• Nutrition Research and Practice
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• 제11권5호
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• pp.430-434
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• 2017

BACKGROUND/OBJECTIVE: Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. MATERIALS/METHODS: Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. RESULTS: Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. CONCLUSIONS: The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes.

• 한방재활의학과학회지
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• 제33권2호
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• pp.1-18
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• 2023

Objectives The purpose of this study was to evaluate the antioxidant, anti-inflammatory and wound healing effects of Samul-tang-ga-dansam water extract (SD) in wound-induced mice. Methods The mice were divided into five groups (n=7): the normal group, the control group, the positive control group, the low-dose SD group and the high-dose SD group. The normal group had no wounds and the other groups were wounded on the back with a leather punch. Distilled water was administered to the control group, 200 mg/kg of vitamin E was administered to the positive control group. In the low-dose SD group and the high-dose SD group, 1.23 g/kg and 2.47 g/kg of SD were administered, respectively. Antioxidant and anti-inflammatory protein levels were evaluated using western blot analysis. Skin tissue was analyzed by H&E, Masson's trichrome staining method. Results Oral administration of the SD significantly reduced the visible skin damage and decreased the reactive oxygen species and ONOO^- activity of the serum. It significantly increased heme oxygenase-1, superoxide dismutase, catalase, GPx-1/2, Nrf2 and Keap-1 which are antioxidant-related factors in skin tissue and reduced NF-κB p65, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor α, interleukin (IL)-1β, IL-6 which are inflammation-related factors. Also, SD significantly decreased NOX2, p22^phox and p47^phox and increased α-smooth muscle actin and COL1A1 protein expression in fibroblasts involved in connective tissue repair. According to histological examination, the thickened epithelial layer was thinned and collagen fibers were increased to accelerate wound healing. Conclusions It is suggested that Samul-tang-ga-dansam has antioxidant and anti-inflammatory effects and promotes wound tissue repair.

• 대한한의학방제학회지
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• 제25권4호
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• pp.457-469
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• 2017

Obesity is one of the most serious health problem because it induced numerous metabolic syndrome and increases the incidence of various disease, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. In 3T3-L1 adipocytes, increases in reactive oxygens species (ROS) occur with lipid accumulation. NADPH oxidase, producing superoxide anion, may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. In this study, we elucidated the effect of Chaenomeles sinensis koehne extract (CSE) against the development of obesity and the inhibition mechanisms in 3T3-L1 preadiocytes. CSE decreased triglyceride content and inhibited the expression of adipogenic transcription factors including peroxisome proliferator-activated receptor $(PPAR){\gamma}$, CCAT/enhancer binding protein $(C/EBP){\alpha}$ and sterol regulatory element-binding protein (SREBP-1). In addition, CSE highly increased antioxidant activity in a dose-dependent manner. CSE remarkably reduced intracellular ROS increase and NAD(P)H oxidase activity, NOX1, NOX4, Rac1 protein expression, and phosphorylation of p47phox and p67phox We also studied the effect of CSE on weight gain induced by high-fat diet. The oral treatment of CSE (500 mg/kg, body weight) in diet-induced obese (DIO) mice showed decrease in triglyceride and adipocyte size. Therefore, these results indicate that the effect of CSE on anti-obese effects, adipocyte differentiation and reducing triglyceride contents as well as adipocyte size in obese mice, may be associated with inhibition of NAD(P)H oxidase-induced ROS production and adipose transcription factors. These results showed the potential to inhibit the obesity by CSE treatment through controlling the activation of NAD(P)H oxidase in vitro and in vivo obese model.

• 생약학회지
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• 제49권3호
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• pp.262-269
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• 2018

Sparassis crispa (Wulf.) is an edible/medicinal mushroom and has been reported to biological activities such as antitumor, anti-angiogenesis, antioxidant and wound healing. However, there have not been many researches on osteoarthritis of S. crispa. The aim of this study was to investigate the effects of S. crispa extract on rats with osteoarthritis induced by MIA. Osteoarthritis is a gradually developmental disease that early stage, causes joint stiffness and complains of joint pain. In addition, it gives rise to edema and hypo-function. The results of this study, S. crispa extract effectively inhibited ROS production, increased the production of antioxidant protein SOD and catalase in knee joint cartilage tissue. In addition, S. crispa extract inhibited the expression of pro-inflammatory cytokines and enzymes such as NOX4 and $P47^{phox}$, which are involved in the expression of COX-2, iNOS and the production of ROS. Also, S. crispa extract inhibited the destruction of synovial tissue, cartilage tissue and proteoglycans in articular cartilage in rats.

