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Article: Ginsenoside Rc, an Active Component of

Kim, Aeyung / Park, Sang-Min / Kim, No Soo / Lee, Haeseung

2023 Volume 12, Issue 8

Abstract: Loss of skeletal muscle mass and function has detrimental effects on quality of life, morbidity, and mortality, and is particularly relevant in aging societies. The enhancement of mitochondrial function has shown promise in promoting muscle ... ...

Abstract	Loss of skeletal muscle mass and function has detrimental effects on quality of life, morbidity, and mortality, and is particularly relevant in aging societies. The enhancement of mitochondrial function has shown promise in promoting muscle differentiation and function. Ginsenoside Rc (gRc), a major component of ginseng, has various pharmacological activities; however, its effect on muscle loss remains poorly explored. In this study, we examined the effects of gRc on the hydrogen peroxide (H
Language	English
Publishing date	2023-08-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12081576
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Isoliquiritin Apioside Suppresses

Kim, Aeyung / Ma, Jin Yeul

Frontiers in pharmacology

2018 Volume 9, Page(s) 1455

Abstract: Several components isolated ... ...

Abstract	Several components isolated from
Language	English
Publishing date	2018-12-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2018.01455
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Article ; Online: Caffeic acid selectively eliminates teratogenic human-induced pluripotent stem cells via apoptotic cell death.

Kim, Aeyung / Lee, Seo-Young / Chung, Sun-Ku

Phytomedicine : international journal of phytotherapy and phytopharmacology

2022 Volume 102, Page(s) 154144

Abstract: Background: Induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells are considered as a promising cell source in cell-based regenerative medicine. To avoid teratoma formation, which is a safety issue in iPSC-based cell ... ...

Abstract	Background: Induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells are considered as a promising cell source in cell-based regenerative medicine. To avoid teratoma formation, which is a safety issue in iPSC-based cell therapy, it is important to selectively remove undifferentiated iPSCs that remain in the differentiated cell product before in vivo transplantation. Caffeic acid (CAA, 3,4-dihydroxy-cinnamic acid) is a phenolic compound synthesized from various vegetables, fruits, and herbs; it has shown various pharmacological activities against inflammation, cancer, infection, diabetes, and neurodegenerative diseases. However, the beneficial effects of CAA in iPSC-based cell therapy, such as the selective elimination of iPSCs and anti-teratoma effects, have not yet been explored. Results: Here, we found that CAA induced apoptotic cell death in iPSCs; this process did not occur in iPSC-derived mesenchymal progenitor cells (MPCs) or human dermal fibroblast (hDFs). Under co-culture conditions with MPCs and hDFs, CAA treatment selectively removed iPSCs. In addition, CAA treatment in mixed cell culture with iPSCs and MPCs prior to grafting markedly suppressed iPSC-derived teratoma formation. Finally, CAA did not induce DNA damage in MPCs or hDFs. Conclusion: Taken together, these results suggest that CAA is effective in preparing safe iPSC-based therapeutic cells without the risk of teratoma formation and DNA damage in normal cells and iPSC-derived differentiated cells.
MeSH term(s)	Adult ; Apoptosis ; Caffeic Acids ; Cell Differentiation ; Humans ; Induced Pluripotent Stem Cells ; Teratogens/metabolism ; Teratogens/pharmacology ; Teratoma/drug therapy
Chemical Substances	Caffeic Acids ; Teratogens ; caffeic acid (U2S3A33KVM)
Language	English
Publishing date	2022-05-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2022.154144
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Article: Caffeic acid selectively eliminates teratogenic human-induced pluripotent stem cells via apoptotic cell death

Kim, Aeyung / Lee, Seo-Young / Chung, Sun-Ku

Phytomedicine. 2022 July 20, v. 102

2022

Abstract: Induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells are considered as a promising cell source in cell-based regenerative medicine. To avoid teratoma formation, which is a safety issue in iPSC-based cell therapy, it is ... ...

