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Kim SE, Chung G, Kim SK. Phytochemical-based therapeutics from traditional eastern medicine: analgesic effects and ion channel modulation. FRONTIERS IN PAIN RESEARCH 2025; 6:1537154. [PMID: 39958366 PMCID: PMC11825757 DOI: 10.3389/fpain.2025.1537154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 01/09/2025] [Indexed: 02/18/2025] Open
Abstract
Pain management remains a major challenge in the healthcare system. While synthetic analgesics are widely used for pain management, their effectiveness in managing chronic pain is often limited due to low efficacy or side effects. Thus, there is growing interest in exploring alternative pain relief methods, particularly using medicinal plants from traditional Eastern medicine and their phytochemicals. Previous studies have demonstrated the modulatory effects of various phytochemicals derived from herbal medicine on pain-related ion channels, such as voltage-gated sodium channels (Nav), calcium channels (Ca2+), and transient receptor potential (TRP) channels. Since these ion channels are integral to the transmission and modulation of pain signals, the ability of specific phytochemicals to activate or inhibit these channels presents a promising avenue for the development of novel analgesics. The goal of this review is to merge herbal insights with ion channel research to highlight the potential of natural compounds for safe and effective pain management. In this regard, we summarize the discovery and characterization of pain-relieving phytochemicals from herbal medicine, and we discuss their mechanisms of action and their potential to mimic or enhance the effects of conventional analgesics through ion channel modulation.
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Affiliation(s)
| | - Geehoon Chung
- Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Sun Kwang Kim
- Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
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Yang Y, Huang S, Wang J, Nie X, Huang L, Li T. Wogonin attenuates vascular remodeling by inhibiting smooth muscle cell proliferation and migration in hypertensive rat. THE KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY : OFFICIAL JOURNAL OF THE KOREAN PHYSIOLOGICAL SOCIETY AND THE KOREAN SOCIETY OF PHARMACOLOGY 2024; 28:39-48. [PMID: 38154963 PMCID: PMC10762488 DOI: 10.4196/kjpp.2024.28.1.39] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 11/23/2023] [Accepted: 11/24/2023] [Indexed: 12/30/2023]
Abstract
Wogonin, extracted from the roots of Scutellaria baicalensis Georgi, has been shown to suppress collagen deposition in spontaneously hypertensive rats (SHRs). This study was performed to investigate the role and mechanism of wogonin underlying vascular remodeling in SHRs. After injection of SHRs with 40 mg/kg of wogonin, blood pressure in rats was measured once a week. Masson's trichrome staining was conducted to observe the changes in aortas and mesenteric arteries. Vascular smooth muscle cells (VSMCs) isolated from rat thoracic aortas were treated with Angiotensin II (Ang II; 100 nM) in the presence or absence of varying concentrations of wogonin. The viability and proliferation of VSMCs were examined using Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine assay, respectively. The migration of VSMCs was examined using wound healing assay and transwell assay. We found that wogonin administration alleviated hypertension, increased lumen diameter, and reduced the thickness of the arterial media in SHRs. Ang II treatment enhanced the viability of VSMCs, which was inhibited by wogonin in a concentration-dependent manner. Wogonin reversed Ang II-induced increases in the viability, proliferation, and migration of VSMCs. Moreover, wogonin inhibited Ang II-induced activation of mitogen-activated protein kinase (MAPK) signaling in VSMCs. Overall, wogonin repressed the proliferative and migratory capacity of VSMCs by regulating the MAPK signaling pathway, thereby attenuating vascular remodeling in hypertensive rats, indicating that wogonin might be a therapeutic agent for the treatment of vascular diseases.
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Affiliation(s)
- Yang Yang
- Department of Cardiovasology, The First Affiliated Hospital, Hainan Medical University, Haikou 570100, China
| | - Shan Huang
- Department of Cardiovasology, The First Affiliated Hospital, Hainan Medical University, Haikou 570100, China
| | - Jun Wang
- Department of Cardiovasology, The First Affiliated Hospital, Hainan Medical University, Haikou 570100, China
| | - Xiao Nie
- Hainan Eye Hospital and Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Haikou 570311, China
| | - Ling Huang
- Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China
| | - Tianfa Li
- Department of Cardiovasology, The First Affiliated Hospital, Hainan Medical University, Haikou 570100, China
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Rák T, Kovács-Valasek A, Pöstyéni E, Csutak A, Gábriel R. Complementary Approaches to Retinal Health Focusing on Diabetic Retinopathy. Cells 2023; 12:2699. [PMID: 38067127 PMCID: PMC10705724 DOI: 10.3390/cells12232699] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 11/20/2023] [Accepted: 11/20/2023] [Indexed: 12/18/2023] Open
Abstract
Diabetes mellitus affects carbohydrate homeostasis but also influences fat and protein metabolism. Due to ophthalmic complications, it is a leading cause of blindness worldwide. The molecular pathology reveals that nuclear factor kappa B (NFκB) has a central role in the progression of diabetic retinopathy, sharing this signaling pathway with another major retinal disorder, glaucoma. Therefore, new therapeutic approaches can be elaborated to decelerate the ever-emerging "epidemics" of diabetic retinopathy and glaucoma targeting this critical node. In our review, we emphasize the role of an improvement of lifestyle in its prevention as well as the use of phytomedicals associated with evidence-based protocols. A balanced personalized therapy requires an integrative approach to be more successful for prevention and early treatment.
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Affiliation(s)
- Tibor Rák
- Department of Ophthalmology, Clinical Centre, Medical School, University of Pécs, Rákóczi út 2., 7623 Pécs, Hungary; (T.R.)
| | - Andrea Kovács-Valasek
- Department of Neurobiology, University of Pécs, Ifjúság útja 6, 7624 Pécs, Hungary
- János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, 7624 Pécs, Hungary
| | - Etelka Pöstyéni
- Department of Neurobiology, University of Pécs, Ifjúság útja 6, 7624 Pécs, Hungary
| | - Adrienne Csutak
- Department of Ophthalmology, Clinical Centre, Medical School, University of Pécs, Rákóczi út 2., 7623 Pécs, Hungary; (T.R.)
| | - Róbert Gábriel
- Department of Neurobiology, University of Pécs, Ifjúság útja 6, 7624 Pécs, Hungary
- János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, 7624 Pécs, Hungary
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Ji L, Song T, Ge C, Wu Q, Ma L, Chen X, Chen T, Chen Q, Chen Z, Chen W. Identification of bioactive compounds and potential mechanisms of scutellariae radix-coptidis rhizoma in the treatment of atherosclerosis by integrating network pharmacology and experimental validation. Biomed Pharmacother 2023; 165:115210. [PMID: 37499457 DOI: 10.1016/j.biopha.2023.115210] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 07/18/2023] [Accepted: 07/19/2023] [Indexed: 07/29/2023] Open
Abstract
OBJECTIVE This study aims at investigating the potential targets and functional mechanisms of Scutellariae Radix-Coptidis Rhizoma (QLYD) against atherosclerosis (AS) through network pharmacology, molecular docking, bioinformatic analysis and experimental validation. METHODS The compositions of QLYD were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature, where the main active components of QLYD and corresponding targets were identified. The potential therapeutic targets of AS were excavated using the OMIM database, DrugBank database, DisGeNET database, CTD database and GEO datasets. The protein-protein interaction (PPI) network of common targets was constructed and visualized by Cytoscape 3.7.2 software. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to analyze the function of core targets in the PPI network. Molecular docking was carried out using AutoDockTools, AutoDock Vina, and PyMOL software to verify the correlation between the main components of QLYD and the core targets. Mouse AS model was established and the results of network pharmacology were verified by in vivo experiments. RESULTS Totally 49 active components and 225 corresponding targets of QLYD were obtained, where 68 common targets were identified by intersecting with AS-related targets. Five hub genes including IL6, VEGFA, AKT1, TNF, and IL1B were screened from the PPI network. GO functional analysis reported that these targets had associations mainly with cellular response to oxidative stress, regulation of inflammatory response, epithelial cell apoptotic process, and blood coagulation. KEGG pathway analysis demonstrated that these targets were correlated to AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, and NF-kappa B signaling pathway. Results of molecular docking indicated good binding affinity of QLYD to FOS, AKT1, and TNF. Animal experiments showed that QLYD could inhibit inflammation, improve blood lipid levels and reduce plaque area in AS mice to prevent and treat AS. CONCLUSION QLYD may exert anti-inflammatory and anti-oxidative stress effects through multi-component, multi-target and multi-pathway to treat AS.
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Affiliation(s)
- Lingyun Ji
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250355, China
| | - Ting Song
- Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250011, China
| | - Chunlei Ge
- Department of Respiratory Medicine, Linyi Tradition Chinese Medical Hospital, Linyi, Shandong Province 276600, China
| | - Qiaolan Wu
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250355, China
| | - Lanying Ma
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250355, China
| | - Xiubao Chen
- Department of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250011, China
| | - Ting Chen
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250355, China
| | - Qian Chen
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250355, China
| | - Zetao Chen
- Department of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250011, China; Subject of Integrated Chinese and Western Medicine,Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250355, China.
| | - Weida Chen
- Department of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250011, China.
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Kovács-Valasek A, Rák T, Pöstyéni E, Csutak A, Gábriel R. Three Major Causes of Metabolic Retinal Degenerations and Three Ways to Avoid Them. Int J Mol Sci 2023; 24:ijms24108728. [PMID: 37240082 DOI: 10.3390/ijms24108728] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 05/10/2023] [Accepted: 05/11/2023] [Indexed: 05/28/2023] Open
Abstract
An imbalance of homeostasis in the retina leads to neuron loss and this eventually results in a deterioration of vision. If the stress threshold is exceeded, different protective/survival mechanisms are activated. Numerous key molecular actors contribute to prevalent metabolically induced retinal diseases-the three major challenges are age-related alterations, diabetic retinopathy and glaucoma. These diseases have complex dysregulation of glucose-, lipid-, amino acid or purine metabolism. In this review, we summarize current knowledge on possible ways of preventing or circumventing retinal degeneration by available methods. We intend to provide a unified background, common prevention and treatment rationale for these disorders and identify the mechanisms through which these actions protect the retina. We suggest a role for herbal medicines, internal neuroprotective substances and synthetic drugs targeting four processes: parainflammation and/or glial cell activation, ischemia and related reactive oxygen species and vascular endothelial growth factor accumulation, apoptosis and/or autophagy of nerve cells and an elevation of ocular perfusion pressure and/or intraocular pressure. We conclude that in order to achieve substantial preventive or therapeutic effects, at least two of the mentioned pathways should be targeted synergistically. A repositioning of some drugs is considered to use them for the cure of the other related conditions.
