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1
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Choi S, Shin M, Kim WY. Targeting the DNA damage response (DDR) of cancer cells with natural compounds derived from Panax ginseng and other plants. J Ginseng Res 2025; 49:1-11. [PMID: 39872282 PMCID: PMC11764321 DOI: 10.1016/j.jgr.2024.04.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Revised: 03/30/2024] [Accepted: 04/01/2024] [Indexed: 01/30/2025] Open
Abstract
DNA damage is a driver of cancer formation, leading to the impairment of repair mechanisms in cancer cells and rendering them susceptible to DNA-damaging therapeutic approaches. The concept of "synthetic lethality" in cancer clinics has emerged, particularly with the use of PARP inhibitors and the identification of DNA damage response (DDR) mutation biomarkers, emphasizing the significance of targeting DDR in cancer therapy. Novel approaches aimed at genome maintenance machinery are under development to further enhance the efficacy of cancer treatments. Natural compounds from traditional medicine, renowned for their anti-aging and anticarcinogenic properties, have garnered attention. Ginseng-derived compounds, in particular, exhibit anti-carcinogenic effects by suppressing reactive oxygen species (ROS) and protecting cells from DNA damage-induced carcinogenesis. However, the anticancer therapeutic effect of ginseng compounds has also been demonstrated by inducing DNA damage and blocking DDR. This review concentrates on the biphasic effects of ginseng compounds on DNA mutations-both inhibiting mutation accumulation and impairing DNA repair. Additionally, it explores other natural compounds targeting DDR directly, providing potential insights into enhancing cancer therapy efficacy.
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Affiliation(s)
- SeokGyeong Choi
- College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea
| | - Minwook Shin
- College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea
| | - Woo-Young Kim
- College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea
- Muscle Physiome Research Center, Sookmyung Women's University, Seoul, Republic of Korea
- Research Institute of Pharmaceutical Sciences, Sookmyung Women's University, Seoul, Republic of Korea
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2
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Shi Y, Gu J, Zhang C, Mi R, Ke Z, Xie M, Jin W, Shao C, He Y, Shi J, Xie Z. A Janus Microsphere Delivery System Orchestrates Immunomodulation and Osteoinduction by Fine-tuning Release Profiles. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2403835. [PMID: 38984921 DOI: 10.1002/smll.202403835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 06/17/2024] [Indexed: 07/11/2024]
Abstract
Bone regeneration is a well-orchestrated process synergistically involving inflammation, angiogenesis, and osteogenesis. Therefore, an effective bone graft should be designed to target multiple molecular events and biological demands during the bone healing process. In this study, a biodegradable gelatin methacryloyl (GelMA)-based Janus microsphere delivery system containing calcium phosphate oligomer (CPO) and bone morphogenetic protein-2 (BMP-2) is developed based on natural biological events. The exceptional adjustability of GelMA facilitates the controlled release and on-demand application of biomolecules, and optimized delivery profiles of CPO and BMP-2 are explored. The sustained release of CPO during the initial healing stages contributes to early immunomodulation and promotes mineralization in the late stage. Meanwhile, the administration of BMP-2 at a relatively high concentration within the therapeutic range enhances the osteoinductive property. This delivery system, with fine-tuned release patterns, induces M2 macrophage polarization and creates a conducive immuno-microenvironment, which in turn facilitates effective bone regeneration in vivo. Collectively, this study proposes a bottom-up concept, aiming to develop a user-friendly and easily controlled delivery system targeting individual biological events, which may offer a new perspective on developing function-optimized biomaterials for clinical use.
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Affiliation(s)
- Yang Shi
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
| | - Jingyi Gu
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
| | - Chun Zhang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
| | - Rui Mi
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
| | - Zhiwei Ke
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
| | - Mingjun Xie
- Plastic and Reconstructive Surgery Center, Department of Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China
| | - Wenjing Jin
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
| | - Changyu Shao
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
| | - Yong He
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, College of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Liangzhu Laboratory, Zhejiang University, 1369 West Wenyi Road, Hangzhou, 311121, China
- The Second Affiliated Hospital of Zhejiang University and State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou, 310027, China
| | - Jue Shi
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
| | - Zhijian Xie
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
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Xu X, Jin W, Chang R, Ding X. Research progress of SREBP and its role in the pathogenesis of autoimmune rheumatic diseases. Front Immunol 2024; 15:1398921. [PMID: 39224584 PMCID: PMC11366632 DOI: 10.3389/fimmu.2024.1398921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 07/31/2024] [Indexed: 09/04/2024] Open
Abstract
Autoimmune rheumatic diseases comprise a group of immune-related disorders characterized by non-organ-specific inflammation. These diseases include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), gout, among others. Typically involving the hematologic system, these diseases may also affect multiple organs and systems. The pathogenesis of autoimmune rheumatic immune diseases is complex, with diverse etiologies, all associated with immune dysfunction. The current treatment options for this type of disease are relatively limited and come with certain side effects. Therefore, the urgent challenge remains to identify novel therapeutic targets for these diseases. Sterol regulatory element-binding proteins (SREBPs) are basic helix-loop-helix-leucine zipper transcription factors that regulate the expression of genes involved in lipid and cholesterol biosynthesis. The expression and transcriptional activity of SREBPs can be modulated by extracellular stimuli such as polyunsaturated fatty acids, amino acids, glucose, and energy pathways including AKT-mTORC and AMP-activated protein kinase (AMPK). Studies have shown that SREBPs play roles in regulating lipid metabolism, cytokine production, inflammation, and the proliferation of germinal center B (GCB) cells. These functions are significant in the pathogenesis of rheumatic and immune diseases (Graphical abstract). Therefore, this paper reviews the potential mechanisms of SREBPs in the development of SLE, RA, and gout, based on an exploration of their functions.
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Affiliation(s)
| | | | | | - Xinghong Ding
- Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
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Sah DK, Arjunan A, Lee B, Jung YD. Reactive Oxygen Species and H. pylori Infection: A Comprehensive Review of Their Roles in Gastric Cancer Development. Antioxidants (Basel) 2023; 12:1712. [PMID: 37760015 PMCID: PMC10525271 DOI: 10.3390/antiox12091712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 08/14/2023] [Accepted: 08/30/2023] [Indexed: 09/29/2023] Open
Abstract
Gastric cancer (GC) is the fifth most common cancer worldwide and makes up a significant component of the global cancer burden. Helicobacter pylori (H. pylori) is the most influential risk factor for GC, with the International Agency for Research on Cancer classifying it as a Class I carcinogen for GC. H. pylori has been shown to persist in stomach acid for decades, causing damage to the stomach's mucosal lining, altering gastric hormone release patterns, and potentially altering gastric function. Epidemiological studies have shown that eliminating H. pylori reduces metachronous cancer. Evidence shows that various molecular alterations are present in gastric cancer and precancerous lesions associated with an H. pylori infection. However, although H. pylori can cause oxidative stress-induced gastric cancer, with antioxidants potentially being a treatment for GC, the exact mechanism underlying GC etiology is not fully understood. This review provides an overview of recent research exploring the pathophysiology of H. pylori-induced oxidative stress that can cause cancer and the antioxidant supplements that can reduce or even eliminate GC occurrence.
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Affiliation(s)
| | | | - Bora Lee
- Department of Biochemistry, Chonnam National University Medical School, Seoyang Ro 264, Jeonnam, Hwasun 58128, Republic of Korea; (D.K.S.); (A.A.)
| | - Young Do Jung
- Department of Biochemistry, Chonnam National University Medical School, Seoyang Ro 264, Jeonnam, Hwasun 58128, Republic of Korea; (D.K.S.); (A.A.)
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Li N, Lin G, Zhang H, Sun J, Gui M, Liu Y, Li W, Zhan Z, Li Y, Pan S, Liu J, Tang J. Lyn attenuates sepsis-associated acute kidney injury by inhibition of phospho-STAT3 and apoptosis. Biochem Pharmacol 2023; 211:115523. [PMID: 37003346 DOI: 10.1016/j.bcp.2023.115523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 03/22/2023] [Accepted: 03/23/2023] [Indexed: 04/03/2023]
Abstract
Sepsis-associated acute kidney injury (SA-AKI) is a life-threatening condition associated with high mortality and morbidity. However, the underlying pathogenesis of SA-AKI is still unclear. Lyn belongs to Src family kinases (SFKs), which exert numerous biological functions including modulation in receptor-mediated intracellular signaling and intercellular communication. Previous studies demonstrated that Lyn gene deletion obviously aggravates LPS-induced lung inflammation, but the role and possible mechanism of Lyn in SA-AKI have not been reported yet. Here, we found that Lyn protected against renal tubular injury in cecal ligation and puncture (CLP) induced AKI mouse model by inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation and cell apoptosis. Moreover, Lyn agonist MLR-1023 pretreatment improved renal function, inhibited STAT3 phosphorylation and decreased cell apoptosis. Thus, Lyn appears to play a crucial role in orchestrating STAT3-mediated inflammation and cell apoptosis in SA-AKI. Hence, Lyn kinase may be a promising therapeutic target for SA-AKI.
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Affiliation(s)
- Nannan Li
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
| | - Guoxin Lin
- Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
| | - Hao Zhang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
| | - Jian Sun
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
| | - Ming Gui
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
| | - Yan Liu
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
| | - Wei Li
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
| | - Zishun Zhan
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
| | - Yisu Li
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
| | - Shiqi Pan
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
| | - Jishi Liu
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
| | - Juan Tang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
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Jiang Y, Zhao Q, Li L, Huang S, Yi S, Hu Z. Effect of Traditional Chinese Medicine on the Cardiovascular Diseases. Front Pharmacol 2022; 13:806300. [PMID: 35387325 PMCID: PMC8978630 DOI: 10.3389/fphar.2022.806300] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 01/31/2022] [Indexed: 02/03/2023] Open
Abstract
Background: Traditional Chinese medicine (TCM) is the health care system developed with the help of clinical trials that are based ideally on the scientific model of regulation. Objective: This systematic health care system relies on some specific unique theories and practical experiences to treat and cure diseases, thus enhancing the public's health. Review Methodology: The current review covers the available literature from 2000 to 2021. The data was collected from journals research articles, published books, thesis, and electronic databases, search engines such as Google Scholar, Elsevier, EBSCO, PMC, PubMed, ScienceDirect, Willey Online Library, Springer Link, and CNKI) searching key terms, cardiovascular disease, traditional Chinese medicines, natural products, and bioactive compounds. Full-length articles and abstracts were screened for the collection of information included in the paper. Results: Clinical trials on the TCM and basic research carried out on its mechanism and nature have led to the application and development of the perfect design of the research techniques, for example, twofold striking in acupuncture that aid in overcoming the limitations and resistances in integrating and applicability of these experiences and trials into the pre-existing biomedical models. Furthermore, TCM has also been utilized from ancient times to treat heart diseases in Asia, particularly in China, and is now used by people in many other areas. Cardiovascular disease (CVD) is mainly developed by oxidative stress. Hence antioxidants can be beneficial in treating this particular disease. TCM has a wide variety of antioxidant components. Conclusion: The current review article summarizes the underlying therapeutic property of TCM and its mechanism. It also overviews the evidence of the mechanism of TCM action in CVD prevention by controlling oxidative stress and its signaling pathway.