Abstract	Induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells are considered as a promising cell source in cell-based regenerative medicine. To avoid teratoma formation, which is a safety issue in iPSC-based cell therapy, it is important to selectively remove undifferentiated iPSCs that remain in the differentiated cell product before in vivo transplantation. Caffeic acid (CAA, 3,4-dihydroxy-cinnamic acid) is a phenolic compound synthesized from various vegetables, fruits, and herbs; it has shown various pharmacological activities against inflammation, cancer, infection, diabetes, and neurodegenerative diseases. However, the beneficial effects of CAA in iPSC-based cell therapy, such as the selective elimination of iPSCs and anti-teratoma effects, have not yet been explored. Here, we found that CAA induced apoptotic cell death in iPSCs; this process did not occur in iPSC-derived mesenchymal progenitor cells (MPCs) or human dermal fibroblast (hDFs). Under co-culture conditions with MPCs and hDFs, CAA treatment selectively removed iPSCs. In addition, CAA treatment in mixed cell culture with iPSCs and MPCs prior to grafting markedly suppressed iPSC-derived teratoma formation. Finally, CAA did not induce DNA damage in MPCs or hDFs. Taken together, these results suggest that CAA is effective in preparing safe iPSC-based therapeutic cells without the risk of teratoma formation and DNA damage in normal cells and iPSC-derived differentiated cells.
Keywords	DNA damage ; adults ; apoptosis ; caffeic acid ; coculture ; diabetes ; fibroblasts ; humans ; inflammation ; medicine ; risk ; teratogenicity ; therapeutics
Language	English
Dates of publication	2022-0720
Publishing place	Elsevier GmbH
Document type	Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2022.154144
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Ginsenoside Rc, an Active Component of Panax ginseng, Alleviates Oxidative Stress-Induced Muscle Atrophy via Improvement of Mitochondrial Biogenesis

Kim, Aeyung / Park, Sang-Min / Kim, No Soo / Lee, Haeseung

Antioxidants. 2023 Aug. 07, v. 12, no. 8

2023

Abstract	Loss of skeletal muscle mass and function has detrimental effects on quality of life, morbidity, and mortality, and is particularly relevant in aging societies. The enhancement of mitochondrial function has shown promise in promoting muscle differentiation and function. Ginsenoside Rc (gRc), a major component of ginseng, has various pharmacological activities; however, its effect on muscle loss remains poorly explored. In this study, we examined the effects of gRc on the hydrogen peroxide (H₂O₂)-induced reduction of cell viability in C2C12 myoblasts and myotubes and H₂O₂-induced myotube degradation. In addition, we investigated the effects of gRc on the production of intracellular reactive oxygen species (ROS) and mitochondrial superoxide, ATP generation, and peroxisome proliferator-activated receptor-gamma co-activator 1α (PGC-1α) activity in myoblasts and myotubes under H₂O₂ treatment. Furthermore, to elucidate the mechanism of action of gRc, we conducted a transcriptome analysis of myotubes treated with or without gRc under H₂O₂ treatment. gRc effectively suppressed H₂O₂-induced cytotoxicity, intracellular ROS, and mitochondrial superoxide production, restored PGC-1α promoter activity, and increased ATP synthesis. Moreover, gRc significantly affected the expression levels of genes involved in maintaining mitochondrial mass and biogenesis, while downregulating genes associated with muscle degradation in C2C12 myotubes under oxidative stress. We provide compelling evidence supporting the potential of gRc as a promising treatment for muscle loss and weakness. Further investigations of the pharmacological effects of gRc under various pathological conditions of muscle loss will contribute to the clinical development of gRc as a therapeutic intervention.
Keywords	Panax ginseng ; biogenesis ; cell viability ; cytotoxicity ; ginsenosides ; hydrogen peroxide ; mechanism of action ; mitochondria ; morbidity ; mortality ; muscles ; muscular atrophy ; myoblasts ; myotubes ; oxidative stress ; peroxisome proliferator-activated receptor gamma ; quality of life ; skeletal muscle ; therapeutics ; transcriptomics
Language	English
Dates of publication	2023-0807
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12081576
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: An Ethanol Extract of

Kim, Aeyung / Baek, Su-Jin / Shin, Sarah / Lee, Seo-Young / Chung, Sun-Ku

Nutrients

2023 Volume 15, Issue 10

Abstract: In cell-based regenerative medicine, induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells have emerged as a useful cell source due to the lack of ethical concerns and the low risk of immune rejection. To address the risk ...

