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Zhao J, Han M, Nie Q, Wen X, Geng H, Zou Y, Li S, Xie W. Network pharmacology combined with experimental analysis to explore the mechanism of the XinShuaiNing formula on heart failure. 3 Biotech 2025; 15:110. [PMID: 40191450 PMCID: PMC11965065 DOI: 10.1007/s13205-025-04288-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Accepted: 03/22/2025] [Indexed: 04/09/2025] Open
Abstract
This study was conducted to elucidate the mechanism of action of the Traditional Chinese Medicine XinShuaiNing (XSN) formula in CHF based on network pharmacology. A total of 489 compounds in the XSN formula were screened. These compounds predicted 778 targets. A search of CHF yielded 789 corresponding targets, and 151 intersections between the potential targets of the XSN formula and CHF, involving AKT1, AGT, eNOS, and VEGF. Abdominal aortic coarctation (AAC) was used to establish a CHF rat model, and isoproterenol-induced H9c2 cells to establish a myocardial injury cell model. The results showed that the XSN formula downregulated ET-1, BNP, and Hcy and upregulated the ALB levels and also relieved cardiac histopathological damage. The XSN formula reduced the content of pro-inflammatory factors and inhibited the apoptosis of cardiomyocytes. In addition, the expression of fibronectin, α-SMA, collagen 1, and collagen 3 was downregulated by XSN formula treatment, and the fibrotic areas of myocardial tissue were reduced. The XSN formula promoted phosphorylation of AKT1-induced VEGF and eNOS signaling and inhibited AGT signaling. Besides, the XSN formula can affect the apoptosis of H9c2 cells by affecting AKT1, AGT, eNOS, and VEGF. The XSN formula regulates inflammatory factors by inducing phosphorylation of AKT1, upregulating eNOS and VEGF, and downregulating AGT to protect cardiomyocytes from apoptosis and myocardial fibrosis to alleviate CHF. In conclusion, this study identified the target of XSN prescription through network pharmacology screening and experimental validation and confirmed its anti-inflammatory, antiapoptotic, and antifibrotic effects.
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Affiliation(s)
- Jue Zhao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Mingjun Han
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qian Nie
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xin Wen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hongyu Geng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yu Zou
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Songyun Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wen Xie
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Yang Y, Owusu FB, Wu H, Zhang X, Li R, Liu Z, Zhang S, Leng L, Wang Q. Mitochondria as therapeutic targets for Natural Products in the treatment of Cardiovascular Diseases. JOURNAL OF ETHNOPHARMACOLOGY 2025; 345:119588. [PMID: 40057144 DOI: 10.1016/j.jep.2025.119588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 03/04/2025] [Indexed: 03/20/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Natural products represent a unique medical approach to treating disease and have been used in clinical practice for thousands of years in cardiovascular disease (CVDs). In recent years, natural products have received increasing attention for their high efficiency, safety, and low toxicity, and their targeted regulation of mitochondria offers promising strategies for the treatment of CVDs. However, the potential mechanisms by which natural products target mitochondria for cardiovascular treatment have not been fully elucidated. AIM OF THE STUDY Literature from the past decade is reviewed to emphasize the therapeutic efficacy and potential mechanisms of natural products targeting mitochondria in the treatment of CVDs. MATERIALS AND METHODS In the NCBI PubMed database, relevant literature was searched using 'natural products', 'mitochondria' and 'cardiovascular disease' as search terms, and review papers were excluded. The remaining articles were screened for relevance. Priority was given to articles using rat models, in vivo, ex vivo or in vitro assays. The resulting articles were categorized into natural product categories, including saponins, alkaloids, plant extracts and preparations. This article reviews the research progress on mitochondria as potential therapeutic targets for CVDs and summarizes the application of mitochondria-targeted natural products in the treatment of CVDs. RESULTS Mitochondrial damage may be attributed to impairment of biogenesis (mitochondrial number and mitochondrial DNA damage), dynamics disruption (mitophagy inhibition and overpromotion, fusion and fission),disruption of optimal function including Adenosine triphosphate generation, Reactive oxygen species (ROS) production, fatty acid β oxidation, mitochondrial membrane permeability, calcium homeostasis imbalance, and membrane potential depolarization. Mitochondrial dysfunction or damage leads to cardiomyocyte dysfunction, ion disorders, cell death, and ultimately CVDs, such as myocardial infarction, heart failure, ischemia reperfusion, and diabetic heart disease. Natural products, which include flavonoids, saponins, phenolic acids, alkaloids, polysaccharides, extracts, and formulations, are seen to have significant clinical efficacy in the treatment of CVDs. Mechanistically, natural products regulate mitophagy, mitochondrial fusion and fission, while improving mitochondrial respiratory function, reducing ROS production, and inhibiting mitochondria-dependent apoptosis in cardiomyocytes, thereby protecting myocardial cells and heart function. CONCLUSIONS This paper reviews the potential and mechanism of natural products to regulate mitochondria for the treatment of CVDs, creating more opportunities for understanding their therapeutic targets and derivatization of lead compounds, and providing a scientific basis for advancing CVDs drug research.
