• Journal of Ginseng Research
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• 제46권6호
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• pp.780-789
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• 2022

Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.

• 한국식품영양학회지
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• 제30권2호
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• pp.371-377
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• 2017

Muscle atrophy is characterized by a decrease in the mass of the muscle. With an increase in life expectancy and chronic illnesses, the incidence of muscle atrophy is increasing and the quality of life of patients is decreasing. Thus, reducing muscle atrophy is of high clinical and socio-economic importance. Mistletoe is a semi-parasitic plant that has been used as a traditional medicine in many countries to treat various human illnesses. It has been reported that Korean mistletoe extract (KME) has diverse biological functions including anti-tumor, anti-oxidant, anti-diabetic, anti-obesity properties, and extension of lifespan. Especially, we have recently reported that KME improves exercise endurance in mice, indicating its beneficial roles in enhancing the capacity of skeletal muscle. In this study, we investigated whether KME could activate the signaling pathway related to protein synthesis in a mouse model of muscle atrophy. Interestingly, KME efficiently activated the Akt/mTOR pathway, and Akt and mTOR are important signaling hub molecules for the acceleration of protein synthesis in muscle cells. In addition, KME also increased the activity of S6 kinase which is involved in the regulation of muscle cell size. Moreover, the ERK activity, required for transcription of ribosomal RNA for protein synthesis, was also enhanced in KME-treated mouse muscle. These data support the idea that KME increases muscle mass via increased protein synthesis. Our findings also suggest that Korean mistletoe might be a promising candidate for the development of functional foods that are beneficial for preventing muscle atrophy.

• 한국식품영양학회지
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• 제33권1호
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• pp.17-26
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• 2020

This study was conducted to evaluate the functionality of fermented black garlic extracts under various conditions. Black garlic powder was prepared by aging for 0~72 hours at 80℃ depending on relative humidity (RH). It showed the highest antioxidant effects among the samples; the total antioxidant activity of black garlic powders at RH 75%, 84%, and 90% for 72 hours was increased 31.9 times, 28.2 times, and 22.6 times compared with that of the fresh garlic powder, respectively. Also, the alliin content was gradually decreased. S-ally-L-cysteine and S-ethyl-cysteine levels were increased; the highest values were 495.9 ㎍/g and 1,769.7 ㎍/g after aging for 72 hours at RH 75%. Aspartate transaminase (AST) and alanine transaminase (ALT) levels were increased following high fat diet feeding, but the rise was obviously reduced by administration of black garlic extract. The total cholesterol, LDL/VLDL-cholesterol, and triglyceride contents in serum were significantly lower in methionine and choline deficient (MCD) diet treatment groups than in the positive control group. The concentration was increased following the intake of black garlic and fermented black garlic extracts. Therefore, black garlic extracts could be an ideal material as a dietary supplement in healthy functional foods to improve the effects on fatty liver.

• 대한본초학회지
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• 제27권4호
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• pp.53-58
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• 2012

Objective : Obesity is often defined as a condition associated with accumulations of excessive body fats which resulting from disorder of energy balance in term of energy intake and energy expenditure. Methods : The effects of natural mixture (T) for inhibition of lipid metabolism on the liver, epididymal fat pads and pancreatic zymogen granules of high fat diet (HFD) supplied rats were observed by histopathology and histomorphometry. Results : As results of HFD supply, severe steatohepatitis such as increases of mean diameters of hepatocytes and the percentages regions of fatty changes was detected. In addition, hypertrophy of adipocytes (increase of mean diameters of epididymal fat pads) was also detected with dramatic decreases of pancreatic zymogen granules at histopathological and histomorphometrical observations. However, theses steatohepatitis and hypertrophy of adipocytes induced by HFD supply were inhibited by treatment of 5 % and 10 % T (T5, T10), respectively. Well corresponded as the results of adipocyte hypertrophy and steatohepatitis, the decreases of pancreatic zymogen granules were also dose-dependently inhibited by T treatment as compared with HFD control, respectively. Conclusion : In conclusion, based on the results, it is considered that test materials, T5 and T10, will be showed hepatoprotective and anti-obese effects, may be directly and/or indirectly mediated by pancreatic zymogen granules because they dose-dependently inhibited steatohepatitis, hypertrophy of adipocytes and decreases of pancreatic zymogen granules induced by HFD supply, respectively.

