• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.553-561
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• 2022

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia. However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

• BMB Reports
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• v.55 no.11
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• pp.565-570
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• 2022

Pulmonary arterial hypertension (PAH) is a progressive and devastating disease whose pathogenesis is associated with a phenotypic switch of pulmonary arterial vascular smooth muscle cells (PASMCs). Bone morphogenetic protein (BMP) signaling and potassium two pore domain channel subfamily K member 3 (KCNK3) play crucial roles in PAH pathogenesis. However, the relationship between BMP signaling and KCNK3 expression in the PASMC phenotypic switching process has not been studied. In this study, we explored the effect of BMPs on KCNK3 expression and the role of KCNK3 in the BMP-mediated PASMC phenotypic switch. Expression levels of BMP receptor 2 (BMPR2) and KCNK3 were downregulated in PASMCs of rats with PAH compared to those in normal controls, implying a possible association between BMP/BMPR2 signaling and KCNK3 expression in the pulmonary vasculature. Treatment with BMP2, BMP4, and BMP7 significantly increased KCNK3 expression in primary human PASMCs (HPASMCs). BMPR2 knockdown and treatment with Smad1/5 signaling inhibitor substantially abrogated the BMP-induced increase in KCNK3 expression, suggesting that KCNK3 expression in HPASMCs is regulated by the canonical BMP-BMPR2-Smad1/5 signaling pathway. Furthermore, KCNK3 knockdown and treatment with a KCNK3 channel blocker completely blocked BMP-mediated anti-proliferation and expression of contractile marker genes in HPAMSCs, suggesting that the expression and functional activity of KCNK3 are required for BMP-mediated acquisition of the quiescent PASMC phenotype. Overall, our findings show a crosstalk between BMP signaling and KCNK3 in regulating the PASMC phenotype, wherein BMPs upregulate KCNK3 expression and KCNK3 then mediates BMP-induced phenotypic switching of PASMCs. Our results indicate that the dysfunction and/or downregulation of BMPR2 and KCNK3 observed in PAH work together to induce aberrant changes in the PASMC phenotype, providing insights into the complex molecular pathogenesis of PAH.

• Journal of Life Science
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• v.33 no.1
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• pp.43-49
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• 2023

Houttuynia cordata belongs to the Saururacease family and its leaves, stems, and roots have been used as oriental medicines to treat pneumonia, acute or chronic bronchitis, enteritis, and abscesses and to remove extravasated blood. Recently, the antioxidant, anti-inflammation, antibacterial, and anti-proliferation activities and protection abilities of H. cordata against liver and neuron cell damage have been reported. In this study, ethanol extract and its solvent fractions (fractions of hexane, ethyl acetate, butanol, and water residue) were prepared, and their antithrombosis, antidiabetes, antioxidant, and hemolysis activities were evaluated. The ethyl-acetate fraction of H. cordata (EF-HC) showed the highest polyphenol and flavonoids contents among the fractions and exhibited strong antithrombosis and antioxidant activities. The EF-HC at 5 mg/ml showed 2.09-folds of thrombin time, 2.19-folds of prothrombin time, and 1.69-folds of activated partial thromboplastin time compared to the their solvent control and 30.9, 19.9, and 49.6 ㎍/ml of RC₅₀ against DPPH, ABTS, and nitrite radicals, respectively. Furthermore, the EF-HC did not show any hemolytic activity up to 1 mg/ml, whereas the hexane fraction of H. cordata showed 55% hemolysis at 1 mg/ml. This is the first report of the antithrombosis activity of H. cordata. Our results suggest that quercitirin, hyperoside, orientin, and isoquercitrin in EF-HC are related to its antithrombosis and antioxidant activities and that the EF-HC could be developed as a promising antithrombosis agent.

