• The Korean Journal of Physiology and Pharmacology
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• 제18권2호
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• pp.95-101
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• 2014

Cardiovascular disease is the prime cause of morbidity and mortality and the population ages that may contribute to increase in the occurrence of cardiovascular disease. Arginase upregulation is associated with impaired endothelial function in aged vascular system and thus may contribute to cardiovascular disease. According to recent research, Korean Red Ginseng water extract (KRGE) may reduce cardiovascular disease risk by improving vascular system health. The purpose of this study was to examine mechanisms contributing to age-related vascular endothelial dysfunction and to determine whether KRGE improves these functions in aged mice. Young ($10{\pm}3$ weeks) and aged ($55{\pm}5$ weeks) male mice (C57BL/6J) were orally administered 0, 10, or 20 mg/mouse/day of KRGE for 4 weeks. Animals were sacrificed and the aortas were removed. Endothelial arginase activity, nitric oxide (NO) generation and reactive oxygen species (ROS) production, endothelial nitric oxide synthase (eNOS) coupling, vascular tension, and plasma peroxynitrite production were measured. KRGE attenuated arginase activity, restored nitric oxide (NO) generation, reduced ROS production, and enhanced eNOS coupling in aged mice. KRGE also improved vascular tension in aged vessels, as indicated by increased acetylcholine-induced vasorelaxation and improved phenylephrine-stimulated vasoconstriction. Furthermore, KRGE prevented plasma peroxynitrite formation in aged mice, indicating reduced lipid peroxidation. These results suggest KRGE exerts vasoprotective effects by inhibiting arginase activity and augmenting NO signaling and may be a useful treatment for age-dependent vascular diseases.

• 한국자원식물학회지
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• 제24권2호
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• pp.181-188
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• 2011

본 연구는 회향종자 물 추출물이 비만과 관련된 지질대사를 조절하는 효소들 가운데 lipoprotein lipase(LPL), acyl-CoA synthetase(ACS), hormone sensitive lipase(HSL)의 활성에 미치는 효과를 알아보았다. 정상 마우스에서 회향종자 물 추출물의 LPL 활성은 최고 21.9% 억제되었고, ACS와 HSL의 효소 활성은 각각 151.8%, 174.0% 증가되었다. 고지방식이 유도 비만 마우스에서 LPL은 12.0% 활성이 억제되었으며, ACS와 HSL은 742.0%, 134.4% 활성이 증가하였다. 결과적으로 회향종자 물 추출물이 효과적으로 세포내로 지방산의 유입을 억제하며, 유입된 지방산을 에너지원으로 사용하는 대사과정을 활성화시킴으로서 항비만 효능을 갖는다는 것을 추정할 수 있다.

• The Korean Journal of Pain
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• 제35권2호
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• pp.173-182
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• 2022

Background: Neurokinin-1 (NK1) and calcitonin gene-related peptide (CGRP) play a vital role in pain pathogenesis, and these proteins' antagonists have attracted attention as promising pharmaceutical candidates. The authors investigated the anti-nociceptive effect of co-administration of the CGRP antagonist and an NK1 antagonist on pain models compared to conventional single regimens. Methods: C57Bl/6J mice underwent sciatic nerve ligation for the neuropathic pain model and were injected with 4% formalin into the hind paw for the inflammatory pain model. Each model was divided into four groups: vehicle, NK1 antagonist, CGRP antagonist, and combination treatment groups. The NK1 antagonist aprepitant (BIBN4096, 1 mg/kg) or the CGRP antagonist olcegepant (MK-0869, 10 mg/kg) was injected intraperitoneally. Mechanical allodynia, thermal hypersensitivity, and anxiety-related behaviors were assessed using the von Frey, hot plate, and elevated plus-maze tests. The flinching and licking responses were also evaluated after formalin injection. Results: Co-administration of aprepitant and olcegepant more significantly alleviated pain behaviors than administration of single agents or vehicle, increasing the mechanical threshold and improving the response latency. Anxiety-related behaviors were also markedly improved after dual treatment compared with either naive mice or the neuropathic pain model in the dual treatment group. Flinching frequency and licking response after formalin injection decreased significantly in the dual treatment group. Isobolographic analysis showed a meaningful additive effect between the two compounds. Conclusions: A combination pharmacological therapy comprised of multiple neuropeptide antagonists could be a more effective therapeutic strategy for alleviating neuropathic or inflammatory pain.