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Affiliation(s)
- Andrea Kovács-Valasek
- Department of Experimental Zoology and Neurobiology, University of Pécs, Ifjúság útja 6, 7624 Pécs, Hungary
| | - Tibor Rák
- Department of Ophthalmology, Medical School, University of Pécs, Szigeti út 12, 7624 Pécs, Hungary
| | - Etelka Pöstyéni
- Department of Experimental Zoology and Neurobiology, University of Pécs, Ifjúság útja 6, 7624 Pécs, Hungary
| | - Adrienne Csutak
- Department of Ophthalmology, Medical School, University of Pécs, Szigeti út 12, 7624 Pécs, Hungary
| | - Robert Gábriel
- Department of Experimental Zoology and Neurobiology, University of Pécs, Ifjúság útja 6, 7624 Pécs, Hungary
- János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, 7624 Pécs, Hungary
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Yan Z, Zhong L, Zhu W, Chung SK, Hou P. Chinese herbal medicine for the treatment of cardiovascular diseases ─ targeting cardiac ion channels. Pharmacol Res 2023; 192:106765. [PMID: 37075871 DOI: 10.1016/j.phrs.2023.106765] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 04/04/2023] [Accepted: 04/12/2023] [Indexed: 04/21/2023]
Abstract
Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality, imposing an increasing global health burden. Cardiac ion channels (voltage-gated NaV, CaV, KVs, and others) synergistically shape the cardiac action potential (AP) and control the heartbeat. Dysfunction of these channels, due to genetic mutations, transcriptional or post-translational modifications, may disturb the AP and lead to arrhythmia, a major risk for CVD patients. Although there are five classes of anti-arrhythmic drugs available, they can have varying levels of efficacies and side effects on patients, possibly due to the complex pathogenesis of arrhythmias. As an alternative treatment option, Chinese herbal remedies have shown promise in regulating cardiac ion channels and providing anti-arrhythmic effects. In this review, we first discuss the role of cardiac ion channels in maintaining normal heart function and the pathogenesis of CVD, then summarize the classification of Chinese herbal compounds, and elaborate detailed mechanisms of their efficacy in regulating cardiac ion channels and in alleviating arrhythmia and CVD. We also address current limitations and opportunities for developing new anti-CVD drugs based on Chinese herbal medicines.
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Affiliation(s)
- Zhenzhen Yan
- Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, China
| | - Ling Zhong
- Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, China
| | - Wandi Zhu
- Cardiovascular Medicine Division and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Sookja Kim Chung
- Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, China; Faculty of Medicine & Faculty of Innovation Engineering at Macau University of Science and Technology, Taipa, Macao SAR, China; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China
| | - Panpan Hou
- Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, China; Macau University of Science and Technology Zhuhai MUST Science and Technology Research Institute. Zhuhai, Guangdong, China.
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Deciphering the Mechanism of Wogonin, a Natural Flavonoid, on the Proliferation of Pulmonary Arterial Smooth Muscle Cells by Integrating Network Pharmacology and In Vitro Validation. Curr Issues Mol Biol 2023; 45:555-570. [PMID: 36661523 PMCID: PMC9858126 DOI: 10.3390/cimb45010037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/03/2023] [Accepted: 01/05/2023] [Indexed: 01/11/2023] Open
Abstract
Wogonin is one of the main active components of Scutellaria baicalensis, which has anti-inflammatory, anti-angiogenesis, and anti-fibrosis effects. Nevertheless, the effect of wogonin on pulmonary hypertension (PH) still lacks systematic research. This study aims to elucidate the potential mechanism of wogonin against PH through network pharmacology and further verify it through biological experiments in pulmonary arterial smooth muscle cells (PASMCs). The potential targets and pathways of wogonin against PH were predicted and analyzed by network pharmacology methods and molecular docking technology. Subsequently, the proliferation of PASMCs was induced by platelet-derived growth factor-BB (PDGF-BB). Cell viability and migration ability were examined. The method of Western blot was adopted to analyze the changes in related signaling pathways. Forty potential targets related to the effect of wogonin against PH were obtained. Based on the protein-protein interaction (PPI) network, gene-ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment, and molecular docking, it was shown that the effect of wogonin against PH is closely related to the proliferation of PASMCs and the hypoxia-inducible factor-1α (HIF-1α) pathway. A variety of results from biological experiments verified that wogonin can effectively inhibit the proliferation, migration, and phenotypic transformation of PDGF-BB-mediated PASMCs. In addition, the anti-proliferation effect of wogonin may be achieved by regulating HIF-1/ NADPH oxidase 4 (NOX4) pathway.
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Bai F, Chen Z, Xu S, Han L, Zeng X, Huang S, Zhu Z, Zhou L. Wogonin attenuates neutrophilic inflammation and airway smooth muscle proliferation through inducing caspase-dependent apoptosis and inhibiting MAPK/Akt signaling in allergic airways. Int Immunopharmacol 2022; 113:109410. [DOI: 10.1016/j.intimp.2022.109410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 10/28/2022] [Accepted: 10/29/2022] [Indexed: 11/13/2022]
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Son SH, Kang J, Ahn M, Nam S, Jung YW, Lee KY, Jeon YH, Byun Y, Lee K. Synthesis and Biochemical Evaluation of Baicalein Prodrugs. Pharmaceutics 2021; 13:pharmaceutics13091516. [PMID: 34575592 PMCID: PMC8472512 DOI: 10.3390/pharmaceutics13091516] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/10/2021] [Accepted: 09/14/2021] [Indexed: 12/25/2022] Open
Abstract
Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a flavonoid analog from Scutellaria baicalensis, possesses several pharmacological activities including antioxidant, antiproliferative, and anti-inflammatory activities. We previously reported that baicalein inhibits the thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) signaling pathways and can be used as an active ingredient in the treatment of asthma and atopic dermatitis. However, baicalein is rapidly metabolized to baicalin and baicalein-6-O-glucuronide in vivo, which limits its preclinical and clinical use. In this study, we designed, synthesized, and evaluated baicalein prodrugs that protect the OH group at the 7-position of the A ring in baicalein with the amino acid carbamate functional group. Comprehensive in vitro and in vivo studies identified compound 2 as a baicalein prodrug candidate that improved the plasma exposure of baicalein in mouse animal studies. Our results demonstrated that this prodrug approach could be further adopted to discover oral baicalein prodrugs.
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Affiliation(s)
- Sang-Hyun Son
- College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Korea; (S.-H.S.); (J.K.); (M.A.); (S.N.); (Y.W.J.); (K.Y.L.); (Y.H.J.)
| | - Jinhong Kang
- College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Korea; (S.-H.S.); (J.K.); (M.A.); (S.N.); (Y.W.J.); (K.Y.L.); (Y.H.J.)
| | - Myunghwan Ahn
- College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Korea; (S.-H.S.); (J.K.); (M.A.); (S.N.); (Y.W.J.); (K.Y.L.); (Y.H.J.)
| | - Soyeon Nam
- College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Korea; (S.-H.S.); (J.K.); (M.A.); (S.N.); (Y.W.J.); (K.Y.L.); (Y.H.J.)
| | - Yong Woo Jung
- College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Korea; (S.-H.S.); (J.K.); (M.A.); (S.N.); (Y.W.J.); (K.Y.L.); (Y.H.J.)
- Institute of Pharmaceutical Science and Translational Research, Korea University, 2511 Sejong-ro, Sejong 30019, Korea
| | - Ki Yong Lee
- College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Korea; (S.-H.S.); (J.K.); (M.A.); (S.N.); (Y.W.J.); (K.Y.L.); (Y.H.J.)
- Institute of Pharmaceutical Science and Translational Research, Korea University, 2511 Sejong-ro, Sejong 30019, Korea
| | - Young Ho Jeon
- College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Korea; (S.-H.S.); (J.K.); (M.A.); (S.N.); (Y.W.J.); (K.Y.L.); (Y.H.J.)
- Institute of Pharmaceutical Science and Translational Research, Korea University, 2511 Sejong-ro, Sejong 30019, Korea
| | - Youngjoo Byun
- College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Korea; (S.-H.S.); (J.K.); (M.A.); (S.N.); (Y.W.J.); (K.Y.L.); (Y.H.J.)
- Institute of Pharmaceutical Science and Translational Research, Korea University, 2511 Sejong-ro, Sejong 30019, Korea
- Correspondence: (Y.B.); (K.L.); Tel.: +82-44-860-1619 (Y.B.); +82-44-860-1616 (K.L.)
| | - Kiho Lee
- College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Korea; (S.-H.S.); (J.K.); (M.A.); (S.N.); (Y.W.J.); (K.Y.L.); (Y.H.J.)
- Institute of Pharmaceutical Science and Translational Research, Korea University, 2511 Sejong-ro, Sejong 30019, Korea
- Correspondence: (Y.B.); (K.L.); Tel.: +82-44-860-1619 (Y.B.); +82-44-860-1616 (K.L.)
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Lee J, Lee CY, Seo HH, Bazarragchaa B, Batdelger G, Choi S, Hwang KC, Lee S, Lim S. Extract of Oxytropis pseudoglandulosa inhibits vascular smooth muscle cell proliferation and migration via suppression of ERK1/2 and Akt signaling pathways1. Clin Hemorheol Microcirc 2018; 69:277-287. [PMID: 29660921 DOI: 10.3233/ch-189126] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Excessive vascular smooth muscle cell (VSMC) proliferation and migration accelerate the development of occlusive vascular disease. Therefore, finding a means to control the aberrant proliferation and migration of VSMCs has own clinical significance. In the present study, we examined the feasibility of using extract from medicinal plant Oxytropis pseudoglandulosa (OG) to control pathologic proliferation and migration of VSMCs, which never have been tested. Our data indicate that the extract of OG significantly suppressed proliferation and migration of VSMCs without cytotoxic effect, suggesting the OG extract may be an alternative agent to effectively control the aberrant VSMC proliferation and migration without any serious adverse effect. These data suggest that the extract of OG may be a potent therapeutic agent for the treatment of occlusive vascular disease and warrant further studies to identify the major acting ingredient and to validate in vivo efficacy.
