• Nutrition Research and Practice
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• 제12권3호
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• pp.191-198
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• 2018

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

• 생명과학회지
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• 제15권6호
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• pp.955-960
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• 2005

메트로니다졸은 인체 위장질환의 원인균인 헬리코박터 파일로리를 박별하기위해 처방하는 주요 약제이다 그러나 인체로부터 분리한 헬리코박터 파일로리 균주는 메트로니다졸에 내성을 가지는 경우가 일반적이며, 이러한 내성원인은 이 균주의 염색체 상에 존재하는 두 종류의 nitroreductase 유전자인 rdxA와frxA 유전자가 비활성화됨에 따라 유발된다. 본 연구에서는 헬리코박터 파일로리 균에서 rdxA 유전자에 변이를 도입하여 메트로니다졸에 내성을 가지는 균주를 구축하여, 메트로니다졸 내성이 균주에 미치는 생물학적 영향을 관찰하고자 하였다. In vitro상에서 메트로니다졸 내성균주는 대조균과 비교하여 exponential phase에서는 거의 차이 없이 증식하였으나 stationary phase에서는 빠르게 생육활성을 잃는 것을 관찰할 수 있었다. 또한 생쥐를 이용한 동물 실험에서 메트로니다졸 내성균주는 생쥐의 위장 내에서 서식하는 능력을 상실함을 알 수 있었다. 그러나 이러한 생육 활성을 회복시켜주는 compensate템 mutation을 가진 균주를 쉽게 얻을 수 있었으며 이 균주는 생쥐에 감염시키면 위장 내에서 서식하는 능력을 회복함을 알 수 있었다.

• 한국식품과학회지
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• 제46권5호
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• pp.622-629
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• 2014

생쥐에서의 으름의 열매 추출물의 경구 투여가 알코올로 인한 급성 간독성 상태에서 간보호 효과에 대한 영향을 조사 하였다. 즉, 생쥐 (C57BL/6)에게 1주간 으름 열매 추출물을 투여 하고 희생 전 알코올의 경구 투여를 통해 급성 알코올 간독성을 유발한 후 간 조직 형상, 간 기능 지표(ALT, AST), 간 세포내 GSH 합성 효소(GCLM, GCLC, GSS)의 mRNA 발현량, GSH 농도의 측정, 산화 스트레스 지표인 NOX4의 mRNA 발현량과 염증 반응 지표인 TNF-${\alpha}$의 mRNA 발현량을 조사 하였다. 그 결과, 으름 열매 추출물의 경구 투여는 알코올로 유발된 급성 간독성 상태에서 간 조직내 지방의 축적을 완화 하였고, 혈청 AST, ALT 수치를 개선하였으며, 간조직 내 항산화 물질인 GSH의 농도를 증가시켰다. 더불어 활성산소기를 생성하는 NOX4의 mRNA 발현을 억제 하는 것으로 분석되었으며 염증 반응 지표인 TNF-의 mRNA 발현도 억제 하는 것으로 분석되었다. 따라서 으름의 열매 추출물은 알코올로 유발된 산화 스트레스, 염증 반응에 대한 간보호 효과 가능성을 나타내는 것으로 판단된다.

• 한국식품영양과학회지
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• 제44권1호
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• pp.7-13
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• 2015

본 연구에서는 아로니아 열매 추출물(AF-H)의 항염증 활성을 조사하기 위하여 LPS 자극에 의해 유도된 RAW 264.7 macrophage의 염증반응에서 AF-H의 염증매개인자 및 염증성 사이토카인 분비 억제활성과 이에 관련된 세포 내 작용기전 해석을 수행하였다. LPS($1{\mu}g/mL$)로 RAW 264.7 세포를 24시간 자극하는 염증모델에서 세포독성을 나타내지 않는 안전한 농도의 AF-H($0{\sim}500{\mu}g/mL$)를 LPS 처리 12시간 전에 처리하여 NO 및 PGE2의 분비 억제활성을 측정하였다. 그 결과 AF-H 처리에 의해 NO와 PGE2의 생성이 처리 농도에 의존하여 유의하게 억제되었으며, 이들 염증매개인자의 생합성 효소인 iNOS 및 COX-2의 세포 내 발현도 현저하게 억제되는 것으로 관찰되었다. 또한 AF-H의 처리에 의해 염증성 사이토카인인 $TNF-{\alpha}$와 IL-6의 분비도 유의하게 억제되는 것으로 확인하였다. 이러한 AF-H에 의한 항염증 활성의 세포 내 기전을 해석하기 위하여 LPS 자극에 의해 유도되는 MAPK와 $NF-{\kappa}B$ 전사인자의 활성화에 대한 억제 효과를 조사하였다. 그 결과 AF-H는 MAPK의 인산화에는 별다른 영향을 미치지 않고 $NF-{\kappa}B$의 활성화($I{\kappa}B$ 인산화)를 효과적으로 억제하는 것으로 확인되었다. 한편 LPS에 의한 in vivo 패혈증 모델에서 AF-H에 의한 패혈증 억제활성을 측정한 결과 비록 통계학적으로 유의하지는 않으나 AF-H 투여에 의해 생존율과 50% 사망률의 연장 효과가 관찰되었다. 이들 결과를 종합해 보면 아로니아 열매 열수추출물은 $NF-{\kappa}B$의 활성화 억제를 통해 NO, PGE2, $TNF-{\alpha}$ 및 IL-6 등의 염증매개인자와 사이토카인의 생성을 억제하는 항염증 활성을 지니는 것으로 확인되었다.