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Affiliation(s)
- Yang Jiang
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China.,Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha, China
| | - Qi Zhao
- Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha, China
| | - Lin Li
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Shumin Huang
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Shuai Yi
- Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha, China
| | - Zhixi Hu
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
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7
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Kim HS, Lim JW, Kim H. Korean Red Ginseng Extract Inhibits IL-8 Expression via Nrf2 Activation in Helicobacter pylori-Infected Gastric Epithelial Cells. Nutrients 2022; 14:nu14051044. [PMID: 35268019 PMCID: PMC8912635 DOI: 10.3390/nu14051044] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 02/25/2022] [Accepted: 02/27/2022] [Indexed: 12/28/2022] Open
Abstract
Helicobacter pylori (H. pylori) causes gastric diseases by increasing reactive oxygen species (ROS) and interleukin (IL)-8 expression in gastric epithelial cells. ROS and inflammatory responses are regulated by the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of Nrf2 target genes, superoxide dismutase (SOD) and heme oxygenase-1 (HO-1). We previously demonstrated that Korean red ginseng extract (RGE) decreases H. pylori-induced increases in ROS and monocyte chemoattractant protein 1 in gastric epithelial cells. We determined whether RGE suppresses the expression of IL-8 via Nrf2 activation and the expression of SOD and HO-1 in H. pylori-infected gastric epithelial AGS cells. H. pylori-infected cells were treated with RGE with or without ML385, an Nrf2 inhibitor, or zinc protoporphyrin (ZnPP), a HO-1 inhibitor. Levels of ROS and IL-8 expression; abundance of Keap1, HO-1, and SOD; levels of total, nuclear, and phosphorylated Nrf2; indices of mitochondrial dysfunction (reduction in mitochondrial membrane potential and ATP level); and SOD activity were determined. As a result, RGE disturbed Nrf2–Keap1 interactions and increased nuclear Nrf2 levels in uninfected cells. H. pylori infection decreased the protein levels of SOD-1 and HO-1, as well as SOD activity, which was reversed by RGE treatment. RGE reduced H. pylori-induced increases in ROS and IL-8 levels as well as mitochondrial dysfunction. ML385 or ZnPP reversed the inhibitory effect of RGE on the alterations caused by H. pylori. In conclusion, RGE suppressed IL-8 expression and mitochondrial dysfunction via Nrf2 activation, induction of SOD-1 and HO-1, and reduction of ROS in H. pylori-infected cells.
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Affiliation(s)
| | | | - Hyeyoung Kim
- Correspondence: ; Tel.: +82-2-2123-3125; Fax: +82-2-364-5781
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Fawzy MA, Maher SA, El-Rehany MA, Welson NN, Albezrah NKA, Batiha GES, Fathy M. Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways. Molecules 2022; 27:1383. [PMID: 35209172 PMCID: PMC8879001 DOI: 10.3390/molecules27041383] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/11/2022] [Accepted: 02/15/2022] [Indexed: 02/06/2023] Open
Abstract
Pantoprazole has an antioxidant function against reactive oxygen species (ROS). Vincamine, a herbal candidate, is an indole alkaloid of clinical use against brain sclerosis. The aim of the present experiment is to evaluate, on a molecular level for the first time, the value of vincamine in addition to pantoprazole in treating experimentally induced renal ischemia/reperfusion injury (IRI). One-hundred-and-twenty-eight healthy male Wistar albino rats were included. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were assessed. ELISA was used to estimate the pro-inflammatory cytokines. The expression of Bcl-2 and Bax genes was assessed by quantitative real-time PCR. ERK1/2, JNK1/2, p38, cleaved caspase-3, and NF-κB proteins expressions were estimated using western blot assay. The kidneys were also histopathologically studied. The IRI resulted in impaired cellular functions with increased creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, and IL-1β serum levels, and up-regulated NF-ĸB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it down-regulated the expression of the Bcl-2 gene and upregulated the Bax gene. The treatment with vincamine, in addition to pantoprazole multiple doses, significantly alleviated the biochemical and histopathological changes more than pantoprazole or vincamine alone, whether the dose is single or multiple, declaring their synergistic effect. In conclusion, vincamine with pantoprazole multiple doses mitigated the renal IRI through the inhibition of apoptosis, attenuation of the extracellular signaling pathways through proinflammatory cytokines' levels, and suppression of the MAPK (ERK1/2, JNK, p38)-NF-κB intracellular signaling pathway.
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Affiliation(s)
- Michael A. Fawzy
- Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;
| | - Sherif A. Maher
- Department of Biochemistry, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt; (S.A.M.); (M.A.E.-R.)
| | - Mahmoud A. El-Rehany
- Department of Biochemistry, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt; (S.A.M.); (M.A.E.-R.)
| | - Nermeen N. Welson
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef University, Beni-Suef 62511, Egypt;
| | - Nisreen K. A. Albezrah
- Department of Obstetrics and Gynecology, College of Medicine, Taif University, Taif 21944, Saudi Arabia;
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt;
| | - Moustafa Fathy
- Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;
- Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
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Ha S, Vetrivel P, Kim S, Bhosale P, Kim H, Pak J, Heo J, Kim Y, Kim G. Inhibitory effect of membrane‑free stem cell components derived from adipose tissues on skin inflammation in keratinocytes. Mol Med Rep 2022; 25:125. [DOI: 10.3892/mmr.2022.12641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 01/24/2022] [Indexed: 11/05/2022] Open
Affiliation(s)
- Sang Ha
- Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam‑do 52828, Republic of Korea
| | - Preethi Vetrivel
- Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam‑do 52828, Republic of Korea
| | - Seong Kim
- Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam‑do 52828, Republic of Korea
| | - Pritam Bhosale
- Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam‑do 52828, Republic of Korea
| | - Hun Kim
- Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam‑do 52828, Republic of Korea
| | - Jung Pak
- T‑Stem Co., Ltd., Changwon, Gyeongsangnam‑do 51573, Republic of Korea
| | - Jeong Heo
- Biological Resources Research Group, Bioenvironmental Science and Toxicology Division, Gyeongnam Branch Institute, Korea Institute of Toxicology (KIT), Jinju, Gyeongsangnam‑do 52834, Republic of Korea
| | - Young Kim
- T‑Stem Co., Ltd., Changwon, Gyeongsangnam‑do 51573, Republic of Korea
| | - Gon Kim
- Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam‑do 52828, Republic of Korea
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10
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You JY, Kang SJ, Rhee WJ. Isolation of cabbage exosome-like nanovesicles and investigation of their biological activities in human cells. Bioact Mater 2021; 6:4321-4332. [PMID: 33997509 PMCID: PMC8105599 DOI: 10.1016/j.bioactmat.2021.04.023] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 03/18/2021] [Accepted: 04/10/2021] [Indexed: 02/08/2023] Open
Abstract
There are extensive studies on the applications of extracellular vesicles (EVs) produced in cell culture for therapeutic drug development. However, large quantities of EVs are needed for in vivo applications, which requires high production costs and time. Thus, the development of new EV sources is essential to facilitate their use. Accordingly, plant-derived exosome-like nanovesicles are an emerging alternative for culture-derived EVs. Until now, however, few studies have explored their biological functions and uses. Therefore, it is necessary to elucidate biological activities of plant-derived exosome-like nanovesicles and harness vesicles for biomedical applications. Herein, cabbage and red cabbage were used as nanovesicle sources owing to their easy cultivation. First, an efficient method for nanovesicle isolation from cabbage (Cabex) and red cabbage (Rabex) was developed. Furthermore, isolated nanovesicles were characterized, and their biological functions were assessed. Both Cabex and Rabex promoted mammalian cell proliferation and, interestingly, suppressed inflammation in immune cells and apoptosis in human keratinocytes and fibroblasts. Finally, therapeutic drugs were encapsulated in Cabex or Rabex and successfully delivered to human cells, demonstrating the potential of these vesicles as alternative drug delivery vehicles. Overall, the current results provide strong evidence for the wide application of Cabex and Rabex as novel therapeutic biomaterials.
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Affiliation(s)
- Jae Young You
- Department of Bioengineering and Nano-Bioengineering, Incheon National University Incheon, 22012, Republic of Korea
| | - Su Jin Kang
- Department of Bioengineering and Nano-Bioengineering, Incheon National University Incheon, 22012, Republic of Korea
| | - Won Jong Rhee
- Department of Bioengineering and Nano-Bioengineering, Incheon National University Incheon, 22012, Republic of Korea
- Division of Bioengineering, Incheon National University Incheon 22012, Republic of Korea
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11
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Fawzy MA, Maher SA, Bakkar SM, El-Rehany MA, Fathy M. Pantoprazole Attenuates MAPK (ERK1/2, JNK, p38)-NF-κB and Apoptosis Signaling Pathways after Renal Ischemia/Reperfusion Injury in Rats. Int J Mol Sci 2021; 22:ijms221910669. [PMID: 34639009 PMCID: PMC8508698 DOI: 10.3390/ijms221910669] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 09/23/2021] [Accepted: 09/28/2021] [Indexed: 01/01/2023] Open
Abstract
Ischemia/reperfusion injury (IRI) in the kidney is the most common cause of acute renal dysfunction through different cell damage mechanisms. This study aimed to investigate, on molecular basics for the first time, the effect of pantoprazole on renal IRI in rats. Different biochemical parameters and oxidative stress markers were assessed. ELISA was used to estimate proinflammatory cytokines. qRT-PCR and western blot were used to investigate the gene and protein expression. Renal histopathological examination was also performed. IRI resulted in tissue damage, elevation of serum levels of creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, IL-1β, up-regulation of NF-κB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it up-regulated the expression of the Bax gene and down-regulated the expression of the Bcl-2 gene. Treatment of the injured rats with pantoprazole, either single dose or multiple doses, significantly alleviated IRI-induced biochemical and histopathological changes, attenuated the levels of proinflammatory cytokines, down-regulated the expression of NF-κB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins, and the Bax gene, and up-regulated Bcl-2 gene expression. Moreover, treatment with pantoprazole multiple doses has an ameliorative effect that is greater than pantoprazole single-dose. In conclusion, pantoprazole diminished renal IRI via suppression of apoptosis, attenuation of the pro-inflammatory cytokines’ levels, and inhibition of the intracellular signaling pathway MAPK (ERK1/2, JNK, p38)–NF-κB.