Abstract	In cell-based regenerative medicine, induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells have emerged as a useful cell source due to the lack of ethical concerns and the low risk of immune rejection. To address the risk of teratoma formation, which is a safety issue in iPSC-based cell therapy, it is essential to selectively remove undifferentiated iPSCs remaining in the iPSC-derived differentiated cell product prior to in vivo transplantation. In this study, we explored whether an ethanol extract of coptidis rhizoma (ECR) exhibited anti-teratoma activity and identified the active components involved in the selective elimination of undifferentiated iPSCs. Transcriptome analysis of iPSCs confirmed that cell death-related pathways were significantly altered by ECR treatment. Our results demonstrate that ECR effectively induced apoptotic cell death and DNA damage in iPSCs, and that reactive oxygen species generation, mitochondrial damage, caspase activation, and p53 activation were involved in ECR-mediated iPSC death. However, in iPSC-derived differentiated cells (iPSC-Diff), reduced cell viability and the DNA damage response were not observed after ECR treatment. We co-cultured iPSCs and iPSC-Diff and found that ECR treatment selectively removed iPSCs, whereas iPSC-Diff remained intact. Prior to in ovo implantation, ECR treatment of a mixed cell culture of iPSCs and iPSC-Diff significantly suppressed iPSC-derived teratoma formation. Among the main components of the ECR, berberine and coptisine showed selective cytotoxicity to iPSCs but not to iPSC-Diff. Together, these results indicate the usefulness of ECRs in preparing safe and effective iPSC-based therapeutic cell products with no risk of teratoma formation.
MeSH term(s)	Humans ; Adult ; Induced Pluripotent Stem Cells/metabolism ; Drugs, Chinese Herbal/pharmacology ; Ethanol/pharmacology ; Apoptosis ; Cell Differentiation
Chemical Substances	Drugs, Chinese Herbal ; Ethanol (3K9958V90M)
Language	English
Publishing date	2023-05-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15102364
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Article ; Online: Astragalus Complanatus Ethanol Attenuates Septic Shock by Exerting Anti-Inflammatory Effects on Macrophages.

Hwang, Yo Sep / Lim, Jeewon / Yoon, Hyang Ran / Park, Seong-Hoon / Kim, Aeyung / Jang, Jun-Pil / Cho, Hee Jun / Lee, Hee Gu

International journal of molecular sciences

2023 Volume 25, Issue 1

Abstract: Sepsis is a systemic inflammatory syndrome that results in multiple-organ failure caused by a dysregulated host immune response to microbial infection. Astragali complanati semen extract (ACSE) exhibits pharmacological activities, including antioxidant, ... ...

Abstract	Sepsis is a systemic inflammatory syndrome that results in multiple-organ failure caused by a dysregulated host immune response to microbial infection. Astragali complanati semen extract (ACSE) exhibits pharmacological activities, including antioxidant, anticancer, antiaging, and anti-diabetes effects. It is widely used in traditional medicine to treat liver and kidney diseases; however, the protective effect of ACSE on sepsis and its mechanisms are unknown. In the present study, we investigated the anti-inflammatory effects and potential mechanisms of the action of ACSE on sepsis. We show that ACSE improved survival rates in mouse models of acute sepsis induced by CLP (cecal ligation and puncture) and LPS stimulation. ACSE administration decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in sepsis-induced mice. Furthermore, ACSE reduced the levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the serum of septic mice. ACSE treatment inhibited the expression of these proinflammatory genes in LPS-stimulated J774 macrophages. Moreover, ACSE inhibited the phosphorylation of the IκB kinase (IKK) and the nuclear translocation of p65 NF-κB by LPS stimulation in macrophages. These results reveal the mechanism underlying the protective effect of ACSE against sepsis by inhibiting NF-κB activation and suggest that ACSE could be a potential therapeutic candidate to treat acute inflammatory diseases.
MeSH term(s)	Animals ; Mice ; Shock, Septic ; Lipopolysaccharides/toxicity ; NF-kappa B ; Sepsis/complications ; Sepsis/drug therapy ; Astragalus Plant ; Ethanol ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use
Chemical Substances	Lipopolysaccharides ; NF-kappa B ; Ethanol (3K9958V90M) ; Anti-Inflammatory Agents
Language	English
Publishing date	2023-12-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25010384
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Article ; Online: Jakyak-gamcho-tang, a decoction of Paeoniae Radix and Glycyrrhizae Radix et Rhizoma, ameliorates dexamethasone-induced muscle atrophy and muscle dysfunction.