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Affiliation(s)
- Yanze Yang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Felix Boahen Owusu
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Han Wu
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xinyue Zhang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ruiqiao Li
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Component-Based Chinese Medicine, Ministry of Education, Tianjin, China
| | - Zhanbiao Liu
- Laboratory Animal Center, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shaozhuo Zhang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
| | - Ling Leng
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Component-Based Chinese Medicine, Ministry of Education, Tianjin, China.
| | - Qilong Wang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Component-Based Chinese Medicine, Ministry of Education, Tianjin, China; Endocrinology Department, Fourth Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
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Guo X, Chen Z, Gao C, Zhang L, Liu Y, Lin M, Zhu P, Yang J, Wang Z, Zhang J, Sun H. 20S-O-Glc-DM treats metabolic syndrome-induced heart failure through regulating gut flora. Eur J Pharmacol 2024; 982:176946. [PMID: 39182541 DOI: 10.1016/j.ejphar.2024.176946] [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: 06/13/2024] [Revised: 07/19/2024] [Accepted: 08/23/2024] [Indexed: 08/27/2024]
Abstract
Heart failure is a multifactorial disease, the percentage of patients with heart failure caused by metabolic syndrome is increasing year by year. The effect of gut flora dysbiosis on metabolic syndrome and heart failure has received widespread attention in recent years. Drugs to treat the condition urgently need to be discovered. C20DM, as a precursor compound of ginsenoside, is a small molecule compound obtained by biosynthetic means and is not available in natural products. In this project, we found that C20DM could improve the diversity of gut flora and elevate the expression of intestinal tight junction proteins-Occludin, Claudin, ZO-1, which inhibited the activity of the TLR4-MyD88-NF-kB pathway, and as a result, reduced myocardial inflammation and slowed down heart failure in metabolic syndrome mice. In conclusion, our study suggests that C20DM can treat heart failure by regulating gut flora, and it may be a candidate drug for treating metabolic syndrome-induced heart failure.
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Affiliation(s)
- Xinyi Guo
- State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China
| | - Zhiwei Chen
- State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China
| | - Chen Gao
- State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China
| | - Lingzhi Zhang
- State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China
| | - Yanxin Liu
- State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China
| | - Modi Lin
- State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China
| | - Ping Zhu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines & NHC Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Jinling Yang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines & NHC Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Zhe Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines & NHC Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Jinlan Zhang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines & NHC Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Hua Sun
- State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
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Song Y, Chen C, Li W. Ginsenoside Rb 1 in cardiovascular and cerebrovascular diseases: A review of therapeutic potentials and molecular mechanisms. CHINESE HERBAL MEDICINES 2024; 16:489-504. [PMID: 39606264 PMCID: PMC11589305 DOI: 10.1016/j.chmed.2024.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 09/03/2024] [Accepted: 09/13/2024] [Indexed: 11/29/2024] Open
Abstract
Cardiovascular and cerebrovascular diseases (CCVDs), which are circulatory system diseases caused by heart defects and vascular diseases, are the major noncommunicable diseases affecting global public health. With the improvement of economic level and the change of human lifestyle, the prevalence of CCVDs continues to increase. Ginseng (Panax ginseng C. A. Mey.) was widely used in traditional diseases due to its supposed tonic properties. Ginsenoside Rb1 (G-Rb1) is the most abundant active ingredient with multiple pharmacological effects extracted from ginseng, which has been shown to have potential benefits on the cardiovascular system through a variety of mechanisms, including anti-oxidation, anti-inflammatory, regulation of vasodilation, reduction of platelet adhesion, influence of calcium ion channels, improvement of lipid distribution, involving in glucose metabolism and controlling blood sugar. This review reviewed the protective effects of G-Rb1 on CCVDs and its potential mechanisms, such as atherosclerosis (AS), hypertension, coronary heart disease (CHD), ischemic stroke (IS) and periocular microvascular retinopathy. Finally, we reviewed and reported the results of in vivo and in vitro experiments using G-Rb1 to improve CCVDs, highlighted its efficacy, safety, and limitations.