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Affiliation(s)
- Jiyun Lee
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea
| | - Chang Youn Lee
- Department of Integrated Omics for Biomedical Sciences, Yonsei University, Seoul, Korea
| | - Hyang-Hee Seo
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea
| | | | - Gantuya Batdelger
- Institute of General and Experimental Biology, Mongolian Academy of Sciences (MAS), Ulaanbaatar, Mongolia
| | - Sangho Choi
- International Biological Material Research Center (IBMRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea
| | - Ki-Chul Hwang
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, Gangwon-do, Korea
| | - Seahyoung Lee
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, Gangwon-do, Korea
| | - Soyeon Lim
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, Gangwon-do, Korea
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Chinese Herbal Compounds for the Prevention and Treatment of Atherosclerosis: Experimental Evidence and Mechanisms. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 2015:752610. [PMID: 26089946 PMCID: PMC4451781 DOI: 10.1155/2015/752610] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Accepted: 10/15/2014] [Indexed: 12/21/2022]
Abstract
Atherosclerosis is a leading cause of disability and death worldwide. Research into the disease has led to many compelling hypotheses regarding the pathophysiology of atherosclerotic lesion formation and the resulting complications such as myocardial infarction and stroke. Herbal medicine has been widely used in China as well as other Asian countries for the treatment of cardiovascular diseases for hundreds of years; however, the mechanisms of action of Chinese herbal medicine in the prevention and treatment of atherosclerosis have not been well studied. In this review, we briefly describe the mechanisms of atherogenesis and then summarize the research that has been performed in recent years regarding the effectiveness and mechanisms of antiatherogenic Chinese herbal compounds in an attempt to build a bridge between traditional Chinese medicine and cellular and molecular cardiovascular medicine.
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Qian M, Tang S, Wu C, Wang Y, He T, Chen T, Xiao X. Synergy between baicalein and penicillins against penicillinase-producing Staphylococcus aureus. Int J Med Microbiol 2015; 305:501-4. [PMID: 26028441 DOI: 10.1016/j.ijmm.2015.05.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Revised: 04/30/2015] [Accepted: 05/05/2015] [Indexed: 11/15/2022] Open
Abstract
The combination of baicalein (the active constituent of Scutellaria baicalensis) with penicillin G/amoxicillin showed potent synergy against 20 clinical penicillinase-producing Staphylococcus aureus strains including 10 isolates that were additionally methicillin-resistant (MRSA). The fractional inhibitory concentration (FIC) indices of penicillins+baiclein ranged from 0.14 to 0.38. Baicalein protected penicillins (penicillin G and amoxicillin) from penicillinase and increased the susceptibility of penicillinase-supplemented S. aureus ATCC 29213 in a dose-dependent manner. The inhibition of penicillinase activity by baicalein should be responsible for the synergism and protective effect. These findings offer us good evidence that the penicillins combined with baicalein showed potent synergistic activity against penicillinase-producing S. aureus and penicillinase-producing MRSA in vitro and might provide promising implications for clinical treatment of these bacterial infections.
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Affiliation(s)
- Minyi Qian
- National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China
| | - Shusheng Tang
- National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China
| | - Congming Wu
- National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China
| | - Yang Wang
- National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China
| | - Tao He
- National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China
| | - Tingting Chen
- National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China
| | - Xilong Xiao
- National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
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Dinda B, SilSarma I, Dinda M, Rudrapaul P. Oroxylum indicum (L.) Kurz, an important Asian traditional medicine: from traditional uses to scientific data for its commercial exploitation. JOURNAL OF ETHNOPHARMACOLOGY 2015; 161:255-78. [PMID: 25543018 DOI: 10.1016/j.jep.2014.12.027] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 12/18/2014] [Accepted: 12/19/2014] [Indexed: 05/21/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Oroxylum indicum\ (L.) Kurz has been used for centuries as a traditional medicine in Asia in ethnomedicinal systems for the prevention and treatment of several diseases, such as jaundice, arthritic and rheumatic problems, gastric ulcers, tumors, respiratory diseases, diabetes, and diarrhea and dysentery, among others. The present review provides scientific evidence supporting the therapeutic potency of the plant for ethnomedicinal uses and identifies gaps for future research to facilitate commercial exploitation. METHODS This review is based on available information on traditional uses and phytochemical, pharmacological, clinical and toxicity data for Oroxylum indicum that was collected from electronic (SciFinder, PubMed, Science Direct, and ACS, among others) and library searches. KEY FINDING A variety of traditional medicinal uses of Oroxylum indicum in different Southeast and South Asian countries have been reported in books describing the uses of these plants. Phytochemical investigations of the different parts of the plant resulted in identification of approximately 111 compounds, among which flavonoids, naphthalenoids and cyclohexylethanoids are the predominant groups. The crude extracts and their isolates exhibit a wide spectrum of in vitro and in vivo pharmacological activities involving antimicrobial, anti-inflammatory, anti-arthritic, anticancer, anti-ulcer, hepatoprotective, antidiabetic, antidiarrheal and antioxidant activities. Flavonoids are the major constituents of all parts of the plant. From a toxicity perspective, only aqueous and ethanolic extracts of stem bark, root bark and fruits have been assessed and found to be safe. The major flavonoids of the stem bark, such as baicalein, chrysin and oroxylin A, were reported for the first time as natural flavonoids with potent inhibitory activity against endoprotease enzymes and proprotein convertases, which play a key role in the growth of cancer and in viral and bacterial infections. Flavonoids are the active components of bioactive extracts. Several Ayurvedic medicines have been formulated either singly using this plant or along with other herbs for the treatment of different diseases. CONCLUSIONS Pharmacological results have supported some traditional medicinal uses of Oroxylum indicum. Several extracts and their isolates have been reported to exhibit interesting pharmacological properties. These components could be useful as sources of modern medicines following future detailed studies to elucidate their underlying mechanisms, toxicity, synergistic effects and clinical trials. Attention should also be focused on pharmacological studies investigating the traditional uses of the plant, which have not been yet addressed, as well as clinical studies investigating commercial Ayurvedic medicines and other ethnomedicinal preparations in human subjects based on this plant to confirm the safety and quality of the preparations.
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Affiliation(s)
- B Dinda
- Department of Chemistry, Tripura University, Suryamaninagar, Agartala-799022, Tripura, India.
| | - I SilSarma
- Department of Chemistry, Tripura University, Suryamaninagar, Agartala-799022, Tripura, India
| | - M Dinda
- Department of Life Science and Biotechnology, Jadavpur University, Jadavpur, Kolkata-700032, India
| | - P Rudrapaul
- Department of Chemistry, Tripura University, Suryamaninagar, Agartala-799022, Tripura, India
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Cho SH, Yoon Y, Yang Y. The Evaluation of the Body Weight Lowering Effects of Herbal Extract THI on Exercising Healthy Overweight Humans: A Randomized Double-Blind, Placebo-Controlled Trial. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2013; 2013:758273. [PMID: 24285976 PMCID: PMC3830815 DOI: 10.1155/2013/758273] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/09/2012] [Revised: 09/14/2013] [Accepted: 09/14/2013] [Indexed: 11/17/2022]
Abstract
We investigated the effects of herbal extracts, a mixture of Scutellariae Radix and Platycodi Radix containing the active ingredients Baicalin and Saponin (target herbal ingredient (THI)), on lowering body weight. The present study was a prospective, randomized, double-blind, and placebo-controlled trial carried out at the outpatient department of a hospital over a period of 2 months. Group 1 patients (n = 30) received THI, and group 2 patients (n = 23) received placebo three times a day before meals. Weight, waist circumference, BMI, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and glucose were measured at baseline and again at the 2nd month. For safety evaluation, various hematological and biochemical parameters were assessed. Values of mean change of weight in the THI-treated group were -1.16 ± 1.41 kg and in the placebo-treated group were -0.24 ± 1.70 kg, respectively. The difference in mean change of weight in the THI-treated group compared with that in the placebo-treated group was statistically significant (P < 0.05). The incidence of subjective and objective adverse drug reactions was insignificant (P > 0.05). THI was statistically significant in its effectiveness on the weight loss.
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Affiliation(s)
- Soo Hyun Cho
- Department of Family Medicine, College of Medicine, Chung-Ang University Hospital, Seoul 156-755, Republic of Korea
| | - Yoosik Yoon
- Department of Microbiology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea
| | - Young Yang
- Department of Life Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea
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Baicalein inhibits DMBA/TPA-induced skin tumorigenesis in mice by modulating proliferation, apoptosis, and inflammation. Inflammation 2013; 36:457-67. [PMID: 23108957 DOI: 10.1007/s10753-012-9566-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Baicalein, one of the four major flavanoids extracted from the root of Scutellaria baicalensis, has been shown to exert chemopreventive effect against several cancers, including skin cancer. However, the precise mechanisms remain to be elucidated. In the present study, we investigated the chemopreventive activity of baicalein against 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated skin tumorigenesis in C57BL/6 mice. We found that topical treatment with baicalein resulted in a significant inhibitory effect on DMBA/TPA-mediated tumor promotion. Furthermore, we observed that baicalein suppressed cell proliferation and promoted apoptosis in DMBA/TPA-mediated group. Additionally, pretreatment with baicalein inhibited the production of inflammatory cells in DMBA/TPA-induced skin/tumors. Further experiments showed that baicalein reduced TPA-induced skin hyperplasia as well as infiltration of polymorphonuclear leukocytes in the dermis. In conclusion, our data suggest that baicalein inhibits DMBA/TPA-induced skin tumorigenesis by suppressing proliferation and inflammation and promoting apoptosis.
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17
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12S-Lipoxygenase is necessary for human vascular smooth muscle cell survival. Exp Cell Res 2013; 319:1586-93. [DOI: 10.1016/j.yexcr.2013.04.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2013] [Revised: 03/31/2013] [Accepted: 04/01/2013] [Indexed: 11/19/2022]
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Pimaric acid from Aralia cordata has an inhibitory effect on TNF-α-induced MMP-9 production and HASMC migration via down-regulated NF-κB and AP-1. Chem Biol Interact 2012; 199:112-9. [PMID: 22705379 DOI: 10.1016/j.cbi.2012.06.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Revised: 05/14/2012] [Accepted: 06/05/2012] [Indexed: 11/20/2022]
Abstract
Many studies have indicated that activation of matrix metalloproteinase (MMP)-9 and smooth muscle cell (SMC) migration are involved in neointimal formation and atherosclerosis. In this study, we revealed that pimaric acid (PiMA) purified from Aralia cordata had an inhibitory effect on MMP-9 production and migration of human aortic smooth muscle cells (HASMCs) induced by tumor necrosis factor (TNF)-α. Down-regulated MMP-9 mRNA transcription was detected in PiMA-treated cells using RT-PCR and the luciferase-tagged MMP-9 promoter assay. Results of an electrophoretic mobility shift assay indicated that PiMA-treated HASMCs showed decreased binding activity of nuclear factor (NF)-κB and activator protein-1 transcription factors. A Western-blot analysis using nuclear extract demonstrated that PiMA reduced the levels of NF-κB p65, c-Fos, p-c-Jun, Jun-D, and p-ATF2 proteins in the nucleus. In addition, TNF-α stimulated mitogen activated protein kinase (MAPK) containing extracellular signal regulated kinase 1 and 2, p38, and c-Jun N-terminal kinase was inhibited by PiMA. Using the Transwell system, we found that PiMA inhibited TNF-α stimulated HASMC migration/invasion in a dose-dependent manner. To confirm whether MAPK mediated MMP-9 expression, we used MAPK inhibitors including U0126, SB253580, and SP600125 and found that those inhibitors reduced MMP-9 expression and HASMC migration/invasion. These results suggest that PiMA has potent anti-atherosclerotic activity with inhibitory action on MMP-9 production and cell migration in TNF-α-induced HASMCs.
