• 대한본초학회지
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• 제36권5호
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• pp.81-91
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• 2021

Objectives : Osteoporosis is a systemic skeletal disease that decreases bone density and increases the risk of fractures. Bisphosphonates and SERMs are mainly used to treat osteoporosis, but, long-term use increases the risk of side effects such as jaw bone necrosis and breast cancer. Therefore, it is necessary to develop a therapeutic agent for a natural product with few side effects. Water extract of Lonicerae Japonicae Flos (wLF) was mainly found to have anti-cancer and anti-inflammatory effects. However, the effect of wLF on osteoporosis has not been elucidated. Therefore, this experiment investigated the effect of wLF on osteoclasts, osteoblasts and osteoporosis models. Methods : In order to study the effect of wLF on osteoporosis, the OVX-induced rat model was used for in vivo study. After 8 weeks, we measured body weight, uterine weight, liver weight, femur weight, bone density, trabecular area and tibia ash weight. To determine the effect of wLF on osteoclast differentiation, we measured the number of TRAP-positive cells and TRAP activity. To examine the effect of wLF on the expression of osteoblast-related genes, we measured the mRNA expression of alkaline phosphatase (ALP, Alpl) and osteocalcin (OCN, Bglap2). Results : In vivo experiment, wLF inhibited the reduction of femur weight, trabecular area, bone density and tibia ash weight. In vitro experiment, wLF had no significant effect on osteoclast differentiation. However, wLF increased the mRNA expression of Alpl and Bglap2 in MC3T3-E1 cell. Conclusions : This result suggested that wLF may be used for the treatment and prevention of postmenopausal osteoporosis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권2호
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• pp.173-186
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• 2021

Purpose: Biliary atresia (BA) is a disease that manifests as jaundice after birth and leads to progressive destruction of the ductal system in the liver. The aim of this study was to investigate histopathological changes and immunohistochemically examine the expression of glial cell line-derived neurotrophic factor (GDNF), synaptophysin, and S-100 protein in the gallbladder of BA patients. Methods: The study included a BA group of 29 patients and a control group of 41 children with cholecystectomy. Gallbladder tissue removed during surgery was obtained and examined immunohistochemically and histopathologically. Tissue samples of both groups were immunohistochemically assessed in terms of GDNF, S-100 protein, and synaptophysin expression. Expression was classified as present or absent. Inflammatory activity assessment with hematoxylin and eosin staining and fibrosis assessment with Masson's trichrome staining were performed for tissue sample sections of both groups. Results: Ganglion cells were not present in gallbladder tissue samples of the BA group. Immunohistochemically, GDNF, synaptophysin, and S-100 expression was not detected in the BA group. Histopathological examination revealed more frequent fibrosis and slightly higher inflammatory activity in the BA than in the control group. Conclusion: We speculate that GDNF expression will no longer continue in this region, when the damage caused by inflammation of the extrahepatic bile ducts reaches a critical threshold. The study's findings may represent a missing link in the chain of events forming the etiology of BA and may be helpful in its diagnosis.

• 대한한의학방제학회지
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• 제29권2호
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• pp.71-80
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• 2021

Objectives : This study investigated cellular-protective effects of Nardotidis seu Sulculii Concha water extract (NSCE) against oxidative stress induced by arachidonic acid (AA)+iron or tert-butylhydroperoxide (tBHP). Methods : In vitro, MTT assay was assessed for cell viability, and immunoblotting analysis was performed to detect expression of AMP-activated kinase (AMPK) signaling pathway and autophagy related proteins. In vivo, mice were orally administrated with the aqueous extract of NSCE of 500 mg/kg for 3 days, and then injected with CCl₄ 0.5 mg/kg body weight to induce acute damage. The level of liver damage was measured by serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) analysis. Results : Treatment with NSCE inhibited cell death induced by AA+iron and tBHP. NSCE induced the phosphorylation of AMPK, and this compound also induced the phosphorylation of LKB1, an upstream kinase of AMPK, and Acetyl-CoA carboxylase (ACC), a primary downstream target of AMPK. NSCE increased the protein levels of autophagic markers (LC3II and beclin-1) and decreased the phosphorylation of mammalian target of rapamycin (mTOR) and simultaneously increased the phosphorylation of unc-51-like kinase-1 (ULK-1) in time-dependent manner. Conclusions : NSCE has the ability 1) to protect cells against oxidative stress induced by AA+iron or tBHP. NSCE 2) to activate AMP-activated protein kinase (AMPK), and 3) to regulate autophagy, an important regulator in cell survival.

• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.207-216
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• 2021

Supplement of high-protein food plays an important role in improving the symptoms of malnutrition and the immune capacity of the body, but the association of high-protein diet and gut microbiota remained unaddressed. Here, we systematically analyzed the internal organs and gut microbiota in C57(WT) or PD-1H-depleted (KO) mice (T cells were activated) fed with pupae or feed for six weeks. We observed that the body weight gain in the mice fed with pupae increased less significantly than that of the feed group, while the villi and small intestine lengths in the pupa group were reduced compared with that of mice given feed. However, the average body weight of the KO mice increased compared with that of the WT mice fed with pupae or feed. Pupae increased the concentration of blood glucose in WT, but not in KO mice. Moreover, in the feed group, there was no difference in the weight of the internal organs between the WT and KO mice, but in the pupae-fed group, liver weight was decreased and spleen weight was increased compared with that of KO mice. The amounts/plural/amounts of Melainabacteria, Chloroflexi, and Armatimonadetes were specifically upregulated by pupae, and this upregulation was weakened or eliminated by PD-1H depletion. Some bacteria with high abundance in the feed-fed KO mice, such as Deferribacteres, Melainabacteria, Acidobacteria, Bacteroidetes, Spirochaetes and Verrucomicrobia, were decreased in pupae-fed KO mice, and Proteobacteria and Deinococcus were specifically enriched in pupae-fed KO mice. Bacteroidetes, Firmicutes and Akkermansia were associated with weight loss in the pupae-fed group while Lachnospiraceae and Anaerobiospirillum were related glucose metabolism and energy consumption. Based on high-throughput sequencing, we discovered that some gut bacteria specifically regulated the metabolism of a high-protein diet, and PD-1H deficiency improved life quality and sustained blood glucose. Moreover, PD-1H responses to high-protein diet through modulating the type and quantity of gut bacteria. These findings provide evidence about the association among gut microbiota, T cell activation (for PD-1H depletion) and high-protein diet metabolism, have important theoretical significance for nutrition and health research.

• Advances in nano research
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• 제13권6호
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• pp.575-585
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• 2022

Due to its biofilm formation and colonization of the osteocyte-lacuno canalicular network (OLCN), Staphylococcus aureus (S.aureus) implant-associated bone infection (SIABI) is difficult to cure thoroughly, and may occur recurrently subsequently after a long period dormant. It is essential to explore an alternative therapeutic strategy that can eradicate the pathogens in the infected foci. To address this, the polymethylmethacrylate (PMMA) bone cement and Fe3O4 nanoparticles compound cylinder were developed as implants based on their size and mechanical properties for the alternative magnetic field (AMF) induced thermal ablation, The PMMA mixed with optimized 2% Fe₃O₄ nanoparticles showed an excellent antibacterial efficacy in vitro. It was evaluated by the CFU, CT scan and histopathological staining on a rabbit 1-stage transtibial screw model. The results showed that on week 7, the CFU of infected soft tissue and implants, and the white blood cells (WBCs) of the PMMA+2% Fe₃O₄+AMF group decreased significantly from their controls (p<0.05). PMMA+2% Fe₃O₄+AMF group did not observe bone resorption, periosteal reaction, and infectious reactive bone formation by CT images. Further histopathological H&E and Gram Staining confirmed there was no obvious inflammatory cell infiltration, neither pathogens residue nor noticeably burn damage around the infected screw channel in the PMMA+2% Fe₃O₄+AMF group. Further investigation of nanoparticle distributions in bone marrow medullary and vital organs of heart, liver, spleen, lung, and kidney. There were no significantly extra Fe₃O₄ nanoparticles were observed in the medullary cavity and all vital organs either. In the current study, PMMA+2% Fe₃O₄+AMF shows promising therapeutic potential for SIABI by providing excellent mechanical support, and promising efficacy of eradicating the residual pathogenic bacteria in bone infected lesions.

