• Title/Summary/Keyword: HT22 Cells

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Gintonin, a Panax ginseng-derived LPA receptor ligand, attenuates kainic acid-induced seizures and neuronal cell death in the hippocampus via anti-inflammatory and anti-oxidant activities

  • Jong Hee Choi;Tae Woo Kwon;Hyo Sung Jo;Yujeong Ha;Ik-Hyun Cho
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.390-399
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    • 2023
  • Background: Gintonin (GT), a Panax ginseng-derived lysophosphatidic acid receptor (LPAR) ligand, has positive effects in cultured or animal models for Parkinson's disease, Huntington's disease, and so on. However, the potential therapeutic value of GT in treating epilepsy has not yet been reported. Methods: Effects of GT on epileptic seizure (seizure) in kainic acid [KA, 55mg/kg, intraperitoneal (i.p.)]-induced model of mice, excitotoxic (hippocampal) cell death in KA [0.2 ㎍, intracerebroventricular (i.c.v.)]-induced model of mice, and levels of proinflammatory mediators in lipopolysaccharide (LPS)-induced BV2 cells were investigated. Results: An i.p. injection of KA into mice produced typical seizure. However, it was significantly alleviated by oral administration of GT in a dose-dependent manner. An i.c.v. injection of KA produced typical hippocampal cell death, whereas it was significantly ameliorated by administration of GT, which was related to reduced levels of neuroglial (microglia and astrocyte) activation and proinflammatory cytokines/enzymes expression as well as increased level of the Nrf2-antioxidant response via the upregulation of LPAR 1/3 in the hippocampus. However, these positive effects of GT were neutralized by an i.p. injection of Ki16425, an antagonist of LPA1-3. GT also reduced protein expression level of inducible nitric-oxide synthase, a representative proinflammatory enzyme, in LPS-induced BV2 cells. Treatment with conditioned medium clearly reduced cultured HT-22 cell death. Conclusion: Taken together, these results suggest that GT may suppress KA-induced seizures and excitotoxic events in the hippocampus through its anti-inflammatory and antioxidant activities by activating LPA signaling. Thus, GT has a therapeutic potential to treat epilepsy.

Protective effect of Codium fragile extract on fine dust (PM2.5)-induced toxicity in nasal cavity, lung, and brain cells (미세먼지(PM2.5)로 유도된 세포(비강, 폐, 뇌)독성에 대한 청각(Codium fragile)의 보호효과)

  • Kim, Gil Han;Park, Seon Kyeong;Kang, Jin Yong;Kim, Jong Min;Shin, Eun Jin;Moon, Jong Hyeon;Kim, Min Ji;Lee, Hyo Lim;Jeong, Hye Rin;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.53 no.2
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    • pp.223-229
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    • 2021
  • To evaluate the protective effect of Codium fragile on fine dust (PM2.5)-induced cytotoxicity, we investigated its antioxidant activity and cell protective effect on PM2.5-exposed cells. The 40% ethanolic extract of C. fragile showed the highest total phenolic content, whereas the water extract of C. fragile showed the highest total polysaccharide content. The protective effect of the extracts on PM2.5-induced oxidative damage in nasal cavity (RPMI2650), lung (A549), brain (MC-IXC), hippocampus (HT-22), and microglia (BV-2) cells was evaluated by measuring the intracellular reactive oxygen species (ROS) content and cell viability. The results showed that the 40% ethanolic extract more efficiently inhibited ROS production than the water extract. In contrast, PM2.5-exposed cells treated with the water extract showed higher viability than those treated with the 40% ethanolic extract.

Antitumor and Immunological Effects of Tuna Extract (참치 추출물의 항암 및 면역효과)

  • 황우익;백나경;황윤경;이성동
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.21 no.4
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    • pp.353-366
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    • 1992
  • This study was devised to purify the compound from tuna that have cytotoxic activities against various cancer cell lines and to observe its immunopotentiating activities. The cytotoxic compound was partially purified 277 fold, from petroleum ehter extract (crude extract) of tuna by silicic acid column chromatography (fraction D) and thin layer chromatography (Spot I). Cytotoxic activity was monitored using human colon cancer cell, HCT-48. The active compound (Spot I) was composed of seven materials which are fatty acids of four kinds ($C_{14:0},\;C_{16:0},\;C_{17:1},\;and\;C_{18:0}$) and unknown three fat materials. The active compound has cytotoxic activities against various cancer cell lines, that is, murine leukemic lymphocytes (L1210, P388) and human rectal (HRT-18) and colon cancer cells (HCT-48, HT-29). The patterns of size distribution of HCT-48 cells in the medium containing tuna extract were shifted to direction of the small size region. Also, the microscopic shape of HCT-48 cells were shrinked and distracted. The number of plaque forming cell and immunoglobin fraction of serum protein obtained from tuna-treated mice were increased, but natural killer cell activity was not affected.