• Nutrition Research and Practice
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• 제15권3호
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• pp.279-293
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• 2021

BACKGROUND/OBJECTIVES: The steamed ginger has been shown to have antioxidative effects and a protective effect against obesity. In the present study, we investigated the effects of ethanolic extract of steamed ginger (SGE) on adipogenesis in 3T3-L1 preadipocytes and diet-induced obesity (DIO) mouse model. MATERIALS/METHODS: The protective effects of SGE on adipogenesis were examined in 3T3-L1 adipocytes by measuring lipid accumulations and genes involved in adipogenesis. Male C57BL/6J mice were fed a normal diet (ND, 10% fat w/w), a high-fat diet (HFD, 60% fat w/w), and HFD supplemented with either 40 mg/kg or 80 mg/kg of SGE for 12 weeks. Serum chemistry was measured, and the expression of genes involved in lipid metabolism was determined in the adipose tissue. Histological analysis and micro-computed tomography were performed to identify lipid accumulations in epididymal fat pads. RESULTS: In 3T3-L1 cells, SGE significantly decreased lipid accumulation, with concomitant decreases in the expression of adipogenesis-related genes. SGE significantly attenuated the increase in body, liver, and epididymal adipose tissue weights by HFD. Serum total cholesterol and triglyceride levels were significantly lower in SGE fed groups compared to HFD. In adipose tissue, SGE significantly decreased adipocyte size than that of HFD and altered adipogenesis-related genes. CONCLUSIONS: In conclusion, steamed ginger exerted anti-obesity effects by regulating genes involved in adipogenesis and lipogenesis in 3T3-L1 cell and epididymal adipose tissue of DIO mice.

• Journal of Ginseng Research
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• 제47권4호
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• pp.543-551
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• 2023

Background: Panax ginseng Meyer is a representative Chinese herbal medicine with antioxidant and anti-inflammatory activity. 20(S)-Protopanaxadiol (PPD) has been isolated from ginseng and shown to have promising pharmacological activities. However, effects of PDD on pulmonary fibrosis (PF) have not been reported. We hypothesize that PDD may reverse inflammation-induced PF and be a novel therapeutic strategy. Methods: Adult male C57BL/6 mice were used to establish a model of PF induced by bleomycin (BLM). The pulmonary index was measured, and histological and immunohistochemical examinations were made. Cell cultures of mouse alveolar epithelial cells were analyzed with Western blotting, coimmunoprecipitation, immunofluorescence, immunohistochemistry, siRNA transfection, cellular thermal shift assay and qRT-PCR. Results: The survival rate of PPD-treated mice was higher than that of untreated BLM-challenged mice. Expression of fibrotic hallmarks, including α-SMA, TGF-β1 and collagen I, was reduced by PPD treatment, indicating attenuation of PF. Mice exposed to BLM had higher STING levels in lung tissue, and this was reduced by phosphorylated AMPK after activation by PPD. The role of phosphorylated AMPK in suppressing STING was confirmed in TGF-b1-incubated cells. Both in vivo and in vitro analyses indicated that PPD treatment attenuated BLM-induced PF by modulating the AMPK/STING signaling pathway. Conclusion: PPD ameliorated BLM-induced PF by multi-target regulation. The current study may help develop new therapeutic strategies for preventing PF.

• Journal of Ginseng Research
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• 제48권4호
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• pp.405-416
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• 2024

Background: Hypoxic pulmonary hypertension (HPH) is the main pathological change in vascular remodeling, a complex cardiopulmonary disease caused by hypoxia. Some research results have shown that ginsenoside Rg1 (Rg1) can improve vascular remodeling, but the effect and mechanism of Rg1 on hypoxia-induced pulmonary hypertension are not clear. The purpose of this study was to discuss the potential mechanism of action of Rg1 on HPH. Methods: C57BL/6 mice, calpain-1 knockout mice and Pulmonary artery smooth muscle cells (PASMCs) were exposed to a low oxygen environment with or without different treatments. The effect of Rg1 and calpain-1 silencing on inflammation, fibrosis, proliferation and the protein expression levels of calpain-1, STAT3 and p-STAT3 were determined at the animal and cellular levels. Results: At the mouse and cellular levels, hypoxia promotes inflammation, fibrosis, and cell proliferation, and the expression of calpain-1 and p-STAT3 is also increased. Ginsenoside Rg1 administration and calpain-1 knockdown, MDL-28170, and HY-13818 treatment showed protective effects on hypoxia-induced inflammation, fibrosis, and cell proliferation, which may be associated with the downregulation of calpain-1 and p-STAT3 expression in mice and cells. In addition, overexpression of calpain 1 increased p-STAT3 expression, accelerating the onset of inflammation, fibrosis and cell proliferation in hypoxic PASMCs. Conclusion: Ginsenoside Rg1 may ameliorate hypoxia-induced pulmonary vascular remodeling by suppressing the calpain-1/STAT3 signaling pathway.