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Affiliation(s)
- Michael A. Fawzy
- Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;
| | - Sherif A. Maher
- Department of Biochemistry, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt; (S.A.M.); (M.A.E.-R.)
| | - Sally M. Bakkar
- Department of Biochemistry, Faculty of Medicine, Assiut University, Assiut 71515, Egypt;
| | - Mahmoud A. El-Rehany
- Department of Biochemistry, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt; (S.A.M.); (M.A.E.-R.)
| | - Moustafa Fathy
- Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;
- Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
- Correspondence: or
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12
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Dias AA, Silva CADME, da Silva CO, Linhares NRC, Santos JPS, Vivarini ADC, Marques MÂDM, Rosa PS, Lopes UG, Berrêdo-Pinho M, Pessolani MCV. TLR-9 Plays a Role in Mycobacterium leprae-Induced Innate Immune Activation of A549 Alveolar Epithelial Cells. Front Immunol 2021; 12:657449. [PMID: 34456901 PMCID: PMC8397448 DOI: 10.3389/fimmu.2021.657449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 07/27/2021] [Indexed: 12/18/2022] Open
Abstract
The respiratory tract is considered the main port of entry of Mycobacterium leprae, the causative agent of leprosy. However, the great majority of individuals exposed to the leprosy bacillus will never manifest the disease due to their capacity to develop protective immunity. Besides acting as a physical barrier, airway epithelium cells are recognized as key players by initiating a local innate immune response that orchestrates subsequent adaptive immunity to control airborne infections. However, to date, studies exploring the interaction of M. leprae with the respiratory epithelium have been scarce. In this work, the capacity of M. leprae to immune activate human alveolar epithelial cells was investigated, demonstrating that M. leprae-infected A549 cells secrete significantly increased IL-8 that is dependent on NF-κB activation. M. leprae was also able to induce IL-8 production in human primary nasal epithelial cells. M. leprae-treated A549 cells also showed higher expression levels of human β-defensin-2 (hβD-2), MCP-1, MHC-II and the co-stimulatory molecule CD80. Furthermore, the TLR-9 antagonist inhibited both the secretion of IL-8 and NF-κB activation in response to M. leprae, indicating that bacterial DNA sensing by this Toll-like receptor constitutes an important innate immune pathway activated by the pathogen. Finally, evidence is presented suggesting that extracellular DNA molecules anchored to Hlp, a histone-like protein present on the M. leprae surface, constitute major TLR-9 ligands triggering this pathway. The ability of M. leprae to immune activate respiratory epithelial cells herein demonstrated may represent a very early event during infection that could possibly be essential to the generation of a protective response.
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Affiliation(s)
- André Alves Dias
- Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
| | | | - Camila Oliveira da Silva
- Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
| | | | - João Pedro Sousa Santos
- Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
| | - Aislan de Carvalho Vivarini
- Laboratory of Molecular Parasitology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Maria Ângela de Mello Marques
- Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University (CSU), Fort Collins, CO, United States
| | | | - Ulisses Gazos Lopes
- Laboratory of Molecular Parasitology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Márcia Berrêdo-Pinho
- Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
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Effect of Reactive Oxygen Species on the Endoplasmic Reticulum and Mitochondria during Intracellular Pathogen Infection of Mammalian Cells. Antioxidants (Basel) 2021; 10:antiox10060872. [PMID: 34071633 PMCID: PMC8229183 DOI: 10.3390/antiox10060872] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 05/24/2021] [Accepted: 05/24/2021] [Indexed: 02/06/2023] Open
Abstract
Oxidative stress, particularly reactive oxygen species (ROS), are important for innate immunity against pathogens. ROS directly attack pathogens, regulate and amplify immune signals, induce autophagy and activate inflammation. In addition, production of ROS by pathogens affects the endoplasmic reticulum (ER) and mitochondria, leading to cell death. However, it is unclear how ROS regulate host defense mechanisms. This review outlines the role of ROS during intracellular pathogen infection, mechanisms of ROS production and regulation of host defense mechanisms by ROS. Finally, the interaction between microbial pathogen-induced ROS and the ER and mitochondria is described.
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14
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STAT3 Differentially Regulates TLR4-Mediated Inflammatory Responses in Early or Late Phases. Int J Mol Sci 2020; 21:ijms21207675. [PMID: 33081347 PMCID: PMC7589049 DOI: 10.3390/ijms21207675] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 10/02/2020] [Accepted: 10/14/2020] [Indexed: 12/17/2022] Open
Abstract
Toll-like receptor 4 (TLR4) signaling is an important therapeutic target to manage lipopolysaccharide (LPS)-induced inflammation. The transcription factor signal transducer and activator of transcription 3 (STAT3) has been identified as an important regulator of various immune-related diseases and has generated interest as a therapeutic target. Here, we investigated the time-dependent roles of STAT3 in LPS-stimulated RAW264.7 macrophages. STAT3 inhibition induced expression of the pro-inflammatory genes iNOS and COX-2 at early time points. STAT3 depletion resulted in regulation of nuclear translocation of nuclear factor (NF)-κB subunits p50 and p65 and IκBα/Akt/PI3K signaling. Moreover, we found that one Src family kinase, Lyn kinase, was phosphorylated in STAT3 knockout macrophages. In addition to using pharmacological inhibition of NF-κB, we found out that STAT3KO activation of NF-κB subunit p50 and p65 and expression of iNOS was significantly inhibited; furthermore, Akt tyrosine kinase inhibitors also inhibited iNOS and COX-2 gene expression during early time points of LPS stimulation, demonstrating an NF-κB- Akt-dependent mechanism. On the other hand, iNOS expression was downregulated after prolonged treatment with LPS. Activation of NF-κB signaling was also suppressed, and consequently, nitric oxide (NO) production and cell invasion were repressed. Overall, our data indicate that STAT3 differentially regulates early- and late-phase TLR4-mediated inflammatory responses.
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15
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Li H, Xu CX, Gong RJ, Chi JS, Liu P, Liu XM. How does Helicobacter pylori cause gastric cancer through connexins: An opinion review. World J Gastroenterol 2019; 25:5220-5232. [PMID: 31558869 PMCID: PMC6761244 DOI: 10.3748/wjg.v25.i35.5220] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 08/12/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a Gram-negative bacterium with a number of virulence factors, such as cytotoxin-associated gene A, vacuolating cytotoxin A, its pathogenicity island, and lipopolysaccharide, which cause gastrointestinal diseases. Connexins function in gap junctional homeostasis, and their downregulation is closely related to gastric carcinogenesis. Investigations into H. pylori infection and the fine-tuning of connexins in cells or tissues have been reported in previous studies. Therefore, in this review, the potential mechanisms of H. pylori-induced gastric cancer through connexins are summarized in detail.
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Affiliation(s)
- Huan Li
- Department of Gastroenterology, the Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Can-Xia Xu
- Department of Gastroenterology, the Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Ren-Jie Gong
- Department of Gastroenterology, the Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Jing-Shu Chi
- Department of Gastroenterology, the Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Peng Liu
- Department of Gastroenterology, the Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Xiao-Ming Liu
- Department of Gastroenterology, the Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
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16
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Li H, Xu CX, Gong RJ, Chi JS, Liu P, Liu XM. How does Helicobacter pyloricause gastric cancer through connexins: An opinion review. World J Gastroenterol 2019. [DOI: 10.3748/wjg.v25.i355220] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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17
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Zhou Y, Xu W, Zhu H. CXCL8 (3-72) K11R/G31P protects against sepsis-induced acute kidney injury via NF-κB and JAK2/STAT3 pathway. Biol Res 2019; 52:29. [PMID: 31084615 PMCID: PMC6513525 DOI: 10.1186/s40659-019-0236-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Accepted: 04/25/2019] [Indexed: 01/03/2023] Open
Abstract
Background Acute kidney injury (AKI), which is mainly caused by sepsis, has high morbidity and mortality rates. CXCL8(3–72) K11R/G31P (G31P) can exert therapeutic effect on inflammatory diseases and malignancies. We aimed to investigate the effect and mechanism of G31P on septic AKI. Methods An AKI mouse model was established, and kidney injury was assessed by histological analysis. The contents of serum creatinine (SCr) and blood urea nitrogen (BUN) were measured by commercial kits, whereas neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were detected by enzyme-linked immunosorbent assay (ELISA) kits. The expressions of CXCL8 in serum and kidney tissues were determined using ELISA and immunohistochemical analysis, respectively. Apoptosis rate of renal tissue was detected by terminal deoxynucleotidyl transfer-mediated dUTP nick end labeling (TUNEL) analysis. The expressions of inflammatory cytokines were measured by quantitative real-time PCR and Western blot, respectively. The apoptosis-related proteins, JAK2, STAT3, NF-κB and IκB were determined by Western blot. Results G31P could reduce the levels of SCr, BUN, HGAL and KIM-1 and inhibit the renal tissue injury in AKI mice. G31P was also found to suppress the serum and nephric CXCL8 expressions and attenuated the apoptosis rate. The levels of inflammatory cytokines, pro-apoptotic proteins were decreased, while the anti-apoptotic proteins were increased by G31P in AKI mice. G31P also inhibited the activation of JAK2, STAT3 and NF-κB in AKI mice. Conclusion These results suggest that G31P could protect renal function and attenuate the septic AKI. Our findings provide a potential target for the treatment of AKI.
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Affiliation(s)
- Yunfeng Zhou
- Department of Intensive Medicine, The Third Hospital of Nanchang, Nanchang, Jiangxi, China
| | - Wenda Xu
- Department of Intensive Medicine, The Third Hospital of Nanchang, Nanchang, Jiangxi, China
| | - Hong Zhu
- Department of Intensive Medicine, Ruian People's Hospital, No. 108 Wansong Road, Yuhai Street, Ruian, Wenzhou, 325200, Zhejiang, China.
