|
1
|
Chen Q, Huang Z, Chen J, Tian X, Zhang R, Liang Q, Liu Z, Cheng Y. Notoginsenoside R1 attenuates ischemic heart failure by modulating MDM2/β arrestin2-mediated β2-adrenergic receptor ubiquitination. Biomed Pharmacother 2024; 177:117004. [PMID: 38955084 DOI: 10.1016/j.biopha.2024.117004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 06/10/2024] [Accepted: 06/17/2024] [Indexed: 07/04/2024] Open
Abstract
β2 adrenergic receptor (β2AR) is a G-protein-coupled receptor involved in cardiac protection. In chronic heart failure (CHF), persistent sympathetic nervous system activation occurs, resulting in prolonged β2AR activation and subsequent receptor desensitization and downregulation. Notoginsenoside R1 (NGR1) has the functions of enhancing myocardial energy metabolism and mitigating myocardial fibrosis. The mechanisms of NGR1 against ischemic heart failure are unclear. A left anterior descending (LAD) artery ligation procedure was performed on C57BL/6 J mice for four weeks. From the 4th week onwards, they were treated with various doses (3, 10, 30 mg/kg/day) of NGR1. Subsequently, the impacts of NGR1 on ischemic heart failure were evaluated by assessing cardiac function, morphological changes in cardiac tissue, and the expression of atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). H9c2 cells were protected by NGR1 when exposed to OGD/R conditions. H9c2 cells were likewise protected from OGD/R damage by NGR1. Furthermore, NGR1 increased β2AR levels and decreased β2AR ubiquitination. Mechanistic studies revealed that NGR1 enhanced MDM2 protein stability and increased the expression of MDM2 and β-arrestin2 while inhibiting their interaction. Additionally, under conditions produced by OGD/R, the protective benefits of NGR1 on H9c2 cells were attenuated upon administration of the MDM2 inhibitor SP141. According to these findings, NGR1 impedes the interplay between β-arrestin2 and MDM2, thereby preventing the ubiquitination and degradation of β2AR to improve CHF.
Collapse
Affiliation(s)
- Qi Chen
- Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Ziwei Huang
- Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Jing Chen
- Department of Cardiovascular Disease, The First Afliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Xiaoyu Tian
- Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Rong Zhang
- Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Qi Liang
- Shenzhen Bao'an Traditional Chinese Medicine Hospital Group, Shenzhen 518000, China.
| | - Zhongqiu Liu
- Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
| | - Yuanyuan Cheng
- Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
| |
Collapse
|
|
2
|
Demirel S. Vasorelaxant effects of biochemical constituents of various medicinal plants and their benefits in diabetes. World J Diabetes 2024; 15:1122-1141. [PMID: 38983824 PMCID: PMC11229960 DOI: 10.4239/wjd.v15.i6.1122] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 03/07/2024] [Accepted: 05/06/2024] [Indexed: 06/11/2024] Open
Abstract
Endothelial function plays a pivotal role in cardiovascular health, and dysfunction in this context diminishes vasorelaxation concomitant with endothelial activity. The nitric oxide-cyclic guanosine monophosphate pathway, prostacyclin-cyclic adenosine monophosphate pathway, inhibition of phosphodiesterase, and the opening of potassium channels, coupled with the reduction of calcium levels in the cell, constitute critical mechanisms governing vasorelaxation. Cardiovascular disease stands as a significant contributor to morbidity and mortality among individuals with diabetes, with adults afflicted by diabetes exhibiting a heightened cardiovascular risk compared to their non-diabetic counterparts. A plethora of medicinal plants, characterized by potent pharmacological effects and minimal side effects, holds promise in addressing these concerns. In this review, we delineate various medicinal plants and their respective biochemical constituents, showcasing concurrent vasorelaxant and anti-diabetic activities.
Collapse
Affiliation(s)
- Sadettin Demirel
- Medicine School, Physiology Department, Bursa Uludag University, Bursa 16059, Türkiye
| |
Collapse
|
|
3
|
Wang Y, Feng Y, Li M, Yang M, Shi G, Xuan Z, Yin D, Xu F. Traditional Chinese Medicine in the Treatment of Chronic Kidney Diseases: Theories, Applications, and Mechanisms. Front Pharmacol 2022; 13:917975. [PMID: 35924053 PMCID: PMC9340222 DOI: 10.3389/fphar.2022.917975] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 06/01/2022] [Indexed: 11/18/2022] Open
Abstract
Chronic kidney disease (CKD) is a common and progressive disease that has become a major public health problem on a global scale. Renal fibrosis is a common feature in the pathogenesis of CKD, which is mainly related to the excessive accumulation and deposition of extracellular matrix caused by various inflammatory factors. No ideal treatment has yet been established. In recent years, based on the traditional Chinese medicine (TCM) theory of CKD and its molecular mechanism, clinical evidence or experimental studies have confirmed that a variety of Chinese materia medica (CMM) and their effective components can delay the progress of CKD. TCM believes that the pathogenesis of CKD is the deficiency in the root and excess in the branch, and the deficiency and excess are always accompanied by the disease. The strategies of TCM in treating CKD are mainly based on invigorating Qi, tonifying the kidneys, promoting blood circulation, removing stasis, eliminating heat and dampness, removing turbidity, and eliminating edema, and these effects are multitargeted and multifunctional. This review attempts to summarize the theories and treatment strategies of TCM in the treatment of CKD and presents the efficacy and mechanisms of several CMMs supported by clinical evidence or experimental studies. In addition, the relationship between the macroscopic of TCM and the microscopic of modern medicine and the problems faced in further research were also discussed.
Collapse
Affiliation(s)
- Yunlai Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui Academy of Chinese Medicine, Hefei, China
| | - Ye Feng
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Manman Li
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Mo Yang
- Scientific Research and Technology Center, Anhui University of Chinese Medicine, Hefei, China
| | - Gaoxiang Shi
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Zihua Xuan
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Dengke Yin
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- *Correspondence: Dengke Yin, ; Fan Xu,
| | - Fan Xu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- *Correspondence: Dengke Yin, ; Fan Xu,
| |
Collapse
|
|
4
|
Zhu T, Wang L, Xie W, Meng X, Feng Y, Sun G, Sun X. Notoginsenoside R1 Improves Cerebral Ischemia/Reperfusion Injury by Promoting Neurogenesis via the BDNF/Akt/CREB Pathway. Front Pharmacol 2021; 12:615998. [PMID: 34025400 PMCID: PMC8138209 DOI: 10.3389/fphar.2021.615998] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 04/26/2021] [Indexed: 12/15/2022] Open
Abstract
Notoginsenoside R1 (R1), a major component isolated from P. notoginseng, is a phytoestrogen that exerts many neuroprotective effects in a rat model of ischemic stroke. However, its long-term effects on neurogenesis and neurological restoration after ischemic stroke have not been investigated. The aim of this study was to evaluate the effects of R1 on neurogenesis and long-term functional recovery after ischemic stroke. We used male Sprague-Dawley rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). R1 was administered by intraperitoneal (i.p.) injection immediately postischemia. We showed that R1 significantly decreased infarct volume and neuronal loss, restored neurological function, and stimulated neurogenesis and oligodendrogenesis in rats subjected to MCAO/R. More importantly, R1 promoted neuronal proliferation in PC12 cells in vitro. The proneurogenic effects of R1 were associated with the activation of Akt/cAMP responsive element-binding protein, as shown by the R1-induced increase in brain-derived neurotrophic factor (BDNF) expression, and with the activation of neurological function, which was partially eliminated by selective inhibitors of BDNF and PI3K. We demonstrated that R1 is a promising compound that exerts neuroprotective and proneurogenic effects, possibly via the activation of BDNF/Akt/CREB signaling. These findings offer insight into exploring new mechanisms in long-term functional recovery after R1 treatment of ischemic stroke.
Collapse
Affiliation(s)
- Ting Zhu
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.,Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
| | - Lei Wang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.,Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China.,China Pharmaceutical University, Jiangsu, China
| | - Weijie Xie
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.,Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiangbao Meng
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.,Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
| | - Yicheng Feng
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.,Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China.,Beijing University of Chemical Technology, Beijing, China
| | - Guibo Sun
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.,Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaobo Sun
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.,Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
| |
Collapse
|
|
5
|
Tang F, Yan HL, Wang LX, Xu JF, Peng C, Ao H, Tan YZ. Review of Natural Resources With Vasodilation: Traditional Medicinal Plants, Natural Products, and Their Mechanism and Clinical Efficacy. Front Pharmacol 2021; 12:627458. [PMID: 33867985 PMCID: PMC8048554 DOI: 10.3389/fphar.2021.627458] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 01/29/2021] [Indexed: 12/11/2022] Open
Abstract
For decades, chronic diseases including cardiovascular and cerebrovascular diseases (CCVDs) have plagued the world. Meanwhile, we have noticed a close association between CCVDs and vascular lesions, such as hypertension. More focus has been placed on TMPs and natural products with vasodilation and hypotension. TMPs with vasodilatory and hypotensive activities are mainly from Compositae, Lamiaceae, and Orchidaceae (such as V. amygdalina Del., T. procuinbens L., M. glomerata Spreng., K. galanga L., etc.) whereas natural products eliciting vasorelaxant potentials were primarily from flavonoids, phenolic acids and alkaloids (such as apigenin, puerarin, curcumin, sinomenine, etc.). Furthermore, the data analysis showed that the vasodilatory function of TMPs was mainly concerned with the activation of eNOS, while the natural products were primarily correlated with the blockage of calcium channel. Thus, TMPs will be used as alternative drugs and nutritional supplements, while natural products will be considered as potential therapies for CCVDs in the future. This study provides comprehensive and valuable references for the prevention and treatment of hypertension and CCVDs and sheds light on the further studies in this regard. However, since most studies are in vitro and preclinical, there is a need for more in-depth researches and clinical trials to understand the potential of these substances.