• Journal of Nutrition and Health
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• 제44권6호
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• pp.481-487
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• 2011

본 연구에서는 성장기 마우스 모델을 이용하여 고지방식 이를 제공한 후 이에 따른 염증지표와 골의 형태학적 미세구조의 변화를 살펴보았다. C57BL/6J 4주령 수컷 마우스를 난괴법에 의해 대조군 (n = 6)과 실험군 (n = 6)로 분류하여 대조군에는 10% Kcal fat 식이와 고지방식이군에는 45% Kcal fat 식이를 12주 동안 자유급식 방법으로 제공하였다. 혈액검사와 염증지표를 분석하였으며 micro-CT를 이용하여 대퇴부 뼈의 형태학적 미세구조를 측정하였다. 대조군과 고지방식이군의 체중 증가는 각각 $5.85{\pm}1.84g$, $16.06{\pm}5.64g$로 유의한 차이를 보였으며 (p < 0.01), 혈당은 각각 $115.00{\pm}16.88mg/dL$, $188.33{\pm}13.29mg/dL$ (p < 0.01), 중성지방은 각각 $65.00{\pm}6.19mg/dL$, $103.33{\pm}8.02mg/dL$ (p < 0.05)로 나타났다. 렙틴과 IL-6는 고지방식이군에서 유의적으로 높게 나타났다 (p < 0.01). 골대사의 생화학적지표 분석 결과 오스테오칼신은 고지방식이군에서 낮게 나타났으나 유의적이지 않았으며, CTx은 고지방식이군에서 유의적으로 높게 나타났다 (p < 0.01). 골밀도는 고지방식이군에서 낮게 나타났으나 유의적인 차이는 보이지 않았다. 그러나 골의 형태학적 미세구조 분석결과 골소주의 두께는 고지방식이 군이 대조군보다 유의적으로 좁게 나타났으며 (p < 0.05), 골소주의 간격은 고지방식이군이 유의적으로 넓게 나타났다 (p < 0.05). 골의 형태학적 미세구조인 골소주의 간격과 IL-6가 양의 상관성이 나타났다 (p < 0.05). 본 연구결과 최대골밀도가 형성되는 단계의 성장기 마우스에서 고지방식이 공급을 통한 비만 유도 현상은 골소주의 수와 골소주가 차지하는 비율의 변화를 유발하여 골 미세구조에 영향을 미치는 것으로 나타났으며, 염증지표와 상관성이 나타났다. 이에 성장기에 염증지표 증가를 억제하고 정상적인 골형성을 위하여 과잉의 지방섭취 제한이 필요할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제45권4호
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• pp.835-845
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• 1998

연구배경: 유리규산(silica)이 폐장내로 흡입되면 폐장내 염증세포의 축적이 발생하고 폐실질과 간질에 섬유화가 발생한다. Silica가 폐장내로 흡입되면 대삭세포에 탐식되어 염증매개물을 분비한다. 대식세포에서 염증반응에 중요하게 관여히는 cytokines은 IL-1$\beta$, IL-6, TNF-$\alpha$ 등이 있으며 후기 섬유화에 관계하는 TGF-$\beta$ 등이 분비되어 폐섬유화의 진행과 유지에 중요한 역할을 한다. 그러나 silica에 의한 폐섬유화 과정에서 각 cytokine의 역할과 분비부위 시간에 따른 변화에 대해서는 아직 확실히 규명된 바 없다. 방 법: silica 투여시 폐섬유화증이 잘 유발되어지는 C57BL/6J(ref) mouse의 폐장내로 silica를 투여 후 1 일, 2 일, 7 일, 2 주, 4주, 8주, 12주째마다 폐장을 적출하여 시간에 따른 폐조직의 변화와 면역화학조직염색법을 이용하여 IL-1$\beta$, IL-6, TNF-$\alpha$, TGF-$\beta$ 단백 발현의 변화와 분비부위를 관찰하였다. 결 과: Silica군에서는 2주부터 육안적 소견의 변화가 관찰되었으며 8주째 변화가 가장 심하였고 초기에 염증세포의 침윤이 기관지와 세기관지 주위로 시작되어 8 주째는 기관지 주위의 심한 염증세포 침윤과 섬유화 결절에 의해서 기관지가 완전히 폐쇄되는 소견을 보였다. IL-6 의 발현은 혈관에서는 변화없이 지속적으로 발현되었고 시간 경과에 따라 기도상피세포와 혈판내피세포에서 IL-6 발현이 관찰되어 IL-6의 형성은 혈관에서 기도내로 이동하는 염증세포에 의해 과형성됨을 알 수 있었다. IL-1는 정상군의 혈관내피세포에서 1도 정도의 경한 발현이 있은 후 큰 변화없이 12주까지 지속적으로 발현되었다. TNF-$\alpha$는 기도상피세포에서 발현이 점차 증가하였고 2주째 기관지 주위에 염증세포의 침윤이 심해지면서 형성된 결절에서 강한 발현이 나타난 후 8주까지 지속되었다. TGF-$\beta$는 기관지 주위에서 초기에 발현을 관찰할 수 없었으나 염증 세포의 침윤이 심해지는 2 주째부터 강한 발현이 나타난 후 12주까지 지속적으로 높은 발현을 나타내었다. 결 론: Silica를 폐장내 투여시 IL-1$\beta$, IL-6, TNF-$\alpha$가 조기에 분비되어 모두 폐섬유화의 염증반응에 관여하고 TGF-$\beta$는 후기의 폐섬유화에 유지에 관여할 것으로 추정되며 silica에 의한 폐섬유화의 조절방법으로는 TNF-$\alpha$의 형성조절이 좋은 방법이 될 수 있을 것으로 사료된다.