• Journal of Korea Entertainment Industry Association
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• v.13 no.2
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• pp.253-259
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• 2019

Prostate cancer(PrCa) is a leading cause of cancer-related death in man. Medicinal plants are exploited for many drugs to treat various ailments. The drugs derived from the plants promote health, augmented the resistance of the body against disease. Pueraia lobata(wild) Ohwi(P. Lobata), kudzu, which is a twining perennial woody herb native to China, Korea, Japan, India, and the United States. Plants such as Moringa oleifera, have hypoglycemic properties and other beneficial properties. The objective of the study was to analyze the effects of kadzu and moringa, natural plant products on antioxidant activity and proliferation of the hormone-sensitive prostate cancer LNCaP cells. MTT assay, flow cytometry analysis were employed to investigate the anticancer mechanism and DPPH assay was determined to the antioxidant activity to scavenge free radicals in extract of these. All two extracts showed significantly antioxidant activity at 10 and 50mg/ml of concentration. kadzu and moringa reduced LNCaP cell viability in a dose dependent manner. Specially moringa extract was more potent cytotoxic than kadzu extract. Statistical analyses revealed kadzu and moringa exhibited significantly higher (P < 0.05) cytotoxicity and antioxidant activity in LNCaP. The finding of this study provides a scientific basis for using kadzu and moringa in future development of chemotherapeutic drugs against hormone-sensitive prostate cancer.

• Journal of Life Science
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• v.33 no.4
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• pp.343-348
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• 2023

Acne is one of the most common skin diseases, mainly occurring in adolescence. The pathophysiology of acne involves not only hormonal, genetic and environmental factors, but also other factors including hyperseborrhea, inflammation, over-keratinization of follicular keratinocytes and overgrowth of Cutibacterium acnes (C. acnes). Cannabidiol (CBD) is known to relieve pain, stress and inflammation. Moreover, cannabis extracts containing CBD have been reported to be effective in treating acne. However, the therapeutic effect of CBD on acne remains unclear. Therefore, this study aimed to investigate the effect and mechanism of CBD on lipogenesis in SEB-1 sebocytes. We treated sebocytes with CBD and found that it not only inhibited lipid synthesis, but also inhibited cell proliferation by inducing apoptosis. We then demonstrated that sterol response element-binding protein-1 (SREBP-1) mediates the inhibitory effect of CBD on lipogenesis. Furthermore, Akt and adenosine monophosphate-activated protein kinase (AMPK), upstream regulators of SREBP-1, were regulated by CBD treatment. Taken together, our studies demonstrate that CBD inhibits adipogenesis by regulating the Akt/AMPK-SREBP-1 signaling pathway, providing potential for use as a therapeutic agent for acne. Further research is needed to confirm the effect of CBD on inflammation caused by hyperkeratosis, which will increase the possibility of using CBD for acne treatment.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.3
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• pp.1-24
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• 2009

Purpose: This study was performed to investigate the effects of Bojungikgi-Tang on the development of experimentally-induced endometriosis in rats. Methods: Endometriosis was induced in rats by autotransplanting uterine tissue to the peritoneum and we divided the rats into three groups: (1) sham-operated group (n=8), (2) surgically induced endometriosis and untreated control group(n=8), (3) surgically induced endometriosis and Bojungikgi-Tang treated group. Bojungikgi-Tang was orally administrated for 15 days after operation. Then we measured the body weight, the volume of endometriotic implants, the weight of uterus and ovary, and analysed the concentration of cytokines(MCP-1, TNF-${\alpha}$, IL-1${\beta}$, IL-6) in peritoneal fluids. Histopathology, immunohistochemistry for COX-2 and VEGF, and histochemistry for mast cell in transplanted uterine tissue were also performed. Results: 1. The volume($mm^3$) of endometriotic implants in Bojungikgi-Tang treated group(129${\pm}$39) was significantly decreased(p<0.05) compared with control group(222${\pm}$109). 2. The concentration(pg/$m{\ell}$) of MCP-1 in peritoneal fluids in Bojungikgi-Tang treated group(1012${\pm}$248) was significantly decreased(p<0.05) compared with control group(1413${\pm}$346). 3. The concentration(pg/$m{\ell}$ of TNF-${\alpha}$ in peritoneal fluids in Bojungikgi-Tang treated group(887${\pm}$196) was significantly decreased(p<0.05) compared with control group(1126${\pm}$140). 4. Histopathologically, proliferation of endometriotic epithelia, infiltration of inflammatory cells and angiogenesis in transplanted uterine tissue of Bojungikgi-Tang treated group were weakly observed than those of control group. 5. The percentage of positive epithelial layers for COX-2 in Bojungikgi-Tang treated group(56${\pm}$17) was significantly decreased(p<0.05) compared with control group(75${\pm}$16). 6. The VEGF expression of endometriotic epithelia, neovascular endothelia and stromal cells in transplanted uterine tissue of Bojungikgi-Tang treated group were weakly observed than those of control group. Conclusion: On the basis of these results, we concluded that Bojungikgi-Tang has inhibiting effects on the development of transplanted uterine tissue. And these effects may be related with decreased production of MCP-1, TNF-${\alpha}$, and decreased expression of COX-2 and VEGF infiltration by administration of Bojungikgi-Tang.