Collapse
Affiliation(s)
- Fei Tang
- State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hong-Ling Yan
- State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Li-Xia Wang
- State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jin-Feng Xu
- State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Cheng Peng
- State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hui Ao
- Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yu-Zhu Tan
- State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| |
Collapse
|
|
6
|
Karmazyn M, Gan XT. Chemical components of ginseng, their biotransformation products and their potential as treatment of hypertension. Mol Cell Biochem 2020; 476:333-347. [PMID: 32940821 DOI: 10.1007/s11010-020-03910-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Accepted: 09/07/2020] [Indexed: 02/06/2023]
Abstract
Ginseng is an ancient perennial herb belonging to the family Araliaceae and genus Panax which has been used for medical therapeutics for thousands of years, particularly in China and other Asian cultures although increasing interest in ginseng has recently emerged in western societies. Ginseng is a complex substance containing dozens of bioactive and potentially effective therapeutic compounds. Among the most studied are the ginsenosides, which are triterpene saponins possessing a wide array of potential therapeutic effects for many conditions. The quantity and type of ginsenoside vary greatly depending on ginseng species and their relative quantity in a given ginseng species is greatly affected by extraction processes as well as by subjecting ginseng to various procedures such as heating. Adding to the complexity of ginsenosides is their ability to undergo biotransformation to bioactive metabolites such as compound K by enteric bacteria following ingestion. Many ginsenosides exert vasodilatating effects making them potential candidates for the treatment of hypertension. Their vascular effects are likely dependent on eNOS activation resulting in the increased production of NO. One proposed end-mechanism involves the activation of calcium-activated potassium channels in vascular smooth cells resulting in reduced calcium influx and a vasodilatating effect, although other mechanisms have been proposed as discussed in this review.
Collapse
|
|
7
|
Wang W, Huang L, Hu Y, Thomas ER, Li X. Neuroprotective effects of notoginsenoside R1 by upregulating Trx-1 on acrylamide-induced neurotoxicity in PC12. Hum Exp Toxicol 2020; 39:797-807. [DOI: 10.1177/0960327120901586] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Acrylamide (ACR) is a water-soluble chemical that is commonly used in chemical and cosmetic manufacture. Many studies have been carried out to investigate the neurotoxicity mechanisms of ACR, resulting in oxidative stress and nerve damages. One of the commonly used traditional Chinese medicines is notoginsenoside R1 (NR1). However, its mitochondrial-mediated apoptotic effect caused in ACR-induced neurotoxicity has not been reported. Our results have shown that NR1 resisted the neurotoxicity induced by ACR by upregulating the levels of thioredoxin-1 (Trx-1) in Rat adrenal chromaffin cell tumor (PC12) cells. NR1 inhibited the increase in levels of Bax, caspase-9, and caspase-3, which was instigated by ACR. Moreover, NR1 inhibited the decrease in levels of B-cell lymphoma 2 and Trx-1 induced by ACR. The downregulation of Trx-1 aggravated the mitochondrial-mediated apoptosis and increased the expression of the above molecules, which was induced by ACR. In contrast, overexpression of Trx-1 attenuated the mitochondrial-mediated apoptosis and inhibited the expression of the mentioned molecules induced by ACR. Our results suggested that NR1 protected ACR-induced mitochondrial apoptosis by upregulating Trx-1.
Collapse
Affiliation(s)
- W Wang
- Institute for Cancer Medicine and School of Basic Medical Sciences, Southwest Medical University, Luzhou, China
- The authors contributed equally to this work
| | - L Huang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Southwest Medical University, Luzhou, China
- The authors contributed equally to this work
| | - Y Hu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Southwest Medical University, Luzhou, China
| | - ER Thomas
- Department of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong, Meghalaya, India
| | - X Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Southwest Medical University, Luzhou, China
| |
Collapse
|
|
8
|
Xiao J, Zhu T, Yin YZ, Sun B. Notoginsenoside R1, a unique constituent of Panax notoginseng, blinds proinflammatory monocytes to protect against cardiac hypertrophy in ApoE-/- mice. Eur J Pharmacol 2018; 833:441-450. [DOI: 10.1016/j.ejphar.2018.07.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 07/01/2018] [Accepted: 07/02/2018] [Indexed: 12/24/2022]
|
|
9
|
Kim DH, Paudel P, Yu T, Ngo TM, Kim JA, Jung HA, Yokozawa T, Choi JS. Characterization of the inhibitory activity of natural tanshinones from Salvia miltiorrhiza roots on protein tyrosine phosphatase 1B. Chem Biol Interact 2017; 278:65-73. [DOI: 10.1016/j.cbi.2017.10.013] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 10/07/2017] [Accepted: 10/11/2017] [Indexed: 11/27/2022]
|
|
10
|
Cao HY, Ding RL, Li M, Yang MN, Yang LL, Wu JB, Yang B, Wang J, Luo CL, Wen QL. Danshensu, a major water-soluble component of Salvia miltiorrhiza, enhances the radioresponse for Lewis Lung Carcinoma xenografts in mice. Oncol Lett 2016; 13:605-612. [PMID: 28356936 PMCID: PMC5351344 DOI: 10.3892/ol.2016.5508] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Accepted: 09/15/2016] [Indexed: 12/21/2022] Open
Abstract
The molecule 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid (danshensu), a herbal preparation used in traditional Chinese medicine, has been found to possess potential antitumor and anti-angiogenesis effects. The aim of the present study was to investigate the efficacy of the combination of radiation therapy (RT) with danshensu in the treatment of Lewis lung carcinoma (LLC) xenografts, whilst exploring and evaluating the mechanism involved. In total, 8-week old female C57BL/6J mice were randomly assigned into 3 groups to receive: RT, RT + cisplatin and RT + danshensu, respectively, when LLC reached 100–150 mm3. Each group was divided into 7 subgroups according to the different irradiation doses that were administered. Tumor growth curves were created and the sensitization enhancement ratios of the drugs were calculated. The experiment was then repeated, and the 4 groups of tumor-bearing mice were treated with natural saline, danshensu, RT + danshensu and RT, respectively. The mice were sacrificed on day 7, and tumor tissue and blood were collected to determine microvessel density, the expression of proangiogenic factors, and the levels of blood thromboxane B2 and 6-keto-prostaglandin-F1α. Tumor hypoxia was also detected using in vivo fluorescence imaging. With respect to LLC xenografts, treatment with danshensu + RT significantly enhanced the effects of tumor growth inhibition (P<0.05). Furthermore, tumor vasculature was remodeled and microcirculation was improved, which significantly reduced tumor hypoxia (P<0.05). The present study demonstrated that danshensu significantly enhanced the radioresponse of LLC xenografts in mice. The mechanism involved may be associated with the alleviation of tumor cell hypoxia following treatment with danshensu + RT, caused by the improvement of tumor microcirculation and the remodeling of tumor vasculature.
Collapse
Affiliation(s)
- Hong-Ying Cao
- Department of Emergency, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China
| | - Rui-Lin Ding
- Department of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China
| | - Meng Li
- Department of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China
| | - Mao-Nan Yang
- Department of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China
| | - Ling-Lin Yang
- Department of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China
| | - Jing-Bo Wu
- Department of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China
| | - Bo Yang
- Department of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China
| | - Jing Wang
- Department of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China
| | - Cui-Lian Luo
- Department of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China
| | - Qing-Lian Wen
- Department of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China
| |
Collapse
|
|
11
|
Rastogi S, Pandey MM, Rawat AKS. Traditional herbs: a remedy for cardiovascular disorders. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2016; 23:1082-9. [PMID: 26656228 DOI: 10.1016/j.phymed.2015.10.012] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 10/22/2015] [Indexed: 05/05/2023]
Abstract
BACKGROUND Medicinal plants have been used in patients with congestive heart failure, systolic hypertension, angina pectoris, atherosclerosis, cerebral insufficiency, venous insufficiency and arrhythmia since centuries. A recent increase in the popularity of alternative medicine and natural products has revived interest in traditional remedies that have been used for the treatment of cardiovascular diseases. AIM The purpose of this review is to provide updated, comprehensive and categorized information on the history and traditional uses of some herbal medicines that affect the cardiovascular system in order to explore their therapeutic potential and evaluate future research opportunities. METHODS Systematic literature searches were carried out and the available information on various medicinal plants traditionally used for cardiovascular disorders was collected via electronic search (using Pubmed, SciFinder, Scirus, GoogleScholar, JCCC@INSTIRC and Web of Science) and a library search for articles published in peer-reviewed journals. No restrictions regarding the language of publication were imposed. RESULTS This article highlights the cardiovascular effects of four potent traditional botanicals viz. Garlic (Allium sativum), Guggul (Commiphora wightii), Hawthorn (Crataegus oxyacantha) and Arjuna (Terminalia arjuna). Although these plants have been used in the treatment of heart disease for hundreds of years, current research methods show us they can be utilized effectively in the treatment of cardiovascular diseases including ischemic heart disease, congestive heart failure, arrhythmias and hypertension. CONCLUSION Although the mechanisms of action are not very clear, there is enough evidence of their efficacy in various cardiovascular disorders. However, for bringing more objectivity and also to confirm traditional claims, more systematic, well-designed animal and randomized clinical studies with sufficient sample sizes are necessary. Multidisciplinary research is still required to exploit the vast potential of these plants. Potential synergistic and adverse side effects of herb-drug interactions also need to be studied. These approaches will help in establishing them as remedies for cardiovascular diseases and including them in the mainstream of healthcare system.
