• Title/Summary/Keyword: therapeutic potential

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Activity-guided Screening of Anti-inflammatory Compounds from the Hexane Extracts of Schisandra chinensis Fruit (생리활성분획 추적방법을 통한 오미자 추출물의 항염증 활성 분석)

  • Choi, Hee Jung;Choi, Young-Whan;Baek, Sun-Yong;Kim, Bong-Seon;Ahn, Soon Cheol;Rhee, Moon-Soo;Yoon, Sik
    • Journal of Life Science
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    • v.23 no.2
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    • pp.311-318
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    • 2013
  • Schisandra chinensis containing a variety of pharmacologically active lignans has been traditionally used in oriental medicine. In this study, anti-inflammatory compounds were screened from the hexane extracts of S. chinensis by activity-guided fractionation. First, we investigated the regulatory effects on the expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) with 38 fractions from the hexane extracts of S. chinensis in human umbilical vein endothelial cells (HUVECs). As a result, SCKH1 among the 38 fractions from the hexane extract of S. chinensis was selected for further analysis based on its unique regulatory effect on cell adhesion molecules, especially on VCAM-1, in LPS-stimulated HUVECs. The subsequent activity-guided fractionation of SCKH1 resulted in the purification of SCKH1PAIBPB, which was found to suppress the expression of VCAM-1, MCP-1, IL-6 and IL-8 in HUVECs stimulated with LPS, and to inhibit the adhesive capacity between HUVECs and monocytes. Taken together, our data indicate that SCKH1PAIBPB can be proposed as an effective anti-inflammatory compound that may have a potential therapeutic use for the prevention and treatment of various inflammatory diseases as well as ischemic vascular diseases.

Tat-Fused Recombinant Human SAG Prevents Dopaminergic Neurodegeneration in a MPTP-Induced Parkinson's Disease Model

  • Sohn, Eun Jeong;Shin, Min Jea;Kim, Dae Won;Ahn, Eun Hee;Jo, Hyo Sang;Kim, Duk-Soo;Cho, Sung-Woo;Han, Kyu Hyung;Park, Jinseu;Eum, Won Sik;Hwang, Hyun Sook;Choi, Soo Young
    • Molecules and Cells
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    • v.37 no.3
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    • pp.226-233
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    • 2014
  • Excessive reactive oxygen species (ROS) generated from abnormal cellular process lead to various human diseases such as inflammation, ischemia, and Parkinson's disease (PD). Sensitive to apoptosis gene (SAG), a RING-FINGER protein, has anti-apoptotic activity and anti-oxidant activity. In this study, we investigate whether Tat-SAG, fused with a Tat domain, could protect SH-SY5Y neuroblastoma cells against 1-methyl-4-phenylpyridinium ($MPP^+$) and dopaminergic (DA) neurons in the substantia nigra (SN) against 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) toxicity. Western blot and immunohistochemical analysis showed that, unlike SAG, Tat-SAG transduced efficiently into SH-SY5Y cells and into the brain, respectively. Tat-SAG remarkably suppressed ROS generation, DNA damage, and the progression of apoptosis, caused by $MPP^+$ in SH-SY5Y cells. Also, immunohistochemical data using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that Tat-SAG obviously protected DA neurons in the SN against MPTP toxicity in a PD mouse model. Tat-SAG-treated mice showed significant enhanced motor activities, compared to SAG- or Tat-treated mice. Therefore, our results suggest that Tat-SAG has potential as a therapeutic agent against ROS-related diseases such as PD.

Therapeutic Benefits of Mesenchymal Stromal Cells in a Rat Model of Hemoglobin-Induced Hypertensive Intracerebral Hemorrhage

  • Ding, Rui;Lin, Chunnan;Wei, ShanShan;Zhang, Naichong;Tang, Liangang;Lin, Yumao;Chen, Zhijun;Xie, Teng;Chen, XiaoWei;Feng, Yu;Wu, LiHua
    • Molecules and Cells
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    • v.40 no.2
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    • pp.133-142
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    • 2017
  • Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-$1{\beta}$ and TNF-${\alpha}$). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.