• Journal of Nutrition and Health
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• 제54권3호
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• pp.321-333
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• 2021

본 연구에서는 진피-황금 혼합물 (CS)이 급성 역류성 식도염에 미치는 식도 점막 보호 효과를 평가하기 위하여 CS를 경구투여한 후 수술을 통해 역류성 식도염을 유발하였으며, 실험 종료 후 혈액 채취 및 식도 조직을 적출하였다. 동물에게서 적출한 식도 점막의 손상 정도를 육안으로 확인한 결과 CS투여군에서 식도 점막의 손상이 유의하게 감소하였으며, H&E staining을 통해 관찰한 결과 마찬가지로 CS투여군에서 식도 상피의 탈락 및 염증세포의 침윤이 현저하게 감소한 것을 확인하였다. 혈액을 이용하여 역류성 식도염의 원인으로 유효하다고 알려진 ROS의 수치를 확인한 결과, CS투여군에서 ROS 수치가 유의적으로 감소하였으며, western blotting을 통해 NADPH oxidase인 NOX4, p47^phox, p22^phox의 발현을 확인한 결과, 마찬가지로 CS 투여군에서 유의하게 감소하였고, 특히 CS200투여군에서 Normal군과 비슷한 수치를 나타냈다. 또한, CS투여는 염증성 단백질인 MAPK와 NF-κB 경로를 유의적으로 억제하였을 뿐 아니라 tight junction 단백질인 claudin-1과 claudin-4의 발현을 유의하게 조절한 것을 확인하였다. 이상의 결과를 종합해보면 진피-황금 추출물은 산화적 스트레스를 억제함으로써 염증성 단백질의 발현을 조절할 뿐 아니라 tight junction 단백질의 발현을 조절하여 식도 점막을 보호하는 것으로 판단되나 역류성 식도염은 음식물의 섭취와 밀접한 관련이 있는 만큼 추후 동물의 식이 섭취량을 조사하는 등 세부적인 추가 연구가 필요할 것으로 보인다.

• Journal of Nutrition and Health
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• 제54권2호
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• pp.224-237
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• 2021

본 연구는 백작약 열수 추출물의 in vitro 항산화능을 평가하였으며, TAA를 유발한 급성 간손상 동물 모델을 이용하여 항산화 활성으로 인한 산화적 스트레스 억제 효과와 간 기능 보호효과 여부를 검증하였다. 총 폴리페놀, 총 플라보노이드 함량, DPPH 및 ABTS 자유 라디칼 소거능 측정 결과 높은 항산화능을 나타냈으며, 체중, 간무게 및 간중량 비율 (%)이 대조군에 비해 S100군과 PR100군보다 PR200군에서 더욱 감소하였다. 약물투여군의 혈중 암모니아, GOT 및 GPT 수준의 유의적인 감소를 확인하였으며, western blot 실시 후 대부분의 인자에서 유의적인 차이를 확인하였다. 이 결과를 토대로 백작약 열수 추출물이 Nrf2-Keap1경로의 활성화를 통해 항산화 효소를 증가시켰으며, 항산화능을 통한 산화적 스트레스 개선에 긍정적인 효과가 있음을 확인할 수 있었다. 따라서 백작약 열수 추출물은 급성 간손상시 간보호 효과를 위한 후보 소재로서 가능성이 있다고 판단된다.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제19권6호
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• pp.491-497
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• 2015