• 대한본초학회지
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• 제31권6호
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• pp.73-81
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• 2016

Objectives : $18{\beta}$-Glycyrrhetinic acid (18betaGA) is an metabolite of glycyrrhizin in Glycyrrhiza (licorice). The present study investigated anti-inflammatory and anti-apoptosis effect of 18betaGA on the brain tissue of lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : 18betaGA was administered orally with low (30 mg/kg) and high (100 mg/kg) doses for 3 days prior to LPS (3 mg/kg) injection. Pro-inflammatory cytokines mRNA including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, IL-6, and inflammatory enzyme cyclooxygenase-2 (COX-2) mRNA were measured in the cerebral cortex, hippocampus, and hypothalamus tissue using real-time polymerase chain reaction at 24 h after the LPS injection. Histological changes of Cornu ammonis area 1 (CA1) neurons, Bax, Bcl-2, and caspase-3 expression in the hippocampus was also evaluated by immunohistochemistry and Western blotting method. Results : 18betaGA significantly attenuated the up-regulation of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 mRNA, and COX-2 mRNA expression in the brain tissues induced by the LPS injection. 18betaGA also significantly attenuated the reductions of the thickness of CA1 and the number of CA1 neurons. The up-regulation of Bax protein expression in the hippocampal tissue by the LPS injection was significantly attenuated, while the ratio of Bcl-2/Bax expression was increased by 18betaGA treatment. 18betaGA also significantly attenuated the up-regulation of Bax and caspase-3 expression in the CA1 of the hippocampus. Conclusion : This results indicate that 18betaGA has anti-inflammatory and anti-apoptosis effect under neuroinflammation induced by the LPS injection and suggest that 18betaGA may be a beneficial drug for various brain diseases accompanied with the brain tissue inflammation.

• 한방재활의학과학회지
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• 제29권4호
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• pp.29-45
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• 2019

Objectives This study is to investigate anti-obesity effects of Banggihwanggi-tang-hap-yeonggyechulgam-tang (BY), an herbal formula, in high fat diet induced obese mice model. Methods Fourty five male C57Bl/6J mice were randomly assigned to normal group fed with normal research diet (Nor, n=9), high fat diet control group treated with water (Veh, n=9), high fat diet group treated with orlistat (Oris; n=9, Orlistat 40 mg/kg), high fat diet group treated with low concentraion BY (BYL; n=6, BY 0.87 g/kg) and high fat diet group treated with high concentration BY (BYH; n=6, BY 1.74 g/kg). Results Seven weeks later, antioxidative capacity, body weight, epididymal fat pad and liver weight, reactive oxygen species (ROS), peroxynitrite ($ONOO^-$), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol, triglyceride, high density lipoprotein (HDL), low density lipoprotein (LDL), superoxide dismutase (SOD), catalase, glutathione peroxidase (Gpx), heme oxygenase (HO)-1 and histology of liver were evaluated. In the BYH group, 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis (3 ethybenzothiazoline-6-sulfonic acid) radical scavenging activity were more than L-ascorbic acid. Body weight gain were significantly less than Veh group. Epididymal fat pad and liver weight gain were significantly less than Veh group. ROS and $ONOO^-$ were significantly less than with Veh group. ALT and AST were significantly less than with Veh group. Total cholesterol, triglyceride and LDL were significantly less, HDL were significantly more than Veh group. SOD, catalase, Gpx, HO-1 significantly increased compared with Veh group. Injury on liver was lesser than Veh group. Conclusions It can be suggested that BY has anti-obesity effects in high fat diet induced obese mice model.

• 한방안이비인후피부과학회지
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• 제25권2호
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• pp.61-67
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• 2012

Objective : The endpoint of this trial is to verify therapeutical availability of conventional western eyedrops combined with acupuncture treatment by means of BUT(tear film break-up time), Schirmer's test, which have been considered to be typical methods for diagnosing dry eye syndrome. Methods : The subjects of this trial included the outpatients who had been diagnosed with dry eye syndrome in Pusan national university hospital and underwent acupuncture treatment from March 2011 to April 2011. They received acupuncture treatment once a week, three times while constantly using Restasis or artificial tears. We collated and analyzed the outcome data of Schirmer's test and BUT conducted at the beginning of this trial and three times more after each acupuncture treatments. Acupoints, such as, Chanjuk(BL2), Eoryo, Sajukgong(TE23), Taeyang, Sabaek(ST2), limited around both eyes were selected based on their clinical effects referring to medical books. Results : 1. From BUT test results, Restasis and acupuncture combined group showed statistically significant difference, however, artificial tears and acupuncture combined group showed difference only between before and after the treatment, which is not statistically significant. 2. From Schirmer's test results, Restasis and acupuncture combined group showed statistically significant difference, however, artificial tears and acupuncture combined group showed difference only between before and after the treatment, which is not statistically significant. 3. The average duration of treatment was statistically 16.3 days for Restasis and acupuncture combined group. Conclusions : Combination of acupuncture and Restasis for dry eye syndrome can shorten the duration of treatment. Therefore, clinical benefit is expected to be worth.