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18
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The Role of Traditional Chinese Medicine in the Regulation of Oxidative Stress in Treating Coronary Heart Disease. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:3231424. [PMID: 30918578 PMCID: PMC6409025 DOI: 10.1155/2019/3231424] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Revised: 01/19/2019] [Accepted: 02/04/2019] [Indexed: 02/06/2023]
Abstract
Oxidative stress has been closely related with coronary artery disease. In coronary heart disease (CHD), an excess of reactive oxygen species (ROS) production generates endothelial cell and smooth muscle functional disorders, leading to a disequilibrium between the antioxidant capacity and prooxidants. ROS also leads to inflammatory signal activation and mitochondria-mediated apoptosis, which can promote and increase the occurrence and development of CHD. There are several kinds of antioxidative and small molecular systems of antioxidants, such as β-carotene, ascorbic acid, α-tocopherol, and reduced glutathione (GSH). Studies have shown that antioxidant treatment was effective and decreased the risk of CHD, but the effect of the treatment varies greatly. Traditional Chinese medicine (TCM) has been utilized for thousands of years in China and is becoming increasingly popular all over the world, especially for the treatments of cardiovascular diseases. This review will concentrate on the evidence of the action mechanism of TCM in preventing CHD by modulating oxidative stress-related signaling pathways.
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19
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Li R, Hong P, Zheng X. β-carotene attenuates lipopolysaccharide-induced inflammation via inhibition of the NF-κB, JAK2/STAT3 and JNK/p38 MAPK signaling pathways in macrophages. Anim Sci J 2018; 90:140-148. [DOI: 10.1111/asj.13108] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 08/02/2018] [Accepted: 08/19/2018] [Indexed: 12/26/2022]
Affiliation(s)
- Ruonan Li
- College of Animal Science and Technology; Jilin Agricultural University; Changchun China
| | - Pan Hong
- College of Animal Science and Technology; Jilin Agricultural University; Changchun China
| | - Xin Zheng
- College of Animal Science and Technology; Jilin Agricultural University; Changchun China
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20
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Kang H, Lim JW, Kim H. Inhibitory effect of Korean Red Ginseng extract on DNA damage response and apoptosis in Helicobacter pylori-infected gastric epithelial cells. J Ginseng Res 2018; 44:79-85. [PMID: 32148392 PMCID: PMC7033323 DOI: 10.1016/j.jgr.2018.08.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 07/10/2018] [Accepted: 08/08/2018] [Indexed: 12/11/2022] Open
Abstract
Background Helicobacter pylori increases reactive oxygen species (ROS) and induces oxidative DNA damage and apoptosis in gastric epithelial cells. DNA damage activates DNA damage response (DDR) which includes ataxia-telangiectasia-mutated (ATM) activation. ATM increases alternative reading frame (ARF) but decreases mouse double minute 2 (Mdm2). Because p53 interacts with Mdm2, H. pylori–induced loss of Mdm2 stabilizes p53 and induces apoptosis. Previous study showed that Korean Red Ginseng extract (KRG) reduces ROS and prevents cell death in H. pylori–infected gastric epithelial cells. Methods We determined whether KRG inhibits apoptosis by suppressing DDRs and apoptotic indices in H. pylori–infected gastric epithelial AGS cells. The infected cells were treated with or without KRG or an ATM kinase inhibitor KU-55933. ROS levels, apoptotic indices (cell death, DNA fragmentation, Bax/Bcl-2 ratio, caspase-3 activity) and DDRs (activation and levels of ATM, checkpoint kinase 2, Mdm2, ARF, and p53) were determined. Results H. pylori induced apoptosis by increasing apoptotic indices and ROS levels. H. pylori activated DDRs (increased p-ATM, p-checkpoint kinase 2, ARF, p-p53, and p53, but decreased Mdm2) in gastric epithelial cells. KRG reduced ROS and inhibited increase in apoptotic indices and DDRs in H. pylori–infected gastric epithelial cells. KU-55933 suppressed DDRs and apoptosis in H. pylori–infected gastric epithelial cells, similar to KRG. Conclusion KRG suppressed ATM-mediated DDRs and apoptosis by reducing ROS in H. pylori–infected gastric epithelial cells. Supplementation with KRG may prevent the oxidative stress-mediated gastric impairment associated with H. pylori infection.
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Affiliation(s)
- Hyunju Kang
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Republic of Korea
| | - Joo Weon Lim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Republic of Korea
| | - Hyeyoung Kim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Republic of Korea
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Chung JW, Kim SY, Park HJ, Chung CS, Lee HW, Lee SM, Kim I, Pak JH, Lee GH, Jeong JY. In Vitro Activity of Diphenyleneiodonium toward Multidrug-Resistant Helicobacter pylori Strains. Gut Liver 2018; 11:648-654. [PMID: 28750485 PMCID: PMC5593327 DOI: 10.5009/gnl16503] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Revised: 01/06/2017] [Accepted: 02/13/2017] [Indexed: 12/16/2022] Open
Abstract
Background/Aims The increased resistance of Helicobacter pylori to antibiotics has increased the need to develop new treatments for this bacterium. The aim of our study was to identify new drugs with anti-H. pylori activity. Methods We screened a small molecule library—the library of pharmacologically active compounds (LOPAC), which includes 1,280 pharmacologically active compounds—to identify inhibitors of H. pylori growth. The minimal inhibitory concentrations (MICs) of antibiotics against multidrug-resistant H. pylori strains were determined using the agar dilution method. Results We identified diphenyleneiodonium (DPI) as a novel anti-H. pylori agent. The MIC values for DPI were <0.03 μg/mL against all tested H. pylori strains. DPI also exhibited strong antibacterial activity against common gram-negative and gram-positive pathogenic bacteria. Conclusions DPI may be a candidate anti-H. pylori drug for future development.
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Affiliation(s)
- Jun-Won Chung
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Su Young Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Hee Jung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chang Su Chung
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Hee Woo Lee
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Sun Mi Lee
- Department of Convergence Medicine and Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Inki Kim
- Department of Convergence Medicine and Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jhang Ho Pak
- Department of Convergence Medicine and Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gin Hyug Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin-Yong Jeong
- Department of Convergence Medicine and Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Folic acid supplementation repressed hypoxia-induced inflammatory response via ROS and JAK2/STAT3 pathway in human promyelomonocytic cells. Nutr Res 2018; 53:40-50. [PMID: 29685624 DOI: 10.1016/j.nutres.2018.03.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Revised: 01/15/2018] [Accepted: 03/15/2018] [Indexed: 12/16/2022]
Abstract
Hypoxia is associated with inflammation and various chronic diseases. Folic acid is known to ameliorate inflammatory reactions, but the metabolism of folic acid protecting against hypoxia-induced injury is still unclear. In our study, we examined the inflammatory signal transduction pathway in human promyelomonocytic cells (THP-1 cells) with or without treatment with folic acid under hypoxic culture conditions. Our results indicated that supplementation with folic acid significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in hypoxic conditions. Treating THP-1 cells with folic acid suppressed oxidative stress and hypoxia-inducible factor-1α in a dose-dependent manner. Folic acid targeted the activation of Janus kinase 2, downregulated the phosphorylation of signal transducer and activator of transcription 3, and decreased the expression of nuclear factor-κB p65 protein in cells. However, the absence of folic acid did not make cells more vulnerable under hypoxic conditions. In conclusion, folic acid efficiently inhibited the inflammatory response of THP-1 cells under hypoxic conditions by inhibiting reactive oxygen species production and the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. Our study supports a basis for treatment with folic acid for chronic inflammation, which correlated with hypoxia.
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Korean Red Ginseng enhances pneumococcal Δ pep27 vaccine efficacy by inhibiting reactive oxygen species production. J Ginseng Res 2017; 43:218-225. [PMID: 30962736 PMCID: PMC6437420 DOI: 10.1016/j.jgr.2017.11.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 11/14/2017] [Accepted: 11/22/2017] [Indexed: 12/17/2022] Open
Abstract
Background Streptococcus pneumoniae, more than 90 serotypes of which exist, is recognized as an etiologic agent of pneumonia, meningitis, and sepsis associated with significant morbidity and mortality worldwide. Immunization with a pneumococcal pep27 mutant (Δpep27) has been shown to confer comprehensive, long-term protection against even nontypeable strains. However, Δpep27 is effective as a vaccine only after at least three rounds of immunization. Therefore, treatments capable of enhancing the efficiency of Δpep27 immunization should be identified without delay. Panax ginseng Mayer has already been shown to have pharmacological and antioxidant effects. Here, the ability of Korean Red Ginseng (KRG) to enhance the efficacy of Δpep27 immunization was investigated. Methods Mice were treated with KRG and immunized with Δpep27 before infection with the pathogenic S. pneumoniae strain D39. Total reactive oxygen species production was measured using lung homogenates, and inducible nitric oxide (NO) synthase and antiapoptotic protein expression was determined by immunoblotting. The phagocytic activity of peritoneal macrophages was also tested after KRG treatment. Results Compared with the other treatments, KRG significantly increased survival rate after lethal challenge and resulted in faster bacterial clearance via increased phagocytosis. Moreover, KRG enhanced Δpep27 vaccine efficacy by inhibiting reactive oxygen species production, reducing extracellular signal–regulated kinase apoptosis signaling and inflammation. Conclusion Taken together, our results suggest that KRG reduces the time required for immunization with the Δpep27 vaccine by enhancing its efficacy.
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Liu H, Wang C, Qiao Z, Xu Y. Protective effect of curcumin against myocardium injury in ischemia reperfusion rats. PHARMACEUTICAL BIOLOGY 2017; 55:1144-1148. [PMID: 28224816 PMCID: PMC6130472 DOI: 10.1080/13880209.2016.1214741] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Revised: 07/06/2016] [Accepted: 07/12/2016] [Indexed: 06/06/2023]
Abstract
CONTEXT Curcumin has long been used as a condiment and a traditional medicine worldwide. OBJECTIVE The current study investigates the possible protective effect of curcumin on heart function in myocardium ischemia-reperfusion (MIR) rats. MATERIALS AND METHODS We fed Sprague-Dawley (SD) rats (10 in each group) either curcumin (10, 20 or 30 mg/kg/d) or saline. Twenty days later, the rats were subjected to myocardial injuries by ligating the left anterior descending coronary artery (60 min), and subsequently, the heart (3 h) reperfused by releasing the ligation. Then, lipid profile, lipid peroxidation products, antioxidant enzymes and gene expression were assessed in myocardium tissue. RESULTS Only the rats that were supplemented with curcumin (10, 20 or 30 mg/kg/d) showed significant (p < 0.05) reductions in oxidative stress (3-fold), infarct size (2.5-fold), which was smaller than that of the control group. The percentage of infarct size in MIR rats with curcumin at 10, 20 or 30 mg/kg/d decreased (from 49.1% to 18.3%) compared to ischemia-reperfusion (I/R). The enhanced phosphorylation of STAT3 was further strengthened by curcumin (10, 20 or 30 mg/kg/d) in a dose-dependent manner. DISCUSSION AND CONCLUSION Curcumin intake might reduce the risk of coronary heart disease by stimulating JAK2/STAT3 signal pathway, decreasing oxidative damage and inhibiting myocardium apoptosis.