• Journal of Food Hygiene and Safety
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• v.38 no.1
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• pp.19-25
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• 2023

Addition of spice for inhibition of bacterial growth in ground chicken meat was investigated. The ground chicken meat approximately contained 72.98±0.15% moisture, 23.37±0.46% crude protein, 1.00±0.03% crude fat, and 1.90±0.03% ashes. Addition of rosemary showed the maximum bacterial inhibition, followed by garlic and mustard. The inhibitory effect increased with the addition of a greater quantity of spices. The optimal added concentration of spices for inhibition of total viable cell and proliferation of Escherichia coli in ground chicken meat was 2%, 4%, and 1.2% for rosemary, garlic, and mustard, respectively. The growth inhibition of total viable cells and E. coli differed during storage period for MixA (97.4%) > rosemary (96.9%) > MixB (96.3%) > garlic (53.7%) > mustard (33.3%). The addition of sterilized garlic to ground chicken meat showed that the total viable cells was low at 2.6-3.0 log CFU/g on the 0-day and 2.4-3.2 log CFU/g on the 9-day, and the number decreased as the storage lengthened. Non-sterilized garlic treatment showed a higher number of total viable cells than the control group, and this increased with elapse of storage time. The number of E. coli, was low at 0.4-1.0 log CFU/g on the 0-day and 0.5-1.5 log CFU/g on the 9-day for the sterilized group, and the change during the storage showed a similar trend for the total viable cells. In conclusion, the microbial safety of ground chicken meat products was improved by various mixed applications of rosemary, garlic, and mustard.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.36 no.4
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• pp.30-50
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• 2023

Objectives : To investigate the active compounds and therapeutic mechanisms of Atractylodes Lancea(Thunb.) D.C. and Magnolia Officinalis Rehder et Wilson in the treatment of dermatitis accompanied by pruritus, as well as their potential to complement or replace standard drugs. Methods : We conducted the network pharmacological analysis. We selected effective ingredients among the active compounds of research target herbs. Then we explore pathway/terms of the common target proteins among research target herbs, fexofenadine and disease. Results : We selected 9 active compounds are selected from Atractylodes lancea and identified 231 target proteins. Among them, 74 proteins are associated with inflammatory skin diseases that cause pruritus. These proteins are involved in various pathways including, 'Nitric-oxide synthase regulator activity', 'Hydroperoxy icosatetraenoate dehydratase activity, Aromatase activity', 'RNA-directed DNA polymerase activity', 'Arachidonic acid metabolism', 'Peptide hormone processing', 'Chemokine binding' and 'Sterol biosynthetic process'. Additionally, coregenes are involved in 'IL-17 signaling pathway'. Similarly, we selected 2 active compounds from Magnolia officinalis and identified 133 target proteins. Among them, 33 proteins are related to inflammatory skin diseases that cause pruritus. These proteins are primarily involved in 'Vascular associated smooth muscle cell proliferation' and 'Arachidonic acid metabolism'. There is no significant difference between the pathways in which coregenes are involved. Conclusions : It is expected that Atractylodes Lancea will be able to show direct or indirect anti-pruritus and anti-inflammatory effects on skin inflammation accompanied pruritus through suppressing inflammation and protecting skin barrier. Meanwhile, it is expected that Magnolia Officinalis will only be able to show indirect anti-inflammation effects. Therefore, Atractylodes Lancea and fexofenadine are believed to complement each other, whereas Magnolia Officialinalis is expected to provide supplementary support on skin disease.