• Journal of Applied Biological Chemistry
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• 제65권3호
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• pp.143-152
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• 2022

본 연구는 고지방식이(HFD)를 제공한 비만동물모델에서 Momordica charanatia (MC)와 Withania somnifera (WS) 추출물의 혈청 콜레스테롤 및 내장지방 감소효과를 분석하였다. 유산균으로 발효한 MC와 WS 추출물의 조합(FMCWS) 및 비발효 추출물(MCWS)의 조합을 HFD로 유도된 비만마우스에 8주 동안 경구 투여하였다. 실험 기간 동안 체중, 식이섭취량, 총 콜레스테롤, 중성지방, HDL-콜레스테롤 수치를 분석하였다. 체중과 총 콜레스테롤 및 중성지방 수치는 정상대조(NC)군과 비교하여 HFD를 섭취한 HFD군에서 유의하게 증가했다. 그러나, 추출물의 투여로 인해 비만마우스의 체중증가가 감소되는 경향을 확인하였고 더불어 HDL-콜레스테롤의 증가와 함께 총 콜레스테롤 및 중성지방 수치를 유의적으로 감소시켰다. 복부지방 무게와 부고환 지방조직 내 지방세포의 크기는 NC군에 비해 HFD군에서 유의하게 증가하였다. 그러나, FMCWS와 MCWS를 각각 투여한 군은 HFD군에 비해 복부지방 무게와 부고환 지방세포의 크기가 유의하게 감소하였다. 또한, HFD군의 간 조직에서 관찰되는 거대 소포성 지방구의 침착이 이들 군에서는 현저하게 감소하였다. 이러한 결과는 MC와 WS 추출물의 조합이 체중 증가에 대한 감소 경향이 있을 뿐만 아니라 내장지방 및 혈청 지질 수준을 현저히 낮추는 데 강력한 시너지 효과가 있어 HFD 유발 비만마우스에서 항비만 활성을 향상시키는 효능이 있음을 시사한다.

• Journal of Periodontal and Implant Science
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• 제29권1호
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• pp.1-14
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• 1999

Ursodeoxycholic acid(UDCA) is a hydrophilic gall bladder acid and has been used as a effective drug for liver disease related to in1munity. This drug inhibits secretions of IL-2, IL-4, and $IFN-{\gamma}$ from T-cells and production of immunoglobulin from B-cells. Also it has been reported that UDCA inhibits production of IL-1 related to the progression of periodontal disease and activation of collagenases. The purpose of the present study was to elucidate the effects of UDCA on inhibition of periodontal disease progression using clinical, microbiological and histometrical parameters. Twelve pure bred, 16 month-old-beagle dogs were used in the study. After ligature-induced periodontal diseases were formed, experimental drugs were applied twice a day and then the results of clinical, microbiological, and histometrical parameters were measured at baselie(initiation of experiment) , 4weeks and 8weeks. The gel with UDCA(concentration 0.5%, 5% 3 dogs in each) was applied to experimental group, chlorhexidine to positive control group(3dogs) and the gel without UDCA(base) to negative control group. After induction of general anesthesia, the maxillary 2nd, 3rd premolars and 1st molar and the mandibular 2nd, 3rd, 4th premolars and 1st molar were ligated in one side selected randomly and were not ligated in the opposite side. The plaque index(PI), gingival index(GI), pocket depth(PD) and gingival crevicular fluid(GCF) volum were measured clinically. The PI and GI were measured at 3 buccal points of all experimental teeth and the GCF was measured only at the 3rd premolar in the maxilla and the 4th premolar in the mandible. In the microbiological study, the samples extracted from the 3rd premolar of the maxilla and the 4th premolar of the mandible at the center of buccal surface were analyzed aerobics, anaerobics and Streptococcus colony forming units, After clinical and microbiological examination at 8weeks, the dogs were sacrificed by carotid artery perfusion. The samples were fixed and sectioned including interproximal area, and the distance from cementoenamel junction(CEJ) to alveolar crest was measured. The results were that PI, GI and PD increased until 4 weeks and decreased at 8 weeks in three groups but the differences between all the groups were not significant. The 0.5% UDCA in non-ligated group showed remarkable decrease of GCF. The experimental group applied 5% UDCA decreased the number of aerobics and anaerobics. The distance from CEJ to alveolar crest was greater in the negative control group on both ligated and non-ligated sides, but the differences were not significant stastically.

