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Kim, Kwang-Youn,Park, Kwang-Il,Lee, Seul Gi,Baek, Su Youn,Lee, Eun Hye,Kim, Sang Chan,Kim, Sang-Hun,Park, Sul-Gi,Yu, Sun-Nyoung,Oh, Tae Woo,Kim, Joung-Hee,Kim, Keuk-Jun,Ahn, Soon-Cheol,Kim, Young Woo Elsevier 2018 Chemico-biological interactions Vol.294 No.-
<P><B>Abstract</B></P> <P>Deoxypodophyllotoxin (DPT) is a naturally occurring flavolignan in <I>Anthriscus sylvestris</I> known as cow parsley or wild chervil, and has been reported to have inhibitory effects against several pathological processes including cancer, inflammation and infection. Here, we report the effects of DPT in the fatty liver induced by high fat diet <I>in vivo</I> as well as its regulatory mechanism related with the transcription factor for lipogenic genes such as sterol regulatory element binding protein-1c (SREBP-1c) <I>in vitro</I>. C57BL/6 mice were fed high fat diet for 10 weeks and also orally administrated with DPT for additional 4 weeks. 5 and 10 mg/kg of DPT decreased lipid accumulation in the liver induced by high fat diet, as indicated by histological parameters such as Oil Red O staining and hematoxylin & eosin as well as the contents of hepatic triglyceride and cholesterol. In hepatocytes, DPT inhibited the liver X receptor α-mediated SREBP-1c induction and expression of the lipogenic genes, including fatty acid synthase, acetyl-CoA carboxylase and stearoyl-CoA desaturase-1. Moreover, DPT induced AMP-activated protein kinase (AMPK) activation, which has been known to inhibit the expression of SREBP-1c in hepatocyte. Also this compound restored the dysregulation of AMPK and SREBP-1c induced by high fat diet in mice. In conclusion, we demonstrated that DPT significantly inhibited fatty liver by adjusting lipid metabolism coordinated with AMPK activation and SREBP-1c inhibition.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Deoxypodophyllotoxin (DPT), a chemopreventive flavolignan, inhibited diet-induced fatty liver. </LI> <LI> DPT inhibited the LXR-α-mediated sterol regulatory element binding protein (SREBP)-1c. </LI> <LI> DPT blocked the expression of <I>de novo</I> lipogenic genes including FAS and ACC. </LI> <LI> DPT activated AMPK related with SREBP-1c inhibition. </LI> <LI> DPT might be a pharmaceutical candidate for hepatic steatosis. </LI> </UL> </P>
Lee, Kyunghee,Kim, Hyunsoo,Kim, Jin-Man,Kim, Jae-Ryong,Kim, Keuk-Jun,Kim, Yong-Jin,Park, Se-Il,Jeong, Jae-Ho,Moon, Young-mi,Lim, Hyun-Sook,Bae, Dong-Won,Kwon, Joseph,Ko, Chang-Yong,Kim, Han-Sung,Shin, Blackwell Publishing Ltd 2011 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Vol.15 No.10
<P>Systemic transplantation of adipose-derived stem cells (ASCs) is emerging as a novel therapeutic option for functional recovery of diverse damaged tissues. This study investigated the effects of systemic transplantation of human ASCs (hASCs) on bone repair. We found that hASCs secrete various bone cell-activating factors, including hepatocyte growth factor and extracellular matrix proteins. Systemic transplantation of hASCs into ovariectomized mice induced an increased number of both osteoblasts and osteoclasts in bone tissue and thereby prevented bone loss. We also observed that conditioned medium from hASCs is capable of stimulating proliferation and differentiation of osteoblasts <I>via</I> Smad/extracellular signal-regulated kinase (ERK)/JNK (c-jun NH<SUB>2</SUB>-terminal kinase) activation as well as survival and differentiation of osteoclasts <I>via</I> ERK/JNK/p38 activation <I>in vitro</I>. Overall, our findings suggest that paracrine factors secreted from hASCs improve bone repair and that hASCs can be a valuable tool for use in osteoporosis therapy.</P>
포도전정가지 추출물이 UVB에 유도된 HR-1 mice의 피부손상에 대한 광보호 효과
김정희(Joung-Hee Kim),김종국(Jong Guk Kim),김선건(Sun-Gun Kim),정승일(Seung-IL Jeong),장민정(Min-Jung Jang),김길수(Kil-Soo Kim),김극준(Keuk-Jun Kim),곽승준(Seung-Jun Kwack) 한국생명과학회 2017 생명과학회지 Vol.27 No.4