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Affiliation(s)
- Yueqin Song
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Chen Chen
- School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia
| | - Wei Li
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun 130118, China
- Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Changchun 130118, China
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Qiu B, Qiao S, Shi X, Shen L, Deng B, Ma Z, Zhou D, Wei Y. Shen'ge Formula Protects Cardiac Function in Rats with Pressure Overload-Induced Heart Failure. Drug Des Devel Ther 2024; 18:1875-1890. [PMID: 38831869 PMCID: PMC11146625 DOI: 10.2147/dddt.s451720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 05/20/2024] [Indexed: 06/05/2024] Open
Abstract
Background In China, Shen'ge formula (SGF), a Traditional Chinese Medicine blend crafted from ginseng and gecko, holds a revered place in the treatment of cardiovascular diseases. However, despite its prevalent use, the precise cardioprotective mechanisms of SGF remain largely uncharted. This study aims to fill this gap by delving deeper into SGF's therapeutic potential and underlying action mechanism, thus giving its traditional use a solid scientific grounding. Methods In this study, rats were subjected to abdominal aortic constriction (AAC) to generate pressure overload. Following AAC, we administered SGF and bisoprolol intragastrically at specified doses for two distinct durations: 8 and 24 weeks. The cardiac function post-treatment was thoroughly analyzed using echocardiography and histological examinations, offering insights into SGF's influence on vital cardiovascular metrics, and signaling pathways central to cardiac health. Results SGF exhibited promising results, significantly enhanced cardiac functions over both 8 and 24-week periods, evidenced by improved ejection fraction and fractional shortening while moderating left ventricular parameters. Noteworthy was SGF's role in the significant mitigation of myocardial hypertrophy and in fostering the expression of vital proteins essential for heart health by the 24-week mark. This intervention markedly altered the dynamics of the Akt/HIF-1α/p53 pathway, inhibiting detrimental processes while promoting protective mechanisms. Conclusion Our research casts SGF in a promising light as a cardioprotective agent in heart failure conditions induced by pressure overload in rats. Central to this protective shield is the modulation of the Akt/HIF-1α/p53 pathway, pointing to a therapeutic trajectory that leverages HIF-1α promotion and p53 nuclear transport inhibition.
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Affiliation(s)
- Boyong Qiu
- Heart Center/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, The First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan, People’s Republic of China
- Cardiovascular Department, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
| | - Siyu Qiao
- Cardiovascular Department, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
| | - Xiujuan Shi
- Cardiovascular Department, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
| | - Lin Shen
- Cardiovascular Department, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
| | - Bing Deng
- Cardiovascular Department, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
| | - Zilin Ma
- Cardiovascular Department, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
| | - Duan Zhou
- Cardiovascular Department, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
| | - Yihong Wei
- Cardiovascular Department, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
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Qin J, Yang Q, Wang Y, Shi M, Zhao X, Zhou Y. The role of pyroptosis in heart failure and related traditional chinese medicine treatments. Front Pharmacol 2024; 15:1377359. [PMID: 38868667 PMCID: PMC11168204 DOI: 10.3389/fphar.2024.1377359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 05/09/2024] [Indexed: 06/14/2024] Open
Abstract
Pyroptosis is a type of programmed cell death that is mediated by both typical and atypical pathways and ultimately leads to the lysis and rupture of cell membranes and the release of proinflammatory factors, triggering an intense inflammatory response. Heart failure (HF) is a serious and terminal stage of various heart diseases. Myocardial hypertrophy, myocardial fibrosis, ventricular remodeling, oxidative stress, the inflammatory response and cardiomyocyte ionic disorders caused by various cardiac diseases are all risk factors for and aggravate HF. Numerous studies have shown that pyroptosis can induce and exacerbate these reactions, causing progression to HF. Therefore, targeting pyroptosis is a promising strategy to treat HF. This paper summarizes the role of pyroptosis in the development of HF and the underlying mechanism involved. Recent research progress on the ability of traditional Chinese medicine (TCM) extracts and formulas to inhibit pyroptosis and treat HF was summarized, and some traditional Chinese medicine extracts and formulas can alleviate different types of HF, including heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), and heart failure with midrange ejection fraction (HFmrEF), by targeting pyroptosis. These findings may provide new ideas and evidence for the treatment or adjuvant treatment of HF by targeting pyroptosis.