• Journal of Ginseng Research
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• 제45권5호
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• pp.583-590
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• 2021

Background: Gintonin, isolated from ginseng, acts as a ginseng-derived lysophosphatidic acid (LPA) receptor ligand and elicits the [Ca²⁺]_i transient through six LPA receptor subtypes (LPARSs). However, the long-term effects of gintonin-enriched fraction (GEF) on the gene expression of six LPARSs remain unknown. We examined changes in the gene expression of six LPA receptors in the mouse whole brain, heart, lungs, liver, kidneys, spleen, small intestine, colon, and testis after long-term oral GEF administration. Methods: C57BL/6 mice were divided into two groups: control vehicle and GEF (100 mg/kg, p.o.). After 21-day saline or GEF treatment, total RNA was extracted from nine mouse organs. Quantitative-real-time PCR (qRT-PCR) and western blot were performed to quantify changes in the gene and protein expression of the six LPARSs, respectively. Results: qRT-PCR analysis before GEF treatment revealed that the LPA6 RS was predominant in all organs except the small intestine. The LPA2 RS was most abundant in the small intestine. Long-term GEF administration differentially regulated the six LPARSs. Upon GEF treatment, the LPA6 RS significantly increased in the liver, small intestine, colon, and testis but decreased in the whole brain, heart, lungs, and kidneys. Western blot analysis of the LPA6 RS confirmed the differential effects of GEF on LPA6 receptor protein levels in the whole brain, liver, small intestine, and testis. Conclusion: The LPA6 receptor was predominantly expressed in all nine organs examined; long-term oral GEF administration differentially regulated LPA3, LPA4, and LPA6 receptors in the whole brain, heart, lungs, liver, kidneys, small intestine, and testis.

• 한방재활의학과학회지
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• 제31권2호
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• pp.1-14
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• 2021

Objectives We evaluated the improving effects of Taeksa-tang (TST) using 3T3-L1 cells and C57BL/6 mice were fed on a high-fat diet. Methods The anti-radical activities of TST were studied using 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid). The content of total polyphenol was measured using Folin-Ciocalteu reagent, whereas aluminum chloride colorimetric method was used for the content of total flavonoid. Moreover, the factors related to lipid profile and the protein expressions such as 𝛽-oxidation and anti-oxidant enzyme were analyzed using serum and western blotting of 3T3-L1 cells. Additionally, we examined lipolysis through glycerol appearance in mouse adipose tissue. Results TST treatment showed strong free radical scavenging activities with half maximal inhibitory concentration and the presence of a amount of total polyphenol and total flavonoid. TST treatment significantly increased factors related to 𝛽-oxidation such as carnitine palmitoyl transferase-1 and uncoupling protein 2 via the phosphorlyation of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK). Moreover, the protein expressions of anti-oxidant enzyme and lipolysis were significantly elevated by TST administration. In addition, TST supplementation lowered serum malondialdehyde, triglyceride, and total cholesterol levels compared with the control group. Taken together, these data suggest that TST treatment regulated lipid parameters via the increase of 𝛽-oxidation by LKB1-AMPK signaling pathway. Conclusions TST may have a potential remedy in the prevention and treatment of obesity. Therefore, this study may provide the scientific basis for TST use.

• 한국해양바이오학회지
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• 제13권2호
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• pp.86-93
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• 2021

A high salt diet contributes to kidney damage by causing hypoxia and oxidative stress. Recently, an increase in dietary salt has been reported to induce an inflammatory phenotype in immune cells, further contributing to kidney damage. However, studies on the exact mechanism and role of a high salt diet on the inflammatory response in the kidneys are still insufficient. In this study, a cisplatin-induced acute kidney injury model using C57BL/6 mice was used to analyze the effect of salt intake on kidney injury. Results showed that high salt administration aggravated kidney edema in mice induced by treatment with cisplatin. Moreover, the indicators of kidney and liver function impairment were significantly increased in the group cotreated with high salt compared with that treated with cisplatin alone. Furthermore, the exacerbation of kidney damage by high salt administration was also associated with a decrease in the number of cells in the immune regulatory system. Additionally, high salt administration further decreased renal perfusion functions along with increased cisplatin-induced damage to proximal tubules. This was accompanied by increased expression of T cell immunoglobulin, mucin domain 1 (a biomarker of kidney injury), and Bax (a pro-apoptotic factor). Moreover, cisplatin-induced expression of proinflammatory mediators and cytokines, including cyclooxygenase-2 and tumor necrosis factor-α in kidney tissue, was further increased by high salt intake. Therefore, these results indicate that the kidney's inflammatory response by high salt treatment can further promote kidney damage caused by various pathological factors.