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19
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Liu YM, Wang X, Nawaz A, Kong ZH, Hong Y, Wang CH, Zhang JJ. Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway. Acta Pharmacol Sin 2011; 32:1475-1482. [PMID: 21986573 PMCID: PMC4010212 DOI: 10.1038/aps.2011.120] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2011] [Accepted: 07/25/2011] [Indexed: 02/08/2023]
Abstract
AIM To investigate the effects of wogonin (5,7-dihydroxy-8-methoxyflavone) extracted from Scutellaria baicalensis Georgi (S baicalensis) on lipotoxicity-induced apoptosis of vascular smooth muscle cells (VSMCs) and the underlying mechanisms. METHODS Cultured VSMCs were used. Apoptosis of VSMCs was induced by palmitate (0.75 mmol/L), and detected using TUNEL assay. The expression levels of protein and phosphorylated protein were measured using Western blot analysis. RESULTS Treatment of VSMCs with wogonin (10, 25 and 50 μmol/L) significantly attenuated the apoptosis and endoplasmic reticulum (ER) stress induced by palmitate in concentration- and time-dependent manners. Wogonin (50 μmol/L) decreased palmitate-induced reactive oxygen species (ROS) generation. The ER stress inhibitor 4-phenyl butyric acid (5 mmol/L) significantly decreased palmitate-induced apoptotic cells, and occluded the anti-apoptotic effect of wogonin (25 μmol/L). Wogonin (10, 25 and 50 μmol/L) significantly reduced the intracellular diacylglycerol (DAG) accumulation and expression levels of phosphorylated PKCs in palmitate-treated VSMCs. CONCLUSION Our results suggest that wogonin inhibits lipotoxicity-induced apoptosis of VSMCs via suppressing the intracellular DAG accumulation and subsequent inhibition of PKC phosphorylation. Wogonin has therapeutic potential for the prevention and treatment of atherosclerosis.
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Affiliation(s)
- Yu-min Liu
- Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Xiong Wang
- Department of Pathophysiology, Hubei University of Medicine, Shiyan 442000, China
| | - Ahmed Nawaz
- Department of Pathophysiology, Wuhan University School of Medicine, Wuhan 430070, China
| | - Zhao-hong Kong
- Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Yan Hong
- Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Chang-hua Wang
- Department of Pathophysiology, Wuhan University School of Medicine, Wuhan 430070, China
| | - Jun-jian Zhang
- Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
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Lin YL, Lin RJ, Shen KP, Dai ZK, Chen IJ, Wu JR, Wu BN. Baicalein, isolated from Scutellaria baicalensis, protects against endothelin-1-induced pulmonary artery smooth muscle cell proliferation via inhibition of TRPC1 channel expression. JOURNAL OF ETHNOPHARMACOLOGY 2011; 138:373-381. [PMID: 21963569 DOI: 10.1016/j.jep.2011.09.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2011] [Revised: 09/14/2011] [Accepted: 09/15/2011] [Indexed: 05/31/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE We investigated the antiproliferative effects of baicalein, isolated from Scutellaria baicalensis (Huang-qin), on ET-1-mediated pulmonary artery smooth muscle cells (PASMCs) proliferation and the mechanisms underlying these effects. MATERIALS AND METHODS Intrapulmonary artery smooth muscle cells were isolated and cultured from female Sprague-Dawley rats and used during passages 3-6. The proliferation of PASMCs was quantified by cell counting and XTT assay. The protein expression of TRPC1 and PKCα were determined by western blotting. The cell cycle pattern was assayed by flow cytometry. The intracellular calcium concentrations ([Ca(2+)](i)) were measured using the fluorescent indicator fura-2-AM and flow cytometry. RESULTS Baicalein (0.3-3 μM) inhibited PASMCs proliferation, promoted cell cycle progression, enhanced [Ca(2+)](i) levels, increased capacitative Ca(2+) entry (CCE), upregulated the canonical transient receptor potential 1 (TRPC1) channel and membrane protein kinase Cα (PKCα) expression induced by ET-1 (0.1 μM). The PKC activator PMA (1 μM) reversed the inhibitory effects of baicalein on ET-1-induced upregulation of TRPC1 expression and S phase accumulation, while the PKC inhibitor chelerythrine (1 μM) potentiated baicalein-mediated G(2)/M phase arrest and TRPC1 channel inhibition. CONCLUSION Our findings suggest that baicalein protects against ET-1-induced PASMCs proliferation via modulation of the PKC-mediated TRPC channel.
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Affiliation(s)
- Yi-Ling Lin
- Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Preparation and characterization of the inclusion complex of baicalein with γ-cyclodextrin: an antioxidant ability study. J INCL PHENOM MACRO 2011. [DOI: 10.1007/s10847-011-0048-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Chao J, Su J, Li J, Zhao W, Huang S, Du R. Investigation on the inclusion behaviour of baicalein with β-cyclodextrin and derivatives and their antioxidant ability study. Supramol Chem 2011. [DOI: 10.1080/10610278.2011.593630] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Jianbin Chao
- a The Institute of Applied Chemistry of Shanxi University , Taiyuan , 030006 , China
| | - Jian Su
- a The Institute of Applied Chemistry of Shanxi University , Taiyuan , 030006 , China
| | - Jinxia Li
- a The Institute of Applied Chemistry of Shanxi University , Taiyuan , 030006 , China
| | - Wei Zhao
- a The Institute of Applied Chemistry of Shanxi University , Taiyuan , 030006 , China
| | - Shuping Huang
- a The Institute of Applied Chemistry of Shanxi University , Taiyuan , 030006 , China
| | - Rui Du
- b Department of Engineering , Shanxi Coal Mining Administrators College , Taiyuan , 030006 , China
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Multifunctional baicalein blended poly(vinyl alcohol) composite nanofibers via electrospinning. Colloids Surf A Physicochem Eng Asp 2011. [DOI: 10.1016/j.colsurfa.2011.05.009] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Li J, Zhang M, Chao J, Shuang S. Preparation and characterization of the inclusion complex of Baicalin (BG) with beta-CD and HP-beta-CD in solution: an antioxidant ability study. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2009; 73:752-756. [PMID: 19423384 DOI: 10.1016/j.saa.2009.03.025] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2008] [Revised: 02/21/2009] [Accepted: 03/19/2009] [Indexed: 05/27/2023]
Abstract
The formation of the complexes of BG with beta-CD and HP-beta-CD was studied by UV-vis absorption spectroscopy, fluorescence spectra, Phase-solubility measurements and nuclear magnetic resonance spectroscopy (NMR) in solution. The formation constants (K) of complexes were determined by fluorescence method and Phase-solubility measurements. The results showed that the inclusion ability of beta-CD and its derivatives was the order: HP-beta-CD>beta-CD. In addition, the experimental resulted confirmed the existence of 1:1 inclusion complex of BG with CDs. The antioxidant ability studies of BG and CDs complexes were done. The results obtained indicated that the BG/HP-beta-CD complex was the most reactive form, and then was the BG/beta-CD complex; the last was BG. Special configuration of complex has been proposed on NMR technique.
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Affiliation(s)
- Jinxia Li
- The Institute of Applied Chemistry of Shanxi University, Taiyuan 030006, PR China
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25
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Deoxypodophyllotoxin, flavolignan, from Anthriscus sylvestris Hoffm. inhibits migration and MMP-9 via MAPK pathways in TNF-α-induced HASMC. Vascul Pharmacol 2009; 51:13-20. [PMID: 19013539 DOI: 10.1016/j.vph.2008.10.004] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2008] [Revised: 09/30/2008] [Accepted: 10/15/2008] [Indexed: 11/23/2022]
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Suh SJ, Cho KJ, Moon TC, Chang HW, Park YG, Kim CH. 3,4,5-trihydroxybenzaldehyde fromGeum japonicumhas dual inhibitory effect on matrix metalloproteinase 9; inhibition of gelatinoytic activity as well as MMP-9 expression in TNF-α induced HASMC. J Cell Biochem 2008; 105:524-33. [PMID: 18773430 DOI: 10.1002/jcb.21854] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Pinkaew D, Cho SG, Hui DY, Wiktorowicz JE, Hutadilok-Towatana N, Mahabusarakam W, Tonganunt M, Stafford LJ, Phongdara A, Liu M, Fujise K. Morelloflavone blocks injury-induced neointimal formation by inhibiting vascular smooth muscle cell migration. Biochim Biophys Acta Gen Subj 2008; 1790:31-9. [PMID: 18930785 DOI: 10.1016/j.bbagen.2008.09.006] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2008] [Revised: 08/23/2008] [Accepted: 09/16/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND In-stent restenosis, or renarrowing within a coronary stent, is the most ominous complication of percutaneous coronary intervention, caused by vascular smooth muscle cell (VSMC) migration into and proliferation in the intima. Although drug-eluting stents reduce restenosis, they delay the tissue healing of the injured arteries. No promising alternative anti-restenosis treatments are currently on the horizon. METHODS In endothelium-denudated mouse carotid arteries, oral morelloflavone-an active ingredient of the Thai medicinal plant Garcinia dulcis-significantly decreased the degree of neointimal hyperplasia, without affecting neointimal cell cycle progression or apoptosis as evaluated by Ki-67 and TUNEL staining, respectively. At the cellular level, morelloflavone robustly inhibited VSMC migration as shown by both scratch wound and invasion assays. In addition, morelloflavone prevented VSMCs from forming lamellipodia, a VSMC migration apparatus. Mechanistically, the inhibition by morelloflavone of VSMC migration was through its negative regulatory effects on several migration-related kinases, including FAK, Src, ERK, and RhoA. Consistently with the animal data, morelloflavone did not affect VSMC cell cycle progression or induce apoptosis. RESULTS These data suggest that morelloflavone blocks injury-induced neointimal hyperplasia via the inhibition of VSMC migration, without inducing apoptosis or cell cycle arrest. GENERAL SIGNIFICANCE We propose morelloflavone to be a viable oral agent for the prevention of restenosis, without compromising effects on the integrity and healing of the injured arteries.