• 대한약리학회지
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• 제17권1호
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• pp.17-25
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• 1981

No evidence has accumulated that lead compound is an essential component for biological function in animals. Lead is absorbed primarily through the epithelial mucosal cells in duodenum and the absorption can be enhanced by the substances which bind lead and increase its solubility. Iron, zinc and calcium ions, however, decrease the absorption of lead without affecting its solubility, probably by competing for shared absorptive receptors in the intestinal mucosa. Therefore, the absorption of lead is increased in iron deficient animals. Lead shows a strong affinity for ligands such as phosphate, cysteinyl and histidyl side chains of proteins, pterins and porphyrins. Hence lead can act on various active sites of enzymes, inhibiting the enzymes which has functional sulfhydryl groups. lead inhibits the activity of ${\delta}$-aminolevulinic acid dehydratase for the biosynthesis of hemoproteins and cytochrome, which catalyzed the synthesis of monopyrrole prophobilinogen from ${\delta}$-aminolevulinic acid. Accordingly lead decrease hepatic cytochrome p-450 content, resulting an inhibition of the activity of demethylase and hydroxylase in liver. Little informations are available on the effect of lead on digestive system although the catastrophic effects of lead intoxication are well documented. The present study was, therefore, attempted to investigate the effect of lead on pancreaticobiliary secretion in rats. Albino rats of both sexes weighing $170{\sim}230g$ were used for this study. The animals were divided into one control and three treated groups, i.e., control (physiologic saline 1.5ml/kg i.p.), lead acetate $(l0{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and EDTA$(each\;10{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and $FeSO_4(each\;l0{\mu}mole/kg/day\;hp)$. The pancreatico-biliary juice was collected under urethane anesthesia, and activities of amylase and lipase were determined by employing Sumner's and Cherry and Crandall's methods. The summarized results are follows. 1) In the experiment for acute toxicity of lead acetate, 20% of mortality was observed in rat treated with lead acetate as well as inhibition of the activity of amylase in the juice at the 3 rd day of the treatment. 2) No increases in body weight were observed in rats treated with lead acetate, while in control group the significant increases were observed. However, the body weights of animals were increased in the group lead acetate plus EDTA or $FeSO_4$. 3) Lead acetate decreased significantly the volume of pancreatico-biliary juice whereas additional treatment of EDTA and $FeSO_4$ prevented it. 4) Total activity of amylase was markedly reduced due to lead acetate treatment, but no change was showed following additional treatment with EDTA and $FeSO_4$. 5) No changes in the cholate and lipase output were observed in rats treated with lead acetate as compared with that of control rats. 6) Increase in bilirubin output in rats treated with lead acetate was shown on the 2nd and 3rd weeks treatment. 7) In the case of in vitro experiment, lead acetate also markedly inhibited release of amylase from pancreatic fragment. 8) Histologic finding indicated that acini vacuolation was induced in the pancreatic tissue of rat treated with lead acete. From the above results, it might be concluded that lead acetate decreases the volume of pancreatico-biliary secretion and inhibits the amylase activity, by acting directly on pancreatic cells.