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Affiliation(s)
- Jie Qin
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Qianhe Yang
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Yan Wang
- Department of Cardiovascular Medicine, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Mengdi Shi
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Xin Zhao
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Yabin Zhou
- Department of Cardiovascular Medicine, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
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She J, Lu F, Chi Y, Cao L, Zuo Y, Yang N, Zhang X, Dai X. Ginseng Extract Attenuates the Injury from Ultraviolet Irradiation for Female Drosophila melanogaster through the Autophagy Signaling Pathway. J Med Food 2024; 27:348-358. [PMID: 38387003 DOI: 10.1089/jmf.2023.k.0195] [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] [Indexed: 02/24/2024] Open
Abstract
Ginseng is an ancient medicinal and edible plant with many health benefits, and can serve as a drug and dietary supplement, but there are few relevant studies on its use to ease ultraviolet (UV) irradiation damage. After 0.8 mg/mL ginseng extract (GE) was added to the medium of female Drosophila melanogaster subjected to UV irradiation, the lifespan, climbing ability, sex ratio, developmental cycle, and antioxidant capacity of flies were examined to evaluate the GE function. In addition, the underlying mechanism by which GE enhances the irradiation tolerance of D. melanogaster was explored. With GE supplementation, female flies subjected to UV irradiation exhibited an extension in their lifespan, enhancement in their climbing ability, improvement in their offspring sex ratio, and restoration of the normal development cycle by increasing their antioxidant activity. Finally, further experiments indicated that GE could enhance the irradiation tolerance of female D. melanogaster by upregulating the gene expressions of SOD, GCL, and components of the autophagy signaling pathway. Finally, the performance of r4-Gal4;UAS-AMPKRNAi flies confirmed the regulatory role of the autophagy signaling pathway in mitigating UV irradiation injury.
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Affiliation(s)
- JiaYi She
- College of Life Sciences, China Jiliang University, Hangzhou, China
| | - FangYuan Lu
- College of Life Sciences, China Jiliang University, Hangzhou, China
| | - YiQing Chi
- College of Life Sciences, China Jiliang University, Hangzhou, China
| | - LingYao Cao
- College of Life Sciences, China Jiliang University, Hangzhou, China
| | - Yaqi Zuo
- College of Life Sciences, China Jiliang University, Hangzhou, China
| | - Na Yang
- College of Life Sciences, China Jiliang University, Hangzhou, China
| | - Xing Zhang
- Zhejiang Shengshi Bio-technology Co., Ltd, Anji, China
| | - XianJun Dai
- College of Life Sciences, China Jiliang University, Hangzhou, China
- Key Laboratory of Specialty Agri-product Quality and Hazard Controlling Technology of Zhejiang Province, Hangzhou, China
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Vijayakumar A, Kim JH. Ginseng and ginsenosides on cardiovascular and pulmonary diseases; Pharmacological potentials for the coronavirus (COVID-19). J Ginseng Res 2024; 48:113-121. [PMID: 38465214 PMCID: PMC10920003 DOI: 10.1016/j.jgr.2023.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 09/20/2023] [Accepted: 10/26/2023] [Indexed: 03/12/2024] Open
Abstract
Since its outbreak in late 2019, the Coronavirus disease 2019 (COVID-19) pandemic has profoundly caused global morbidity and deaths. The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has major complications in cardiovascular and pulmonary system. The increased rate of mortality is due to delayed detection of certain biomarkers that are crucial in the development of disease. Furthermore, certain proteins and enzymes in cellular signaling pathways play an important role in replication of SARS-CoV-2. Most cases are mild to moderate symptoms, however severe cases of COVID-19 leads to death. Detecting the level of biomarkers such as C-reactive protein, cardiac troponin, creatine kinase, creatine kinase-MB, procalcitonin and Matrix metalloproteinases helps in early detection of the severity of disease. Similarly, through downregulating Renin-angiotensin system, interleukin, Mitogen-activated protein kinases and Phosphoinositide 3-kinases pathways, COVID-19 can be effectively controlled and mortality could be prevented. Ginseng and ginsenosides possess therapeutic potential in cardiac and pulmonary complications, there are several studies performed in which they have suppressed these biomarkers and downregulated the pathways, thereby inhibiting the further spread of disease. Supplementation with ginseng or ginsenoside could act on multiple pathways to reduce the level of biomarkers significantly and alleviate cardiac and pulmonary damage. Therefore, this review summarizes the potential of ginseng extract and ginsenosides in controlling the cardiovascular and pulmonary diseases by COVID-19.