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Protective effect of Eucommia ulmoides oliver leaves against PM2.5-induced oxidative stress in neuronal cells in vitro (미세먼지(PM2.5)로 유도된 산화적 스트레스에 대한 두충(Eucommia ulmoides Oliver) 잎의 in vitro 뇌 신경세포 보호 효과)

  • Kim, Min Ji;Kang, Jin Yong;Park, Seon Kyeong;Kim, Jong Min;Moon, Jong Hyun;Kim, Gil Han;Lee, Hyo Lim;Jeong, Hye Rin;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.53 no.4
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    • pp.423-433
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    • 2021
  • This study was performed to examine the neuroprotective effect of the ethyl acetate fraction from Eucommia ulmoides oliver leaf (EFEL) on PM2.5-induced cytotoxicity. EFEL had higher total phenolic and flavonoid contents than the other fractions. In ABTS and DPPH radical scavenging activities, the IC50 of EFEL was measured as 212.80 and 359.13 ㎍/mL, respectively. To investigate the neuroprotective effect of EFEL, MTT and DCF-DA assays were performed on HT22, MC-IXC, and BV-2 cells. EFEL effectively decreased PM2.5-induced intercellular reactive oxygen species (ROS) content and inhibited PM2.5-induced cell death. In the results of protein expression related to cellular cytotoxicity on microglial cells (BV-2), EFEL had an improvement effect on cell apoptosis and inflammatory pathways. Rutin and chlorogenic acid were identified as the main physiological compounds. Moreover, it was expected that EFEL, including rutin and chlorogenic acid, could be functional food substances with neuroprotective effects against PM2.5-induced oxidative stress.

Biological Activity of Oenothera Biennis Seed Extracts (달맞이꽃 종자 추출물의 생리활성)

  • Cho, Hyun-Dong;Kim, Du-Hyun;Kim, Min-Geun;Lee, Yong-Suk;Seo, Kwon-Il
    • Journal of Life Science
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    • v.28 no.9
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    • pp.1048-1055
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    • 2018
  • In the current study, comparisons of Oenothera Biennis seed extracts with water, ethanol, methanol, and 70% ethanol in their total polyphenolics contents, anti-oxidant, anti-neurotoxicity, anti-cancer, and immune-modulatory activities were investigated. Compared with other extracts, those concentrations of total phenolics and flavonoids were the highest in MeOH extract (31.90 mg GAE/g and 20.66 mg QE/g). The radical scavenging and reducing power activities were dose-dependently increased by treatment of O. Biennis seed water, EtOH, MeOH, and 70% EtOH extracts. Furthermore, pretreatment of water, EtOH, and MeOH extracts significantly reduced glutamate-induced cytotoxicity in HT22 hipocampal neuron cells. In the case of cancer cells, MeOH extracts showed lower $IC_{50}$ values in HepG2 ($74.21{\mu}g/ml$), A549 ($188.24{\mu}g/ml$), MCF-7 ($186.42{\mu}g/ml$), and B16 ($101.80{\mu}g/ml$) than other extracts, where those water ($101.96{\mu}g/ml$) and EtOH ($788.39{\mu}g/ml$) extracts showed the lowest $IC_{50}$ activity in HT-29 and PC-3 cells, respectively. O. Biennis seed extracts did not show any cytotoxicity in RAW 264.7 macrophages at the concentration of $1-10{\mu}g/ml$, whereas 70% EtOH extract dose-dependently enhanced nitric oxide (NO) production in RAW 264.7 cells. Overall, we evaluated that various bioactive potentials of O. Biennis seed extracts which would relate with phenolic compounds abundance, thus these can be useful to future developments as functional food ingredients and natural medicines.