• Journal of dental hygiene science
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• v.23 no.4
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• pp.282-295
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• 2023

Background: Secretory leukocyte protease inhibitor (SLPI) protects tissues from proteases and promotes cell proliferation and healing. SLPI also reduces periodontal inflammation and alveolar bone resorption by inhibiting proinflammatory cytokine expression in rat periodontal tissues and osteoblasts. However, little is known of the role of SLPI in the expression of osteoclast regulatory factors from osteoblasts, which are crucial for the interaction between osteoblasts and osteoclasts. Therefore, we aimed to determine the effects of SLPI on the regulation of osteoclasts and osteoblasts in LPS-treated alveolar bone and osteoblasts. Methods: Periodontitis was induced in rats using LPS. After each LPS injection, SLPI was injected into the same area. Immunohistochemical analysis was performed with antibodies against SLPI, RANKL, OPG, and Runx2 in the periodontal tissue. RT-PCR and western blotting were performed to determine the expression levels of SLPI, RANKL, OPG, and Runx2 in LPS- and SLPI/LPS-treated MC3T3-E1 cells. SLPI/LPS-treated MC3T3-E1 cells were also stained with Alizarin Red S. Results: Immunohistochemical analysis showed that the expression levels of SLPI, OPG, and Runx2 were higher while that of RANKL was lower in the LPS/SLPI group relative to those in the LPS group. The mRNA and protein expression of SLPI, OPG, and Runx2 was higher in SLPI/LPS/MC3T3-E1 cells than in LPS/MC3T3-E1 cells, and RANKL expression was lower. During differentiation, OPG and Runx2 protein levels were higher whereas RANKL levels were lower in SLPI/LPS/MC3T3-E1 than in LPS/MC3T3-E1 cells on days 0, 4, 7, and 10. In addition, mineralization and matrix deposition were higher in SLPI/LPS/MC3T3-E1 than in LPS/MC3T3-E1 on days 7 and 10. SLPI decreased RANKL expression in LPS-treated alveolar bone and osteoblasts but increased the expression of OPG and Runx2. Conclusion: SLPI can be considered as a regulatory molecule that indirectly regulates osteoclast activation via osteoblasts and promotes osteoblast differentiation.

• Journal of Life Science
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• v.33 no.12
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• pp.978-986
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• 2023

Inflammation by the innate immune system is a protective mechanism of the organism against infection-mediated environmental factors. It is also responsible for the pathogenesis of various human diseases, including the progression of cancer. Lichens are receiving increasing attention as a source of bioactive molecules with therapeutic potential for a variety of diseases. Additionally, the antioxidant, anti-inflammatory, and anticancer potential of lichen and its secondary metabolites have been widely reported. However, the underlying mechanism is still unknown. In the present study, to investigate molecular mechanisms of anti-inflammation and anti-cancer activity in the Antarctic lichen, Usnea aurantiaco-atra, methanol extract of Usnea aurantiaco-atra (MEUS) was used in vitro assays in RAW 264.7 macrophages cell and HCT116 colon cancer cells. Based on our data, MEUS had the anti-inflammatory activity through the modulation of main inflammatory indicators such as COX-2, IL-6, iNOS, TNF-α and NO production in a concentration-dependent manner. In addition, we observed that MEUS had cytotoxic activity against HCT116 colon cancer cells in a concentration-dependent manner, leading to a significantly reduced proliferation of the cancer cells through apoptotic induction by activating caspase-3. Taken together, this work firstly reported the anti-inflammatory and anti-cancer activities of an Antarctic lichen, Usnea aurantiaco-atra, and MEUS may provide a new insight into the molecular mechanisms underlying a link between inflammation and cancer.