• Journal of Ginseng Research
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• 제45권1호
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• pp.48-57
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• 2021

Background: Ginsenoside Rh2 is well known for many pharmacological activities, such as anticancer, antidiabetes, antiinflammatory, and antiobesity properties. Glycosyltransferases (GTs) are ubiquitous enzymes present in nature and are widely used for the synthesis of oligosaccharides, polysaccharides, glycoconjugates, and novel derivatives. We aimed to synthesize new ginsenosides from Rh2 using the recombinant GT enzyme and investigate its cytotoxicity with diverse cell lines. Methods: We have used a GT gene with 1,224-bp gene sequence cloned from Lactobacillus rhamnosus (LRGT) and then expressed in Escherichia coli BL21 (DE3). The recombinant GT protein was purified and demonstrated to transform Rh2 into two novel ginsenosides, and they were characterized by nuclear magnetic resonance (NMR) techniques and evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay. Results: Two novel ginsenosides with an additional glucopyranosyl (6→1) and two additional glucopyranosyl (6→1) linked with the C-3 position of the substrate Rh2 were synthesized, respectively. Cell viability assay in the lung cancer (A549) cell line showed that glucosyl ginsenoside Rh2 inhibited cell viability more potently than ginsenoside Rg3 and Rh2 at a concentration of 10 μM. Furthermore, glucosyl ginsenoside Rh2 did not exhibit any cytotoxic effect in murine macrophage cells (RAW264.7), mouse embryo fibroblasts cells (3T3-L1), and skin cells (B16BL6) at a concentration of 10 μM compared with ginsenoside Rh2 and Rg3. Conclusion: This is the first report on the synthesis of two novel ginsenosides, namely, glucosyl ginsenoside Rh2 and diglucosyl ginsenoside Rh2 from Rh2 by using recombinant GT isolated from L. rhamnosus. Moreover, diglucosyl ginsenoside Rh2 might be a new candidate for treatment of inflammation, obesity, and skin whiting, and especially for anticancer.

• 대한한방내과학회지
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• 제30권2호
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• pp.399-409
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• 2009

Objectives : The aim of this study was to experiment the antitumor activity of Agrimonia pilosa Ledebour (APL) in human stomach cancer (AGS) cell lines (in vitro) and male C57BL/6J mouse (in vivo). Methods : The effects of the ethanol extract from the plant on several transplantable rodent tumors were investigated in vitro by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. DNA content analysis and Western blot analysis. Agrimonia pilosa Ledebour (APL) was given to rats with Lewis Lung Carcinoma (LLC) cells. The experimental rats were divided into 3 groups in vivo. Saline was injected into the abdominal cavity in the first group, 50 mg/kg APL was injected into the abdominal cavity in the second group and 100 mg/kg was injected into the abdominal cavity in the third group. After that, we checked their tumor volume periodically. Results : At first, human gastric cancer (AGS) cell lines (in vitro) showed decreased cell viability, and increased $sub-G_1$ contents. When we experimented rat intestinal epithelial (RIE)l as same condition, this result didn't show. With this, compared to normal cells, Agrimonia pilosa Ledebour (APL) led selectively to the extinction of cells only in human gastric cancer. Moreover, we showed that the traditional herbal medicine APL induced caspase-dependent apoptosis in AGS cells. Next, APL inhibited the growth of LLC-bearing mouse tumor. However, we could not verify APL induced caspase-dependent apoptosis in LLC-bearing mouse tumor. Conclusions : The roots of Agrimonia pilosa Ledebour (APL) contain some antitumor constituents.