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Affiliation(s)
- HuaJin Liu
- Shanghai Tenth Clinical Medical School of Nanjing Medical University, Shanghai, China
| | | | - Zengyong Qiao
- Shanghai Tenth Clinical Medical School of Nanjing Medical University, Shanghai, China
| | - Yawei Xu
- Shanghai Tenth Clinical Medical School of Nanjing Medical University, Shanghai, China
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Mesalam A, Khan I, Lee KL, Song SH, Chowdhury M, Uddin Z, Park KH, Kong IK. 2-Methoxystypandrone improves in vitro -produced bovine embryo quality through inhibition of IKBKB. Theriogenology 2017; 99:10-20. [DOI: 10.1016/j.theriogenology.2017.05.012] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Revised: 04/26/2017] [Accepted: 05/13/2017] [Indexed: 10/19/2022]
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Zeng Q, Ko CH, Siu WS, Li LF, Han XQ, Yang L, Bik-San Lau C, Hu JM, Leung PC. Polysaccharides of Dendrobium officinale Kimura & Migo protect gastric mucosal cell against oxidative damage-induced apoptosis in vitro and in vivo. JOURNAL OF ETHNOPHARMACOLOGY 2017; 208:214-224. [PMID: 28684298 DOI: 10.1016/j.jep.2017.07.006] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 06/11/2017] [Accepted: 07/02/2017] [Indexed: 06/07/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Dendrobium officinale Kimura & Migo (DO) is a valuable Traditional Chinese Medicine to nourish stomach, in which polysaccharides are identified as active ingredients. However, limited scientific evidences have been reported on the gastroprotective efficacy of DO. The aim of the current study was to investigate the protective effects and underlying mechanism of polysaccharides from DO(DOP) on gastric mucosal injury. MATERIAL AND METHODS For in vitro study, HFE145 cells were pretreated with DOP before induction of cell apoptosis by H2O2. Cell apoptosis and related proteins expression were detected. In the in vivo study, absolute ethanol was administered orally to induce gastric mucosal injury in rat. The gastric mucosal injury area and histological examination were used to evaluate the effects of DOP treatment on the recovery of the gastric mucosal injury. RESULTS H2O2 treatment for 6h significantly induced cell apoptosis in HFE145 cells. However, the destructive effects of H2O2 on HFE 145 cells could be reversed by the pretreatment with DOP. The increased ROS level induced by H2O2 for 4h was reduced after DOP pretreatment. The number of apoptotic cells in both early and late apoptosis stages decreased significantly and the nuclei morphology changes were improved with DOP pretreatment. Furthermore, DOP inhibited caspase 3 activation and PARP cleavage, downregulated Bax expression and upregulated Bcl2 expression in cell model. Further study revealed that pretreatment of DOP inhibited p -NF-κBp65/NF-κBp65 level, indicating DOP inhibited H2O2-mediated apoptosis via suppression of NF-κB activation. In addition, DOP treatment could ameliorate gastric mucosal injury and inhibit mucin loss induced by ethanol in animal model. DOP treatment also interfered with ethanol-induced apoptosis process by downregulating Bax/Bcl2 ratio in gastric mucosa. CONCLUSIONS The present study was the first one to demonstrate the gastroprotective effect of DOP through inhibiting oxidative stress-induced apoptosis. This study provided a solid evidence for the potential use of DO as a therapy or health supplement for gastric mucosal diseases.
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Affiliation(s)
- Qiang Zeng
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China.
| | - Chun-Hay Ko
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China.
| | - Wing-Sum Siu
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China.
| | - Long-Fei Li
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China.
| | - Xiao-Qiang Han
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China.
| | - Liu Yang
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China.
| | - Clara Bik-San Lau
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China.
| | - Jiang-Miao Hu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China.
| | - Ping-Chung Leung
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China.
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Korean Red Ginseng extract and ginsenoside Rg3 have anti-pruritic effects on chloroquine-induced itch by inhibition of MrgprA3/TRPA1-mediated pathway. J Ginseng Res 2017; 42:470-475. [PMID: 30337807 PMCID: PMC6187082 DOI: 10.1016/j.jgr.2017.05.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 05/12/2017] [Indexed: 01/04/2023] Open
Abstract
Background It was previously found that Korean Red Ginseng water extract (KRGE) inhibits the histamine-induced itch signaling pathway in peripheral sensory neurons. Thus, in the present study, we investigated whether KRGE inhibited another distinctive itch pathway induced by chloroquine (CQ); a representative histamine-independent pathway mediated by MrgprA3 and TRPA1. Methods Intracellular calcium changes were measured by the calcium imaging technique in the HEK293T cells transfected with both MrgprA3 and TRPA1 ("MrgprA3/TRPA1"), and in primary culture of mouse dorsal root ganglia (DRGs). Mouse scratching behavior tests were performed to verify proposed antipruritic effects of KRGE and ginsenoside Rg3. Results CQ-induced Ca2+ influx was strongly inhibited by KRGE (10 μg/mL) in MrgprA3/TRPA1, and notably ginsenoside Rg3 dose-dependently suppressed CQ-induced Ca2+ influx in MrgprA3/TRPA1. Moreover, both KRGE (10 μg/mL) and Rg3 (100 μM) suppressed CQ-induced Ca2+ influx in primary culture of mouse DRGs, indicating that the inhibitory effect of KRGE was functional in peripheral sensory neurons. In vivo tests revealed that not only KRGE (100 mg) suppressed CQ-induced scratching in mice [bouts of scratching: 274.0 ± 51.47 (control) vs. 104.7 ± 17.39 (KRGE)], but also Rg3 (1.5 mg) oral administration significantly reduced CQ-induced scratching as well [bouts of scratching: 216.8 ± 33.73 (control) vs. 115.7 ± 20.94 (Rg3)]. Conclusion The present study verified that KRGE and Rg3 have a strong antipruritic effect against CQ-induced itch. Thus, KRGE is as a promising antipruritic agent that blocks both histamine-dependent and -independent itch at peripheral sensory neuronal levels.
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Resokaempferol-mediated anti-inflammatory effects on activated macrophages via the inhibition of JAK2/STAT3, NF-κB and JNK/p38 MAPK signaling pathways. Int Immunopharmacol 2016; 38:104-14. [PMID: 27261558 DOI: 10.1016/j.intimp.2016.05.010] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Revised: 05/16/2016] [Accepted: 05/16/2016] [Indexed: 11/21/2022]
Abstract
The excessive or prolonged production of inflammatory mediators can result in numerous chronic diseases, such as rheumatoid arthritis, atherosclerosis, diabetes, and cancer. Therefore, for many inflammatory-related diseases, pharmaceutical intervention is required to restrain the excessive release of such inflammatory mediators. Novel therapeutics and mechanistic insight are sought for the management of chronic inflammatory diseases. Resokaempferol (RES) is a type of flavonoid recently reported to demonstrate anti-cancer properties. However, the anti-inflammatory capacity of RES has not been studied to date. Therefore, this study investigated whether RES is capable of suppressing the inflammatory response to lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the mechanism by which this is achieved. We found that RES attenuated the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1) and IL-6. RES also inhibited the nuclear translocation of signal transducer and activator of transcription (STAT) 3 and reduced the LPS-mediated phosphorylation of Janus kinase (JAK) 2 and STAT3 at the sites of Ser727 and Tyr705. RES also inhibited the activation of NF-κB and JNK/p38 MAPK signaling pathways in LPS-induced RAW264.7 cells. Additionally, RES inhibited the activation of the JAK2/STAT3 pathway in exogenous IL-6-activated RAW264.7 macrophages. We conclude that RES inhibits the inflammatory response in activated macrophages by blocking the activation of the JAK2/STAT3 pathway by both LPS and IL-6 signaling.
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Yu T, Rhee MH, Lee J, Kim SH, Yang Y, Kim HG, Kim Y, Kim C, Kwak YS, Kim JH, Cho JY. Ginsenoside Rc from Korean Red Ginseng (Panax ginseng C.A. Meyer) Attenuates Inflammatory Symptoms of Gastritis, Hepatitis and Arthritis. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2016; 44:595-615. [DOI: 10.1142/s0192415x16500336] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Korean Red Ginseng (KRG) is an herbal medicine prescribed worldwide that is prepared from Panax ginseng C.A. Meyer (Araliaceae). Out of ginseng’s various components, ginsenosides are regarded as the major ingredients, exhibiting anticancer and anti-inflammatory activities. Although recent studies have focused on understanding the anti-inflammatory activities of KRG, compounds that are major anti-inflammatory components, precisely how these can suppress various inflammatory processes has not been fully elucidated yet. In this study, we aimed to identify inhibitory saponins, to evaluate the in vivo efficacy of the saponins, and to understand the inhibitory mechanisms. To do this, we employed in vitro lipopolysaccharide-treated macrophages and in vivo inflammatory mouse conditions, such as collagen (type II)-induced arthritis (CIA), EtOH/HCl-induced gastritis, and lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-triggered hepatitis. Molecular mechanisms were also verified by real-time PCR, immunoblotting analysis, and reporter gene assays. Out of all the ginsenosides, ginsenoside Rc (G-Rc) showed the highest inhibitory activity against the expression of tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-1[Formula: see text], and interferons (IFNs). Similarly, this compound attenuated inflammatory symptoms in CIA, EtOH/HCl-mediated gastritis, and LPS/D-galactosamine (D-GalN)-triggered hepatitis without altering toxicological parameters, and without inducing gastric irritation. These anti-inflammatory effects were accompanied by the suppression of TNF-[Formula: see text] and IL-6 production and the induction of anti-inflammatory cytokine IL-10 in mice with CIA. G-Rc also attenuated the increased levels of luciferase activity by IRF-3 and AP-1 but not NF-[Formula: see text]B. In support of this phenomenon, G-Rc reduced TBK1, IRF-3, and ATF2 phosphorylation in the joint and liver tissues of mice with hepatitis. Therefore, our results strongly suggest that G-Rc may be a major component of KRG with useful anti-inflammatory properties due to its suppression of IRF-3 and AP-1 pathways.
