• Title/Summary/Keyword: MMP2

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Protective Effects of Hyperoside from Juglans sinensis Leaves against 1-methyl-4-phenylpyridinium-Induced Neurotoxicity (1-methyl-4-phenylpyridinium으로 유도된 신경 손상에 대한 호두나무잎에서 분리된 Hyperoside의 보호 효과)

  • Pariyar, Ramesh;Svay, Thida;Seo, Jungwon
    • Korean Journal of Pharmacognosy
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    • v.49 no.3
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    • pp.231-239
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    • 2018
  • Parkinson's disease (PD), one of common neurodegenerative diseases, is caused by the death of dopaminergic neurons in the substantia nigra pars compacta. The loss of dopaminergic neurons in PD is associated with oxidative stress and mitochondrial dysfunction. Hyperoside (quercetin 3-O-${\beta}$-D-galactopyranoside) was reported to have protective properties against oxidative stress by reducing intracellular reactive oxygen species (ROS) and increasing antioxidant enzyme activity. In this study, we examined the neuroprotective effect of hyperoside against 1-methyl-4-phenyl pyridinium ($MPP^+$)-induced cell model of PD and the underlying molecular mechanisms. Hyperoside significantly decreased $MPP^+$-induced cell death, accompanied by a reduction in poly ADP-ribose polymerase (PARP) cleavage. Furthermore, it attenuated $MPP^+$-induced intracellular ROS and disruption of mitochondrial membrane potential (MMP), with the reduction of Bax/Bcl-2 ratio. Moreover, hyperoside significantly increased the phosphorylation of Akt, but it has no effects on $GSK3{\beta}$ and MAPKs. Pharmacological inhibitor of PI3K/Akt abolished the cytoprotective effects of hyperoside against $MPP^+$. Taken together, these results demonstrate that hyperoside significantly attenuates $MPP^+$-induced neurotoxicity through PI3K/Akt signaling pathways in SH-SY5Y cells. Our findings suggest that hyperoside might be one of the potential candidates for the treatment of PD.

Effects of Ginsenoside-$Rg_1$ on Post-thawed Miniature Pig Sperm Motility, Mitochondria Activity, and Membrane Integrity

  • Hwang, You Jin;Kim, Dae Young
    • Journal of Embryo Transfer
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    • v.28 no.1
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    • pp.63-71
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    • 2013
  • In this study, we used flow a cytometric assay to evaluate plasma membrane integrity and mitochondrial activity in post-thawed sperm that was supplemented with ginsenoside-$Rg_1$. Varying concentrations of ginsenoside-$Rg_1$ (0, 25, 50 and $100{\mu}M/ml$) were used in the extender during cryopreservation to protect the DNA of thawed sperm, thereby increasing the viability and motility rate as evaluated using a computer-assisted sperm analysis (CASA) method. The results derived from CASA were used to compare the fresh, control, and ginsenoside-$Rg_1$ groups. Sperm motility and the number of progressively motile sperm were significantly (p<0.05) higher in the $50{\mu}M/ml$ ginsenoside-Rg1 group ($61.0{\pm}4.65%$) than in the control ($46.6{\pm}7.02%$), $25{\mu}M/ml$ ($46.2{\pm}4.76%$), and $100{\mu}M/ml$ ginsenoside-$Rg_1$ ($52.0{\pm}1.90%$) groups. However, the velocity distribution of post-thawed sperm did not differ significantly. Membrane integrity and MMP staining as revealed using flow cytometry were significantly (p<0.05) higher ($91.6{\pm}0.82%$) in the $50{\mu}M/ml$ ginsenoside-$Rg_1$ group than in the other groups. Here, we report that ginsenoside-$Rg_1$ affects the motility and viability of boar spermatozoa. Moreover, ginsenoside-$Rg_1$ can be used as a protective additive for the suppression of intracellular mitochondrial oxidative stress caused by cryopreservation.

Apoptosis and Autophagy Induction of A549 Human Lung Cancer Cells by Methylene Chloride Extracts of Morus alba L. (A549 인체폐암세포에서 상백피 메틸렌클로라이드 추출물에 의한 Apoptosis 및 Autophagy 유발)