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Affiliation(s)
- Decha Pinkaew
- Division of Cardiology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA
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Benavente-García O, Castillo J. Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2008; 56:6185-205. [PMID: 18593176 DOI: 10.1021/jf8006568] [Citation(s) in RCA: 732] [Impact Index Per Article: 43.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Significantly, much of the activity of Citrus flavonoids appears to impact blood and microvascular endothelial cells, and it is not surprising that the two main areas of research on the biological actions of Citrus flavonoids have been inflammation and cancer. Epidemiological and animal studies point to a possible protective effect of flavonoids against cardiovascular diseases and some types of cancer. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their biological action are still not completely known. Many of the pharmacological properties of Citrus flavonoids can be linked to the abilities of these compounds to inhibit enzymes involved in cell activation. Attempts to control cancer involve a variety of means, including the use of suppressing, blocking, and transforming agents. Suppressing agents prevent the formation of new cancers from procarcinogens, and blocking agents prevent carcinogenic compounds from reaching critical initiation sites, while transformation agents act to facilitate the metabolism of carcinogenic components into less toxic materials or prevent their biological actions. Flavonoids can act as all three types of agent. Many epidemiological studies have shown that regular flavonoid intake is associated with a reduced risk of cardiovascular diseases. In coronary heart disease, the protective effects of flavonoids include mainly antithrombotic, anti-ischemic, anti-oxidant, and vasorelaxant. It is suggested that flavonoids decrease the risk of coronary heart disease by three major actions: improving coronary vasodilatation, decreasing the ability of platelets in the blood to clot, and preventing low-density lipoproteins (LDLs) from oxidizing. The anti-inflammatory properties of the Citrus flavonoids have also been studied. Several key studies have shown that the anti-inflammatory properties of Citrus flavonoids are due to its inhibition of the synthesis and biological activities of different pro-inflammatory mediators, mainly the arachidonic acid derivatives, prostaglandins E 2, F 2, and thromboxane A 2. The anti-oxidant and anti-inflammatory properties of Citrus flavonoids can play a key role in their activity against several degenerative diseases and particularly brain diseases. The most abundant Citrus flavonoids are flavanones, such as hesperidin, naringin, or neohesperidin. However, generally, the flavones, such as diosmin, apigenin, or luteolin, exhibit higher biological activity, even though they occur in much lower concentrations. Diosmin and rutin have a demonstrated activity as a venotonic agent and are present in several pharmaceutical products. Apigenin and their glucosides have been shown a good anti-inflammatory activity without the side effects of other anti-inflammatory products. In this paper, we discuss the relation between each structural factor of Citrus flavonoids and the anticancer, anti-inflammatory, and cardiovascular protection activity of Citrus flavonoids and their role in degenerative diseases.
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Affiliation(s)
- O Benavente-García
- Research and Development Department of Nutrafur-Furfural Español S.A., Camino Viejo de Pliego s/n, 80320 Alcantarilla, Murcia, Spain.
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Baicalein attenuates intimal hyperplasia after rat carotid balloon injury through arresting cell-cycle progression and inhibiting ERK, Akt, and NF-κB activity in vascular smooth-muscle cells. Naunyn Schmiedebergs Arch Pharmacol 2008; 378:579-88. [DOI: 10.1007/s00210-008-0328-1] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2008] [Accepted: 06/25/2008] [Indexed: 02/01/2023]
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Zhang K, Guo QL, You QD, Yang Y, Zhang HW, Yang L, Gu HY, Qi Q, Tan Z, Wang X. Wogonin induces the granulocytic differentiation of human NB4 promyelocytic leukemia cells and up-regulates phospholipid scramblase 1 gene expression. Cancer Sci 2008; 99:689-95. [PMID: 18377421 PMCID: PMC11158147 DOI: 10.1111/j.1349-7006.2008.00728.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Previous studies have firmly demonstrated that wogonin, a naturally occurring monoflavonoid extracted from the root of the Chinese herb medicine Scutellaria baicalensis, could effectively inhibit the proliferation of several cancer cell lines. However, little is known about the effect of wogonin on differentiation induction of leukemic cells. Here we investigate the potential role of wogonin in the proliferation and differentiation of NB4, a human promyelocytic leukemia cell line derived from a patient with acute promyelocytic leukemia. Our results indicated that wogonin significantly suppressed the proliferation and efficiently induced the differentiation of NB4 cells. NB4 cell growth was inhibited by 55-60% after treatment with 50 microM wogonin for a period of 5 days. The results of the nitroblue tetrazolium (NBT) reduction test (with 67.13% positive cells by 50 microM wogonin for 5 days), Giemsa staining (with 67.24% positive cells by 50 microM wogonin for 5 days), and the expression of mature-related cell-surface differentiation antigens CD11b and CD14 (with 70.94% CD11b(+) and 5.82% CD14(+) cells by 50 microM wogonin for 5 days) demonstrated an increase in the differentiation-inducing action of wogonin on the NB4 cells, which was accompanied by an increase in mRNA and protein expression of phospholipids scramblase 1 (PLSCR1). Meanwhile, the level of phosphorylated PKC delta (Ser643) was dramatically increased in wogonin treated NB4 cells. Interestingly, wogonin treatment displayed little effect on the apoptosis of NB4 cells. Taken together, the results reported here demonstrated that wogonin could promote the granulocytic differentiation of NB4 cells by up-regulating the expression of PLSCR1 gene.
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Affiliation(s)
- Kun Zhang
- Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China
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Chung HL, Yue GGL, To KF, Su YL, Huang Y, Ko WH. Effect of Scutellariae Radix extract on experimental dextran-sulfate sodium-induced colitis in rats. World J Gastroenterol 2007; 13:5605-11. [PMID: 17948935 PMCID: PMC4172740 DOI: 10.3748/wjg.v13.i42.5605] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the effect of Scutellariae Radix extract (SRE) on ulcerative colitis (UC) in rats induced by dextran-sulfate sodium (DSS).
METHODS: Colitis was induced in male Sprague-Dawley (SD) rats (170-180 g) by 4% dextran sulfate sodium (DSS, wt/v; MW 54000) in drinking water for 8 d. The treated rats received 4% DSS and SRE orally (100 mg/kg per day). Control rats received either tap water or SRE only. Macroscopic assessment which included body weight changes, fecal occult blood and stool consistency were determined daily. At the appointed time, the rats were sacrificed and the entire colons were removed. The colon length and the myeloperoxidase (MPO) activity were measured. The severity of colitis was graded by morphological and histological assessments. The ion transport activity of the colonic mucosa was assessed by electrophysiological technique.
RESULTS: Rats treated with oral administration of 4% DSS regularly developed clinical and macroscopic signs of colitis. Treatment with SRE relieved the symptoms, including the reduction in body weight, shortening and ulceration of the colon. Administration of SRE also significantly reduced the histological damage induced by DSS. Moreover, the ISC responses of the colonic mucosa to forskolin were suppressed after the induction of colitis. The stimulated ion transport activity of DSS-rats treated with SRE displayed significant improvement in the secretory responsiveness.
CONCLUSION: SRE was effective in treating acute DSS-induced ulcerative colitis, as gauged by reduced clinical disease, improved macroscopic and histological damage scores, and enhanced recovery of normal colonic secretory function.
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Ha KT, Kim KW, Suh SJ, Kwak CG, Kim JK, Kim CH. Inhibitory effect of Uncaria sinensis on human aortic smooth muscle cell migration is based on matrix metalloproteinase-9 inhibitory activity. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2007; 24:218-222. [PMID: 21783814 DOI: 10.1016/j.etap.2007.05.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2007] [Revised: 05/13/2007] [Accepted: 05/23/2007] [Indexed: 05/31/2023]
Abstract
Medicinal extracts of Cho-Deung-san and Uncaria sinensis Havil. (UR) have previously been shown to have inhibitory effects on migration of vascular smooth muscle cells (VSMC) and matrix metalloproteinase (MMP)-2/9 production, which play key roles in the development of atherosclerosis. In this study, we have more extensively investigated the inhibitory effect of UR on MMP-9 activity and TNF-α induced human aortic smooth muscle cells (HASMC) migration. The result from gelatin zymography showed that UR inhibited MMP-9 activity in a dose-dependent manner (IC(50)=55μg/ml). In addition, UR strongly inhibited the migration of HASMC induced by TNF-α treatment (IC(50)=125μg/ml), although it has very low cytotoxic effect on HASMC (IC(50)>500μg/ml). These results suggest that UR is a potential anti-atherosclerotic agent through inhibition of MMP-9 activity and VSMC migration.
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Affiliation(s)
- Ki-Tae Ha
- Department of Pathology and Cardiovascular MRC, Dongguk University, Kyungju 780-714, South Korea
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33
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Suh SJ, Jin UH, Choi HJ, Chang HW, Son JK, Lee SH, Jeon SJ, Son KH, Chang YC, Lee YC, Kim CH. Cryptotanshinone from Salvia miltiorrhiza BUNGE has an inhibitory effect on TNF-α-induced matrix metalloproteinase-9 production and HASMC migration via down-regulated NF-κB and AP-1. Biochem Pharmacol 2006; 72:1680-9. [PMID: 16999937 DOI: 10.1016/j.bcp.2006.08.013] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2006] [Revised: 08/08/2006] [Accepted: 08/09/2006] [Indexed: 11/24/2022]
Abstract
Matrix metalloproteinases (MMP-9 and MMP-2) production and smooth muscle cell (SMC) migration may play key roles in the phathogenesis of neointima formation and atherosclerosis. Especially inducible MMP-9 expression was directly involved in the cancer cell invasion and SMC migration through vascular wall. In this study, we reveal that cryptotanshinone (CT) purified from Salvia miltiorrhiza BUNGE had an inhibitory effect on MMP-9 production and migration of human aortic smooth muscle cells treated with TNF-alpha in a dose-dependent manner. The down regulation of transcription of MMP-9 mRNA was evidenced by RT-PCR and MMP-9 promoter assay using luciferase reporter gene. Eletrophoretic mobility shift assay showed NF-kappaB and AP-1 nuclear translocations were suppressed. In addition, Western blot analysis indicated that extracellular signal regulated kinase 1 and 2, p38 and JNK MAP kinase signaling pathways were inhibited. From the results, it is suggested that CT has anti-atherosclerosis and anti-neointimal formation activity.