Protective Effects of Akebia quinata Fruit Extract on Acute Alcohol-induced Hepatotoxicity in Mice (급성 알코올 간독성을 유발한 생쥐에 있어서 으름 열매 추출물의 간 기능 보호효과)

  • Lee, Sang Hoon;Song, Young Sun;Lee, Seo Yeon;Kim, So Young;Ko, Kwang Suk
    • Korean Journal of Food Science and Technology
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    • v.46 no.5
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    • pp.622-629
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    • 2014
  • We studied the effects of Akebia quinata fruit extract (AQ) on acute alcohol-induced hepatotoxicity in mice. AQ (30-1,000 mg/kg body weight (BW) per day) was orally administered to the study group, once daily for 1 week. On the last day of AQ treatment, ethanol (6 mg/kg BW) was orally administered to induce acute liver injury. The AQ-treated group showed significantly lower levels of alanine aminotransferase and aspartate aminotransferase, compared to the only ethanol-treated group (ETG). The glutathione level in the AQ-treated group elevated up to 20.6%, compared to that observed in the ETG. The mRNA expression of glutathione synthetic enzymes was also higher in the AQ-treated group, compared to the ETG. The AQ-treated group also exhibited lower levels of expression of NADPH oxidase 4 and tumor necrosis factor alpha mRNA. Thus, these results show that AQ treatment can be a potential method to reduce oxidative stress and inflammation in ethanol-treated mouse liver and also that AQ can be a useful therapeutic agent for acute alcohol-induced hepatotoxicity.

Biological Function of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6 for the Enhancement of Adipose-Derived Stem Cell Survival against Oxidative Stress (지방유래 줄기세포의 생존능 향상을 위한 CEACAM 6의 생물학적 기능에 대한 연구)

  • Koh, Eun-Young;You, Ji-Eun;Jung, Se-Hwa;Kim, Pyung-Hwan
    • Korean Journal of Clinical Laboratory Science
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    • v.51 no.4
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    • pp.475-483
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    • 2019
  • The use of stem cells in cell-based therapy has attracted extensive interest in the field of regenerative medicine, and it has been applied to numerous incurable diseases due to the inherent abilities of self-renewal and differentiation. However, there still exist some severe obstacles, such as requirement of cell expansion before the treatment, and low survival at the treated site. To overcome these disadvantages of stem cells, we used the carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM 6) gene, which functions to increase cell-cell interaction as well as anti-apoptosis. We first confirmed whether CEACAM 6 is expressed in various cell lines at the protein level (including in stem cells), followed by evaluating and selecting the optimal transfection conditions into stem cells. The CEACAM 6 gene was transfected into stem cells to prolong cell survival and preserve from damage by oxidative stress. After confirming the CEACAM 6 expression in transfected stem cells, the cell survival was assessed under oxidative condition by exposing to hydrogen peroxide (H2O2) to mimic the chronic environment-induced cellular damage. CEACAM 6 expressing stem cells show increased cell viability compared to the non-CEACAM 6 expressing cells. We propose that the application of the CEACAM 6 gene is a potential option, capable of expanding and enhancing the therapeutic effects of stem cells.

Gender-independent efficacy of mesenchymal stem cell therapy in sex hormone-deficient bone loss via immunosuppression and resident stem cell recovery