  • Park, Shin-Hyoung;Chi, Gyoo-Yong;Choi, Yung-Hyun;Eom, Hyun-Sup
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.6
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    • pp.942-949
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    • 2010
  • Morus alba L., a kind of Oriental medicinal herbs, has been traditionally used to treat pulmonary asthma and congestion. According to recent studies, extracts of M. alba L. have showed anti-inflammatory, anti-oxidant, anti-tumor and hypoglycemic effects. However, the molecular mechanisms on how it acts as a death-inducer in cancer cells have not been fully understood. In this study, we investigated the cell death effects of methylene chloride extracts of M. alba L. (MEMA) in A549 human lung carcinoma cells. It was shown that MEMA induced the apoptotic cell death proved by increased sub-G1 phase cell population, apoptotic body formation and chromatin condensation. MEMA treatment induced the expression of death receptor-related proteins such as death receptor (DR) 4, DR5, Fas and FasL, which further triggered the activation of caspase-8 and the cleavage of Bid in a concentration-dependent manner. However, MEMA reduced anti-apoptotic Bcl-2 and Bcl-xL expression which contributed to the loss of mitochondrial membrane potential (MMP), and the activations of caspase-9 and caspase-3. Meanwhile, the morphological study indicated a characteristic finding of autophagy, such as the formation of autophagosomes in MEMA-treated cells. Furthermore, markers of autophagy, namely, the increased MDC-positive cells, conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II and increased beclin-1 accumulation, were observed. Taken together, these findings demonstrated that MEMA triggered both autophagy and apoptosis in A549 cancer cells. They might suggest that M. alba L. could be a prospective clinical application to treat human lung cancers.

Enhancement of Anti-wrinkle Activities of Abeliophyllum distichum Nakai through Low Temperature Extraction Process (미선나무의 저온 추출 공정에 의한 항주름 활성 증진)

  • Kim, Nam Young;Lee, Hyeon Yong
    • Korean Journal of Medicinal Crop Science
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    • v.23 no.3
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    • pp.231-236
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    • 2015
  • Skin anti-wrinkle activities of the stems and leaves of Abeliophyllum distichum Nakai were evaluated by the extracts obtained from various extraction processes such as using hot water at $100^{\circ}C$, 70% ethanol at $85^{\circ}C$, and 70% ethanol with ultrasonication at $60^{\circ}C$ The ultrasonicated extract showed 95.62% of the highest cell viability in addition of $0.3mg/m{\ell}$ of the extracts into the normal human fibroblast cell, CCD-986sk. For antioxidant activities, the extracts using ultrasonicated extract showed the highest DPPH free radical scavenging as 80.27%, followed by 75.88% and 62.44% for the extracts using ethanol extract and water extract. The ultrasonicated extract also showed the highest elastase inhibition activity as 25.32%, compared to ethanol extract and water extract based method at 22.01% and 12.88%, respectively. MMP-1 production was most effectively decreased down to $2908.1pg/m{\ell}$ with ultrasonicated extract while $6640.8pg/m{\ell}$ with water extract and $3609.3pg/m{\ell}$ with ethanol extract, in addition of $0.3mg/m{\ell}$. Collagen production was increased up to $154.7ng/m{\ell}$ in addition of ultrasonicated extract, and followed by $121.4ng/m{\ell}$ and $31.2ng/m{\ell}$ for ethanol extract and water extract, respectively. These results indicate that the ethanol extract should have skin anti-wrinkling activities and can be improved by the ultrasonication process that high energy input elute more amounts of bioactive substances eluting more amounts of bioactive substances from the high energy input of ultrasonication.

Anti-inflammatory Effects of Ponciri Fructus Extracts on Raw 264.7 Cells

  • Lee, Jin Wook;Jung, Hyuk-Sang;Sohn, Youngjoo;Kang, Yoon Joong
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.04a
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    • pp.91-91
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    • 2018
  • Poncirus Fructus (PF) is obtained by drying the trifoliate orange fruit belonging to the Rutaceae family. In our country of medicine, PF has been used as a treatment of indigestion, allergy and inflammation. But Mechanism and medical data for PF is insignificant. Recently, the effect of the study PF of biological activity was reported, such as anti- thrombosis, anti-bacteria, anti-virus, anti- allergic. We investigated that the effect of PF on anti-inflammatory in murine macrophage-like cell line Raw264.7 cells. Our results show that the expression level of Nitric Oxide (NO) and Matrix-metallopeptidase-9 (MMP-9) significantly decreased. Moreover, to determine the expression level of pro-inflammatory cytokines such as Tumor Necrosis Factor ($TNF-{\alpha}$) and Interleukin-6 (IL-6) and the phosphorylation pattern of signaling molecules of mitogen-activated protein kinase (MAPK) family, we performed ELISA and westren blot in Raw264.7 cells. In addition, nuclear factor-kappa B ($NF-{\kappa}B$) pathway was confirmed. PF extract inhibited the production of $TNF-{\alpha}$ and IL-6. The extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of $NF-{\kappa}B$ p65 in activated cells. Our results suggest that PF can be used as a potential therapeutic agent or functional food to relieve inflammation.