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Affiliation(s)
- Seok-Jong Suh
- Department of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Republic of Korea
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Lee SO, Jeong YJ, Yu MH, Lee JW, Hwangbo MH, Kim CH, Lee IS. Wogonin suppresses TNF-alpha-induced MMP-9 expression by blocking the NF-kappaB activation via MAPK signaling pathways in human aortic smooth muscle cells. Biochem Biophys Res Commun 2006; 351:118-25. [PMID: 17052690 DOI: 10.1016/j.bbrc.2006.10.006] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2006] [Accepted: 10/02/2006] [Indexed: 11/24/2022]
Abstract
Matrix metalloproteinase-9 (MMP-9) plays a major role in the pathogenesis of atherosclerosis and restenosis by regulating both migration and proliferation of vascular smooth muscle cells (VSMC) after an arterial injury. In this study, we examined the inhibitory effect of three major flavonoids in Scutellariae Radix, baicalin, baicalein, and wogonin, on TNF-alpha-induced MMP-9 expression in human aortic smooth muscle cells (HASMC). Wogonin, but not baicalin and baicalein, significantly and selectively suppressed TNF-alpha-induced MMP-9 expression in HASMC. Reporter gene, electrophoretic mobility shift, and Western blotting assays showed that wogonin inhibits MMP-9 gene transcriptional activity by blocking the activation of NF-kappaB via MAPK signaling pathways. Moreover, the Matrigel migration assay showed that wogonin reduced TNF-alpha-induced HASMC migration. These results suggest that wogonin effectively suppresses TNF-alpha-induced HASMC migration through the selective inhibition of MMP-9 expression and represents a potential agent for the prevention of vascular disorders related to the migration of VSMC.
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MESH Headings
- Aorta/cytology
- Aorta/drug effects
- Aorta/metabolism
- Cells, Cultured
- Dose-Response Relationship, Drug
- Drug Combinations
- Enzyme Activation/drug effects
- Flavanones/administration & dosage
- Gene Expression Regulation, Enzymologic/drug effects
- Gene Expression Regulation, Enzymologic/physiology
- Humans
- MAP Kinase Signaling System/drug effects
- MAP Kinase Signaling System/physiology
- Matrix Metalloproteinase 9/metabolism
- Muscle, Smooth, Vascular/drug effects
- Muscle, Smooth, Vascular/metabolism
- Myocytes, Smooth Muscle/drug effects
- Myocytes, Smooth Muscle/metabolism
- NF-kappa B/metabolism
- Tumor Necrosis Factor-alpha/administration & dosage
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Affiliation(s)
- Syng-Ook Lee
- Department of Food Science and Technology and The Center for Traditional Microorganism Resources (TMR), Keimyung University, 1000 Sindang-Dong, Dalseo-Gu, Daegu 704-701, Republic of Korea
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35
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Jin UH, Kang SK, Suh SJ, Hong SY, Park SD, Kim DW, Chang HW, Son JK, Lee SH, Son KH, Kim CH. Inhibitory effect of Salvia miltiorrhia BGE on matrix metalloproteinase-9 activity and migration of TNF-α-induced human aortic smooth muscle cells. Vascul Pharmacol 2006; 44:345-53. [PMID: 16540379 DOI: 10.1016/j.vph.2006.01.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2005] [Revised: 12/28/2005] [Accepted: 01/18/2006] [Indexed: 01/17/2023]
Abstract
The migration and matrix metalloproteinases (MMPs) production of vascular smooth muscle cells (VSMC) may play a key role in the development of atherosclerosis. The Radix of Salvia miltiorrhiza Bunge (Labiatae) (SM), an eminent herb, is often included as an ingredient in various herbal remedies recommended for vascular therapies and has been used to treat vascular diseases for many centuries. In this study, we investigated the inhibitory effect of SM on TNF-alpha induced human aortic smooth muscle cells (HASMC) migration and MMP-9 activity. Various extracts prepared from stems of SM were tested for cytotoxic activity on HASMC using the XTT assay method. The ethanol extract (IC50 > 100 microg/ml), water extract (IC50 > 100 microg/ml) and chloroform (IC50 = 90 microg/ml) fraction exhibited weak cytotoxic activity. However, buthanol (IC50 = 80 microg/ml) and ethyl acetate (EtOAc; IC50 = 70 microg/ml) fraction exhibited strongly cytotoxic activity. Also, the extracts and fractions were investigated the inhibitory effects on MMP-9 activity using gelatin zymography. Gelatin zymography showed that the TNF-alpha-treated HASMC secreted MMP, probably including MMP-9, which may be involved in HASMC migration. The EtOAc fraction showed stronger inhibitory effect of proteolytic activity than other fractions. The EtOAc fraction was able to decrease the proteolytic activity of MMP-9 in a concentration-dependent manner on zymography. The Matrigel migration assay showed that SM effectively inhibited the TNF-alpha induced migration of HASMC as compared with the control group in a dose-dependent manner (IC50 = 65 microg/ml) and that the EtOAc fraction effectively inhibited the migration of HASMC, as compared with the control group in a dose-dependent manner. These results suggest that SM could be used as potential anti-atherosclerotic agent for anti-migration in TNF-alpha treated HASMC.
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Affiliation(s)
- Un-Ho Jin
- Department of Biological Science, Sungkyunkwan University and National Research Laboratory for Glycobiology, Chunchun-Dong, Jangan-Gu, Suwon City, Kyunggi 440-746, Korea
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Liu J, Qiu L, Gao J, Jin Y. Preparation, characterization and in vivo evaluation of formulation of baicalein with hydroxypropyl-beta-cyclodextrin. Int J Pharm 2006; 312:137-43. [PMID: 16459034 DOI: 10.1016/j.ijpharm.2006.01.011] [Citation(s) in RCA: 83] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2005] [Revised: 01/05/2006] [Accepted: 01/09/2006] [Indexed: 10/25/2022]
Abstract
The interaction of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and a poorly water-soluble flavonoid, baicalein (Ba), chemically 5,6,7-trihydroxy flavone in solution and solid-state was studied. Ba/HP-beta-CD solid systems were prepared by freeze-drying method. The formation of Ba/HP-beta-CD complex in aqueous solution was demonstrated by UV spectroscopy, while Ba/HP-beta-CD co-lyophilized product was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Through complexation with HP-beta-CD, the solubility of Ba in neutral aqueous solution was improved significantly. The phase-solubility profile was AP-type, indicating the formation of higher-order complexes or complex aggregates. Ba/HP-beta-CD solid powders were amorphous and show a significantly improved dissolution rate in comparison with free Ba. Comparison of the pharmacokinetics between Ba/HP-beta-CD co-lyophilized product and free Ba was also performed in rats. The concentration of Ba and its mainly conjugated metabolite, 7-O-glucuronide of baicalein (BG) in rat plasma was determined by HPLC method. The in vivo results show that Ba/HP-beta-CD co-lyophilized product exhibits the similar pharmacokinetics as that of free Ba after intravenous administration. Ba/HP-beta-CD co-lyophilized product displays earlier tmax and higher Cmax of BG than free Ba after oral dosing. By comparing the AUC0-infinity of BG between oral dosing, the relative bioavailability of Ba/HP-beta-CD co-lyophilized product to free Ba was 165.0%, which highlighted the evidence of significantly improved bioavailability of formulation of Ba with HP-beta-CD.
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Affiliation(s)
- Jun Liu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, PR China
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Tilak JC, Devasagayam TP, Adhikari S, Lele RD, Kon T, Handa O, Naito Y, Yoshikawa T. Cellular Membrane Protection Against Reactive Oxygen Species by Terminalia Arjuna and Its Active Component Baicalein. J Clin Biochem Nutr 2006. [DOI: 10.3164/jcbn.39.75] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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Zhang XP, Li ZF, Liu XG, Wu YT, Wang JX, Wang KM, Zhou YF. Effects of emodin and baicalein on rats with severe acute pancreatitis. World J Gastroenterol 2005; 11:2095-100. [PMID: 15810074 PMCID: PMC4305777 DOI: 10.3748/wjg.v11.i14.2095] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the therapeutic effects of emodin in combination with baicalein on severe acute pancreatitis (SAP) rats and to explore the mechanism of SAP.
METHODS: A total of 112 SAP rats induced by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct, randomly assigned to a untreated group and three treated groups emodin group, combined emodin and baicalein group, and sandostatin group. Meanwhile, another 28 other rats were selected as sham operation (SO) group. There were 28 rats in each group, 8 rats were in 3 and 6 h groups respectively, and 12 rats in 12 h group. At each time-points, survival rates, ascites volumes, pathological lesion scores of pancreas tissues, serum amylase, tumor necrosis factor-α and IL-6 levels were determined as the indexes of therapeutic effects.
RESULTS: The survival rate at 12 h was significantly higher in three treated groups than in untreated group. The ascites volume at 12 h was remarkably less in combined and sandostatin groups than in emodin group, but there was no difference between combined group and sandostatin group (P>0.05). Serum amylase levels at all time-points were significantly lower in three treated groups than in untreated group. However, they had no difference among treated groups (P>0.05). Serum TNF-α were lower in three treated groups than in untreated group at all time points. Among the three treated groups, at 6 h, the TNF-α levels of combination and sandostatin groups were lower than those of emodin group. These was no difference between combined and sandostantin. Serum IL-6 concentration at 3 h were lower in combined and sandostatin groups than in untreated group, but at 6 and 12 h they were lower in all treated groups than in untreated group and the combined and sandostatin groups and in emodin group, no difference was found between combined and sandostatin groups at all time-points (P>0.05). The pathological scores of pancreas at all time points were significantly lower in three treated groups than in the untreated group, and at 6, 12 h, the scores of combined and sandostatin groups were lower than in emodin group. There was no difference between combined and sandostatin groups (P>0.05).
CONCLUSION: Combination of emodin with baicalein has significant therapeutic effects on SAP rats.
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Affiliation(s)
- Xi-Ping Zhang
- Department of General Surgery, First People's Hospital of Hangzhou, Hangzhou 310006, Zhejiang Province, China.