Collapse
Affiliation(s)
- Subha Rastogi
- Pharmacognosy & Ethnopharmacology Division, CSIR- National Botanical Research Institute, Lucknow 226 001, India.
| | - Madan Mohan Pandey
- Pharmacognosy & Ethnopharmacology Division, CSIR- National Botanical Research Institute, Lucknow 226 001, India
| | - A K S Rawat
- Pharmacognosy & Ethnopharmacology Division, CSIR- National Botanical Research Institute, Lucknow 226 001, India
| |
Collapse
|
|
12
|
Mutoh T, Mutoh T, Taki Y, Ishikawa T. Therapeutic Potential of Natural Product-Based Oral Nanomedicines for Stroke Prevention. J Med Food 2016; 19:521-7. [PMID: 27136062 DOI: 10.1089/jmf.2015.3644] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Cerebral stroke is the leading cause of death and permanent disability in elderly persons. The impaired glucose and oxygen transport to the brain during ischemia causes bioenergetic failure, leading to oxidative stress, inflammation, blood-brain barrier dysfunction, and eventually cell death. However, the development of effective therapies against stroke has been hampered by insufficient oral absorption of pharmaceuticals and subsequent delivery to the brain. Nanotechnology has emerged as a new method of treating cerebral diseases, with the potential to fundamentally change currently available therapeutic approaches using compounds with low bioavailability. This perspective review provides an overview of the therapeutic potential of oral nanomedicines for stroke, focusing on novel natural product-loaded delivery system with potent antioxidant and anti-inflammatory effects.
Collapse
Affiliation(s)
- Tatsushi Mutoh
- 1 Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University , Sendai, Japan .,2 Department of Surgical Neurology, Research Institute for Brain and Blood Vessels-AKITA , Akita, Japan
| | - Tomoko Mutoh
- 1 Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University , Sendai, Japan
| | - Yasuyuki Taki
- 1 Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University , Sendai, Japan
| | - Tatsuya Ishikawa
- 2 Department of Surgical Neurology, Research Institute for Brain and Blood Vessels-AKITA , Akita, Japan
| |
Collapse
|
|
13
|
Matthäus B, Özcan MM. The lipid fraction of seeds from Salvia columbariae grown in Arizona. QUALITY ASSURANCE AND SAFETY OF CROPS & FOODS 2016. [DOI: 10.3920/qas2014.0565] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- B. Matthäus
- Max Rubner-Institut, Federal Research Institute for Nutrition and Food, Working group for Lipid Research, Schützenberg 12, 32756 Detmold, Germany
| | - M. M. Özcan
- University of Selçuk, Faculty of Agriculture, Department of Food Engineering, 42031 Konya, Turkey
| |
Collapse
|
|
14
|
Li RWS, Yang C, Shan L, Zhang Z, Wang Y, Kwan Y, Lee SM, Hoi MP, Chan S, Cheung AC, Cheung K, Leung GP. Relaxation effect of a novel Danshensu/tetramethylpyrazine derivative on rat mesenteric arteries. Eur J Pharmacol 2015; 761:153-60. [DOI: 10.1016/j.ejphar.2015.04.041] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Revised: 04/21/2015] [Accepted: 04/22/2015] [Indexed: 12/13/2022]
|
|
15
|
Dippenaar JM. Herbal and alternative medicine: the impact on anesthesia. SOUTHERN AFRICAN JOURNAL OF ANAESTHESIA AND ANALGESIA 2015. [DOI: 10.1080/22201181.2015.1013321] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
|
|
16
|
Salvianolic acids T and U: A pair of atropisomeric trimeric caffeic acids derivatives from root of Salvia miltiorrhiza. Fitoterapia 2014; 98:248-53. [DOI: 10.1016/j.fitote.2014.08.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2014] [Revised: 08/14/2014] [Accepted: 08/20/2014] [Indexed: 11/19/2022]
|
|
17
|
Zhou N, Tang Y, Keep RF, Ma X, Xiang J. Antioxidative effects of Panax notoginseng saponins in brain cells. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2014; 21:1189-95. [PMID: 24916704 PMCID: PMC4111966 DOI: 10.1016/j.phymed.2014.05.004] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Revised: 04/01/2014] [Accepted: 05/11/2014] [Indexed: 05/26/2023]
Abstract
Oxidative stress resulting from accumulation of reactive oxygen species (ROS) is involved in cell death associated with neurological disorders such as stroke, Alzheimer's disease and traumatic brain injury. Antioxidant compounds that improve endogenous antioxidant defenses have been proposed for neural protection. The purpose of this study was to investigate the potential protective effects of total saponin in leaves of Panax notoginseng (LPNS) on oxidative stress and cell death in brain cells in vitro. Lactate dehydrogenase (LDH) assay indicated that LPNS (5 μg/ml) reduced H2O2-induced cell death in primary rat cortical astrocytes (23±8% reduction in LDH release vs. control). Similar protection was found in oxygen and glucose deprivation/reoxygenation induced SH-SY5Y (a human neuroblastoma cell line) cell damage (78±7% reduction vs. control). The protective effects of LPNS in astrocytes were associated with attenuation of reactive oxygen species (ROS) accumulation. These effects involved activation of Nrf2 (nuclear translocation) and upregulation of downstream antioxidant systems including heme oxygenase-1 (HO-1) and glutathione S-transferase pi 1 (GSTP1). These results demonstrate for the first time that LPNS has antioxidative effects which may be neuroprotective in neurological disorders.
Collapse
Affiliation(s)
- Ningna Zhou
- Department of Neurosurgery, Medical School, University of Michigan, Ann Arbor, MI, USA; Department of Pharmacology, Yunnan University of Traditional Chinese Medicine, Kunming, China
| | - Yang Tang
- Department of Neurosurgery, Medical School, University of Michigan, Ann Arbor, MI, USA
| | - Richard F Keep
- Department of Neurosurgery, Medical School, University of Michigan, Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, Medical School, University of Michigan, Ann Arbor, MI, USA
| | - Xiaoxia Ma
- Department of Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, China
| | - Jianming Xiang
- Department of Neurosurgery, Medical School, University of Michigan, Ann Arbor, MI, USA.
| |
Collapse
|
|
18
|
Gao B, Huang L, Liu H, Wu H, Zhang E, Yang L, Wu X, Wang Z. Platelet P2Y₁₂ receptors are involved in the haemostatic effect of notoginsenoside Ft1, a saponin isolated from Panax notoginseng. Br J Pharmacol 2014; 171:214-23. [PMID: 24117220 DOI: 10.1111/bph.12435] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Revised: 08/29/2013] [Accepted: 09/23/2013] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND AND PURPOSE Saponins isolated from Panax notoginseng (Burk.) F.H. Chen have been shown to relieve thrombogenesis and facilitate haemostasis. However, it is not known which saponin accounts for this haemostatic effect. Hence, in the present study we aimed to identify which saponins contribute to its haemostatic activity and to elucidate the possible underlying mechanisms. EXPERIMENTAL APPROACH Platelet aggregation was analysed using a platelet aggregometer. Prothrombin time, activated partial thromboplastin time and thrombin time were measured using a blood coagulation analyser, which was further corroborated with bleeding time and thrombotic assays. The interaction of notoginsenoside Ft1 with the platelet P2Y₁₂ receptor was determined by molecular docking analysis, cytosolic Ca(2+) and cAMP measurements, and phosphorylation of PI3K and Akt assays. KEY RESULTS Among the saponins examined, Ft1 was the most potent procoagulant and induced dose-dependent platelet aggregation. Ft1 reduced plasma coagulation indexes, decreased tail bleeding time and increased thrombogenesis. Moreover, it potentiated ADP-induced platelet aggregation and increased cytosolic Ca(2+) accumulation, effects that were attenuated by clopidogrel. Molecular docking analysis suggested that Ft1 binds to platelet P2Y₁₂ receptors. The increase in intracellular Ca(2+) evoked by Ft1 in HEK293 cells overexpressing P2Y₁₂ receptors could be blocked by ticagrelor. Ft1 also affected the production of cAMP and increased phosphorylation of PI3K and Akt downstream of P2Y₁₂ signalling pathways. CONCLUSION AND IMPLICATIONS Ft1 enhanced platelet aggregation by activating a signalling network mediated through P2Y₁₂ receptors. These novel findings may contribute to the effective utilization of this compound in the therapy of haematological disorders.
