• 대한본초학회지
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• 제34권2호
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• pp.15-23
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• 2019

Objective : Reflux esophagitis (RE) is a disease that caused gastric acid reflux and inflammation due to unstable gastroesophageal sphincter, as increasing worldwide respectively. This study was conducted to evaluate the effect of Evodiae Fructus (EF) extract on chronic reflux esophagitis in rats. Methods : The EF was measured antioxidant activity, such as total polyphenol and total flavonoid contents, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethyl-enzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity. Rats were divided into 3 groups; Nor (normal group), Con (chronic acid reflux esophagitis rats treatment with water), EF (chronic acid reflux esophagitis rat treatment with EF 200 mg/kg body weight group). A surgically-induced chronic acid reflux esophagitis (CARE) model was established in SD rats, and treated with water or EF 200 mg/kg body weight for 14 consecutive days. Results : Administration of EF to rats of induction of chronic acid reflux esophagitis was found to reduce esophagus tissues injury. Reactive oxygen species (ROS) and produces peroxynitrite ($ONOO^-$) levels of esophagus tissues were significantly decreased in EF compared to Con group. As results of esophagus protein analyses, EF effectively reduce inflammatory-related factors ($NF-{\kappa}Bp65$, $p-I{\kappa}B{\alpha}$, iNOS, $TNF-{\alpha}$, IL-6), and increase anti-oxidant enzyme (Nrf2, HO-1, SOD, catalase, GPx-1/2). Conclusions : These results suggest that EF administration comfirmed that decreased esophagus tissues injury, oxidantive stress, anti-inflammation effect, and increased anti-oxidant effect. Therefore, EF was the potential to be used as a natural therapeutic drug.

• 대한본초학회지
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• 제33권6호
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• pp.19-28
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• 2018

Objectives : The objective of this study was to investigate the protective effect of Flaxseed oil and Chrysanthemi Indici Flos 50% ethanol extract in an HCl/ethanol induced acute gastritis model. Methods : ICR mice were divided into 6 groups; normal mice (Nor), gastritic mice with distilled water (Veh), gastritic mice with 10 mg/kg sucralfate (SC), gastritic mice with 16 g/㎏ Flaxseed oil (FO), gastritic mice with FO + 50 mg/kg Chrysanthemi Indici Flos (FCL), and gastritic mice with FO + 100 mg/kg Chrysanthemi Indici Flos (FCH). Then, mice were orally administered with 150 mM HCl/60% ethanol and caused acute gastritis. After 1 hr, mice were sacrificed, and blood and stomach tissue were collected. Results : Administration of FCL and FCH to mice prior to the induction of gastritis was found to reduce gastric injury. reactive oxygen species (ROS) and peroxy nitrite ($ONOO^-$) levels of stomach tissues were significantly decreased in FO, FCL, and FCH compared to Veh group. As results of stomach protein analyses, FCL and FCH effectively reduce inflammatory-related factors such as inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and interleukin 1 beta ($IL-1{\beta}$) in gastric lesion mice. In addition, nuclear factor kappa B p65 ($NF-{\kappa}B$ p65) and phosphorylation inhibitor of nuclear factor kappa $B{\alpha}(p-I{\kappa}B{\alpha})$ were down-regulated in FCL and FCH administrated gastric lesion mice. Conclusions : These results suggest that FCL and FCH has an inhibitory effect against gastric injury. Therefore, FCL and FCH has the potential to be used as a natural therapeutic drug.

• 생명과학회지
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• 제32권3호
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• pp.210-221
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• 2022

비스테로이드소염제(NSAID)와 γ-secretase 저해제(DAPT) 또는 SIRT1저해제(MHY2245)의 병용 효과를 인간 대장암(KM12) 및 간암(SNU475) 세포를 대상으로 조사한 결과, celecoxib (CCB) 및 2, 5-dimethyl celecoxib (DMC)를 포함하는 NSAID는 DAPT 또는 MHY2245와의 병용에 의하여 COX-2활성과 상관없이 NSAID의 암세포 증식 억제능이 현저히 증강되었다. DAPT와 MHY2245는 p62단백질 감소와 동시에 Notch1, CD44, CD133, octamer- binding transcription factor 4 (Oct4) 등의 다수의 종양 줄기세포 표지자 및 NICD1 발현 양을 감소시켰지만, activating transcription factor 4 (ATF4) 발현은 증강시켰다. 또한 NSAID 단독처리 보다 NSAID/DAPT 및 NSAID/MHY2245 병용 처리에 의하여 오토파지가 촉진되므로서 종양 줄기세포 표지자의 발현 및 단백질양의 감소가 가속화되고, 이에 따라 PARP 활성화 및 세포사멸이 현저히 증강 되었다. 결론적으로 NSAID/DAPT 및 NSAID/MHY2245의 병용 투여는 종양 줄기세포 표지자를 발현하는 인간 암세포의 증식 억제 및 제거에 효과적인 처리방법으로, 임상에 적용시킬 수 있는 학문적 근거로서 제공 될 수 있다.