  • Sui, Bing-Dong;Chen, Ji;Zhang, Xin-Yi;He, Tao;Zhao, Pan;Zheng, Chen-Xi;Li, Meng;Hu, Cheng-Hu;Jin, Yan
    • Experimental and Molecular Medicine
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    • v.50 no.12
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    • pp.12.1-12.14
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    • 2018
  • Osteoporosis develops with high prevalence in both postmenopausal women and hypogonadal men. Osteoporosis results in significant morbidity, but no cure has been established. Mesenchymal stem cells (MSCs) critically contribute to bone homeostasis and possess potent immunomodulatory/anti-inflammatory capability. Here, we investigated the therapeutic efficacy of using an infusion of MSCs to treat sex hormone-deficient bone loss and its underlying mechanisms. In particular, we compared the impacts of MSC cytotherapy in the two genders with the aim of examining potential gender differences. Using the gonadectomy (GNX) model, we confirmed that the osteoporotic phenotypes were substantially consistent between female and male mice. Importantly, systemic MSC transplantation (MSCT) not only rescued trabecular bone loss in GNX mice but also restored cortical bone mass and bone quality. Unexpectedly, no differences were detected between the genders. Furthermore, MSCT demonstrated an equal efficiency in rectifying the bone remodeling balance in both genders of GNX animals, as proven by the comparable recovery of bone formation and parallel normalization of bone resorption. Mechanistically, using green fluorescent protein (GFP)-based cell-tracing, we demonstrated rapid engraftment but poor inhabitation of donor MSCs in the GNX recipient bone marrow of each gender. Alternatively, MSCT uniformly reduced the $CD3^+T$-cell population and suppressed the serum levels of inflammatory cytokines in reversing female and male GNX osteoporosis, which was attributed to the ability of the MSC to induce T-cell apoptosis. Immunosuppression in the microenvironment eventually led to functional recovery of endogenous MSCs, which resulted in restored osteogenesis and normalized behavior to modulate osteoclastogenesis. Collectively, these data revealed recipient sexually monomorphic responses to MSC therapy in gonadal steroid deficiency-induced osteoporosis via immunosuppression/anti-inflammation and resident stem cell recovery.

Anti-Cancer Activity of the Leave Extracts of Rodgersia podophylla through β-catenin Proteasomal Degradation in Human Cancer Cells (도깨비부채(Rodgersia podophylla) 잎 추출물의 인간 암세포의 β-catenin 분해 유도 활성)

  • Kim, Ha Na;Kim, Jeong Dong;Son, Ho-Jun;Park, Gwang Hun;Eo, Hyun Ji;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.32 no.5
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    • pp.442-447
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    • 2019
  • In this study, we evaluated the effect of Rodgersia podophylla leave extracts (RPL) on ${\beta}-catenin$ level in human cancer cells. RPL dose-dependently inhibited cell proliferation in SW480, A549, MDA-MB-231, PC-3 and AsPC-1 cells. RPL dramatically decreased ${\beta}-catenin$ protein level in all cancer cells. However, decreased level of ${\beta}-catenin$ mRNA expression was observed in A549 and AsPC-1 cells. In addition, RPL dramatically attenuated cyclin D1 mRNA expression in all cancer cells. MG132 decreased the downregulation of ${\beta}-catenin$ protein level induced by RPL in all cancer cells, while RPL-induced downregulation of ${\beta}-catenin$ was inhibited by the inhibition of $GSK-3{\beta}$ by LiCl in MDA-MB-231 cells. RPL phosphorylated ${\beta}-catenin$ and $GSK-3{\beta}$. In addition, the inhibition of $GSK-3{\beta}$ by LiCl attenuated RPL-induced ${\beta}-catenin$ phosphorylation. Based on these findings, RPL may be a potential candidate for the development of chemopreventive or therapeutic agents for human cancer.