Collapse
Affiliation(s)
- B Gao
- Shanghai Key laboratory of Complex Prescriptions, The Ministry of Education Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China
| | | | | | | | | | | | | | | |
Collapse
|
|
19
|
Zhu J, Fan X, Cheng Y, Agarwal R, Moore CMV, Chen ST, Tong W. Chemometric analysis for identification of botanical raw materials for pharmaceutical use: a case study using Panax notoginseng. PLoS One 2014; 9:e87462. [PMID: 24498109 PMCID: PMC3909187 DOI: 10.1371/journal.pone.0087462] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Accepted: 12/28/2013] [Indexed: 11/18/2022] Open
Abstract
The overall control of the quality of botanical drugs starts from the botanical raw material, continues through preparation of the botanical drug substance and culminates with the botanical drug product. Chromatographic and spectroscopic fingerprinting has been widely used as a tool for the quality control of herbal/botanical medicines. However, discussions are still on-going on whether a single technique provides adequate information to control the quality of botanical drugs. In this study, high performance liquid chromatography (HPLC), ultra performance liquid chromatography (UPLC), capillary electrophoresis (CE) and near infrared spectroscopy (NIR) were used to generate fingerprints of different plant parts of Panax notoginseng. The power of these chromatographic and spectroscopic techniques to evaluate the identity of botanical raw materials were further compared and investigated in light of the capability to distinguishing different parts of Panax notoginseng. Principal component analysis (PCA) and clustering results showed that samples were classified better when UPLC- and HPLC-based fingerprints were employed, which suggested that UPLC- and HPLC-based fingerprinting are superior to CE- and NIR-based fingerprinting. The UPLC- and HPLC- based fingerprinting with PCA were able to correctly distinguish between samples sourced from rhizomes and main root. Using chemometrics and its ability to distinguish between different plant parts could be a powerful tool to help assure the identity and quality of the botanical raw materials and to support the safety and efficacy of the botanical drug products.
Collapse
Affiliation(s)
- Jieqiang Zhu
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Xiaohui Fan
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
- * E-mail: (XF); (RA); (WT)
| | - Yiyu Cheng
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Rajiv Agarwal
- Office of New Drug Quality Assessment, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, Maryland, United States of America
- * E-mail: (XF); (RA); (WT)
| | - Christine M. V. Moore
- Office of New Drug Quality Assessment, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, Maryland, United States of America
| | - Shaw T. Chen
- Office of New Drugs, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, Maryland, United States of America
| | - Weida Tong
- National Center for Toxicological Research (NCTR), US Food and Drug Administration, Jefferson, Arkansas, United States of America
- * E-mail: (XF); (RA); (WT)
| |
Collapse
|
|
20
|
Shi HB, Chen JD, Chen XH, He Y, Yang ZJ. Effects of salvianolic acid and notoginseng triterpenes on angiogenesis in EA-hy926 cells in vitro. Chin J Nat Med 2013; 11:254-7. [PMID: 23725837 DOI: 10.1016/s1875-5364(13)60024-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2013] [Indexed: 01/01/2023]
Abstract
AIM To investigate the different effects of salvianolic acid and notoginseng triterpenes on proliferation, angiogenesis and expression of vascular endothelial growth factor in EA-hy926 cells in vitro. METHODS EA-hy926 cells were cultured in vitro. Salvianolic acid and notoginseng triterpenes at concentrations of 0.4, 0.8 and 1.2 mg·L(-1) were used to culture EA-hy926 cells. EA-hy926 cells in a blank control group were grown in culture solution only. Viability of cells was assessed by CCK-8, and after treated for 12 h, capillary-like structures were examined. After 24 h culture, the expression of VEGF was detected by real-time PCR. RESULTS Salvianolic acid at 0.4, 0.8 mg·L(-1), the same as notoginseng triterpenes, increased VEGF content in EA-hy926 cells. Expression of VEGF protein in the salvianolic acid at 1.2 mg·L(-1) group, was up-regulated as compared with notoginseng triterpenes group (P < 0.05). CONCLUSION Salvianolic acid and notoginseng triterpenes can promote EA-hy926 cell proliferation, angiogenesis and expression of VEGF protein. This analysis also provided evidence that salvianolic acid had the better effects as compared with notoginseng triterpenes.
Collapse
Affiliation(s)
- Hai-Bo Shi
- Nanjing Medical University, Nanjing, China
| | | | | | | | | |
Collapse
|
|
21
|
Luo SL, Dang LZ, Li JF, Zou CG, Zhang KQ, Li GH. Biotransformation of Saponins by Endophytes Isolated fromPanax notoginseng. Chem Biodivers 2013; 10:2021-31. [DOI: 10.1002/cbdv.201300005] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2013] [Indexed: 11/05/2022]
|
|
22
|
Regulation of water-soluble phenolic acid biosynthesis in Salvia miltiorrhiza Bunge. Appl Biochem Biotechnol 2013; 170:1253-62. [PMID: 23673485 DOI: 10.1007/s12010-013-0265-4] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2012] [Accepted: 04/23/2013] [Indexed: 10/26/2022]
Abstract
Salvia miltiorrhiza Bunge (Lamiaceae) root, generally called Danshen, is an important herb in Chinese medicine widely used for treatment of various diseases. Phenolic acids in S. miltiorrhiza, as important effective compounds, have become a new research focus in plant secondary metabolism in recent years. This review summarizes the recent advances in the regulation of water-soluble phenolic acid biosynthesis in S. miltiorrhiza via regulators at molecular level, such as the phenylalanine ammonia-lyase gene (PAL), cinnamic acid 4-hydroxylase gene (C4H), 4-coumarate-CoA ligase gene (4CL), tyrosine aminotransferase gene (TAT), 4-hydroxyphenylpyruvate reductase gene (HPPR), 4-hydroxyphenylpyruvated dioxygenase gene (HPPD), hydroxycinnamoyl-CoA:hydroxyphenyllactate hydroxycinnamoyl transferase-like gene (RAS-like), and v-myb avian myeloblastosis viral oncogene homolog 4 gene (MYB4), and production of anthocyanin pigmentation 1 gene (AtPAP1), and via regulators at cell level, such as methyl jasmonate, salicylic acid, abscisic acid, polyamines, metal ions, hydrogen peroxide (H₂O₂), ultraviolet-B radiation, and yeast elicitor.
Collapse
|
|
23
|
Sun B, Xiao J, Sun XB, Wu Y. Notoginsenoside R1 attenuates cardiac dysfunction in endotoxemic mice: an insight into oestrogen receptor activation and PI3K/Akt signalling. Br J Pharmacol 2013; 168:1758-70. [PMID: 23170834 PMCID: PMC3605881 DOI: 10.1111/bph.12063] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2012] [Revised: 10/10/2012] [Accepted: 11/13/2012] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND AND PURPOSE Notoginsenoside R1 (NG-R1), a novel phytoestrogen isolated from Panax notoginseng, is believed to have anti-inflammatory, anti-oxidative and anti-apoptotic properties. However, its cardioprotective properties and underlying mechanisms are largely unknown. Here we have assessed the contribution of the anti-inflammatory effects of NG-R1 to the amelioration of septic cardiac dysfunction and inflammation in mice. EXPERIMENTAL APPROACH We assessed cardiac function in mice by echocardiography. We studied the protein or mRNA levels of some inflammatory factors, apoptotic factors and oestrogen receptors (ERs) in heart tissues upon stimulation with bacterial LPS, NG-R1 or some pharmacological inhibitors. KEY RESULTS Six hours after LPS administration (10 mg·kg(-1) , i.p.) cardiac function was decreased, an effect attenuated by NG-R1 pretreatment (25 mg·kg(-1) ·d(-1) , i.p.). NG-R1 also improved the imbalance between iNOS and eNOS, prevented activation of NF-κB and the subsequent myocardial inflammatory and apoptotic responses in endotoxemic mice. The effects of NG-R1 were closely associated with activation of the oestrogen receptor ERα and of PI3K/PKB (Akt) signalling, as characterized by NG-R1-induced preservation in ERα, phospho-Akt, phospho-GSK3β and I-κBα, and of cardiac function that was partially blocked by selective inhibitors of ERα or PI3K. However, NG-R1 had no effect on LPS-activated TLR-4. CONCLUSIONS AND IMPLICATIONS NG-R1 is a promising compound for protecting the heart from septic shock, possibly via the activation of ERα and PI3K/Akt signalling. This mechanism produces blockade of NF-κB activation and attenuation of the pro-inflammatory state and apoptotic stress in the myocardium.
Collapse
Affiliation(s)
- Bing Sun
- Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing, China
| | - Jing Xiao
- Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing, China
| | - Xiao-Bo Sun
- Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing, China
| | - Ying Wu
- Academy of Chinese Materia Medica, Wenzhou Medical CollegeWenzhou, China
| |
Collapse
|
|
24
|
Chow DHK, Lai A, Tang FH, Leung MCP. Effects of Panax ginseng-containing herbal plasters on compressed intervertebral discs in an in vivo rat tail model. Chin Med 2013; 8:4. [PMID: 23419188 PMCID: PMC3585783 DOI: 10.1186/1749-8546-8-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2012] [Accepted: 02/14/2013] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Tienchi (Panax notoginseng) has been used in conservative treatments for back pain as a major ingredient of many herbal medicines. This study aims to investigate the effects of a herbal medicine containing tienchi on compressed intervertebral discs in rats. METHODS Using an in vivo rat tail model, intervertebral disc compression was simulated in the caudal 8-9 discs of 25 rats by continuous static compression (11 N) for 2 weeks. An herbal medicine plaster (in which the major ingredient was tienchi) was externally applied to the compressed disc (n=9) for three weeks, and held in place by an adhesive bandage, in animals in the Chinese Medicine (CM) group. The effect of the bandage was evaluated in a separate placebo group (n=9), while no intervention with unrestricted motion was provided to rats in an additional control group (n=7). Disc structural properties were quantified by in vivo disc height measurement and in vitro morphological analysis. RESULTS Disc height decreased after the application of compression (P < 0.001). The disc height decreased continuously in the control (P = 0.006) and placebo (P = 0.003) groups, but was maintained in the CM group (P = 0.494). No obvious differences in disc morphology were observed among the three groups (P = 0.896). CONCLUSION The tienchi-containing herbal plaster had no significant effect on the morphology of compressed discs, but maintained disc height in rats.