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Affiliation(s)
- Tao Yu
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
- Medical College, Qingdao University, Qingdao 266021, P. R. China
| | - Man Hee Rhee
- College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Jongsung Lee
- Department of Genetic Engineering, Sungkyunkwan University, 2066 Seobu-ro Jangan-gu, Suwon 16419, Republic of Korea
| | - Seung Hyung Kim
- Institute of Traditional Medicine and Bioscience, Daejeon University, Daejeon 34520, Republic of Korea
| | - Yanyan Yang
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
- Medical College, Qingdao University, Qingdao 266021, P. R. China
| | - Han Gyung Kim
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Yong Kim
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Chaekyun Kim
- Department of Pharmacology, Inha University School of Medicine, Incheon 22212, Republic of Korea
| | - Yi-Seong Kwak
- Korean Ginseng Corporation, Central Research Institute, Daejeon 34337, Republic of Korea
| | - Jong-Hoon Kim
- Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University, Iksan 54596, Republic of Korea
| | - Jae Youl Cho
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
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Lee YM, Yoon H, Park HM, Song BC, Yeum KJ. Implications of red Panax ginseng in oxidative stress associated chronic diseases. J Ginseng Res 2016; 41:113-119. [PMID: 28413314 PMCID: PMC5386131 DOI: 10.1016/j.jgr.2016.03.003] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 03/02/2016] [Accepted: 03/04/2016] [Indexed: 11/28/2022] Open
Abstract
The steaming process of Panax ginseng has been reported to increase its major known bioactive components, ginsenosides, and, therefore, its biological properties as compared to regular Panax ginseng. Biological functions of red Panax ginseng attenuating pro-oxidant environments associated with chronic diseases are of particular interest, since oxidative stress can be a key contributor to the pathogenesis of chronic diseases. Additionally, proper utilization of various biomarkers for evaluating antioxidant activities in natural products, such as ginseng, can also be important to providing validity to their activities. Thus, studies on the effects of red ginseng against various diseases as determined in cell lines, animal models, and humans were reviewed, along with applied biomarkers for verifying such effects. Limitations and future considerations of studying red ginseng were been discussed. Although further clinical studies are warranted, red ginseng appears to be beneficial for attenuating disease-associated symptoms via its antioxidant activities, as well as for preventing oxidative stress-associated chronic diseases.
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Affiliation(s)
- Yoon-Mi Lee
- Division of Food Bioscience, College of Biomedical and Health Sciences, Konkuk University, Chungju, Korea
| | - Haelim Yoon
- Division of Food Bioscience, College of Biomedical and Health Sciences, Konkuk University, Chungju, Korea
| | - Hyun-Min Park
- Division of Food Bioscience, College of Biomedical and Health Sciences, Konkuk University, Chungju, Korea
| | - Byeng Chun Song
- Division of Food Bioscience, College of Biomedical and Health Sciences, Konkuk University, Chungju, Korea
| | - Kyung-Jin Yeum
- Division of Food Bioscience, College of Biomedical and Health Sciences, Konkuk University, Chungju, Korea
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Oh MJ, Kim HJ, Park EY, Ha NH, Song MG, Choi SH, Chun BG, Kim DH. The effect of Korean Red Ginseng extract on rosiglitazone-induced improvement of glucose regulation in diet-induced obese mice. J Ginseng Res 2016; 41:52-59. [PMID: 28123322 PMCID: PMC5223077 DOI: 10.1016/j.jgr.2015.12.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 12/16/2015] [Accepted: 12/30/2015] [Indexed: 01/08/2023] Open
Abstract
Background Korean Red Ginseng extract (KRG, Panax ginseng Meyer) and its constituents have been used for treating diabetes. However, in diet-induced obese mice, it is unclear whether KRG can enhance the glucose-lowering action of rosiglitazone (ROSI), a peroxisome proliferator-activated receptor gamma synthetic activator. Methods Oral glucose tolerance tests (oGTTs) were performed after 4 days of treatment with a vehicle (CON), KRG [500 mg/kg body weight (b.w.)], ROSI (3.75 mg/kg b.w, 7.5 mg/kg b.w, and 15 mg/kg b.w.), or ROSI and KRG (RK) in obese mice on a high-fat diet. Adipose tissue morphology, crown-like structures (CLSs), and inflammation were compared by hematoxylin-eosin staining or quantitative reverse transcription polymerase chain reaction. Results The area under the glucose curve (AUC) was significantly lower in the RK group (15 mg/kg b.w. and 500 mg/kg b.w. for ROSI and KRG, respectively) than in the CON group. There was no significant difference in the AUC between the CON and the other groups. Furthermore, the AUC was significantly lower in the RK group than in the ROSI group. The expression of the Ccl2 gene and the number of CLSs were significantly reduced in the RK group than in the CON group. Conclusion Our results show a potential enhancement of ROSI-induced improvement of glucose regulation by the combined treatment with KRG.
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Affiliation(s)
- Mi-Jeong Oh
- Department of Pharmacology, Korea University College of Medicine, Seoul, Korea
| | - Hyun-Ju Kim
- Department of Pharmacology, Korea University College of Medicine, Seoul, Korea
| | - Eun-Young Park
- Department of Pharmacology, Korea University College of Medicine, Seoul, Korea
| | - Na-Hee Ha
- Department of Pharmacology, Korea University College of Medicine, Seoul, Korea
| | - Mun-Gyu Song
- Department of Pharmacology, Korea University College of Medicine, Seoul, Korea
| | - Sang-Hyun Choi
- Department of Pharmacology, Korea University College of Medicine, Seoul, Korea
| | - Boe-Gwun Chun
- Department of Pharmacology, Korea University College of Medicine, Seoul, Korea
| | - Dong-Hoon Kim
- Department of Pharmacology, Korea University College of Medicine, Seoul, Korea
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Jung S, Lee MS, Shin Y, Kim CT, Kim IH, Kim Y. High Hydrostatic Pressure Extract of Red Ginseng Attenuates Inflammation in Rats with High-fat Diet Induced Obesity. Prev Nutr Food Sci 2015; 20:253-9. [PMID: 26770912 DOI: 10.3746/pnf.2015.20.4.253] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 09/25/2015] [Indexed: 01/30/2023] Open
Abstract
Chronic low-grade inflammation is associated with obesity. This study investigated effect of high hydrostatic pressure extract of red ginseng (HRG) on inflammation in rats with high-fat (HF) diet induced obesity. Male, Sprague-Dawley rats (80~110 g) were randomly divided into two groups, and fed a 45% HF diet (HF) and a 45% HF diet containing 1.5% HRG (HF+HRG) for 14 weeks. At the end of the experiment, the serum leptin level was reduced by the HRG supplementation. The mRNA expression of genes related to adipogenesis including peroxisome proliferator-activated receptor-gamma and adipocyte protein 2 was down-regulated in the white adipose tissue (WAT). The mRNA levels of major inflammatory cytokines such as tumor necrosis factor-α, monocyte chemoattractant protein 1, and interleukin-6 were remarkably down-regulated by the HRG in WAT. These results suggest that HRG might be beneficial in ameliorating the inflammation-associated health complications by suppressing adipogenic and pro-inflammatory gene expression.
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Affiliation(s)
- Sunyoon Jung
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea
| | - Mak-Soon Lee
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea
| | - Yoonjin Shin
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea
| | - Chong-Tai Kim
- Functional Materials Research Group, Korea Food Research Institute, Seongnam, Gyeonggi 13539, Korea
| | - In-Hwan Kim
- Department of Food and Nutrition, Korea University, Seoul 02841, Korea
| | - Yangha Kim
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea
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Cho YS, Kim CH, Ha TS, Ahn HY. Inhibition of STAT3 phosphorylation by sulforaphane reduces adhesion molecule expression in vascular endothelial cell. Can J Physiol Pharmacol 2015; 94:1220-1226. [PMID: 27681094 DOI: 10.1139/cjpp-2015-0150] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) play key roles in the initiation of vascular inflammation. In this study, we explored whether sulforaphane, a dietary phytochemical, can inhibit the expression of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS), and the mechanisms involved. Sulforaphane prevented the LPS-mediated increase in ICAM-1 and VCAM-1 expression, (P < 0.01) in HUVEC. Sulforaphane also prevented the LPS-mediated increase in the phosphorylation of signal transducer and activator of transcription 3 (STAT3) (P < 0.01). Stattic, a STAT3 inhibitor, reduced the LPS-induced expression of ICAM-1 and VCAM-1, and STAT3 phosphorylation (P < 0.01). STAT3 small interfering RNA treatment reduced the LPS-induced expression of ICAM-1, VCAM-1, and STAT3 (P < 0.01). Sulforaphane reduced LPS-mediated THP-1 monocyte adhesion to HUVEC (P < 0.01). In C57BL/6 mice, injection of LPS increased aortic ICAM-1 and VCAM-1 expression, and this effect was prevented by sulforaphane. These data provide insight into the mechanism through which sulforaphane partly reduces the expression of ICAM-1 and VCAM-1 on the vascular wall by inhibiting STAT3 phosphorylation.