• 대한한의학회지
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• 제44권2호
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• pp.119-131
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• 2023

Objectives: Betula Platyphylla(BP) has been used as a analgesic, anti-microbial, anti-oxidant drug in Eastern Asia. However, it is still unknown whether BP ethanol extract could exhibit the inhibitory activities against ultraviolet B(UVB)-induced skin injury on human keratinocytes, HaCaT cells. This study was aimed to investigate the protective activity of BP ethanol extract on UVB-irradiated skin injury in HaCaT cells. Methods: The skin injury model of HaCaT cells was established under UVB stimulation. HaCaT keratinocyte cells were pre-treated with BP ethanol extract for 1 h, and then stimulated with UVB. Then, the cells were harvested to measure the cell viability, production of reactive oxygen species(ROS), pro-inflammatory cytokines such as interleukin(IL) 1-beta, IL-6, and tumor necrosis factor(TNF)-𝛼, hyaluronidase, type 1 collagen, matrix metalloproteinase(MMP)s. In addition, we examined the mitogen activated protein kinases(MAPKs) and inhibitory kappa B alpha(I𝜅;-B𝛼) as inhibitory mechanisms of BP ethanol extract. Results: The treatment of BP ethanol extract inhibited the UVBinduced cell death and ROS production in HaCaT cells. BP ethanol extract treatment inhibited the UVB-induced increase of IL-1beta, IL-6, and TNF-𝛼. BP ethanol extract treatment inhibited the increase of hyaluronidase, MMP and decrease of collagen. BP ethanol extract treatment inhibited the activation of MAPKs and the degradation of I𝜅-B𝛼. Conclusions: Our result suggest that treatment of BP ethanol extract could inhibit the UVB-induced skin injury via deactivation of MAPKs and nuclear factor kappa B(NF-𝜅B) in HaCaT cells. This study could suggest that BP ethanol extract could be a beneficial agent to prevent skin damage or inflammation.

• 대한한방내과학회지
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• 제44권3호
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• pp.402-417
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• 2023

Objective: Liver fibrosis is a highly conserved wound-healing response and the final common pathway of chronic inflammatory injury. This study aimed to evaluate the potential anti-fibrotic effect of the combination of Rhei Radix et Rhizoma water extract (RW) and silymarin in a thioacetamide (TAA)-induced liver fibrosis model. Methods: The liver fibrosis mouse model was established through the intraperitoneal injection of TAA (1 week 100 mg/kg, 2-3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg) three times per week for eight weeks. Animal experiments were conducted in five groups; Normal, Control (TAA-induced liver fibrosis mice), Sily (silymarin 50 mg/kg), RSL (RW 50 mg/kg+silymarin 50 mg/kg), and RSH (RW 100 mg/kg+silymarin 50 mg/kg). Biochemical analyses were measured in serum, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), and ammonia levels. Liver inflammatory cytokines and fibrous biomarkers were measured by Western blot analysis, and liver histopathology was evaluated through tissue staining. Results: A significant decrease in the liver function markers AST and ALT and a reduction in ammonia and total bilirubin were observed in the group treated with RSL and RSH. Measurement of reactive oxygen species and MDA revealed a significant decrease in the RSL and RSH administration group compared to the TAA induction group. The expression of extracellular matrix-related proteins, such as transforming growth factor β1, α-smooth muscle actin, and collagen type I alpha 1, was likewise significantly decreased. All drug-administered groups had increased matrix metalloproteinase-9 but a decreasing tissue inhibitor of matrix metalloproteinase-1. RSL and RSH exerted a significant upregulation of NADPH oxidase 2, p22^phox, and p47^phox, which are oxidative stress-related factors. Furthermore, pro-inflammatory proteins such as cyclooxygenase 2 and interleukin-1β were markedly suppressed through the inhibition of nuclear factor kappa B activation. Conclusions: The administration of RW and silymarin suppressed the NADPH oxidase factor protein level and showed a tendency to reduce inflammation-related enzymes. These results suggest that the combined administration of RW and silymarin improves acute liver injury induced by TAA.