Collapse
Affiliation(s)
- Daniel H K Chow
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, SAR, PR China.
| | | | | | | |
Collapse
|
|
25
|
Wang CZ, He H, Wang X, Yuan CS. Trends in Scientific Publications of Chinese Medicine. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2012; 40:1099-108. [DOI: 10.1142/s0192415x12500814] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Traditional Chinese medicine (TCM) is an important component of complementary and alternative medicine (CAM). The fast economic growth of mainland China in the past two decades has promoted the use of TCM beyond Chinese-speaking countries. Chinese researchers have published more TCM research studies in CAM-related professional journals, including the American Journal of Chinese Medicine (AJCM), the highest impact journal in Chinese medicine. The consistent increase of the impact factor of the AJCM suggests a growth in TCM popularity. This study analyzed articles published in the AJCM between 2004 and 2011. Our data show that while enthusiasm towards cardiovascular, nervous system and inflammation related research remained high, more herbal investigations and cancer studies were published. Furthermore, a reduction in TCM formulation studies was replaced by increasing botanical single constituent research. Examples of frequently cited studies, including those before 2004, are presented. These data are not only important to the scientific community for recognition of trends in TCM research, but also for providing information to TCM researchers who are targeting potentially highly cited studies.
Collapse
Affiliation(s)
- Chong-Zhi Wang
- Tang Center for Herbal Medicine Research, The University of Chicago, Chicago, Illinois 60637, USA
- Department of Anesthesia and Critical Care, The University of Chicago, Chicago, Illinois 60637, USA
| | - Hui He
- Tang Center for Herbal Medicine Research, The University of Chicago, Chicago, Illinois 60637, USA
| | - Xiaoyu Wang
- Tang Center for Herbal Medicine Research, The University of Chicago, Chicago, Illinois 60637, USA
| | - Chun-Su Yuan
- Tang Center for Herbal Medicine Research, The University of Chicago, Chicago, Illinois 60637, USA
- Department of Anesthesia and Critical Care, The University of Chicago, Chicago, Illinois 60637, USA
| |
Collapse
|
|
26
|
Zhang J, Han X, Li X, Luo Y, Zhao H, Yang M, Ni B, Liao Z. Core-shell hybrid liposomal vesicles loaded with panax notoginsenoside: preparation, characterization and protective effects on global cerebral ischemia/reperfusion injury and acute myocardial ischemia in rats. Int J Nanomedicine 2012; 7:4299-310. [PMID: 22915851 PMCID: PMC3419509 DOI: 10.2147/ijn.s32385] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2012] [Indexed: 12/30/2022] Open
Abstract
PURPOSE Novel panax notoginsenoside-loaded core-shell hybrid liposomal vesicles (PNS-HLV) were developed to resolve the restricted bioavailability of PNS and to enhance its protective effects in vivo on oral administration. METHODS Physicochemical characterizations of PNS-HLV included assessment of morphology, particle size and zeta potential, encapsulation efficiency (EE%), stability and in vitro release study. In addition, to evaluate its oral treatment potential, we compared the effect of PNS-HLV on global cerebral ischemia/reperfusion and acute myocardial ischemia injury with those of PNS solution, conventional PNS-loaded nanoparticles, and liposomes. RESULTS In comparison with PNS solution, conventional PNS-loaded nanoparticles and liposomes, PNS-HLV was stable for at least 12 months at 4°C. Satisfactory improvements in the EE% of notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were shown with the differences in EE% shortened and the greater controlled drug release profiles were exhibited from PNS-HLV. The improvements in the physicochemical properties of HLV contributed to the results that PNS-HLV was able to significantly inhibit the edema of brain and reduce the infarct volume, while it could markedly inhibit H(2)O(2), modified Dixon agar, and serum lactate dehydrogenase, and increase superoxide dismutase (P < 0.05). CONCLUSION The results of the present study imply that HLV has promising prospects for improving free drug bioactivity on oral administration.
Collapse
Affiliation(s)
- Jing Zhang
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | | | | | | | | | | | | | | |
Collapse
|
|
27
|
Yue QX, Xie FB, Song XY, Wu WY, Jiang BH, Guan SH, Yang M, Liu X, Guo DA. Proteomic studies on protective effects of salvianolic acids, notoginsengnosides and combination of salvianolic acids and notoginsengnosides against cardiac ischemic-reperfusion injury. JOURNAL OF ETHNOPHARMACOLOGY 2012; 141:659-667. [PMID: 21903157 DOI: 10.1016/j.jep.2011.08.044] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2011] [Revised: 08/08/2011] [Accepted: 08/21/2011] [Indexed: 05/31/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Salvia miltiorrhiza and Panax notoginseng are popularly used traditional Chinese medicine for cardiovascular disorders and they are often used in the form of combination. However, mechanisms of their cardioprotective effects were still not clear. In the present study, the protective effects of salvianolic acids (SA), notoginsengnosides (NG) and combination of SA and NG (CSN) against rat cardiac ischemia-reperfusion injury were checked and the protein expression profiles of heart tissues were examined to search their possible protein targets. MATERIALS AND METHODS The cardioprotective effects of SA, NG and CSN were checked in a rat model of ischemia-reperfusion (IR) by temporarily occluding coronary artery for 20 min followed by reperfusion. Rats were grouped into sham-operation group, IR group, IR+SA group, IR+NG group and IR+CSN group. The plasma creatine kinase (CK) activities were measured using commercial kit and the percentages of infarcted area in total ventricle tissue were calculated after nitroblue-tetrazolium (N-BT) staining of heart tissue slices. Two-dimensional protein electrophoresis (2-DE) was used to check the protein expression profiles of heart tissues. Then, proteins differentially expressed between IR group and sham-operation group were identified using matrix assisted laser desorption ionization-time of flight-mass spectrometry/mass spectrometry (MALDI-TOF MS/MS). The regulative effects of SA, NG and CSN on these IR-related proteins were analyzed. RESULTS Treatments including SA, NG and CSN all showed cardioprotective effects against ischemia-reperfusion injury and CSN exhibited to be the best. Eighteen proteins involved in IR injury were found. These proteins are involved in pathways including energy metabolism, lipid metabolism, muscle contraction, heat shock stress, cell survival and proliferation. The regulation of these proteins by SA, NG or CSN suggested possible protein targets in their cardioprotective effects. CONCLUSIONS SA and NG showed both similarity and difference in their protein targets involved in cardioprotective effects. The capability of CSN to regulate both protein targets of SA and NG might be the basis of CSN to show cardioprotective effects better than that of SA or NG.
Collapse
MESH Headings
- Alkenes/isolation & purification
- Alkenes/pharmacology
- Animals
- Creatine Kinase/blood
- Disease Models, Animal
- Drugs, Chinese Herbal/isolation & purification
- Drugs, Chinese Herbal/pharmacology
- Electrophoresis, Gel, Two-Dimensional
- Male
- Medicine, Chinese Traditional
- Myocardial Infarction/metabolism
- Myocardial Infarction/pathology
- Myocardial Infarction/prevention & control
- Myocardial Reperfusion Injury/metabolism
- Myocardial Reperfusion Injury/pathology
- Myocardial Reperfusion Injury/prevention & control
- Myocardium/metabolism
- Myocardium/pathology
- Panax notoginseng/chemistry
- Plants, Medicinal
- Polyphenols/isolation & purification
- Polyphenols/pharmacology
- Proteomics/methods
- Rats
- Rats, Wistar
- Salvia miltiorrhiza/chemistry
- Saponins/isolation & purification
- Saponins/pharmacology
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Time Factors
Collapse
Affiliation(s)
- Qing-Xi Yue
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
28
|
Tam WW, Wong EL, Wong FC, Cheung AW. Citation classics in the integrative and complementary medicine literature: 50 frequently cited articles. Eur J Integr Med 2012. [DOI: 10.1016/j.eujim.2011.12.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
|
|
29
|
Lin YC, Chen YC, Chen TH, Chen HH, Tsai WJ. Acute Kidney Injury Associated with Hepato-protective Chinese Herb – Pien Tze Huang. ACTA ACUST UNITED AC 2011. [DOI: 10.1016/j.jecm.2011.07.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
|
|
30
|
Active ingredients in Chinese medicines promoting blood circulation as Na+/K+ -ATPase inhibitors. Acta Pharmacol Sin 2011; 32:141-51. [PMID: 21293466 DOI: 10.1038/aps.2010.197] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The positive inotropic effect of cardiac glycosides lies in their reversible inhibition on the membrane-bound Na(+)/K(+)-ATPase in human myocardium. Steroid-like compounds containing a core structure similar to cardiac glycosides are found in many Chinese medicines conventionally used for promoting blood circulation. Some of them are demonstrated to be Na(+)/K(+)-ATPase inhibitors and thus putatively responsible for their therapeutic effects via the same molecular mechanism as cardiac glycosides. On the other hand, magnesium lithospermate B of danshen is also proposed to exert its cardiac therapeutic effect by effectively inhibiting Na(+)/K(+)-ATPase. Theoretical modeling suggests that the number of hydrogen bonds and the strength of hydrophobic interaction between the effective ingredients of various medicines and residues around the binding pocket of Na(+)/K(+)-ATPase are crucial for the inhibitory potency of these active ingredients. Ginsenosides, the active ingredients in ginseng and sanqi, substantially inhibit Na(+)/K(+)-ATPase when sugar moieties are attached only to the C-3 position of their steroid-like structure, equivalent to the sugar position in cardiac glycosides. Their inhibitory potency is abolished, however, when sugar moieties are linked to C-6 or C-20 position of the steroid nucleus; presumably, these sugar attachments lead to steric hindrance for the entrance of ginsenosides into the binding pocket of Na(+)/K(+)-ATPase. Neuroprotective effects of cardiac glycosides, several steroid-like compounds, and magnesium lithospermate B against ischemic stroke have been accordingly observed in a cortical brain slice-based assay model, and cumulative data support that effective inhibitors of Na(+)/K(+)-ATPase in the brain could be potential drugs for the treatment of ischemic stroke.
