 days of cultivation in the 200 L bioreactor was measured and increased more than productivity in the basal culture medium in the absence of glucose. Prodigiosin production from 10 L and 200 L fermentation cultures of H. chejuensis was confirmed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) analyses for more accurate identification. Finally, the anticancer activity of crude extracted prodigiosin against human cancerous leukemia THP-1 cells was evaluated and confirmed at various concentrations. Conclusively, we demonstrate that culture conditions for H. chejuensis using a bioreactor with various parameters and ethanol-based extraction procedures were optimized to mass-produce the marine bacterium-derived high purity prodigiosin associated with anti-cancer activity.

• 한국미생물·생명공학회지
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• 제50권2호
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• pp.255-269
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• 2022

Actinomycetes isolated from marine habitats represent a promising source of bioactive substances. Here, we report on the isolation, identification, productivity enhancement and application of the bioactive compounds of Streptomyces qinglanensis H4. Eighteen marine actinomycetes were isolated and tested for resistance to seven bacterial diseases. Using 16S rRNA sequencing analysis (GenBank accession number MW563772), the most powerful isolate was identified as S. qinglanensis. Although the strain produced active compound(s) against a number of Gram-negative and Gram-positive bacteria, it failed to inhibit pathogenic fungi. The obtained inhibition zones were 22.0 ± 1.5, 20.0 ± 1, 16.0 ± 1, 12.0 ± 1, 22.0 ± 1 and 24.0 ± 1 mm against Bacillus subtilis ATCC 6633, Escherichia coli ATCC 19404, Enterococcus faecalis ATCC 29212, Pseudomonas aeruginosa ATCC 9027, Candida albicans ATCC 10231 and Staphylococcus aureus ATCC6538, respectively. To maximize bioactive compound synthesis, the Plackett-Burman design was used. The productivity increased up to 0.93-fold, when S. qinglanensis was grown in optimized medium composed of: (g/l) starch 30; KNO₃ 0.5; K₂HPO₄ 0.25; MgSO₄ 0.25; FeSO₄·7H₂O, 0.01; sea water concentration (%) 100; pH 8.0, and an incubation period of 9 days. Moreover, the anticancer activity of S. qinglanensis was tested against two different cell lines: HepG2 and CACO. The inhibition activities were 42.96 and 57.14%, respectively. Our findings suggest that the marine S. qinglanensis strain, which grows well on tailored medium, might be a source of bioactive substances for healthcare companies.

• 대한본초학회지
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• 제33권2호
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• pp.79-84
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• 2018

Objective : The immune enhance is the main focus of current society that to increase resistance to invasion by pathogenic species of bacteria in body, stimulate the immune system and possibly protect against cancer or inflammatory disease. The present study aimed to evaluate the effect of Gentianae Radix extract on immune regulation in a LPS-induced mice model of acute inflammation. Methods : Gentianae Radix extract was administered orally at doses of 200 mg/kg/day or 400 mg/kg/day for 2 weeks before a intraperitoneally injection of LPS (1 mg/kg of 0.9% saline). After LPS-intraperitoneal injection 3 hours, blood was collected by cardiac puncture under ether anaesthesia from all animals, for the immune regulate efficacy verification based on blood or serum biomarkers (i.e., immune cells, cytokine, $PGE_2$, ROS, and $LTB_4$) analysis. Results : Compared to the control mice, the Gentianae Radix extract treatments significantly increased the count of immune cells (i.e., wite blood cell, neutrophils, and monocyte), and significantly reduced the lymphocyte. In addition, the Gentianae Radix extract treatments significantly decreased the pro-inflammatory cytokine (i.e., $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$), and significantly increased IL-10 of anti-inflammatory cytokine. Furthermore, the Gentianae Radix extracts treatments significantly increased the levels of $PGE_2$ and significantly decreased the levels of ROS, and $LTB_4$. Conclusions : The results indicate that Gentianae Radix extract alleviated acute inflammatory reaction though regulation of immune meditor. Thus, Gentianae Radix extract may raw material of development a health food and medicine option for the immune enhance.

• Journal of Ginseng Research
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• 제46권3호
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• pp.337-347
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• 2022

Coronavirus disease 2019 (COVID-19) is currently a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 are directly associated with hyper-activation of innate immune response that excessively produce pro-inflammatory cytokines and induce cytokine storm, leading to multi-organ-failure and significant morbidity/mortality. Currently, several antiviral drugs such as Paxlovid (nirmatrelvir and ritonavir) and molnupiravir are authorized to treat mild to moderate COVID-19, however, there are still no drugs that can specifically fight against challenges of SARS-CoV-2 variants. Panax ginseng, a medicinal plant widely used for treating various conditions, might be appropriate for this need due to its anti-inflammatory/cytokine/viral activities, fewer side effects, and cost efficiency. To review Panax ginseng and its pharmacologically active-ingredients as potential phytopharmaceuticals for treating cytokine storm of COVID-19, articles that reporting its positive effects on the cytokine production were searched from academic databases. Experimental/clinical evidences for the effectiveness of Panax ginseng and its active-ingredients in preventing or mitigating cytokine storm, especially for the cascade of cytokine storm, suggest that they might be beneficial as an adjunct treatment for cytokine storm of COVID-19. This review may provide a new approach to discover specific medications using Panax ginseng to control cytokine storm of COVID-19.