• 생명과학회지
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• 제9권5호
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• pp.537-547
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• 1999

This study was designed to investigate the effects of sea tangle (Laminaria japonica) extract (Dasi-Ex group: dry base 4.0%) and fucoidan-added (Fuco-I, II, III group: fucoidan of 1.0%, 2.0%, 3.0% added to Dasi-Ex) beverages on the anti-stress action. ICR male mice (20$\pm$2g) were fed basic experimental diets and given free through water bottle filled with these beverages instead of water for 18 days including sociopsychological stress. Body weight gains were consistently lower in Dasi-Ex and Fuco-I,II,III groups compared with control group, expecting in a inhibitory effect of obesity. Dasi-Ex group resulted in a significant decrease of 25% in serum corticosterone (CS) secretion, while Fuco-I,IIand IIIgroups resulted in a marked decreases of 45~55% in serum CS secretion compared with control group. Noradrenaline (NA) secretions were significantly increased about 15% in Dasi-Ex group, and 20~22% in Fuco-I,II,III groups compared with control group. Significant differences in brain MHPG-SO4 levels of Dasi-Ex group could not be obtained, but Fuco-I,II,III groups resulted in a marked decreases of 20~25% in brain MHPG-SO4 ratio of brain, but Fuco-I,II and III groups resulted in a marked increases of 45~60% in NA/MHPG-SO4 ratio of brain compared with control group. These results suggest that fucoidan beverage may play a effective role in a ridding of the sociopsychological stress by pivotal anti-stress effect of fucoidan.

• 생약학회지
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• 제47권1호
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• pp.49-54
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• 2016

In our search for natural products affecting blood circulation, the n-butanol fraction from whole plant of Glehnia littoralis Fr. Schm. (GLB) improved blood lipid parameters, and ameliorated obesity in high-fat-diet (HFD)-fed C57BL/6 mouse model. Hyperlipidemia was induced by high-fat-diet for 4 weeks, and then GLB was orally administrated with 400 mg/kg/day for 4 weeks. GLB-treated group showed that the gain in body weight was significantly attenuated, the levels of total cholesterol and triglyceride significantly lowered on blood chemical analysis, and significantly prolonged the mice bleeding time when compared with those of HFD control group. Concomitantly, phytochemical composition of GLB was investigated by HPLC-hyphenated spectroscopy, and two major phenolic compounds, rutin and chlorogenic acid were identified in the GLB. Taken together, these results indicate that GLB has cardiovascular protective effects and could be a natural medicine candidate for the prevention of cardiovascular disease.

• 동의생리병리학회지
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• 제21권6호
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• pp.1407-1410
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• 2007

We designed to investigate the relationship the cold-hot theory of herbology and body temperature in experimental model. we prepared four kinds of oriental medicine, which consisted of two cold herbs, Daehwang and Seokgo, and two hot herbs, Buja and Padu. Decrease of body temperature by cold exposure for 12 hour was not inhibited by four herbs oral administration for two weeks. Thermogenesis in mammals is an essential physiological function to maintain the body temperature. Mitochondrial uncoupling proteins(UCPs), which have a potential to generate heat by uncoupling oxidative phosphorylation, apper to play a crucial role in thermogenesis. Therefore UCP is commonly recognized as a key molecule in metabolic thermogenesis and its dysfunction contributes to the development of obesity. In these experiments, Daehwang water extracts inhibited the UCP1 mRNA expression increase by cold exposure in brown adipose tissue. But other herbs did not significantly influence on UCPs mRNA expression in white adipose tissue and seleus muscle tissue. Based on this experiment, we will try to clarify the effects of Daehwang water extracts on UCP1 expression and function.