Kim, Aeyung / Kim, Yu Ri / Park, Sang-Min / Lee, Haeseung / Park, Musun / Yi, Jin-Mu / Cha, Seongwon / Kim, No Soo

Phytomedicine : international journal of phytotherapy and phytopharmacology

2023 Volume 123, Page(s) 155057

Abstract: Background: Although chronic treatment with glucocorticoids, such as dexamethasone, is frequently associated with muscle atrophy, effective and safe therapeutics for treating muscle atrophy remain elusive. Jakyak-gamcho-tang (JGT), a decoction of ... ...

Abstract	Background: Although chronic treatment with glucocorticoids, such as dexamethasone, is frequently associated with muscle atrophy, effective and safe therapeutics for treating muscle atrophy remain elusive. Jakyak-gamcho-tang (JGT), a decoction of Paeoniae Radix and Glycyrrhizae Radix et Rhizoma, has long been used to relieve muscle tension and control muscle cramp-related pain. However, the effects of JGT on glucocorticoid-induced muscle atrophy are yet to be comprehensively clarified. Purpose: The objective of the current study was to validate the protective effect of JGT in dexamethasone-induced muscle atrophy models and elucidate its underlying mechanism through integrated in silico - in vitro - in vivo studies. Study design and methods: Differential gene expression was preliminarily analyzed using the RNA-seq data to determine the effects of JGT on C2C12 myotubes. The protective effects of JGT were further validated in dexamethasone-treated C2C12 myotubes by assessing cell viability, myotube integrity, and mitochondrial function or in C57BL/6 N male mice with dexamethasone-induced muscle atrophy by evaluating muscle mass and physical performance. Transcriptomic pathway analysis was also performed to elucidate the underlying mechanism. Results: Based on preliminary gene set enrichment analysis using the RNA-seq data, JGT regulated various pathways related to muscle differentiation and regeneration. Dexamethasone-treated C2C12 myotubes and muscle tissues of atrophic mice displayed substantial muscle protein degradation and muscle loss, respectively, which was efficiently alleviated by JGT treatment. Importantly, JGT-mediated protective effects were associated with observations such as preservation of mitochondrial function, upregulation of myogenic signaling pathways, including protein kinase B/mammalian target of rapamycin/forkhead box O3, inhibition of ubiquitin-mediated muscle protein breakdown, and downregulation of inflammatory and apoptotic pathways induced by dexamethasone. Conclusion: To the best of our knowledge, this is the first report to demonstrate that JGT could be a potential pharmaceutical candidate to prevent muscle atrophy induced by chronic glucocorticoid treatment, highlighting its known effects for relieving muscle spasms and pain. Moreover, transcriptomic pathway analysis can be employed as an efficient in silico tool to predict novel pharmacological candidates and elucidate molecular mechanisms underlying the effects of herbal medications comprising diverse biologically active ingredients.
MeSH term(s)	Male ; Mice ; Animals ; Glucocorticoids ; Paeonia ; Mice, Inbred C57BL ; Muscular Atrophy/chemically induced ; Muscular Atrophy/drug therapy ; Muscle Fibers, Skeletal ; Muscle Proteins/metabolism ; Muscle Proteins/pharmacology ; Muscle Proteins/therapeutic use ; Dexamethasone/pharmacology ; Pain ; Mammals ; Drugs, Chinese Herbal ; Glycyrrhiza
Chemical Substances	glycyrrhizae radix et rhizoma (2788Z9758H) ; Glucocorticoids ; Muscle Proteins ; Dexamethasone (7S5I7G3JQL) ; Drugs, Chinese Herbal
Language	English
Publishing date	2023-09-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2023.155057
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Article ; Online: Systems pharmacology approaches in herbal medicine research: a brief review.

Lee, Myunggyo / Shin, Hyejin / Park, Musun / Kim, Aeyung / Cha, Seongwon / Lee, Haeseung

BMB reports

2022 Volume 55, Issue 9, Page(s) 417–428

Abstract: Herbal medicine, a multi-component treatment, has been extensively practiced for treating various symptoms and diseases. However, its molecular mechanism of action on the human body is unknown, which impedes the development and application of herbal ... ...