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Affiliation(s)
- Young S Cho
- a Department of Pharmacology, College of Medicine, Chungbuk University, Cheongju, 28644 Republic of Korea
| | - Chan H Kim
- a Department of Pharmacology, College of Medicine, Chungbuk University, Cheongju, 28644 Republic of Korea
| | - Tae S Ha
- b Department of Pediatrics, College of Medicine, Chungbuk University, Cheongju, 28644 Republic of Korea
| | - Hee Y Ahn
- a Department of Pharmacology, College of Medicine, Chungbuk University, Cheongju, 28644 Republic of Korea
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Nguyen CT, Luong TT, Lee SY, Kim GL, Kwon H, Lee HG, Park CK, Rhee DK. Panax ginseng aqueous extract prevents pneumococcal sepsis in vivo by potentiating cell survival and diminishing inflammation. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2015; 22:1055-1061. [PMID: 26407948 DOI: 10.1016/j.phymed.2015.07.005] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Revised: 07/14/2015] [Accepted: 07/17/2015] [Indexed: 06/05/2023]
Abstract
BACKGROUND More than 50% of sepsis cases are caused by Streptococcus pneumoniae, and hospital mortality related to sepsis comprises 52% of all hospital deaths. Therefore, sepsis is a medical emergency, and any treatment against the agent that produces it, is welcome. PURPOSE The role of Panax ginseng C.A. Meyer (Araliaceae) aqueous extract in bacterial infection in vivo is not well understood. Here, the protective effect of Korean red ginseng (KRG) extract against pneumococcal infection and sepsis was elucidated. STUDY DESIGN In this study, mice were administrated KRG (25, 50, 100 mg/kg) for 15 days, and then infected with a lethal S. pneumoniae strain. Survival rate, body weight, and colonization were determined. METHODS The RAW 264.7 macrophage cells were infected with S. pneumoniae and cell viability was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Inflammation was examined using an enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin (HE) staining while gene expression was determined using western blotting. RESULTS KRG-pre-treated mice (100 mg/kg of KRG) had significantly higher survival rates and body weights than those of the non-treated controls; KRG-pre-treated mice had lower bacterial number and morbidity than those of the non-treated controls. 100 mg/kg of KRG administration decreased cytokine levels including tumor necrosis factor (TNF)-α (897 and 623 pg/ml, control and KRG groups, respectively, P < 0.05) and interleukin (IL)-1β (175 and 127 pg/ml, control and KRG groups, respectively, P = 0.051), nitric oxide level (149 and 81 nM, control and KRG groups, respectively, P < 0.05), and neutrophil infiltration 48 h post-infection, in vivo. In pneumococcal infection, KRG pre-treatment downregulated toll-like receptor (TLR) 4 and TNF-ɑ expressions in RAW 264.7 macrophage cells and increased cell survival by activating phosphoinositide 3-kinase (PI3K)/AKT signaling. CONCLUSION Taken together, 100 mg/kg of KRG appeared to protect host cells from lethal pneumococcal sepsis by inhibiting inflammation as well as by enhancing bacterial clearance thereby reinforcing cell survival against pneumococcal infection.
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Affiliation(s)
- Cuong Thach Nguyen
- School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Truc Thanh Luong
- School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Seung Yeop Lee
- School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Gyu Lee Kim
- School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Hyogyoung Kwon
- Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Asan 336-745, Republic of Korea
| | - Hong-Gyun Lee
- The Korean Ginseng Research Institute, Korea Ginseng Co., Daejeon 305-805, Republic of Korea
| | - Chae-Kyu Park
- The Korean Ginseng Research Institute, Korea Ginseng Co., Daejeon 305-805, Republic of Korea
| | - Dong-Kwon Rhee
- School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
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Menheniott TR, Judd LM, Giraud AS. STAT3: a critical component in the response to Helicobacter pylori infection. Cell Microbiol 2015; 17:1570-82. [PMID: 26332850 DOI: 10.1111/cmi.12518] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Revised: 08/16/2015] [Accepted: 08/28/2015] [Indexed: 12/15/2022]
Abstract
STAT3 imparts a profound influence on both the epithelial and immune components of the gastric mucosa, and through regulation of key intracellular signal transduction events, is well placed to control inflammatory and oncogenic outcomes in the context of Helicobacter (H.) pylori infection. Here we review the roles of STAT3 in the host immune response to H. pylori infection, from both gastric mucosal and systemic perspectives, as well as alluding more specifically to STAT3-dependent mechanisms that might be exploited as drug targets.
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Affiliation(s)
- Trevelyan R Menheniott
- Murdoch Children's Research Institute, Melbourne, Victoria, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
| | - Louise M Judd
- Murdoch Children's Research Institute, Melbourne, Victoria, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
| | - Andrew S Giraud
- Murdoch Children's Research Institute, Melbourne, Victoria, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
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Cha B, Lim JW, Kim H. Jak1/Stat3 is an upstream signaling of NF-κB activation in Helicobacter pylori-induced IL-8 production in gastric epithelial AGS cells. Yonsei Med J 2015; 56:862-6. [PMID: 25837197 PMCID: PMC4397461 DOI: 10.3349/ymj.2015.56.3.862] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) induces the activation of nuclear factor-kB (NF-κB) and cytokine expression in gastric epithelial cells. The Janus kinase/signal transducers and activators of transcription (Jak/Stat) cascade is the inflammatory signaling in various cells. The purpose of the present study is to determine whether H. pylori-induced activation of NF-κB and the expression of interleukin-8 (IL-8) are mediated by the activation of Jak1/Stat3 in gastric epithelial (AGS) cells. Thus, gastric epithelial AGS cells were infected with H. pylori in Korean isolates (HP99) at bacterium/cell ratio of 300:1, and the level of IL-8 in the medium was determined by enzyme-linked immonosorbent assay. Phospho-specific and total forms of Jak1/Stat3 and IκBα were assessed by Western blot analysis, and NF-κB activation was determined by electrophoretic mobility shift assay. The results showed that H. pylori induced the activation of Jak1/Stat3 and IL-8 production, which was inhibited by a Jak/Stat3 specific inhibitor AG490 in AGS cells in a dose-dependent manner. H. pylori-induced activation of NF-κB, determined by phosphorylation of IκBα and NF-κB-DNA binding activity, were inhibited by AG490. In conclusion, Jak1/Stat3 activation may mediate the activation of NF-κB and the expression of IL-8 in H. pylori-infected AGS cells. Inhibition of Jak1/Stat3 may be beneficial for the treatment of H. pylori-induced gastric inflammation, since the activation of NF-κB is inhibited and inflammatory cytokine expression is suppressed.
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Affiliation(s)
- Boram Cha
- Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea
| | - Joo Weon Lim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea
| | - Hyeyoung Kim
- Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.; Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea.
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De Monte C, Bizzarri B, Gidaro MC, Carradori S, Mollica A, Luisi G, Granese A, Alcaro S, Costa G, Basilico N, Parapini S, Scaltrito MM, Masia C, Sisto F. Bioactive compounds of Crocus sativus L. and their semi-synthetic derivatives as promising anti-Helicobacter pylori, anti-malarial and anti-leishmanial agents. J Enzyme Inhib Med Chem 2015; 30:1027-33. [DOI: 10.3109/14756366.2014.1001755] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Celeste De Monte
- Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, Rome, Italy,
| | - Bruna Bizzarri
- Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, Rome, Italy,
| | - Maria Concetta Gidaro
- Dipartimento di Scienze della Salute, “Magna Graecia” University of Catanzaro, Campus Universitario “S. Venuta”, Viale Europa Loc. Germaneto, Catanzaro, Italy,
| | - Simone Carradori
- Department of Pharmacy, “G. D’Annunzio” University of Chieti-Pescara, Chieti, Italy,
| | - Adriano Mollica
- Department of Pharmacy, “G. D’Annunzio” University of Chieti-Pescara, Chieti, Italy,
| | - Grazia Luisi
- Department of Pharmacy, “G. D’Annunzio” University of Chieti-Pescara, Chieti, Italy,
| | - Arianna Granese
- Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, Rome, Italy,
| | - Stefano Alcaro
- Dipartimento di Scienze della Salute, “Magna Graecia” University of Catanzaro, Campus Universitario “S. Venuta”, Viale Europa Loc. Germaneto, Catanzaro, Italy,
| | - Giosuè Costa
- Dipartimento di Scienze della Salute, “Magna Graecia” University of Catanzaro, Campus Universitario “S. Venuta”, Viale Europa Loc. Germaneto, Catanzaro, Italy,
| | - Nicoletta Basilico
- Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, University of Milan, Milan, Italy, and
| | - Silvia Parapini
- Dipartimento di Scienze Farmacologiche e Biomolecolari, University of Milan, Milan, Italy
| | - Maria Maddalena Scaltrito
- Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, University of Milan, Milan, Italy, and
| | - Carla Masia
- Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, University of Milan, Milan, Italy, and
| | - Francesca Sisto
- Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, University of Milan, Milan, Italy, and
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NADPH oxidases: an overview from structure to innate immunity-associated pathologies. Cell Mol Immunol 2014; 12:5-23. [PMID: 25263488 DOI: 10.1038/cmi.2014.89] [Citation(s) in RCA: 664] [Impact Index Per Article: 60.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Revised: 08/18/2014] [Accepted: 08/18/2014] [Indexed: 12/11/2022] Open
Abstract
Oxygen-derived free radicals, collectively termed reactive oxygen species (ROS), play important roles in immunity, cell growth, and cell signaling. In excess, however, ROS are lethal to cells, and the overproduction of these molecules leads to a myriad of devastating diseases. The key producers of ROS in many cells are the NOX family of NADPH oxidases, of which there are seven members, with various tissue distributions and activation mechanisms. NADPH oxidase is a multisubunit enzyme comprising membrane and cytosolic components, which actively communicate during the host responses to a wide variety of stimuli, including viral and bacterial infections. This enzymatic complex has been implicated in many functions ranging from host defense to cellular signaling and the regulation of gene expression. NOX deficiency might lead to immunosuppression, while the intracellular accumulation of ROS results in the inhibition of viral propagation and apoptosis. However, excess ROS production causes cellular stress, leading to various lethal diseases, including autoimmune diseases and cancer. During the later stages of injury, NOX promotes tissue repair through the induction of angiogenesis and cell proliferation. Therefore, a complete understanding of the function of NOX is important to direct the role of this enzyme towards host defense and tissue repair or increase resistance to stress in a timely and disease-specific manner.
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Elfvin A, Edebo A, Hallersund P, Casselbrant A, Fändriks L. Oxidative and nitrosative stress enzymes in relation to nitrotyrosine in Helicobacter pylori-infected humans. World J Gastrointest Pathophysiol 2014; 5:373-379. [PMID: 25133038 PMCID: PMC4133535 DOI: 10.4291/wjgp.v5.i3.373] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Revised: 04/25/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare a possible relation between Helicobacter pylori (H. pylori) and the oxygen- and nitrogen radical system in humans.
METHODS: Mechanisms for H. pylori to interfere with the oxygen and nitrogen radical system is of great importance for understanding of the H. pylori persistence and pathogenesis. Biopsies were obtained from the gastric wall of 21 individuals. Ongoing infection with H. pylori was detected using direct analyze from the biopsies using campylobacter-like organism test (CLO-test) and/or by using 14C-urea breath test. The individuals were divided in a negative H. pylori and a positive H. pylori group. Expression in the gastric mucosa of inducible nitric oxide syntase (iNOS), nicotinamide adenine dinucleotide phosphate-oxidase (NADPH-oxidase) myeloperoxidase (MPO), and nitrotyrosine were assessed by Western blotting.