• IMMUNE NETWORK
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• 제23권6호
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• pp.45.1-45.22
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• 2023

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

• 대한약침학회지
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• 제27권1호
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• pp.1-13
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• 2024

Background: Diabetic nephropathy (DN) is one of the major complications of chronic hyperglycaemia affecting normal kidney functioning. The ayurvedic medicine curcumin (CUR) is pharmaceutically accepted for its vast biological effects. Objectives: The Curcuma-derived diferuloylmethane compound CUR, loaded on Poly (lactide-co-glycolic) acid (PLGA) nanoparticles was utilized to combat DN-induced renal apoptosis by selectively targeting and modulating Bcl2. Methods: Upon in silico molecular docking and screening study CUR was selected as the core phytocompound for nanoparticle formulation. PLGA-nano-encapsulated-curcumin (NCUR) were synthesized following standard solvent displacement method. The NCUR were characterized for shape, size and other physico-chemical properties by Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS) and Fourier-Transform Infrared (FTIR) Spectroscopy studies. For in vivo validation of nephro-protective effects, Mus musculus were pre-treated with CUR at a dose of 50 mg/kg b.w. and NCUR at a dose of 25 mg/kg b.w. (dose 1), 12.5 mg/kg b.w (dose 2) followed by alloxan administration (100 mg/kg b.w) and serum glucose levels, histopathology and immunofluorescence study were conducted. Results: The in silico study revealed a strong affinity of CUR towards Bcl2 (dock score -10.94 Kcal/mol). The synthesized NCUR were of even shape, devoid of cracks and holes with mean size of ~80 nm having -7.53 mV zeta potential. Dose 1 efficiently improved serum glucose levels, tissue-specific expression of Bcl2 and reduced glomerular space and glomerular sclerosis in comparison to hyperglycaemic group. Conclusion: This study essentially validates the potential of NCUR to inhibit DN by reducing blood glucose level and mitigating glomerular apoptosis by selectively promoting Bcl2 protein expression in kidney tissue.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.213-220
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• 2023

본 연구는 비자나무(Torreya nucifera (L.) Siebold & Zucc, TN)와 생물전환 된 비자나무 추출물(TNB)의 항염증 효과를 평가하기 위해 수행되었으며 이를 위해 C. acnes에 의해 유도된 RAW264.7 염증 모델에서 염증인자의 발현을 조사하였다. 실험 결과, TNB는 50, 100, 200 ㎍/mL 농도에서 TN의 높은 세포독성을 개선하였으며 nitric oxide (NO)와 NO 합성 효소인 inducible NO synthase (iNOS) 및 prostaglandin의 합성 효소인 cyclooxygenase-2 (COX-2)의 발현을 유의하게 억제하였다. 또한 TNB는 염증성 사이토카인인 tumor necrosis factor-α (TNF-α) 및 interleukin (IL)-1β, IL-6, IL-8의 발현을 유의하게 억제하였으며 특히 IL-6, IL-8의 경우 가장 고 농도인 200 ㎍/mL에서 정상세포 수준으로 감소하였다. 이후 진행된 western blot에서 인산화 된 IκB-α 및 NF-κB의 발현이 농도의존적으로 억제됨을 확인하였으며 인산화가 억제되면서 degradation이 감소하여 TNB처리 농도가 높아짐에 따라 IκB-α의 농도가 증가하는 경향을 보였다. 결론적으로, TNB는 NF-κB신호 전달 경로를 차단함으로써 다양한 염증 매개 인자의 발현을 효과적으로 하향 조절할 수 있으며 이를 통해 항 염증 활성을 유도하는 것으로 확인된다. 이러한 결과를 근거로 TNB가 C. acnes에 의해 유발된 염증성질환의 치료에 효과적인 천연물 소재로 적용될 수 있음을 제안한다.

• 대한약리학회지
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• 제25권1호
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• pp.115-134
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• 1989