Protective Effects of Helianthus annuus Seed Extract against Chemical-Induced Neuronal Cell Death (해바라기씨 추출물의 뇌세포에 대한 사멸 보호 효과)

  • Park, Ja-Young;Woo, Sang-Uk;Heo, Jin-Chul;Lee, Sang-Han
    • Food Science and Preservation
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    • v.14 no.2
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    • pp.213-219
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    • 2007
  • To develop an anti-dementia agent with potential therapeutic value in the protection of neuronal cells, we selected a water extract of Helianthus annuus seed for analysis. We measured acetylcholinesterase inhibitory activity in the extract, and analyzed the protective effect of the extract on neuronal cell death induced by hydrogen peroxide, or amyloid ${\beta}-peptide$, of SH-SY5Y neuroblastoma cells. The result showed that the extinct exerted protective effects of 83%, 72% and 53% respectively, on cell death induced by 100M, 200M, and 500M hydrogen peroxide. Also, when 50M of amyloid ${\beta}-peptide$ was added to the cells, the extract showed a protective effect (up to 80%) on cell death. Overall, the results showed that the H. annuus extract inhibited acetylcholinesterase activity in a dose-dependent manner, and the extract also strongly protected against cell death induced by hydrogen peroxide or amyloid ${\beta}-peptide$.

Pancreatic Lipase Inhibitory and Antioxidant Activities of Zingiber officinale Extracts (생강 추출물의 pancreatic lipase 저해 및 항산화 활성)

  • Bae, Jong-Sup;Kim, Tae-Hoon
    • Food Science and Preservation
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    • v.18 no.3
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    • pp.390-396
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    • 2011
  • Ginger (Zingiber officinale) is a well-known herb that is widely consumed as spice for the flavoring of foods. As part of our continuing search for bioactive materials, the in vitro pancreatic lipase inhibition and antioxidant properties of an aqueous ethanolic extract of Z. officinale were investigated. The total phenolic content was determined using a spectrophotometric method. The antioxidant efficacies of the extract was studied with radical scavenging assays using DPPH and $ABTS^+$ radicals. Further more, the antiobesity effect of the extract was evaluated by porcine pancreatic lipase assay. In particularly, the pancreatic lipase inhibitory activity of the ethyl acetate (EtOAc)-soluble portion from Z. officinale was significantly higher than that of the other solvent-soluble portions. The results suggest that Z. officinale may have therapeutic potential that may be useful in development of an anti-obesity agent or its precursors.

Antimicrobial Activity Screening of Sixty-four Evergreen Woody Species According to Extraction Conditions against Trichophyton mentagrophytes (상록성 목본 64종의 추출조건에 따른 무좀원인균의 항균활성 스크리닝)

  • Jang, Bo Kook;Chi, Lai Won;Cho, Ju Sung;Lee, Cheol Hee
    • Korean Journal of Plant Resources
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    • v.31 no.4
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    • pp.330-341
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    • 2018
  • This study was performed to investigate and measure the antimicrobial activity of evergreen woody species extracts on Trichophyton mentagrophytes. To do this, leaves and stems were collected from Wando and Jeju islands, and were used for the extraction with different solvents (i.e., distilled water, 80% ethanol, and 100% methanol), and at different ultrasonic extracting times (i.e., 15, 30, and 45 minutes). The experiment was conducted by using the agar diffusion method. The clear zone was measured after incubating the paper disc containing the plant extract in a bacterial culture medium. The controls were synthetic antimicrobials, methylparaben and phenoxyethanol, at concentrations of 0.4, 1, 2, and 4 mg/disc. Altogether, extracts of 56 out of 64 species used in this study had inhibitory activity, which confirmed their antimicrobial activity against Athlete's foot. Among them, the crude ethanolic extract of Elaeocarpus sylvestris in 45 min showed a zone of inhibition < 20.2 mm, while the clear zone of Actinodaphne lancifolia ethanolic extraction for 30 min was 23.5 mm. Also, Quercus acuta, Dendropanax morbiferus and Daphne odora showed clear zones of 28.0 mm (45 minutes ethanolic extraction), 20.5 mm (45 minutes crude methanolic extraction) and 19.7 mm (45 minutes methanolic extraction), respectively. Thus, these results confirm that the extracts of evergreen woody species have therapeutic potential against Athlete's foot, and suggest that in order to extract adequate amounts of antimicrobial substance from the plant sources, ideal extraction condition has to be considered.