A Screen for Dual-protection Molecules from a Natural Product Library against Neuronal Cell Death and Microglial Cell Activation (신경세포 사멸과 미세아교세포활성화 억제 동시 가능 천연물질 탐색 연구)

  • Min, Ju-Sik;Lee, Dong-Seok
    • Journal of Life Science
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    • v.25 no.6
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    • pp.656-662
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    • 2015
  • Natural products and natural product structures play a general and highly significant role in drug discovery and development process because it has various merits and potentials for new drug source that have extensive clinical experience, development time contraction, excellent stability and safety. In several neurological disorders, neuronal death and excessive activation of microglia (neuro-inflammation) are observed. A number of drug discovery-related neuronal cell death and neuro-inflammation was studied from natural products, respectively. However, until now, it has not been possible to study dual-protection molecules recorded in the Natural Product library. In the present study, using the natural product-derived library of the Institute for Korea Traditional Medical Industry, we investigated dual-protective molecules against glutamate (a classical excitatory neurotransmitter)-induced oxidative stress mediated neuronal cell death and LPS-induced excessive activated microglial cells (immune cells of the brain). Chrysophanol, extracted from Rheum palmatum, had dual-protective effects against both glutamate-induced neuronal cell death and LPS-induced NO production, triggering proinflammatory cytokines and microglia activation and resulting in neuroinflammation. Flow-cytometry analysis revealed that chrysophanol had a scavenger effect, scavenging glutamate- and LPS-induced reactive oxygen species (ROS) produced by neuronal and microglial cells, respectively. Based on the present study, chrysophanol may have an important protective role against neuronal cell death and neuroinflammation in the brain. The results may be helpful for studying drug development candidates for treating central nervous system disorders.

Cognitive Enhancing Activity of the Steamed and Fermented Extracts of Codonopsis lanceolata Radix (양유(洋乳)의 증숙 및 발효 추출물의 인지능 개선 활성)

  • Weon, Jin Bae;Yun, Bo-Ra;Lee, Jiwoo;Eom, Min Rye;Lee, Hyeon Yong;Park, Dong-Sik;Chung, Hee-Chul;Chung, Jae Youn;Ma, Choong Je
    • YAKHAK HOEJI
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    • v.57 no.5
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    • pp.323-329
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    • 2013
  • This study was designed to determine and compare the cognitive enhancing effect of various Codonopsis lanceolata extracts by steaming, fermentation and high hydrostatic pressure process. We prepared water extract of C. lanceolata, steamed C. lanceolata, steamed and fermented C. lanceolata and C.lanceolata by high hydrostatic pressure process and fermentation. Cognitive enhancing effect of extracts was evaluated in scopolamine-induced memory impairment mice using by passive avoidance test and Morris water maze tests. MTT assay was conducted to investigate neuroprotective effect on glutamate induced cell death in HT22 cells. Steamed and fermented C. lanceolata water extract decreased escape latency in Morris water maze test and increased the latency time of the passive avoidance test compared to other extracts. Furthermore, the steamed and fermented C. lanceolata water extract showed neuroprotective effect. These results suggest that steaming and fermentation process more improve cognitive enhancing effect of C. lanceolata than other process.

Expression of a Fusion Protein with Cry1Ac Protein and a Scorpion Insect Toxin in Acrystalliferous Bacillus thuringiensis Strain

  • Roh, Jong-Yul;Li, Ming-Shun;Chang, Jin-Hee;Park, Jae-Young;Shim, Hee-Jin;Shin, Sang-Chul;Boo, Kyung-Saeng;Je, Yeon-Ho
    • International Journal of Industrial Entomology and Biomaterials
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    • v.8 no.1
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    • pp.89-93
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    • 2004
  • Expression of a fusion protein between B. thuringiensis crystal protein, Cry1Ac1 and a scorpion insect toxin (AaIT, Androctonus australis Hector insect toxin) in acrystalliferous B. thuringiensis strain (Cry-B strain) was examined. The cry 1Ac1 gene was cloned in B. thuringiensis-E coli shuttle vector, pHT3101, under the control of the native cry 1Ac1 gene promoter (pProAc) and a gene encoding AaIT was inserted in XhoI site in the middle of the cry 1Ac1 gene (pProAc-ScoR). B. thuringiensis Cry-B strain carrying pProAc-ScoR (PyoAc-ScoR/CB) produced an inclusion body of irregular shape and the expressed fusion protein is approximately 65 kDa in size. Sporulated cells and spore-crystal mixtures of ProAc-ScoR/CB had insecticidal activity against Plutella xylostella larvae, showing $LT_50$ of ProAc-ScoR/CB (22.59 hrs) lower than that of ProAc/CB (30.06 hrs) at $1{\times}{10^7} {CEU/cm^2}$. These results suggest that the fusion protein including a B. thuringiensis crystal protein and an AaIT may be functionally expressed in B. thupingiensis. Moreover, we verified the additive toxicity of AaIT, which is a new feasible candidate for insect control.