Ganciclovir(GCV)와 Vidarabine(ara-A)을 단독으로 또는 동시에 HSV-1에 작용시켰을때 HSV-1의 복제, DNA합성 및 단백질 합성에 미치는 영향을 관찰할 목적으로 본 연구를 시행하였다. 본 실험에서는 4가지의 다른 HSV-1(Wild type KOS, $VCV^r$, $IUdR^r$, 및 $PAA^r5$)를 사용하였다. Virus복제에 미치는 항 virus약의 효과는 Vero 세포단층 배양에서 Yield reduction assay에 의해서 관찰하였다. 항 virus약의 virus DNA 합성에 미치는 영향은 NaI 밀도 구배초원심침전후 $H^3-$표지 virus DNA의 방사능에 의해서 관찰하였다. Virus 단백질의 합성에 미치는 항 virus약의 효과는 $^{35}S$를 표지한 후 polyacrylamide 겔 전기영동법, 자가방사기록법 그러고 virus bands의 음영농도주사법을 이용, 관찰하여 다음과 같은 결과를 얻었다. 1. GCV는 wild trype HSV-1 KOS와 $PAA^r5$의 복제를 강력하게 억제하였으나 $ACV^r$와 $IUdR^r$는 GCV에 대해서 중등도의 저항을 보였다. ara-A는 실험대상의 모든 HSV-(KOS, $ACV^r$, $IUdR^r$ 및 $PAA^r5$)의 복제에 대해서 거의 비슷하게 억제효과를 보였다. GCV와 ara-A 동시첨가는 KOS와 $PAA^r5$의 복제에 대해서 상승적인 억제효과를 보였고 $ACV^r$와 $IUdR^r5$의 복제에 대해서는 상가작용이하의 억제 효과를 보였다. 2. GCV또는 ara-A는 HSV-1감염 Vero세포에서 virus DNA의 합성을 유의하게 억제하였다. GCV와 ara-A의 동시첨가는 KOS 또는 $PAA^r5$ 감염세포에서 virus DNA 합성을 GCV 또는 ara-A를 단독 첨가하였을때 보다 현저하게 억제하였다. $ACV^r$ 또는 $IUdR^r$ 감염세포에서는 이런 현상을 관찰할 수 없었다. 3. Wild type HSV-1 감염세포에서 virus-단백질의 합성은 GCV, ara-A의 단독 첨가 또는 GCV와 ara-A의 동시첨가에 의해서 변경되지 않았다. Wild type HSV-1 감염말기에 GCV 또는 ara-A 단독 혹은 동시첨가에 의해서 virus 단백질의 합성은 경미하나마 유의성있게 증가하였다. Wild type HSV-1과 $PAA^r5$에 의한 단백질의 합성은 GCV 또는 ara-A 단독 첨가에 의해서 유의성있게 억제되었다. GCV또는 ara-A의 동시첨가는 GCV또는 ara-A를 단독으로 첨가했을 경우보다 단백질의 합성을 더욱 억제하였다. 이상의 실험결과로 보아 GCV와 ara-A의 동시사용은 HSV-1 혹은 ACV저항 DNA polymerase변이주인 $PAA^r5$에 대해서 상승적인 억제작용을 나타냈으며 이 효과는 virus DNA 합성 억제에 의한 것으로 생각된다. ACV저항 thymidine kinase 변이주인 $ACV^r$ 및 $IUdR^r$에 대해서는 ara-A가 유효하였다. 항 virus 약물에 의한 virus 단백질합성의 변화는 virus DNA 합성에 대한 억제효과에 인한 것으로 사려된다.

• 생명과학회지
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• 제26권5호
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• pp.509-518
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• 2016

천문동(Asparagus cochinchinensis)은 북아시아 지역에서 열병, 감기, 신장질환, 유방암, 염증질환, 뇌질환 등의 치료에 오랫동안 사용되어온 약용식물(medicinal plant)이다. 비록, 천문동의 항염증(ani-inflammatory) 효능에 대한 일부 연구들이 수행되었지만, 신경세포에서 항염증작용과 신경성장인자(nerve growth factor, NGF)의 연관성에 대한 연구는 수행된바 없다. 따라서, 본 연구에서는 신경세포에서 신경성장인자의 분비와 작용기전에 대한 천문동 열수추출물(aqueous extract from A. cochinchinensis, AEAC)의 영향을 연구하였다. AEAC로 처리된 B35세포의 배양액에 NGF단백질의 농도는 대조물질(vehicle) 처리군에 비하여 유의적으로 증가하였으며, 특별한 독성은 관찰되지 않았다. 또한, NGF mRNA의 발현도 단백질의 농도변화와 유사한 양상을 나타내었다. 더불어, B35세포로부터 분비된 NGF의 생리활성을 확인하기 위해, AEAC-조정배지(conditioned medium)를 미분화된 PC12세포에 처리한 후 이들 세포의 신경염성 성장(neuritic outgrowth)을 관찰하였다. PC12세포의 수상돌기 길이(dendritic length)는 vehicle처리군에 비하여 AEAC-조정배지처리군에서 유의적으로 증가하였다. 또한, High affinity NGF 수용체의 하위신호전달에 포함된 p-TrkA와 p-ERK의 발현은 AEAC-조정배지처리군에서 높았지만, low affinity NGF 수용체의 하위신호전달에서는 낮은 수준으로 관찰되었다. 이러한 결과는 AEAC가 신경세포에서 NGF발현과 분비의 조절에 기여하기 때문에 신경퇴행성질환(neurodegenerative disease) 치료제로서 우수한 후보물질임을 제시하고 있다.