Collapse
|
|
31
|
Choi RCY, Jiang Z, Xie HQ, Cheung AWH, Lau DTW, Fu Q, Dong TT, Chen J, Wang Z, Tsim KWK. Anti-oxidative effects of the biennial flower of Panax notoginseng against H2O2-induced cytotoxicity in cultured PC12 cells. Chin Med 2010; 5:38. [PMID: 21029415 PMCID: PMC2978211 DOI: 10.1186/1749-8546-5-38] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2010] [Accepted: 10/28/2010] [Indexed: 11/29/2022] Open
Abstract
Background Radix notoginseng is used in Chinese medicine to improve blood circulation and clotting; however, the pharmacological activities of other parts of Panax notoginseng have yet to be explored. The present study reports the anti-oxidative effects of various parts of Panax notoginseng. Methods Various parts of Panax notoginseng, including the biennial flower, stem-leaf, root-rhizome, fiber root and sideslip, were used to prepare extracts and analyzed for their anti-oxidation effects, namely suppressing xanthine oxidase activity, H2O2-induced cytotoxicity and H2O2-induced ROS formation. Results Among various parts of the herb (biennial flower, stem-leaf, root-rhizome, fiber root and sideslip), the water extract of the biennial flower showed the strongest effects in (i) inhibiting the enzymatic activity of xanthine oxidase and (ii) protecting neuronal PC12 cells against H2O2-induced cytotoxicity. Only the water extracts demonstrated such anti-oxidative effects while the ethanol extracts did not exert significant effects in suppressing xanthine oxidase and H2O2-induced neuronal cytotoxicity. Conclusions The present study demonstrates the biennial flower of Panax notoginseng to have neuroprotection effect on cultured neurons and the underlying protection mechanism may involve anti-oxidation.
Collapse
Affiliation(s)
- Roy Chi-Yan Choi
- Center for Chinese Medicine and Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Leung SWS, Zhu DY, Man RYK. Effects of the aqueous extract of Salvia Miltiorrhiza (danshen) and its magnesium tanshinoate B-enriched form on blood pressure. Phytother Res 2010; 24:769-74. [PMID: 19943333 DOI: 10.1002/ptr.3047] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Danshen is the dried root and rhizome of the Chinese medicinal plant Salvia miltiorrhiza Bunge (Labiatae), which has been used to treat hypertension and myocardial infarction. One of its water-soluble active components is magnesium tanshinoate B (MTB). The present study examined and compared the cardiovascular effects of the water-soluble extract of danshen (SME) and its MTB-enriched form (containing 70% of MTB (MTB70)). Anaesthetized rats were infused intravenously with saline or phenylephrine to achieve a normal or elevated blood pressure, respectively. Different doses of SME, MTB70 or vehicle were then injected intravenously and their effect on blood pressure was monitored. The results indicate that SME and MTB70 reduce blood pressure dose-dependently. Independently of the initial blood pressure, SME caused a smaller reduction in blood pressure than MTB70. In rats infused with phenylephrine, MTB70 caused greater decreases in blood pressure than in rats infused with saline, while the responses to SME did not differ between the two groups. From these findings, it appears that MTB is one of the major components responsible for the cardiovascular effects of danshen, and that the beneficial cardiovascular effect of the extract is more prominent under conditions of elevated blood pressure.
Collapse
Affiliation(s)
- S W S Leung
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China.
| | | | | |
Collapse
|
|
33
|
Wang J, Dong MQ, Liu ML, Xu DQ, Luo Y, Zhang B, Liu LL, Xu M, Zhao PT, Gao YQ, Li ZC. Tanshinone IIA modulates pulmonary vascular response to agonist and hypoxia primarily via inhibiting Ca2+ influx and release in normal and hypoxic pulmonary hypertension rats. Eur J Pharmacol 2010; 640:129-38. [PMID: 20460121 DOI: 10.1016/j.ejphar.2010.04.047] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2009] [Revised: 04/09/2010] [Accepted: 04/23/2010] [Indexed: 02/01/2023]
Abstract
The present study was designed to investigate the vascular effects and underlying mechanisms of tanshinone IIA on isolated rat pulmonary artery. Isometric tension was recorded in the arteries from normal and hypoxic pulmonary hypertension rats under normoxia or hypoxia condition. The results showed that tanshinone IIA exerted a biphasic effect on rat pulmonary artery. The constriction was attenuated by endothelium-denudation but was enhanced by inhibition of nitric oxide synthase. Pretreatment with tetraethylammonium (Ca2+-activated K+ channel inhibitor) upward shifted the concentration-response curve without affecting the maximum dilatation. Pretreatment with zinc protoporphyrin IX (heme oxygenase-1 inhibitor), 4-aminopyridine (KV channel inhibitor), glibenclamide (KATP channel inhibitor) or BaCl2 (inwardly rectifying K+ channel inhibitor) did not affect the vasoreactivity. Meanwhile, tanshinone IIA almost abolished vasoconstriction induced by extracellular Ca2+. Under hypoxia condition, tanshinone IIA eliminated acute hypoxia-induced initial contraction, potentiated following vasorelaxation, attenuated and reversed sustained contraction to relaxation in pulmonary artery from normal rats, and reversed phenylephrine-induced sustained constriction to sustained relaxation in remodeled pulmonary artery from hypoxic pulmonary hypertension rats. We concluded that the mild constrictive effect induced by tanshinone IIA was affected by integrity of endothelium and production of nitric oxide, while the potent dilative effect was endothelium-independent and produced primarily by inhibiting extracellular Ca2+ influx and partially by inhibiting intracellular Ca2+ release, as well as activating Ca2+-activated K+ channels. The modulation of tanshinone IIA on pulmonary vasoreactivity under both acute and chronic hypoxia condition may provide a new insight for curing hypoxic pulmonary hypertension.
Collapse
Affiliation(s)
- Jing Wang
- Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an, 710032, PR China
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
34
|
Kim MH, Kim SI, Seo DW, Ryu JC, Choi HY. Antioxidant activity of Salvia miltiorrhiza Bunge, a novel foodstuff. Mol Cell Toxicol 2010. [DOI: 10.1007/s13273-010-0009-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
|
|
35
|
Jia L, Zhao Y, Liang XJ. Current evaluation of the millennium phytomedicine- ginseng (II): Collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine. Curr Med Chem 2010; 16:2924-42. [PMID: 19689273 DOI: 10.2174/092986709788803204] [Citation(s) in RCA: 197] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
This review, a sequel to part 1 in the series, collects about 107 chemical entities separated from the roots, leaves and flower buds of Panax ginseng, quinquefolius and notoginseng, and categorizes these entities into about 18 groups based on their structural similarity. The bioactivities of these chemical entities are described. The 'Yin and Yang' theory and the fundamentals of the 'five elements' applied to the traditional Chinese medicine (TCM) are concisely introduced to help readers understand how ginseng balances the dynamic equilibrium of human physiological processes from the TCM perspectives. This paper concerns the observation and experimental investigation of biological activities of ginseng used in the TCM of past and present cultures. The current biological findings of ginseng and its medical applications are narrated and critically discussed, including 1) its antihyperglycemic effect that may benefit type II diabetics; in vitro and in vivo studies demonstrated protection of ginseng on beta-cells and obese diabetic mouse models. The related clinical trial results are stated. 2) its aphrodisiac effect and cardiovascular effect that partially attribute to ginseng's bioactivity on nitric oxide (NO); 3) its cognitive effect and neuropharmacological effect that are intensively tested in various rat models using purified ginsenosides and show a hope to treat Parkinson's disease (PD); 4) its uses as an adjuvant or immunotherapeutic agent to enhance immune activity, appetite and life quality of cancer patients during their chemotherapy and radiation. Although the apoptotic effect of ginsenosides, especially Rh2, Rg3 and Compound K, on various tumor cells has been shown via different pathways, their clinical effectiveness remains to be tested. This paper also updates the antioxidant, anti-inflammatory, anti-apoptotic and immune-stimulatory activities of ginseng, its ingredients and commercial products, as well as common side effects of ginseng mainly due to its overdose, and its pharmacokinetics.