Effect of Steamed Codonopsis lanceolata on Spatial Learning and Memory in Mice (증숙 더덕 추출물의 인지능력 개선 효과)

  • Weon, Jin Bae;Yun, Bo-Ra;Lee, Jiwoo;Eom, Min Rye;Ko, Hyun-Jeong;Lee, Hyeon Yong;Park, Dong-Sik;Chung, Hee-Chul;Chung, Jae Youn;Ma, Choong Je
    • Korean Journal of Pharmacognosy
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    • v.45 no.1
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    • pp.48-54
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    • 2014
  • Alzheimer's disease is progressive neurodegenerative disorder by the loss of memory and learning abilities. Codonopsis lanceolata (C. lanceolata) is traditional medicinal plant used for the treatment of inflammatory diseases. The aim of study was to evaluate the effect of steamed C. lanceolata on scopolamine-induced memory impairment in the Morris water maze test and passive avoidance test. In addition, this study investigated the neuroprotective effects of steamed C. lanceolata on glutamate-induced cell death in HT22 cells using MTT assay. The results showed that steamed C. lanceolata (500 mg/kg body weight, p.o.) reversed spatial memory impairment by scopolamine in Morris water maze test and passive avoidance test. Steamed C. lanceolata attenuated memory impairment by scopolamine compared with common C. lanceolata. In addition, administration of steamed C. lanceolata significantly also reduced cell death. We suggest that steaming process more improve cognitive enhancing and neuroprotective effect of C. lanceolata than common C. lanceolata.

Oral administration of hydrolyzed red ginseng extract improves learning and memory capability of scopolamine-treated C57BL/6J mice via upregulation of Nrf2-mediated antioxidant mechanism

  • Ju, Sunghee;Seo, Ji Yeon;Lee, Seung Kwon;Oh, Jisun;Kim, Jong-Sang
    • Journal of Ginseng Research
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    • v.45 no.1
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    • pp.108-118
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    • 2021
  • Background: Korean ginseng (Panax ginseng Meyer) contains a variety of ginsenosides that can be metabolized to a biologically active substance, compound K. Previous research showed that compound K could be enriched in the red ginseng extract (RGE) after hydrolysis by pectinase. The current study investigated whether the enzymatically hydrolyzed red ginseng extract (HRGE) containing a notable level of compound K has cognitive improving and neuroprotective effects. Methods: A scopolamine-induced hypomnesic mouse model was subjected to behavioral tasks, such as the Y-maze, passive avoidance, and the Morris water maze tests. After sacrificing the mice, the brains were collected, histologically examined (hematoxylin and eosin staining), and the expressions of antioxidant proteins analyzed by western blot. Results: Behavioral assessment indicated that the oral administration of HRGE at a dosage of 300 mg/kg body weight reversed scopolamine-induced learning and memory deficits. Histological examination demonstrated that the hippocampal damage observed in scopolamine-treated mouse brains was reduced by HRGE administration. In addition, HRGE administration increased the expression of nuclear-factor-E2-related factor 2 and its downstream antioxidant enzymes NAD(P)H:quinone oxidoreductase and heme oxygenase-1 in hippocampal tissue homogenates. An in vitro assay using HT22 mouse hippocampal neuronal cells demonstrated that HRGE treatment attenuated glutamate-induced cytotoxicity by decreasing the intracellular levels of reactive oxygen species. Conclusion: These findings suggest that HRGE administration can effectively alleviate hippocampus-mediated cognitive impairment, possibly through cytoprotective mechanisms, preventing oxidative-stress-induced neuronal cell death via the upregulation of phase 2 antioxidant molecules.