본 연구는 포도수확 후 버려지는 가지를 이용한 포도전정가지 추출물(Grape Pruning Stem Extracts, GPSE)에 함유된 polyphenol류 중 항산화, 항염증, 항암 등의 효과가 있다고 알려진 rutin, procyanidin B3, quercetin, kaempferol의 함량을 분석하고, UVB로 유도된 HR-1 mice의 손상된 피부에 대한 피부 보습, 피부 증식 억제, 항염증 등의 효과를 측정하여 기능성식품, 기능성 화장품 소재로서의 응용 가능성을 확인하고자 하였다. 포도전정가지에서 polyphenol 성분을 80% EtOH로 추출하고 여과하여 농축한 후, 동결건조하여 -20℃에 보관하면서 사용하였다. GPSE의 유효성분 함량은 HPLC를 사용하여 분석하였다. 피부손상을 유도하기 위해 UVB를 실험동물에 조사하였고, GPSE의 효능을 확인하기 위하여 TEWL assay, 피부조직의 H&E staining 및 COX-2 단백 발현 측정을 위한 면역조직화학적염색(immunohistochemical stain) 등을 실시하였다. 포도전정가지 시료 53 kg에서 EtOH 분획 추출물 2.34 kg을 추출하여 4.42%의 수율 결과를 얻었다. 유효성분 분석 결과, procyanidin B3, 0.28 mg/g, rutin 12.81 mg/g, quercetin 0.51 mg/g 및 kaempferol 8.24 mg/g로 나타났다. TEWL assay 결과 대조군과 비교, GPSE와 serum base의 혼합물이 도포된 그룹(농도 2,000 mg/kg~125 mg/kg)에서 모두 보습효과가 있는 것을 확인하였다(p<0.05). GPSE의 피부증식억제를 통한 광보호 효과를 확인한 결과 epidermis에는 GPSE 농도 2,000mg/kg의 농도에서 suncream과 유사한 결과를 얻을 수 있었고(p<0.05), dermis의 두께를 측정한 결과 GPSE 농도 2,000 mg/kg~125 mg/kg 모든 농도에서 UVB 조사한 그룹 두께 800 μm와 비교하여 suncream 도포군이 580 μm, GPSE 2,000 mg/kg~125 mg/kg 모든 농도에서 600 μm이하로 나타나 UVB에 의해 손상된 HR-1 mice의 피부증식억제를 확인할 수 있었다(p<0.05). GPSE가 UVB에 의해 손상된 HR-1 mice 피부에 항염증 정도를 확인하기 위해 COX-2 단백발현을 보기위해 immunohistochemical stain한 결과 UVB를 조사한 대조군에 비해 GPSE를 도포한 그룹 모두에서 항염증 효과를 보였지만, GPSE의 농도 1,000 mg/kg에서는 suncream 22%보다 낮은 8%에서 COX-2의 단백발현이 낮은 것으로 나타나 우수한 항염증효과를 얻을 수 있었다(p<0.05). 본 연구 결과에서, GPSE 내 rutin, kaempferol, quercetin, procyanidin B3와 같은 유효성 페놀성 화합물이 확인되었으며, GPSE는 보습효과, 피부증식억제효과, 염증발현억제효과 및 자외선 손상에 의한 피부장벽 기능 개선효과 등이 있는 것으로 확인되었다. 결론적으로 GPSE는 피부보호 효과의 가능성이 있는 기능성 물질로서 기능성 식품 및 기능성 화장품 등의 원료로 활용성이 높을 것으로 판단된다. This study intends to analyze the contents of rutin, procyanidin B3, quercetin, kaempferol, known to have antioxidant, anti-inflammatory and anti-carcinogenic effects, among the polyphenol type contained in the grape pruning stem extracts (GPSE), utilizing grape stems being discarded after harvest, measure the effects on the skin moisture, inhibition of skin cell proliferation, anti-inflammatory on the damaged skin of a HR-1 mice induced with UVB, and verify the applicability as a material for functional food and functional cosmetics. The results of verifying the photoprotection effects through the skin proliferation control through of GPSE showed similar result to suncream was achieved at the GPSE concentration of 2,000 mg/kg on the epidermis (p<0.05). The results showed anti-inflammatory effects on all groups applied with GPSE as compared to the control group irradiated with UVB, but at the GPSE concentration of 1,000 mg/kg, a lower COX-2 protein expression at 8%, lower than the 22% of suncream, was observed to achieve an excellent anti-inflammatory effect (p<0.05). The results of this study confirmed the existence of active polyphenol type, such as rutin, kaempferol, querocetin and procyanidin B3, within the GPSE, and GPSE has improvement effects on moisturizing effects, skin proliferation control effect, inflammatory control effect and improvement effects on the skin barrier function through UV ray damage. GPSE is a functional ingredient with a potential for skin protection effects, and has high utilization as an ingredient for functional food and functional cosmetics.
Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different sources
Sou Hyun Kim,Keuk-Jun Kim,Joung-Hee Kim,Jae-Hwan Kwak,HyunKeun Song,Joon Young Cho,Dae Youn Hwang,Kil Soo Kim,Young-Suk Jung 한국실험동물학회 2017 Laboratory Animal Research Vol.33 No.2
Doxorubicin is a widely used chemotherapeutic agents and is now part of standard therapeutic regimens for a variety of cancers (eg, hematopoietic malignancies and advanced solid tumors of the breast, ovary, thyroid, and bone). However, a potentially lethal and dose-dependent cardiotoxicity that appears within a short time after treatment limits the usage of doxorubicin in cancer patients. Although the mechanism of doxorubicin-induced cardiotoxicity is not completely understood, it is thought that free radical-induced oxidative stress and excessive production of reactive oxygen species are primary drivers of its toxicity. In this study, we compared the doxorubicin-induced cardiotoxicity of ICR mice obtained from three different sources and evaluated the utility of Korl:ICR stock established by the Korean FDA. Because doxorubicin-induced cardiotoxicity is thought to involve the excessive generation of ROS followed by oxidative stress, we determined the representative tissue index of oxidation, lipid peroxidation, and antioxidant, glutathione (GSH), as well as the parameters of heart injury. Doxorubicin treatment successfully induced cardiotoxicity as evidenced by histological examination and serum parameters (eg, levels of LDH and CK activities) in ICR mice. It was accompanied by increased lipid peroxidation and a decrease in both cysteine and GSH, further supporting previous reports that oxidative stress is a potential mechanism of doxorubicin-induced cardiotoxicity. Of interest, we did not observe a significant difference in doxorubicin-induced cardiotoxicity among mice of different origins. Collectively, our results suggest that Korl:ICR strain may be useful in the research of doxorubicin-induced cardiotoxicity.