Collapse
Affiliation(s)
- Lee Jia
- Developmental Therapeutics Program, National Cancer Institute/ NIH, Rockville, MD 20852, USA.
| | | | | |
Collapse
|
|
36
|
Liu J, Morton J, Miedzyblocki M, Lee TF, Bigam DL, Fok TF, Chen C, Lee SK, Davidge ST, Cheung PY. Sodium tanshinone IIA sulfonate increased intestinal hemodynamics without systemic circulatory changes in healthy newborn piglets. Am J Physiol Heart Circ Physiol 2009; 297:H1217-24. [DOI: 10.1152/ajpheart.00477.2009] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In traditional Chinese medicine, tanshinone IIA is a lipid-soluble component of Danshen that has been widely used for various cardiovascular and cerebrovascular disorders, including neonatal asphyxia. Despite promising effects, little is known regarding the hemodynamic effects of tanshinone IIA in newborn subjects. To examine the dose-response effects of sodium tanshinone IIA sulfonate (STS) on systemic and regional hemodynamics and oxygen transport, 12 newborn piglets were anesthetized and acutely instrumented for the placement of femoral arterial and venous, pulmonary arterial catheters to measure mean arterial, central venous, and pulmonary arterial pressures, respectively. The blood flow at the common carotid, renal, pulmonary, and superior mesenteric (SMA) arteries were continuously monitored after treating the piglets with either STS (0.1–30 mg/kg iv) or saline treatment ( n = 6/group). To further delineate the underlying mechanisms for vasorelaxant effects of STS, in vitro vascular myography was carried out to compare its effect on rat mesenteric and carotid arteries ( n = 4–5/group). STS dose-dependently increased the SMA blood flow and the corresponding oxygen delivery with no significant effect on systemic and pulmonary, carotid and renal hemodynamic parameters. In vitro studies also demonstrated that STS selectively dilated rat mesenteric but not carotid arteries. Vasodilation in mesenteric arteries was inhibited by apamin and TRAM-34 (calcium-activated potassium channel inhibitors) but not by meclofenamate (cyclooxygenase inhibitor) or N-nitro-l-arginine methyl ester hydrochloride (nitric oxide synthase inhibitor). In summary, without significant hemodynamic effects on newborn piglets, intravenous infusion of STS selectively increased mesenteric perfusion in a dose-dependent manner, possibly via an endothelium-derived hyperpolarizing factor vasodilating pathway.
Collapse
Affiliation(s)
- Jiangqin Liu
- Department of 1Pediatrics, University of Alberta, Edmonton, Alberta, Canada
- Department of Pediatrics, Children's Hospital of Fudan University, Shanghai; and
| | - Jude Morton
- Department of 3Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada
| | | | - Tze Fun Lee
- Department of 1Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - David L. Bigam
- Department of 4Surgery, University of Alberta, Edmonton, Alberta, Canada
| | - Tai Fai Fok
- Department of Pediatrics, the Chinese University of Hong Kong, Hong Kong, China
| | - Chao Chen
- Department of Pediatrics, Children's Hospital of Fudan University, Shanghai; and
| | - Shoo K. Lee
- Department of 1Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Sandra T. Davidge
- Department of 3Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada
| | - Po-Yin Cheung
- Department of 1Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| |
Collapse
|
|
37
|
Yang D, Yang S, Zhang Y, Liu Y, Meng X, Liang Z. Metabolic profiles of three related Salvia species. Fitoterapia 2009; 80:274-8. [DOI: 10.1016/j.fitote.2009.03.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2008] [Revised: 02/24/2009] [Accepted: 03/03/2009] [Indexed: 11/27/2022]
|
|
38
|
Son HY, Han HS, Jung HW, Park YK. Panax notoginseng Attenuates the Infarct Volume in Rat Ischemic Brain and the Inflammatory Response of Microglia. J Pharmacol Sci 2009; 109:368-79. [PMID: 19305121 DOI: 10.1254/jphs.08197fp] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
The roots of Panax notoginseng (PN) are commonly used as a therapeutic agent to stop hemorrhage and as a tonic to promote health in traditional Korean medicine. Stroke triggers an inflammatory response that not only plays a central role in the pathogenesis of cerebral ischemia, but also induces secondary damage. This study was designed to investigate the neuroprotective effects of the methanol extract of PN on the infarct volume induced by middle cerebral artery occlusion (MCAO) (90-min occlusion and 24-h reperfusion) in rat brains. The PN extract (50 mg/kg, i.p.) was administered 2 h after the onset of MCAO. The PN-treated groups had a reduction in infarct volume by 23.82 +/- 8.9%. In the PN extract-treated groups, the microglial density was significantly decreased in the peri-infarct region; the underlying mechanism was inhibition of inflammatory mediators, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, via blocking of the NF-kappaB pathway. Furthermore, in vitro studies showed that the PN extract significantly reduced the production of iNOS-derived NO and COX-2-derived prostaglandin E(2) through the regulation of gene transcription levels in primary microglia and BV-2 cells. These results suggest that anti-inflammatory and microglial activation inhibitory effects of the PN extract may contribute to its neuroprotective effects in brain ischemia.
Collapse
Affiliation(s)
- Hye Young Son
- Oriental Medicine Drug R&D Center and Oriental Medicine Research Institute, College of Oriental Medicine, Dongguk University, South Korea
| | | | | | | |
Collapse
|
|
39
|
Guo AJ, Choi RCY, Cheung AWH, Li J, Chen IX, Dong TT, Tsim KWK, Lau BWC. Stimulation of Apolipoprotein A-IV expression in Caco-2/TC7 enterocytes and reduction of triglyceride formation in 3T3-L1 adipocytes by potential anti-obesity Chinese herbal medicines. Chin Med 2009; 4:5. [PMID: 19321011 PMCID: PMC2676280 DOI: 10.1186/1749-8546-4-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2008] [Accepted: 03/26/2009] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chinese medicine has been proposed as a novel strategy for the prevention of metabolic disorders such as obesity. The present study tested 17 Chinese medicinal herbs were tested for their potential anti-obesity effects. METHODS The herbs were evaluated in terms of their abilities to stimulate the transcription of Apolipoprotein A-IV (ApoA-IV) in cultured Caco-2/TC7 enterocytes. The herbs that showed stimulating effects on ApoA-IV transcription were further evaluated in terms of their abilities to reduce the formation of triglyceride in differentiated 3T3-L1 adipocytes. RESULTS ApoA-IV transcription was stimulated by Rhizoma Alismatis and Radix Angelica Sinensis in a dose- and time-dependent manner in cultured Caco-2/TC7 cells. Moreover, these two herbs reduced the amount of triglyceride in differentiated 3T3-L1 adipocytes. CONCLUSION The results suggest that Rhizoma Alistmatis and Radix Angelica Sinensis may have potential anti-obesity effects as they stimulate ApoA-IV transcription and reduce triglyceride formation.
Collapse
Affiliation(s)
- Ava Jiangyang Guo
- Department of Biology, Hong Kong University of Science and Technology, Hong Kong SAR, PR China.
| | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Effect of sugar positions in ginsenosides and their inhibitory potency on Na+/K+-ATPase activity. Acta Pharmacol Sin 2009; 30:61-9. [PMID: 19060914 DOI: 10.1038/aps.2008.6] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
AIM To determine whether ginsenosides with various sugar attachments may act as active components responsible for the cardiac therapeutic effects of ginseng and sanqi (the roots of Panax ginseng and Panax notoginseng) via the same molecular mechanism triggered by cardiac glycosides, such as ouabain and digoxin. METHODS The structural similarity between ginsenosides and ouabain was analyzed. The inhibitory potency of ginsenosides and ouabain on Na+/K+-ATPase activity was examined and compared. Molecular modeling was exhibited for the docking of ginsenosides to Na+/K+-ATPase. RESULTS Ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure, equivalent to the sugar position in cardiac glycosides, and possessed inhibitory potency on Na+/K+-ATPase activity. However, their inhibitory potency was significantly reduced or completely abolished when a monosaccharide was linked to the C-6 or C-20 position of the steroid-like structure; replacement of the monosaccharide with a disaccharide molecule at either of these positions caused the disappearance of the inhibitory potency. Molecular modeling and docking confirmed that the difference in Na+/K+-ATPase inhibitory potency among ginsenosides was due to the steric hindrance of sugar attachment at the C-6 and C-20 positions of the steroid-like structure. CONCLUSION The cardiac therapeutic effects of ginseng and sanqi should be at least partly attributed to the effective inhibition of Na+/K+-ATPase by their metabolized ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure.
Collapse
|
|
41
|
Yang DF, Liang ZS, Liu JL. LC Fingerprinting for Assessment of the Quality of the Lipophilic Components of Salvia miltiorrhiza. Chromatographia 2008. [DOI: 10.1365/s10337-008-0918-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
|
|
42
|
Wan AKS, Leung SWS, Zhu DY, Man RYK. Vascular effects of different lipophilic components of "Danshen", a traditional Chinese medicine, in the isolated porcine coronary artery. JOURNAL OF NATURAL PRODUCTS 2008; 71:1825-1828. [PMID: 18855446 DOI: 10.1021/np800119k] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
"Danshen" has been used for the treatment of various cardiovascular diseases in the People's Republic of China for many years. Two different forms of "Danshen" exist, with the roots of Salvia miltiorrhiza being the traditional form and the roots of Salvia przewalskii being a surrogate used in the western areas of mainland China. The most abundant lipophilic diterpene quinones present in S. miltiorrhiza and S. przewalskii roots, tanshinone IIA (1) and cryptotanshinone (2), inhibited contraction of the isolated porcine coronary artery to the thromboxane A(2) analogue, U46619. Przewaquinone A (3), a lipophilic diterpene quinone present only in S. przewalskii, induced a similar but greater inhibitory action on vascular contraction than 1 and 2. This effect of 3 was endothelium-independent and reversible. The present results suggest that 3 is more potent than 1 and 2 and may contribute to a great extent to the ability of S. przewalskii roots to inhibit vascular contractions.