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39
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Labiatae Flavonoids and their Bioactivity. ACTA ACUST UNITED AC 2005. [DOI: 10.1016/s1572-5995(05)80035-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register]
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Ye F, Wang H, Jiang S, Wu J, Shao J, Cheng X, Tu Y, Zhang DY. Quality Evaluation of Commercial Extracts of Scutellaria baicalensis. Nutr Cancer 2004; 49:217-22. [PMID: 15489215 DOI: 10.1207/s15327914nc4902_14] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Botanical products have been widely used for various illnesses and general well-being. However, quality control of botanical products is often not performed due to lack of standardization, resulting in inconsistent efficacies and sometimes serious toxicity. The goals of this study were to determine the correlation between chemical composition and biological activities and to establish a method to measure authenticity, chemical consistency, and biological potency of botanical products. A high-performance liquid chromatography method was used to analyze the authenticity and chemical composition of 10 different commercial extracts. The cell viability assay and prostaglandin E2 (PGE2) enzyme immunoassay were used to analyze biological potency and consistency. Our results showed all extracts contained marker components (baicalein and/or baicalin), confirming their authenticity. However, significant product-to-product and batch-to-batch variation of these marker components was observed with 4 products containing no baicalin at all and baicalein concentration ranging from 0 to 52.3 g/mg. The 50% growth inhibition concentration of the extracts ranged from 0.18 to 2.0 mg/ml, more than an 11-fold variation. PGE2 levels varied from 19.5 to 111.1 pg/106 cells, more than a 5.7-fold difference. These results demonstrated significant variation in chemical composition and biological activities of the commercial extracts and that the amount of marker components may not reflect biological activity levels. Therefore, chemical analysis alone is inadequate for quality control, and biological assays must be included for botanical products to ensure chemical authenticity as well as pharmacological/biological potency and consistency.
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Affiliation(s)
- Fei Ye
- Department of Pathology, Mount Sinai School of Medicine, New York University, New York, USA
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41
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Chen X, Krakauer T, Oppenheim JJ, Howard OMZ. Yin Zi Huang, an Injectable Multicomponent Chinese Herbal Medicine, Is a Potent Inhibitor of T-Cell Activation. J Altern Complement Med 2004; 10:519-26. [PMID: 15253857 DOI: 10.1089/1075553041323687] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES The clinical efficacy of many multiherbal Traditional Chinese Medicines (TCM) is partially attributable to their immunoregulatory properties. In this study we evaluated the effect of eight commonly used, commercially available multiherbal Chinese medicines on T-cell activation. We focused on Yin Zhi Huang (YZH, an injectable herbal medicine commonly used for the treatment of liver diseases in China), because it was the most potent inhibitor of T-cell activation in our experimental system. The effects of 10 ingredient components of YZH were also evaluated. METHODS [3H] thymidine incorporation assay was used to assess mouse T-cell proliferation after stimulation with latex beads coated with anti-CD3/CD28 antibodies. CD25, CD69, PD-1, and I-COS expression by purified mouse CD4+ T cells treated with plate-bound anti-CD3 antibody and soluble anti-CD28 antibody was analyzed by fluorescent-activated cell sorter (FACS). Cytokine/chemokine production by human peripheral blood mononuclear cells (PBMC) stimulated with staphylococcal enterotoxin B (SEB) was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS Among tested herbal medicines, YZH was the most potent inhibitor of T-cell activation. In splenocyte proliferation assays, the inhibitory effect of YZH was dose-dependent, with a 50% inhibition concentration (IC50) of 1:3200-1:1600. Ten (10) purified compounds found in YZH were evaluated for their activity. Among them, ursolic acid (1-10 micromol), luteolin (1-10 micromol), baicalein (1-10 micromol), scopran (5-50 micromol), and crocin (5-50 micromol), exhibited dose-dependent inhibition. YZH also inhibited CD25, CD69, PD-1, and ICOS expression by stimulated mouse CD4+ T cells. In human PBMCs, YZH inhibited SEB-stimulated cytokine (interleukin [IL]-1, IL-2, IL-6, tumor necrosis factor[TNF]-alpha, interferon [IFN]-gamma) and chemokine (IP-10, MCP-1, MIP-1alpha and MIP-1beta) production in a dose-dependent manner. CONCLUSION Our data show for the first time that YZH is a potent inhibitor of T-cell activation, and this property may be the major mechanism underlying the clinical efficacy of YZH. Our experimental results pave the way for identification of active component(s) and/or analysis of synergistic/additive effect of a YZH ingredient in future studies.
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Affiliation(s)
- Xin Chen
- Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA
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Wang Z, Du Q, Wang F, Liu Z, Li B, Wang A, Wang Y. Microarray analysis of gene expression on herbal glycoside recipes improving deficient ability of spatial learning memory in ischemic mice. J Neurochem 2004; 88:1406-15. [PMID: 15009641 DOI: 10.1046/j.1471-4159.2003.02258.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
In order to reveal the mechanism of herbal glycoside recipes retrieving deficient ability of spatial learning memory in mice suffering from cerebral ischemia/reperfusion, a microarray system was used to analyze gene expression in those groups with increasing ability of spatial learning memory who were different from ischemic mice. In this work, we reported a comprehensive characterization of gene expression profiles of mouse hippocampus by the use of cDNA microarray system containing 1176 known genes in middle cerebral artery occlusion (MCAO) ischemic mice after treating with different dosage recipes of glycoside herbs (30, 90, and 270 mg/kg). The ability of spatial learning memory in ischemic mice was found to be decreased. The pathological process in ischemic mouse brain showed that a complex related to 100 genes' expression yielded 1.8-fold. Dose-dependent effects showed an improvement in the deficient ability and reduction in infarct volume when treated with glycoside recipes. Many genes (38-46) in expression were found greater than 1.8-fold in those effective recipes groups, including genes in cell cycle regulation, signal transduction, nerve system transcription factors, DNA binding protein, etc. Nine genes related to retrieving deficient ability of spatial learning memory treated with glycoside recipes were also found in this study. These results suggest that microarray analysis of gene expression might be useful for elucidating the mechanisms of pharmacological function of recipes.
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Affiliation(s)
- Zhong Wang
- The Key Laboratory of Xiyuan Hospital, China Academy of Traditional Chinese Medicine, Beijing, China.
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Qu J, Liang Q, Liang Q, Luo G, Wang Y. Screening and Identification of Glycosides in Biological Samples Using Energy-Gradient Neutral Loss Scan and Liquid Chromatography Tandem Mass Spectrometry. Anal Chem 2004; 76:2239-47. [PMID: 15080733 DOI: 10.1021/ac030413t] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
A rapid, selective, and reliable strategy has been developed for the screening and identification of glycosides in biological samples: a crude extract was directly infused to a triple-quadrupole MS/MS, and major glycosides were screened out with high confidence by an energy-gradient neutral loss scan (EGNLS) for the loss of sugar(s); then these glycosides were further identified with LC/MS/MS. The proposed EGNLS method was established and optimized with 16 representative glycosides (including ginsenosides and the glycosides of flavones, anthraquinones, and terpenoids). The EGNLS method has two major advantages over the conventional fixed-energy neutral loss scan: (1) The latter is liable to '"omit" some target compounds due to the usual mismatch between the preset collision energy and interested compounds' optimal collision energy (OCE), while EGNLS solves this problem by scanning over an energy range. (2) The EGNLS simultaneously measures the screened compounds' OCE, which not only are essential parameters for further LC/MS/MS analysis but also carry some structural information, as proved by this study. This strategy has been successfully demonstrated with the analysis of glycosides in Scutellaria viscidula Bge and transformed Panaxhairy roots (the glycoside constitutions of both had not been studied before): without laborious separation processes; comprehensive glycoside information on those two plants was obtained by a rapid and simple procedure. This strategy is valuable for the study of glycosides in complex samples.
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Affiliation(s)
- Jun Qu
- Department of Chemistry, School of Life Science and Technology, Tsinghua University, Beijing, PR China
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Ha KT, Lee TK, Kwak KH, Kim JK, Kim DI, Choi DY, Kim CH. Inhibitory effect of Cho-Deung-San on human aortic smooth muscle cell migration induced by TNF-α through inhibition of matrix metalloproteinase-2 and -9 activity. Vascul Pharmacol 2004; 41:83-90. [PMID: 15380733 DOI: 10.1016/j.vph.2004.05.003] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2004] [Revised: 05/12/2004] [Accepted: 05/12/2004] [Indexed: 10/26/2022]
Abstract
The migration and matrix metalloproteinases (MMPs) production of vascular smooth muscle cells (VSMC) may play a key role in the development of atherosclerosis. A Korean traditional herbal formulation, Cho-Deung-San (CDS), which is composed of 11 herbal ingredients, has been used to treat vascular diseases for many centuries. In this study, we investigated the inhibitory effect of CDS on tumor necrosis factor-alpha (TNF-alpha)-induced human aortic smooth muscle cells (HASMC) migration and MMP-2 and -9 activity. The cytotoxocity of CDS on HASMC was very low (IC(50)>500 microg/ml) as measured by the XTT assay method. The Matrigel migration assay showed that CDS effectively inhibited the TNF-alpha-induced migration of HASMC as compared with the control group in a dose-dependent manner (IC(50)=85 microg/ml). To explain this inhibitory effect, the extracts prepared from CDS and its herbal ingredients were assayed for gelatin zymography. The results showed that CDS inhibited MMP-2 and -9 activity (IC(50)=180 and 75 microg/ml, respectively). Among the herbal ingredients of CDS, the hooks and stems of Uncaria sinensis (Oliv.) Havil (UR) has shown significant inhibition against MMP-2 and -9 activity. In addition, the inhibitory effect of UR against gelatinolytic activity of MMP-2 and -9 was higher than that of catechin and lower than that of epigallocatechin gallate. These results suggest that CDS could be used as potential antiatherosclerotic agent, and UR is major component of CDS for antimigration in TNF-alpha treated HASMC.