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The Clinical Study on Matrix Metalloprotease-l Gene Polymorphism in Korean Facial Nerve Palsy Patients (구안와사(口眼渦斜) 환자(患者)의 Matrix Metalloprotease-l (MMP-l)의 유전자(遺傳子) 다형성(多形性)에 대한 연구(硏究))

  • Choi, Sung-Hun;Lee, Kyung-Min;Lee, Bong-Hyo;Lim, Seong-Chul;Jung, Tae-Young;Seo, Jung-Chul
    • Journal of Acupuncture Research
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    • v.24 no.2
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    • pp.231-239
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    • 2007
  • Objectives : This study was designed to investigate the relation between the matrix metalloprotease-1 gene polymorphism and facial nerve palsy in Korean population. Methods : This study was carried out on 102 facial nerve palsy patients who were treated with oriental medicine therapy at the department of acupuncture & moxibustion, hospital of Oriental medical college, Daegu Hanny University and 104 healthy control subjects. Blood samples from all subjects were obtained for DNA extraction. We have investigated the genotyping of matrix metalloprotease-1 by using Pyrosequencing. Results : The genotypes of matrix metalloprotease-l gene were G/G homozygotes, A/G heterozygotes and A/A homozygotes. There was no significant difference between the control and facial nerve palsy groups. Conclusion: We concluded that there was no significant association between matrix metalloprotease-1 gene polymorphism and facial nerve palsy in Korean population. However, the findings of this study need to be confirmed in more patients and further studies.

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Study on Antitumor Activity of Hongsamdaibotang(HDT-C) (홍삼대보탕(紅蔘大補湯)의 항암활성(抗癌活性) 및 항전이(抗轉移) 효과(效果)에 관(關)한 연구(硏究))

  • Kim, Sung-Hoon;Choi, Byong-gyun;Kim, Dong-Hee
    • Journal of Haehwa Medicine
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    • v.9 no.1
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    • pp.143-153
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    • 2000
  • To evaluate the antitumor activity and antimetastatic effects of Hongsam -daibotang(HDT-C), studies were done experimentally. The results were obtained as follows: 1. In cytotoxicity against A549, SK-OV-3 and B16-BL6 concentration inhibi ting cell growth up to below 30% of control was recognized at $10^{-3}g/ml$ of HDT-C. 2. The T/C% was 145.4% in HDT-C treated group in S-180 bearing ICR mice. 3. In Inhibitory effect on activity of DNA topoisomerase I, the $IC_{50}$ was shown $100-200{\mu}g/ml$ of HDT-C. 4. The expressing $TNF-{\alpha}$ was increased in HDT-C treated group as compared with control. 5. The expressing MMP-9 was decreased in HDT-C treated group as compared with control. 6. HDT-C extracts exhibited efficient adhesive effect of A549, B16-BL6 cell to complex extracellular matrix. 7. In CAM assays, angiogenesis was significantly inhibited in HDT-C treated group than control group. 8. In pumonary colonization assay, a number of colonies in the lungs were decreased significantly in HDT-C treated group as compared with control group. 9. In hematological changes in B16-BL6 injected C57BL/6, numbers of WBC and were decreased insignificantly and also those of platelet were increased insignificantly in HDT-C treated group as compared with control. 10. In the histological changes of lung in B16-BL6 injected mice, infiltration of cancer cells were inhibited effectively in HDT-C treated groups whereas many cancer cells were infiltrated into erivascular and peribronchiol of control group. These results suggested that HDT-C extracts might be usefully applied for prevention and treatment of cancer.

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Methanolic Extract from Sea Cucumber, Holothuria scabra, Induces Apoptosis and Suppresses Metastasis of PC3 Prostate Cancer Cells Modulated by MAPK Signaling Pathway