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Affiliation(s)
- Ajay Vijayakumar
- College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, Iksan-city, Republic of Korea
| | - Jong-Hoon Kim
- College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, Iksan-city, Republic of Korea
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Chen C, Wang J, Zhu X, Hu J, Liu C, Liu L. Energy metabolism and redox balance: How phytochemicals influence heart failure treatment. Biomed Pharmacother 2024; 171:116136. [PMID: 38215694 DOI: 10.1016/j.biopha.2024.116136] [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: 10/11/2023] [Revised: 12/31/2023] [Accepted: 01/04/2024] [Indexed: 01/14/2024] Open
Abstract
Heart Failure (HF) epitomizes a formidable global health quandary characterized by marked morbidity and mortality. It has been established that severe derangements in energy metabolism are central to the pathogenesis of HF, culminating in an inadequate cardiac energy milieu, which, in turn, precipitates cardiac pump dysfunction and systemic energy metabolic failure, thereby steering the trajectory and potential recuperation of HF. The conventional therapeutic paradigms for HF predominantly target amelioration of heart rate, and cardiac preload and afterload, proffering symptomatic palliation or decelerating the disease progression. However, the realm of therapeutics targeting the cardiac energy metabolism remains largely uncharted. This review delineates the quintessential characteristics of cardiac energy metabolism in healthy hearts, and the metabolic aberrations observed during HF, alongside the associated metabolic pathways and targets. Furthermore, we delve into the potential of phytochemicals in rectifying the redox disequilibrium and the perturbations in energy metabolism observed in HF. Through an exhaustive analysis of recent advancements, we underscore the promise of phytochemicals in modulating these pathways, thereby unfurling a novel vista on HF therapeutics. Given their potential in orchestrating cardiac energy metabolism, phytochemicals are emerging as a burgeoning frontier for HF treatment. The review accentuates the imperative for deeper exploration into how these phytochemicals specifically intervene in cardiac energy metabolism, and the subsequent translation of these findings into clinical applications, thereby broadening the horizon for HF treatment modalities.
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Affiliation(s)
- Cong Chen
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China
| | - Jie Wang
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China.
| | - Xueying Zhu
- Department of Anatomy, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Jun Hu
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China
| | - Chao Liu
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China
| | - Lanchun Liu
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China
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Li Y, Yang K, Zhao L, Xu C, Zhou W, Wang Z, Hu H, You Y. Effects of schisandra lignans on the absorption of protopanaxadiol-type ginsenosides mediated by P-glycoprotein and protopanaxatriol-type ginsenosides mediated by CYP3A4. JOURNAL OF ETHNOPHARMACOLOGY 2024; 318:117057. [PMID: 37597677 DOI: 10.1016/j.jep.2023.117057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 08/02/2023] [Accepted: 08/15/2023] [Indexed: 08/21/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ginseng Radix et Rhizoma (GRR) and Schisandrae Chinensis Fructus (SCF) are frequently used as herb pairs in traditional herbal formulas especially for the synergetic beneficial effects on lung and heart. Shengmai-yin (SMY), a noted formula, was first published in the traditional Chinese medicine classic named Yixue Qiyuan written by Zhang Yuansu in the Jin Dynasty, and has been used for deficiency of both qi and yin, palpitation, shortness of breath and spontaneous sweating. In SMY, GRR, a sovereign herb, plays an essential role in tonifying lung and supplementing qi, and SCF as an adjuvant herb contributes to the effects of nourishing yin and promoting fluid production, both of which are traditionally used as invigorants in China, Korea, Japan, and Russia. However, the underlying compatibility mechanism of GRR-SCF has remained unknown. AIM OF THE STUDY In order to explore