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MESH Headings
- Aorta/pathology
- Catechin/chemistry
- Catechin/classification
- Catechin/pharmacology
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Cell Survival/drug effects
- Cell Survival/physiology
- Cells, Cultured
- Dose-Response Relationship, Drug
- Drug Evaluation, Preclinical/methods
- Gene Expression/drug effects
- Gene Expression/genetics
- Herbal Medicine
- Humans
- Korea
- Medicine, East Asian Traditional
- Muscle, Smooth, Vascular/drug effects
- Muscle, Smooth, Vascular/pathology
- Muscle, Smooth, Vascular/physiology
- Plant Extracts/chemistry
- Plant Extracts/pharmacology
- Plant Stems
- Plants, Medicinal/chemistry
- Rhizome
- Tetrazolium Salts
- Tissue Inhibitor of Metalloproteinase-2/antagonists & inhibitors
- Tissue Inhibitor of Metalloproteinase-2/genetics
- Tumor Necrosis Factor-alpha/antagonists & inhibitors
- Tumor Necrosis Factor-alpha/pharmacology
- Uncaria/chemistry
- Uncaria/metabolism
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Affiliation(s)
- Ki-Tae Ha
- Department of Biochemistry, Molecular Biology, Pathology and Gynecology, College of Oriental Medicine, Dongguk University and National Research Laboratory for Glycobiology, Sukjang-Dong 707, Kyungju City, Kyungbuk 780-714, South Korea
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45
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Huang Y, Wong CM, Lau CW, Yao X, Tsang SY, Su YL, Chen ZY. Inhibition of nitric oxide/cyclic GMP-mediated relaxation by purified flavonoids, baicalin and baicalein, in rat aortic rings. Biochem Pharmacol 2004; 67:787-94. [PMID: 14757179 DOI: 10.1016/j.bcp.2003.10.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The dried roots of Scutellaria baicalensis Georgi (Huangqin) are widely used in traditional Chinese medicine. We purified two flavonoids, baicalin and baicalein from S. baicalensis Georgi and examined their effects on isolated rat aortic rings. Baicalin (3-50 microM) inhibited endothelium/nitric oxide (NO)-dependent relaxation induced by acetylcholine (Ach) or cyclopiazonic acid (CPA). Baicalein at 50 microM abolished Ach-induced relaxation and markedly reduced CPA-induced relaxation. Treatment with 1mM L-arginine partially but significantly reversed the effects of baicalin (50 microM) or baicalein (50 microM) on Ach-induced relaxation. In endothelium-denuded rings, treatment with baicalin, baicalein or methylene blue partially inhibited relaxations induced by the NO donors, sodium nitroprusside (SNP) and hydroxylamine. Both flavonoids markedly reduced the increase in cyclic GMP levels stimulated by Ach in endothelium-intact rings and by SNP in endothelium-denuded rings. In contrast, exposure of endothelium-denuded rings to baicalin or baicalein did not affect relaxations induced by pinacidil or NS 1619, putative K+ channel activators. Neither flavonoids affected agonist-induced increase in the endothelial [Ca2+]i. Our results indicate that baicalin and baicalein attenuated NO-mediated aortic relaxation and cyclic GMP increases, likely through inhibition of NO-dependent guanylate cyclase activity.
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Affiliation(s)
- Yu Huang
- Department of Physiology, Chinese University of Hong Kong, Hong Kong, PR China.
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46
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Wang Z, Lin G, Lue TF, Lin CS. Wogonin suppresses cellular proliferation and expression of monocyte chemoattractant protein 1 in Peyronie's plaque-derived cells. BJU Int 2003; 92:753-7. [PMID: 14616461 DOI: 10.1046/j.1464-410x.2003.04464.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To test the effect of wogonin on cellular proliferation and expression of monocyte chemoattractant protein 1 (MCP-1) in cells derived from normal and diseased tunica albuginea (TA), as related to Peyronie's disease (PD). MATERIALS AND METHODS Cells with characteristics of fibroblasts were isolated from three tissue sources. Those from the plaque of patients with PD were designated as P cells, those from the adjacent, normal-appearing tissue as C cells, and those from the TA of patients without PD as N cells. These cells were treated with wogonin at doses of 0, 10, 20 and 40 micromol/L for 24 h or treated at a fixed dose of 40 micromol/L for 1, 8 and 24 h. Cell proliferation was assayed with a commercial kit, MCP-1 mRNA expression by reverse transcription-polymerase chain reaction, and secreted MCP-1 by enzyme-linked immunosorbent assay. RESULTS Wogonin suppressed cell proliferation in a dose-dependent manner; the effect was more pronounced against P cells at 8 and 24 h. Wogonin down-regulated MCP-1 mRNA expression, especially in P cells. Wogonin suppressed the level of secreted MCP-1 by 59-88%. P cells, which secreted far more MCP-1 than N and C cells at 1 h, were suppressed by 88%. C cells were the least suppressed at all three times. CONCLUSIONS Wogonin suppressed the proliferation, the expression of MCP-1 mRNA, and the expression of secreted MCP-1 in TA-derived cells. In most cases, the effect of wogonin was greatest against cells derived from the plaque. Wogonin appears to be a worthy candidate for preclinical trials in men with PD.
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Affiliation(s)
- Z Wang
- Department of Urology, School of Medicine, University of California, San Francisco, USA
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47
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Lovat PE, Ranalli M, Corazzari M, Raffaghello L, Pearson ADJ, Ponzoni M, Piacentini M, Melino G, Redfern CPF. Mechanisms of free-radical induction in relation to fenretinide-induced apoptosis of neuroblastoma. J Cell Biochem 2003; 89:698-708. [PMID: 12858336 DOI: 10.1002/jcb.10551] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The mechanisms of fenretinide-induced cell death of neuroblastoma cells are complex, involving signaling pathways mediated by free radicals or reactive oxygen species (ROS). The aim of this study was to identify mechanisms generating ROS and apoptosis of neuroblastoma cells in response to fenretinide. Fenretinide-induced ROS or apoptosis of SH-SY5Y or HTLA 230 neuroblastoma cells were not blocked by Nitro l-argenine methyl ester (l-NAME), an inhibitor of nitric oxide synthase. Flavoprotein-dependent superoxide-producing enzymes such as NADPH oxidase were also not involved in fenretinide-induced apoptosis or ROS generation. Similarly, ketoconazole, a cytochrome P450 inhibitor, and inhibitors of cyclooxygenase (COX) were also ineffective. In contrast, inhibition of phospholipase A(2) or lipoxygenases (LOX) blocked the induction of ROS and apoptosis in response to fenretinide. Using specific inhibitors of LOX, blocking 12-LOX but not 5- or 15-LOX inhibited both fenretinide-induced ROS and apoptosis. The effects of eicosatriynoic acid, a specific 12-LOX inhibitor, were reversed by the addition of the 12-LOX products, 12 (S)-hydroperoxyeicosatetraenoic acid and 12 (S)-hydroxyeicosatetraenoic acid. The targeting of 12-LOX in neuroblastoma cells may thus be a novel pathway for the development of drugs inducing apoptosis of neuroblastoma with improved tumor specificity.
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Affiliation(s)
- Penny E Lovat
- Northern Institute for Cancer Research, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom
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Nakahata N, Tsuchiya C, Nakatani K, Ohizumi Y, Ohkubo S. Baicalein inhibits Raf-1-mediated phosphorylation of MEK-1 in C6 rat glioma cells. Eur J Pharmacol 2003; 461:1-7. [PMID: 12568909 DOI: 10.1016/s0014-2999(02)02950-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Baicalein is a flavonoid derived from the Scutellaria root. In investigations of the inhibitors of prostaglandin synthesis in C6 rat glioma cells, we found that baicalein had a potent inhibitory activity on prostaglandin synthesis induced by either histamine or A23187, a Ca(2+) ionophore. Baicalein inhibited histamine- or A23187-induced phosphorylation of p42/p44 extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK), which causes the phosphorylation of cytosolic phospholipase A(2) (PLA(2)). Baicalein also inhibited the phosphorylation of MAPK kinase-1 (MEK-1) induced by histamine or A23187 in the cells. To examine the site of action of baicalein, MEK-1 and Raf-1 were prepared by immunoprecipitation with anti-MEK-1 and anti-Raf-1 antibodies, respectively. Baicalein inhibited the phosphorylation of exogenous MEK-1 by Raf-1 under cell-free conditions, while it did not change the phosphorylation of exogenous p42 MAPK by MEK-1. These results imply that baicalein inhibits the ERK/MAPK cascade, acting on the phosphorylation of MEK-1 by Raf-1.
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Affiliation(s)
- Norimichi Nakahata
- Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
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49
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Martínez C, Yàñez J, Vicente V, Alcaraz M, Benavente-García O, Castillo J, Lorente J, Lozano JA. Effects of several polyhydroxylated flavonoids on the growth of B16F10 melanoma and Melan-a melanocyte cell lines: influence of the sequential oxidation state of the flavonoid skeleton. Melanoma Res 2003; 13:3-9. [PMID: 12569278 DOI: 10.1097/00008390-200302000-00002] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The response of B16F10 melanoma and Melan-a melanocyte cell lines to treatment with five polyhydroxylated flavonoids and gallic acid, after 24 and 72 h of exposure, was determined, and the relationship between any antiproliferative effects observed and the chemical structure is discussed. After 24 h, none of the studied compounds showed significant cytotoxic activity in the B16F10 cell line, whereas compounds with an adjacent trihydroxylated substitution pattern did affect the viability of the Melan-a cell line. After 72 h of exposure, myricetin, baicalein and gallic acid significantly inhibited both B16F10 and Melan-a cell cultures, whereas luteolin and quercetin had only a moderate effect. Eriodictyol only had an effect on Melan-a cell viability, which was reduced slightly. These results suggest that the presence of a C2-C3 double bond and three adjacent hydroxyl groups in the flavonoid A- or B-rings confers greater antiproliferative activity to the flavonoid.
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Affiliation(s)
- C Martínez
- Pathology Department, Faculty of Medicine, University of Murcia, 30100 Espinardo, Murcia, Spain
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50
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Chan HY, Chen ZY, Tsang DSC, Leung LK. Baicalein inhibits DMBA-DNA adduct formation by modulating CYP1A1 and CYP1B1 activities. Biomed Pharmacother 2002; 56:269-75. [PMID: 12224597 DOI: 10.1016/s0753-3322(02)00192-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Flavonoids are phenolic compounds isolated from plants, and several of them like genistein and quercetin, have been documented to be effective in preventing cancer. Baicalein, a flavonoid extracted from the root of Scutellaria species, is widely used as a health supplement and herbal medicine in Asian countries. In this study, the chemopreventive effect of baicalein on 7,12-dimethylbenz[a]anthracene (DMBA)-induced DNA damage was evaluated in an established cell culture model. In a preliminary screening, baicalein was identified to be a strong inhibitor to EROD activities induced by DMBA in MCF-7 cells. Subsequent enzyme kinetic analysis revealed that baicalein was a competitive inhibitor to EROD, and CYP1A1 and CYP1B1 gene expressions were also determined. Baicalein could reduce the CYP1A1/1B1 mRNA expressions induced by DMBA, and the mRNA abundance of CYP1A1 appeared to be more responsive than that of CYP1B1. A XRE-luciferase gene reporter assay indicated that AhR transactivation was suppressed. Since CYP1A1/1B1 were responsible for the biotransformation of polycyclic aromatic hydrocarbons, baicalein also demonstrated its ability to reduce DMBA-DNA adduct formation in MCF-7 cells. This study suggested that the natural occurring baicalein could be an agent preventing carcinogen-DNA adduct formation.
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Affiliation(s)
- Ho Yee Chan
- Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT
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