Abstract	Herbal medicine, a multi-component treatment, has been extensively practiced for treating various symptoms and diseases. However, its molecular mechanism of action on the human body is unknown, which impedes the development and application of herbal medicine. To address this, recent studies are increasingly adopting systems pharmacology, which interprets pharmacological effects of drugs from consequences of the interaction networks that drugs might have. Most conventional network- based approaches collect associations of herb-compound, compound-target, and target-disease from individual databases, respectively, and construct an integrated network of herb-compound- target-disease to study the complex mechanisms underlying herbal treatment. More recently, rapid advances in highthroughput omics technology have led numerous studies to exploring gene expression profiles induced by herbal treatments to elicit information on direct associations between herbs and genes at the genome-wide scale. In this review, we summarize key databases and computational methods utilized in systems pharmacology for studying herbal medicine. We also highlight recent studies that identify modes of action or novel indications of herbal medicine by harnessing drug-induced transcriptome data. [BMB Reports 2022; 55(9): 417-428].
MeSH term(s)	Drugs, Chinese Herbal/pharmacology ; Herbal Medicine ; Humans ; Network Pharmacology ; Phytotherapy ; Transcriptome
Chemical Substances	Drugs, Chinese Herbal
Language	English
Publishing date	2022-07-26
Publishing country	Korea (South)
Document type	News ; Review
ZDB-ID	2410389-5
ISSN	1976-670X ; 1976-6696
ISSN (online)	1976-670X
ISSN	1976-6696
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Piceatannol-3-O-β-D-glucopyranoside (PG) exhibits in vitro anti-metastatic and anti-angiogenic activities in HT1080 malignant fibrosarcoma cells

Kim, Aeyung / Jin Yeul Ma

Phytomedicine. 2019 Apr., v. 57

2019

Abstract: Several components isolated from rhubarb, the root of Rheum undulatum L., including emodin, rhein, rhaponticin, and piceatannol, have been reported to induce cell death and inhibit metastasis in various types of cancer. Recently, piceatannol-3-O-β-D- ... ...

Abstract	Several components isolated from rhubarb, the root of Rheum undulatum L., including emodin, rhein, rhaponticin, and piceatannol, have been reported to induce cell death and inhibit metastasis in various types of cancer. Recently, piceatannol-3-O-β-D-glucopyranoside (PG) isolated from rhubarb was demonstrated to improve vascular dysfunction by inhibiting arginase activity.In this study, we examined the anti-cancer activities of PG, including effects on the proliferation, metastasis, and angiogenesis of endothelial and malignant cancer cells.We found that PG did not affect the proliferation of human fibrosarcoma (HT1080) and human umbilical vein endothelial cells (HUVECs) at treatments up to 100 μM. However, PG efficiently suppressed the metastatic ability of HT1080 cells, as determined by scratch wound migration, transwell migration/invasion assay, and three-dimensional (3D) spheroid invasion assay. PG significantly suppressed the phorbol 12-myristate 13-acetate (PMA)-induced increase of matrix metalloproteinase (MMP)-9 expression as well as gelatinolytic MMP-9 activity, which are essential for cancer metastasis. In addition, PG treatment reduced the production of proangiogenic factors in HT1080 cells under normoxic and hypoxic conditions and suppressed hypoxia-induced activation of the hypoxia-inducible factor (HIF)-1α pathway. We also found that HUVEC angiogenic activity, including migration and tubular structure formation, were significantly reduced by PG treatment. Moreover, in an in ovo chick chorioallantoic membrane assay, spontaneous and vascular endothelial growth factor (VEGF)-induced vessel formation were significantly inhibited by PG treatment.These results collectively indicate that PG has potent anti-metastatic and anti-angiogenic activities with no cytotoxicity. Thus, PG may be useful to limit the hyperplasia of malignant tumors and the spread of cancer to distant secondary organs.
Keywords	anaerobic conditions ; angiogenesis ; antineoplastic activity ; arginase ; cell death ; chicks ; chorioallantoic membrane ; cytotoxicity ; emodin ; enzyme inhibition ; fibrosarcoma ; human umbilical vein endothelial cells ; humans ; hyperplasia ; metalloproteinases ; metastasis ; Rheum undulatum ; rhubarb ; vascular endothelial growth factors
Language	English
Dates of publication	2019-04
Size	p. 95-104.
Publishing place	Elsevier GmbH
Document type	Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2018.12.017
Database	NAL-Catalogue (AGRICOLA)

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