• 대한임상검사과학회지
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• 제49권1호
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• pp.1-7
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• 2017

Zerumbone은 야생 생강의 일종인 Zingiber zerumbet Smith의 정유(essential oil)에 포함되어 있는 주요성분으로, 다양한 연구를 통해 혈액종양을 포함한 암, 염증질환, 활성산소 감소 등에 이용할 가능성이 꾸준히 제기되어왔다. 또한 면역세포들의 증식과 세포주기진행, 사이토카인의 생성 발현에도 효과를 나타낸다고 알려져 있다. 이외에도 간보호, 통증완화, 항동맥경화, 항미생물 등 다양한 생물학적 기능이 보고되었다. 본 연구에서는 zerumbone이 단구의 활성과 기능에 어떠한 영향을 미치는지 알아보고자 하였다. 우선, 단구세포주 THP-1세포의 활성이 zerumbone에 의해 증가되는 것을 확인하였다. LPS 처리 후 가장 강한 THP-1 증식 증가는 $5{\mu}M$의 zerumbone 처리 시 나타났으며, 세포 단독 증식 증가는 $10{\mu}M$의 zerumbone 처리 시 가장 증가하였다. 반면에 $50{\mu}M$ 의 zerumbone 처리 시에는 LPS 존재 여부와 관계없이 급격한 증식 감소가 관찰되었다. LPS의 처리에 의해 유도되는 신호전달 단백질 Erk의 인산화도 zerumbone에 의해 증가되었다. 가장 강한 인산화 증가는 증식 감소가 나타난 $50{\mu}M$의 zerumbone을 처리했을 때 관찰되었다. 전사인자 $NF-{\kappa}B$의 활성은 zerumbone 단독 처리 시에는 큰 변화가 없었지만, LPS 와 동시에 처리했을 경우 증가하는 것으로 관찰되었다. 나아가, $NF-{\kappa}B$에 의해 발현이 조절되는 염증 사이토카인 $TNF-{\alpha}$, IL-8의 전사도 zerumbone 에 의해 증가되는 것을 확인하였다. 이와 같은 결과를 통해 zerumbone이 단핵구의 증식과 활성을 강화시킬 수 있음을 확인하였다. 나아가, zerumbone이 LPS 를 보유한 세균 감염 시 단핵구 활성 증가를 통하여 효과적인 탐식과 면역반응을 강화시켜 효과적인 세균 처리에 도움을 줄 수 있을 것으로 여겨진다.

• Journal of Nutrition and Health
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• 제51권4호
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• pp.275-286
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• 2018

본 연구는 떫은감 청도반시의 분말을 열수 추출하고 칼럼 추출하는 과정에서 획득한 PWE와 TEP에 대한 대사체 프로파일을 분석하고, 유리지방산을 처리한 HepG2 세포와 식이로 고지혈증을 유도한 Wistar계 흰쥐의 간조직을 사용하여 중성지질 및 콜레스테롤 대사 관련 유전자 발현을 측정하였다. 대사체 분석은 가스크로마토그래프-질량분석법과 액체크로마토그래프-질량분석법을 사용하였으며, PLS-DA 분석과 heatmap 분석을 실시한 결과 PWE는 떫은감 분말과 비교적 유사한 대사체 프로파일을, 그리고 TEP는 떫은감 분말과 매우 다른 대사체 프로파일을 가지고 있음을 확인하였다. 세포실험과 또한 세포실험에서 얻어진 결과를 검증하기 위해 수행된 동물실험에서 PWE와 TEP는 모두 SREBP1c와 FAS 유전자 발현을 감소하여 간의 지방축적을 감소시키는 것으로 관찰되었으나, 콜레스테롤 축적을 억제하는 효능은 PWE에 비해 TEP에서 우세하게 증가하는 것이 관찰되었다. 특별히 TEP는 SREBP2, HMGCR 유전자 발현을 억제하고 LDLR 유전자 발현을 촉진하는 것으로 나타났다. TEP는 탄닌 중 Gallic acid 그리고 장쇄지방산아미드인 Oleamide와 Palmitamide 함량이 유의하게 증가되었으므로, 향후 이들 성분과 타깃 유전자의 상관성을 분석하고, 이를 통해 시스템네트워크로 나타내어 대사체 프로파일에 따른 지질 및 콜레스테롤 대사 간 상호 영향을 추가적으로 연구해야 할 것으로 사료된다.