• Clinical and Experimental Reproductive Medicine
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• 제48권3호
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• pp.245-254
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• 2021

Objective: In humans, polycystic ovary syndrome (PCOS) is an androgen-dependent ovarian disorder. Aberrant gene expression in folliculogenesis can arrest the transition of preantral to antral follicles, leading to PCOS. We explored the possible role of altered gene expression in preantral follicles of estradiol valerate (EV) induced polycystic ovaries (PCO) in a mouse model. Methods: Twenty female balb/c mice (8 weeks, 20.0±1.5 g) were grouped into control and PCO groups. PCO was induced by intramuscular EV injection. After 8 weeks, the animals were killed by cervical dislocation. Blood serum (for hormonal assessments using the enzyme-linked immunosorbent assay technique) was aspirated, and ovaries (the right ovary for histological examinations and the left for quantitative real-time polymerase) were dissected. Results: Compared to the control group, the PCO group showed significantly lower values for the mean body weight, number of preantral and antral follicles, serum levels of estradiol, luteinizing hormone, testosterone, and follicle-stimulating hormone, and gene expression of TGFB1, GDF9 and BMPR2 (p<0.05). Serum progesterone levels were significantly higher in the PCO animals than in the control group (p<0.05). No significant between-group differences (p>0.05) were found in BMP6 or BMP15 expression. Conclusion: In animals with EV-induced PCO, the preantral follicles did not develop into antral follicles. In this mouse model, the gene expression of TGFB1, GDF9, and BMPR2 was lower in preantral follicles, which is probably related to the pathologic conditions of PCO. Hypoandrogenism was also detected in this EV-induced murine PCO model.

• 동의생리병리학회지
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• 제33권2호
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• pp.109-115
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• 2019

Aster Yomena (AY) has been used in traditional medicine to treat diseases such as obesity, hyperlipidemia, atherosclerosis, diabetes and osteoarthritis. However, protective effect of AY on acute pancreatitis (AP) has not been reported. The present study examined the anti-inflammatory effects of an ethanol extract of AY on cerulein-induced AP. AP was induced in mice by intraperitoneally injecting cerulein ($50{\mu}g/kg$) hourly for 6 times. 70% ethanol extract of AY (0.1, 0.2, and 0.5 g/kg) was orally administered for 1 week before acute pancreatitis induction. The mouse was killed at 6 hours after the final cerulein injection. The pancreas and lung were rapidly removed for histological examination and myeloperoxidase (MPO) assay. Blood samples were taken to determine serum amylase and lipase activity. In addition real-time reverse transcription-polymerase chain reaction (RT-PCR) was also performed to investigate mRNA expression of proinflammatory cytokines such as $TNF-{\alpha}$. $IL-1{\beta}$, and IL-6. Administration of AY significantly ameliorated pancreatic weight to body weight ratio, histological damages and MPO activity during AP. In addition, AY inhibited the serum amylase and lipase activity during AP. Also, mRNA expression of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 were inhibited by AY against AP. Our results revealed that pre-treatment of AY reduces the severity of cerulein-induced AP. Therefore, AY may have a protective effect drug against AP.

• Laboraroty Animal Research
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• 제34권4호
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• pp.279-287
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• 2018

Placenta specific 8 (PLAC8, also known as ONZIN) is a multi-functional protein that is highly expressed in the intestine, lung, spleen, and innate immune cells, and is involved in various diseases, including cancers, obesity, and innate immune deficiency. Here, we generated a Plac8 knockout mouse using the CRISPR/Cas9 system. The Cas9 mRNA and two single guide RNAs targeting a region near the translation start codon at Plac8 exon 2 were microinjected into mouse zygotes. This successfully eliminated the conventional translation start site, as confirmed by Sanger sequencing and PCR genotyping analysis. Unlike the previous Plac8 deficient models displaying increased adipose tissue and body weights, our male Plac8 knockout mice showed rather lower body weight than sex-matched littermate controls, though the only difference between these two mouse models is genetic context. Differently from the previously constructed embryonic stem cell-derived Plac8 knockout mouse that contains a neomycin resistance cassette, this knockout mouse model is free from a negative selection marker or other external insertions, which will be useful in future studies aimed at elucidating the multi-functional and physiological roles of PLAC8 in various diseases, without interference from exogenous foreign DNA.