RESULTS: The individuals who undervent gastroscopy were divided in a H. pylori neg. [n = 13, m/f = 7/6, age (mean) = 39] and a H. pylori pos. group [n= 8, m/f = 5/3, age (mean) = 53]. Using western blot analysis iNOS was detected as a 130 kDa band. The iNOS expression was upregulated in the antrum of H. pylori infected individuals in comparison to the controls, mean ± SD being 12.6 ± 2.4 vs 8.3 ± 3.1, P < 0.01. There was a markedly upregulated expression of MPO in the antrum of H. pylori infected individuals in comparison to the control group without infection. In several of non-infected controls it was not possible to detect any MPO expression at all, whereas the expression was high in all the infected subjects, mean ± SD being 5.1 ± 3.4 vs 2.1 ± 1.9, P < 0.05. The NADPH-oxidase expression was analysed by detecting the NADPH-oxidase subunit p47-phox expression. P47-phox was detected as a 47 kDa band using Western blot, and showed a significantly higher expression of p47-phox in the antrum of the H. pylori infected individuals compared to the controls, mean ± SD being 3.1 ± 2.2 vs 0.3 ± 0.2, P < 0.01. Regarding nitrotyrosine formation, Western blot did not show any significant increase or decrease compared to controls, 7.0 ± 0.9 vs 6.9 ± 1.1, not significant.
CONCLUSION: iNOS, MPO and NADPH-oxidase was up-regulated among H. pylori infected. Regarding nitrotyrosine no difference was found. This support an H. pylori related inhibition of radical formation.
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Seo SK, Hong Y, Yun BH, Chon SJ, Jung YS, Park JH, Cho S, Choi YS, Lee BS. Antioxidative effects of Korean red ginseng in postmenopausal women: a double-blind randomized controlled trial. JOURNAL OF ETHNOPHARMACOLOGY 2014; 154:753-757. [PMID: 24814037 DOI: 10.1016/j.jep.2014.04.051] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 04/09/2014] [Accepted: 04/22/2014] [Indexed: 06/03/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Red ginseng (RG) has been widely used to treat various diseases in East Asian countries. Previous studies have shown the anti-oxidative and anti-diabetic effects of RG. This study aimed to investigate the effects of RG on oxidative stress and insulin resistance in postmenopausal women. MATERIALS AND METHODS We performed a randomized, double-blind, placebo-controlled trial in 82 postmenopausal women aged 45-60 years. Participants were randomized to receive 3g red ginseng daily or placebo for 12 weeks. Antioxidant enzymes activity (superoxide dismutase, glutathione peroxidase) and oxidative stress markers (malondialdehyde, 8-hydroxydeoxyguanosine) were assessed, and the homeostatic model assessment of insulin resistance index was calculated at the baseline and at the end of the trial. RESULTS A total of 71 postmenopausal women completed the study. Serum superoxide dismutase activity was significantly increased after the 12-week RG supplementation (P<0.001), and these changes were statistically significant compared with the placebo group (P=0.004). Serum malondialdehyde levels showed a tendency to decrease after the 12-week RG supplementation (P=0.001), but these changes were not statistically significant compared with the placebo group (P=0.064). No statistically significant changes in serum glutathione peroxidase and 8-hydroxydeoxyguanosine were noted. Further, RG supplementation showed no effects on fasting glucose, fasting insulin, and insulin resistance. CONCLUSIONS The results suggest that RG may reduce oxidative stress by increasing antioxidant enzyme activity in postmenopausal women.
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Affiliation(s)
- Seok Kyo Seo
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Institute of Women׳s Life Medical Science, Seoul, Korea
| | - Yeon Hong
- Institute of Women׳s Life Medical Science, Seoul, Korea; Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, 146-92 Dogok-dong, Gangnam-gu, Seoul 135-720, Korea
| | - Bo Hyon Yun
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Institute of Women׳s Life Medical Science, Seoul, Korea
| | - Seung Joo Chon
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Institute of Women׳s Life Medical Science, Seoul, Korea
| | - Yeon Soo Jung
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Institute of Women׳s Life Medical Science, Seoul, Korea
| | - Joo Hyun Park
- Institute of Women׳s Life Medical Science, Seoul, Korea; Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, 146-92 Dogok-dong, Gangnam-gu, Seoul 135-720, Korea
| | - SiHyun Cho
- Institute of Women׳s Life Medical Science, Seoul, Korea; Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, 146-92 Dogok-dong, Gangnam-gu, Seoul 135-720, Korea
| | - Young Sik Choi
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Institute of Women׳s Life Medical Science, Seoul, Korea
| | - Byung Seok Lee
- Institute of Women׳s Life Medical Science, Seoul, Korea; Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, 146-92 Dogok-dong, Gangnam-gu, Seoul 135-720, Korea.
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Nguyen CT, Luong TT, Kim GL, Pyo S, Rhee DK. Korean Red Ginseng inhibits apoptosis in neuroblastoma cells via estrogen receptor β-mediated phosphatidylinositol-3 kinase/Akt signaling. J Ginseng Res 2014; 39:69-75. [PMID: 25535479 PMCID: PMC4268566 DOI: 10.1016/j.jgr.2014.06.005] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Revised: 06/02/2014] [Accepted: 06/12/2014] [Indexed: 02/07/2023] Open
Abstract
Background Ginseng has been shown to exert antistress effects both in vitro and in vivo. However, the effects of ginseng on stress in brain cells are not well understood. This study investigated how Korean Red Ginseng (KRG) controls hydrogen peroxide-induced apoptosis via regulation of phosphatidylinositol-3 kinase (PI3K)/Akt and estrogen receptor (ER)-β signaling. Methods Human neuroblastoma SK-N-SH cells were pretreated with KRG and subsequently exposed to H2O2. The ability of KRG to inhibit oxidative stress-induced apoptosis was assessed in MTT cytotoxicity assays. Apoptotic protein expression was examined by Western blot analysis. The roles of ER-β, PI3K, and p-Akt signaling in KRG regulation of apoptosis were studied using small interfering RNAs and/or target antagonists. Results Pretreating SK-N-SH cells with KRG decreased expression of the proapoptotic proteins p-p53 and caspase-3, but increased expression of the antiapoptotic protein BCL2. KRG pretreatment was also associated with increased ER-β, PI3K, and p-Akt expression. Conversely, ER-β inhibition with small interfering RNA or inhibitor treatment increased p-p53 and caspase-3 levels, but decreased BCL2, PI3K, and p-Akt expression. Moreover, inhibition of PI3K/Akt signaling diminished p-p53 and caspase-3 levels, but increased BCL2 expression. Conclusion Collectively, the data indicate that KRG represses oxidative stress-induced apoptosis by enhancing PI3K/Akt signaling via upregulation of ER-β expression.
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Affiliation(s)
| | | | - Gyu-Lee Kim
- School of Pharmacy, Sungkyunkwan University, Su-Won, Korea
| | - Suhkneung Pyo
- School of Pharmacy, Sungkyunkwan University, Su-Won, Korea
| | - Dong-Kwon Rhee
- School of Pharmacy, Sungkyunkwan University, Su-Won, Korea
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Yang Y, Yang WS, Yu T, Sung GH, Park KW, Yoon K, Son YJ, Hwang H, Kwak YS, Lee CM, Rhee MH, Kim JH, Cho JY. ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water extract. JOURNAL OF ETHNOPHARMACOLOGY 2014; 154:218-228. [PMID: 24735861 DOI: 10.1016/j.jep.2014.04.008] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2014] [Revised: 03/04/2014] [Accepted: 04/04/2014] [Indexed: 06/03/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Korean Red Ginseng (KRG) is one of the representative traditional herbal medicines prepared from Panax ginseng Meyer (Araliaceae) in Korea. It has been reported that KRG exhibits a lot of different biological actions such as anti-aging, anti-fatigue, anti-stress, anti-atherosclerosis, anti-diabetic, anti-cancer, and anti-inflammatory activities. Although systematic studies have investigated how KRG is able to ameliorate various inflammatory diseases, its molecular inhibitory mechanisms had not been carried out prior to this study. MATERIALS AND METHODS In order to investigate these mechanisms, we evaluated the effects of a water extract of Korean Red Ginseng (KRG-WE) on the in vitro inflammatory responses of activated RAW264.7 cells, and on in vivo gastritis and peritonitis models by analyzing the activation events of inflammation-inducing transcription factors and their upstream kinases. RESULTS KRG-WE reduced the production of nitric oxide (NO), protected cells against NO-induced apoptosis, suppressed mRNA levels of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and interferon (IFN)-β, ameliorated EtOH/HCl-induced gastritis, and downregulated peritoneal exudate-derived NO production from lipopolysaccharide (LPS)-injected mice. The inhibition of these inflammatory responses by KRG-WE was regulated through the suppression of p38, c-Jun N-terminal kinase (JNK), and TANK-binding kinase 1 (TBK1) and by subsequent inhibition of activating transcription factor (ATF)-2, cAMP response element-binding protein (CREB), and IRF-3 activation. Of ginsensides included in this extract, interestingly, G-Rc showed the highest inhibitory potency on IRF-3-mediated luciferase activity. CONCLUSION These results strongly suggest that the anti-inflammatory activities of KRG-WE could be due to its inhibition of the p38/JNK/TBK1 activation pathway.
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Affiliation(s)
- Yanyan Yang
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Woo Seok Yang
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Tao Yu
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Gi-Ho Sung
- Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 369-873, Republic of Korea
| | - Kye Won Park
- Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Keejung Yoon
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Young-Jin Son
- Department of Pharmacy, Sunchon National University, Suncheon 540-742, Republic of Korea
| | - Hyunsik Hwang
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Yi-Seong Kwak
- Ginseng Corporation Central Research Institute, Daejeon 305-805, Republic of Korea
| | - Chang-Muk Lee
- Metabolic Engineering Division, National Academy of Agricultural Science, Rural Development Administration, Suwon 441-707, Republic of Korea
| | - Man Hee Rhee
- College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea
| | - Jong-Hoon Kim
- Department of Veterinary Physiology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, Jeonju 561-756, Republic of Korea.
| | - Jae Youl Cho
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
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