Collapse
Affiliation(s)
- Alan K S Wan
- Department of Pharmacology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 2/F Faculty of Medicine Building, 21 Sassoon Road, Hong Kong SAR, People's Republic of China
| | | | | | | |
Collapse
|
|
43
|
Aruna AS. Nature's Secrets: Implications of Herbal and Complementary Therapies in HIV. ACTA ACUST UNITED AC 2008. [DOI: 10.3109/10601339909005307] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
|
|
44
|
Ameliorating effects of compounds derived from Salvia miltiorrhiza root extract on microcirculatory disturbance and target organ injury by ischemia and reperfusion. Pharmacol Ther 2008; 117:280-95. [DOI: 10.1016/j.pharmthera.2007.09.008] [Citation(s) in RCA: 260] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2007] [Accepted: 09/21/2007] [Indexed: 11/17/2022]
|
|
45
|
Effects of tanshinone VI on phosphorylation of ERK and Akt in isolated cardiomyocytes and cardiac fibroblasts. Eur J Pharmacol 2008; 580:298-305. [DOI: 10.1016/j.ejphar.2007.11.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2007] [Revised: 10/30/2007] [Accepted: 11/10/2007] [Indexed: 01/18/2023]
|
|
46
|
Wu Y, Wang D. Structural characterization and DPPH radical scavenging activity of an arabinoglucogalactan from Panax notoginseng root. JOURNAL OF NATURAL PRODUCTS 2008; 71:241-245. [PMID: 18186611 DOI: 10.1021/np070323+] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
The structure of an antiradical arabinoglucogalactan ( 1) from Panax notoginseng roots was determined. This polymeric carbohydrate was obtained through successive phosphate buffer (pH 7.0) extraction after cold-water pretreatment and purification by ion-exchange and gel-filtration chromatography. Monosaccharide analysis, permethylation analysis, NaIO 4 and CrO 3 oxidations, Smith degradation, graded acid hydrolysis, and IR and NMR experiments indicated that 1 possesses a backbone of (1-->3)-linked beta- d-galactofuranosyl residues, with branches of alpha- l-Ara f-(1-->4)-beta- d-Glc p-(1--> residues at O-6. Additionally, 1 exhibited high scavenging activity against DPPH free radicals with a 50% scavenging concentration (SC50) of 11.72 +/- 0.91 microg/mL, suggesting that this arabinoglucogalactan is a potential antiradical.
Collapse
Affiliation(s)
- Yalin Wu
- Department of Chemistry, Columbia University, New York, New York 10027, USA.
| | | |
Collapse
|
|
47
|
Wang L, Song Y, Cheng Y, Liu X. Orthogonal array design for the optimization of supercritical fluid extraction of tanshinones from Danshen. J Sep Sci 2008; 31:321-8. [DOI: 10.1002/jssc.200700386] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
|
|
48
|
Wang L, Song Y, Liu X, Cheng Y, Qu H. Development and Validation of a Method for the Determination of Tanshinones in Supercritical Fluid Extraction Products by HPLC. J LIQ CHROMATOGR R T 2008. [DOI: 10.1080/10826070701812772] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Affiliation(s)
- Longhu Wang
- a Department of Chinese Medicine Sciences and Engineeringz , Zhejiang University , Hangzhou , P. R. China
| | - Yanting Song
- a Department of Chinese Medicine Sciences and Engineeringz , Zhejiang University , Hangzhou , P. R. China
| | - Xuesong Liu
- a Department of Chinese Medicine Sciences and Engineeringz , Zhejiang University , Hangzhou , P. R. China
| | - Yiyu Cheng
- a Department of Chinese Medicine Sciences and Engineeringz , Zhejiang University , Hangzhou , P. R. China
| | - Haibin Qu
- a Department of Chinese Medicine Sciences and Engineeringz , Zhejiang University , Hangzhou , P. R. China
| |
Collapse
|
|
49
|
Ojha SK, Nandave M, Arora S, Narang R, Dinda AK, Singh Arya D. Chronic Administration of Tribulus terrestris Linn. Extract Improves Cardiac Function and Attenuates Myocardial Infarction in Rats. INT J PHARMACOL 2007. [DOI: 10.3923/ijp.2008.1.10] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
|
|
50
|
Au-Yeung KK, O K, Choy PC, Zhu DY, Siow YL. Magnesium tanshinoate B protects endothelial cells against oxidized lipoprotein-induced apoptosisThis article is one of a selection of papers published in this special issue (part 2 of 2) on the Safety and Efficacy of Natural Health Products. Can J Physiol Pharmacol 2007; 85:1053-62. [DOI: 10.1139/y07-096] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The activation of c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in the induction of cell apoptosis. We previously reported that magnesium tanshinoate B (MTB), a compound purified from a Chinese herb danshen ( Salvia miltiorrhiza ), could inhibit ischemia/reperfusion-induced myocyte apoptosis in the heart. The objective of the present study was to investigate whether MTB can prevent oxidized lipoprotein-induced apoptosis in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were incubated with copper-oxidized very low density lipoprotein (Cu-OxVLDL) or copper-oxidized low density lipoprotein (Cu-OxLDL). Treatment of cells with Cu-OxVLDL or Cu-OxLDL resulted in a 3-fold increase in the JNK activity. The amount of cytochrome c released and the activity of caspase-3 in cells treated with Cu-OxVLDL or Cu-OxLDL were significantly elevated, indicating the occurrence of apoptosis. The presence of MTB was able to abolish the JNK activation, cytochrome c release, and caspase-3 activation induced by Cu-OxVLDL or Cu-OxLDL, resulting in a marked reduction in apoptosis in endothelial cells. The data from this study indicate that oxidized lipoproteins induce apoptosis in endothelial cells. We postulate that the inhibition of the JNK signaling pathway by MTB is a key mechanism that protects these cells from oxidized lipoprotein-induced apoptosis.
Collapse
Affiliation(s)
- Kathy K.W. Au-Yeung
- Canadian Centre for Agri-Food Research in Health and Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- Canadian Centre for Agri-Food Research in Health and Medicine and Departments of Physiology and Animal Science, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- Department of Biochemistry & Medical Genetics, and Centre for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- State Key Laboratory for Drug Research, Shanghai Institute of Material Medica, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China
- Canadian Centre for Agri-Food Research in Health and Medicine, Departments of Physiology and Biochemistry & Medical Genetics, Faculty of Medicine and Centre for Research and Treatment of Atherosclerosis, University of Manitoba, R2010, Innovative Therapy Research Laboratory, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada
| | - Karmin O
- Canadian Centre for Agri-Food Research in Health and Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- Canadian Centre for Agri-Food Research in Health and Medicine and Departments of Physiology and Animal Science, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- Department of Biochemistry & Medical Genetics, and Centre for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- State Key Laboratory for Drug Research, Shanghai Institute of Material Medica, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China
- Canadian Centre for Agri-Food Research in Health and Medicine, Departments of Physiology and Biochemistry & Medical Genetics, Faculty of Medicine and Centre for Research and Treatment of Atherosclerosis, University of Manitoba, R2010, Innovative Therapy Research Laboratory, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada
| | - Patrick C. Choy
- Canadian Centre for Agri-Food Research in Health and Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- Canadian Centre for Agri-Food Research in Health and Medicine and Departments of Physiology and Animal Science, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- Department of Biochemistry & Medical Genetics, and Centre for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- State Key Laboratory for Drug Research, Shanghai Institute of Material Medica, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China
- Canadian Centre for Agri-Food Research in Health and Medicine, Departments of Physiology and Biochemistry & Medical Genetics, Faculty of Medicine and Centre for Research and Treatment of Atherosclerosis, University of Manitoba, R2010, Innovative Therapy Research Laboratory, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada
| | - Da-yuan Zhu
- Canadian Centre for Agri-Food Research in Health and Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- Canadian Centre for Agri-Food Research in Health and Medicine and Departments of Physiology and Animal Science, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- Department of Biochemistry & Medical Genetics, and Centre for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- State Key Laboratory for Drug Research, Shanghai Institute of Material Medica, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China
- Canadian Centre for Agri-Food Research in Health and Medicine, Departments of Physiology and Biochemistry & Medical Genetics, Faculty of Medicine and Centre for Research and Treatment of Atherosclerosis, University of Manitoba, R2010, Innovative Therapy Research Laboratory, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada
| | - Yaw L. Siow
- Canadian Centre for Agri-Food Research in Health and Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- Canadian Centre for Agri-Food Research in Health and Medicine and Departments of Physiology and Animal Science, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- Department of Biochemistry & Medical Genetics, and Centre for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
- State Key Laboratory for Drug Research, Shanghai Institute of Material Medica, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China
- Canadian Centre for Agri-Food Research in Health and Medicine, Departments of Physiology and Biochemistry & Medical Genetics, Faculty of Medicine and Centre for Research and Treatment of Atherosclerosis, University of Manitoba, R2010, Innovative Therapy Research Laboratory, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada
| |
Collapse
|