Traumatic brain injury (TBI) is a major cause of mortality and long-term disability, which can decrease quality of life. In spite of numerous studies suggesting that Epigallocatechin-3- gallate (EGCG) has been used as a therapeutic agent for a broad range of disorders, the effect of EGCG on TBI remains unknown. In this study, a weight drop model was established to evaluate the therapeutic potential of EGCG on TBI. Rats were administered with 100 mg/kg EGCG or PBS intraperitoneally. At different times following trauma, rats were sacrificed for analysis. It was found that EGCG (100 mg/kg, i.p.) treatment significantly reduced brain water content and vascular permeability at 12, 24, 48, 72 hour after TBI. Real-time PCR results revealed that EGCG inhibited TBI-induced IL-$1{\beta}$ and TNF-${\alpha}$ mRNA expression. Importantly, CD68 mRNA expression decreasing in the brain suggested that EGCG inhibited microglia activation. Western blotting and immunohistochemistry results showed that administering of EGCG significantly inhibited the levels of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression. TBI-induced oxidative stress was remarkably impaired by EGCG treatment, which elevated the activities of SOD and GSH-PX. Conversely, EGCG significantly reduced the contents of MDA after TBI. In addition, EGCG decreased TBI-induced NADPH oxidase activation through inhibition of $p47^{phox}$ translocation from cytoplasm to plasma membrane. These data demonstrate that EGCG treatment may be an effective therapeutic strategy for TBI and the underlying mechanism involves inhibition of oxidative stress.

• Parasites, Hosts and Diseases
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• 제53권5호
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• pp.597-603
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• 2015

Trichomonas vaginalis is a flagellated protozoan parasite that causes vaginitis and cervicitis in women and asymptomatic urethritis and prostatitis in men. Mast cells have been reported to be predominant in vaginal smears and vaginal walls of patients infected with T. vaginalis. Mitogen-activated protein kinase (MAPK), activated by various stimuli, have been shown to regulate the transcriptional activity of various cytokine genes in mast cells. In this study, we investigated whether MAPK is involved in ROS generation and exocytotic degranulation in HMC-1 cells induced by T. vaginalis-derived secretory products (TvSP). We found that TvSP induces the activation of MAPK and NADPH oxidase in HMC-1 cells. Stimulation with TvSP induced phosphorylation of MAPK and $p47^{phox}$ in HMC-1 cells. Stimulation with TvSP also induced up-regulation of CD63, a marker for exocytosis, along the surfaces of human mast cells. Pretreatment with MAPK inhibitors strongly inhibited TvSP-induced ROS generation and exocytotic degranulation. Finally, our results suggest that TvSP induces intracellular ROS generation and exocytotic degranulation in HMC-1 via MAPK signaling.

• 대한한의학회지
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• 제40권3호
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• pp.35-58
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• 2019

Objectives: The aim of this study was to investigate the anti-inflammatory effects of Curcuma longa rhizoma extract in an experimental rat model of osteoarthritis. Methods: Osteoarthritis was induced in rats by injecting monosodium iodoacetate (MIA) into the knee joint cavity of rats. The rats were divided into 5 groups (Normal, Control, positive comparison, low (CL) and high (CH) concentration groups). Rats in the low concentration (CL) group had MIA-induced osteoarthritis; they were treated with Curcuma longa rhizoma extract at a dose of 50mg/kg body weight. Rats in the high concentration (CH) group had MIA-induced osteoarthritis; they were treated with Curcuma longa rhizoma extract at a dose of 100mg/kg body weight. Hind paw weight distribution and ROS levels were measured. At the end of all treatments, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels were analyzed. In addition, inflammatory protein levels were evaluated by western blot analysis. Results: In this study, hind paw weight distribution significantly improved in the CL and CH groups, while. Reactive oxygen species (ROS) production significantly decreased in both. The levels of ALT, AST, BUN, and creatinine did not significantly change in either group. The production of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), $p47^{phox}$, and Ras-related C3 botulinum toxin substrate 1 (RAC1) decreased in both. Catalase, heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) significantly increased in the CL and CH groups, respectively. Nuclear factor erythroid 2 (Nrf2) increased, but there were no significant differences between the experimental and control groups. Inflammatory cytokines, including nuclear factor-kappa Bp65 (NF-${\kappa}Bp65$), interleukin-1beta (IL-$1{\beta}$), and tumor necrosis factor-alpha (TNF-${\alpha}$), decreased significantly in both the CL and CH groups. Conclusions: Our results showed that Curcuma longa rhizoma extract has anti-inflammatory effects. Anti-inflammatory activity is regulated by the inhibition of inflammatory cytokines and mediators, such as NF-${\kappa}B$, therefore, it suppresses cartilage damage as well.