  • Pranweerapaiboon, Kanta;Noonong, Kunwadee;Apisawetakan, Somjai;Sobhon, Prasert;Chaithirayanon, Kulathida
    • Journal of Microbiology and Biotechnology
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    • v.31 no.6
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    • pp.775-783
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    • 2021
  • Sea cucumber, Holothuria scabra, is a well-known traditional Asian medicine that has been used for suppressing inflammation, promoting wound healing, and improving immunity. Moreover, previous studies demonstrated that the extract from H. scabra contains many bioactive compounds with potent inhibitory effect on tumor cell survival and progression. However, the effect of the methanolic extract from the body wall of H. scabra (BWMT) on human prostate cancer cells has not yet been investigated. In this study, we aimed to investigate the effects and underlying mechanism of BWMT on prostate cancer cell viability and metastasis. BWMT was obtained by maceration with methanol. The effect of BWMT on cell viability was assessed by MTT and colony formation assays. The intracellular ROS accumulation was evaluated using a DCFH-DA fluorescence probe. Hoechst 33342 staining and Annexin V-FITC/PI staining were used to examine the apoptotic-inducing effect of the extract. A transwell migration assay was performed to determine the anti-metastasis effect. BWMT significantly reduced cell viability and triggered cellular apoptosis by accumulating intracellular ROS resulting in the upregulation of JNK and p38 signaling pathways. In addition, BWMT also inhibited the invasion of PC3 cells by downregulating MMP-2/-9 expression via the ERK pathway. Consequently, our study provides BWMT from H. scabra as a putative therapeutic agent that could be applicable against prostate cancer progression.

Marein Prevented LPS-Induced Osteoclastogenesis by Regulating the NF-κB Pathway In Vitro

  • Li, Yuling;Zhang, Jing;Yan, Caiping;Chen, Qian;Xiang, Chao;Zhang, Qingyan;Wang, Xingkuan;Jiang, Ke
    • Journal of Microbiology and Biotechnology
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    • v.32 no.2
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    • pp.141-148
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    • 2022
  • Many bone diseases such as osteolysis, osteomyelitis, and septic arthritis are caused by gram-negative bacterial infection, and lipopolysaccharide (LPS), a bacterial product, plays an essential role in this process. Drugs that inhibit LPS-induced osteoclastogenesis are urgently needed to prevent bone destruction in infective bone diseases. Marein, a major bioactive compound of Coreopsis tinctoria, possesses anti-oxidative, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic effects. In this study, we measured the effect of marein on RAW264.7 cells by CCK-8 assay and used TRAP staining to determine osteoclastogenesis. The levels of osteoclast-related genes and NF-κB-related proteins were then analyzed by western blot, and the levels of pro-inflammatory cytokines were quantified by ELISA. Our results showed that marein inhibited LPS-induced osteoclast formation by osteoclast precursor RAW264.7 cells. The effect of marein was related to its inhibitory function on expressions of pro-inflammatory cytokines and osteoclast-related genes containing RANK, TRAF6, MMP-9, CK, and CAII. Additionally, marein leads to markedly inhibited NF-κB signaling pathway activation in LPS-induced RAW264.7 cells. Concurrently, when the NF-κB signaling pathway was inhibited, osteoclast formation and pro-inflammatory cytokine expression were decreased. Collectively, marein could inhibit LPS-induced osteoclast formation in RAW264.7 cells via regulating the NF-κB signaling pathway. Our data demonstrate that marein might be a potential drug for bacteria-induced bone destruction disease. Our findings provide new insights into LPS-induced bone disease.

Deciphering the Core Metabolites of Fanconi Anemia by Using a Multi-Omics Composite Network

  • Xie, Xiaobin;Chen, Xiaowei
    • Journal of Microbiology and Biotechnology
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    • v.32 no.3
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    • pp.387-395
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    • 2022
  • Deciphering the metabolites of human diseases is an important objective of biomedical research. Here, we aimed to capture the core metabolites of Fanconi anemia (FA) using the bioinformatics method of a multi-omics composite network. Based on the assumption that metabolite levels can directly mirror the physiological state of the human body, we used a multi-omics composite network that integrates six types of interactions in humans (gene-gene, disease phenotype-phenotype, disease-related metabolite-metabolite, gene-phenotype, gene-metabolite, and metabolite-phenotype) to procure the core metabolites of FA. This method is applicable in predicting and prioritizing disease candidate metabolites and is effective in a network without known disease metabolites. In this report, we first singled out the differentially expressed genes upon different groups that were related with FA and then constructed the multi-omics composite network of FA by integrating the aforementioned six networks. Ultimately, we utilized random walk with restart (RWR) to screen the prioritized candidate metabolites of FA, and meanwhile the co-expression gene network of FA was also obtained. As a result, the top 5 metabolites of FA were tenormin (TN), guanosine 5'-triphosphate, guanosine 5'-diphosphate, triphosadenine (DCF) and adenosine 5'-diphosphate, all of which were reported to have a direct or indirect relationship with FA. Furthermore, the top 5 co-expressed genes were CASP3, BCL2, HSPD1, RAF1 and MMP9. By prioritizing the metabolites, the multi-omics composite network may provide us with additional indicators closely linked to FA.