the impact and underlying mechanism of schisandra chinensis extract (SCE) on the absorption of ginsenosides Rb1, Rc, Rb2 and Rd belonging to protopanaxdiol (PPD)-type and ginsenosides Rg1 and Re belonging to protopanaxtriol (PPT)-type, pharmacokinetic studies, molecular docking technique and single-pass intestinal perfusion (SPIP) experiment were conducted. MATERIAL AND METHODS Preliminarily, pharmacokinetic characteristics of ginseng extract (GE) in the presence and absence of SCE were studied. Thereafter, molecular docking was used to predict whether ginsenosides were P-glycoprotein (P-gp) or cytochrome P450 isoenzyme 3A4 (CYP3A4) substrates. Finally, the effects and underlying mechanism of SCE on the absorption of GE were further investigated by in situ SPIP experiment. RESULTS Our findings indicated that SCE could increase exposure in vivo and the intestinal absorption of distinct ginsenosides. Additionally, we found that the PPD-type ginsenosides Rb1, Rc, Rb2, and Rd were substrates for P-gp, and the PPT-type ginsenosides Rg1 and Re were substrates for CYP3A4 rather than P-gp. SCE, which has been found with extensive inhibitory effects on P-gp and CYP3A4, could remarkably promote the intestinal absorption of ginsenosides Rg1, Re, Rb1, Rc, Rb2, and Rd, obtaining similar effects comparable with ketoconazole known as a classic dual inhibitor of P-gp and CYP3A4. CONCLUSIONS The study demonstrated that SCE could improve the absorption of GE, and revealed the underlying compatibility mechanism of GRR and SCF from the perspective of P-gp and CYP3A4-mediated interactions to some extent, which provided a certain scientific reference for the compatibility and clinical practice of GRR-SCF as common herb pairs in traditional prescriptions such as SMY. Moreover, this study also furnished a strategy for improving the oral bioavailability of different types of ginsenosides by drug combinations.
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Affiliation(s)
- Yanyan Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Ke Yang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Linxian Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Chunyi Xu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Weiling Zhou
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Zhanguo Wang
- Holistic Integrative Medicine Industry Collaborative Innovation Research Center, Qiang Medicine Standard Research Promotion Base and Collaborative Innovation Research Center, School of Preclinical Medicine, Chengdu University, Chengdu, 610106, China
| | - Huiling Hu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Yu You
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
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Yu T, Xu J, Wang Q, Han X, Tu Y, Wang Y, Luo W, Wang M, Liang G. 20(S)-ginsenoside Rh2 inhibits angiotensin-2 mediated cardiac remodeling and inflammation associated with suppression of the JNK/AP-1 pathway. Biomed Pharmacother 2023; 169:115880. [PMID: 37956481 DOI: 10.1016/j.biopha.2023.115880] [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: 08/29/2023] [Revised: 11/08/2023] [Accepted: 11/09/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Enhanced levels of angiotensin-2 (Ang-II) causes hypertensive heart failure (HHF) through non-hemodynamical and hemodynamical alterations. 20(S)-ginsenoside Rh2 (20(S)-Rh2) is a natural ginseng compound with numerous cardiovascular benefits. This investigation elucidates the influence of 20(S)-Rh2 on Ang-II-induced heart failure and cardiac alterations. METHODS Ang-II was administered in C57BL/6 mice for 4 weeks to induce HHF. In the last 2 weeks of treatment, 20(S)-Rh2 was orally administered in mice to assess the potential 20(S)-Rh2 mechanism. Subsequently, RNA sequencing was carried out. RESULTS It was indicated that 20(S)-Rh2 suppresses myocardial fibrosis, hypertrophy, and inflammation, thereby inhibiting cardiac disruption in Ang-II-challenged mice without affecting blood pressure. According to the RNA sequencing data, this cardio-protective effect was linked with the (JNK)/AP 1 pathway. 20(S)-Rh2 alleviated heart tissue and cardiomyocytes inflammation by inhibiting the Ang-II-mediated JNK/AP-1 pathway. Within cardiomyocytes, JNK or AP-1 absence abolished the anti-inflammatory effects of 20(S)-Rh2. CONCLUSION This study investigation indicated that 20(S)-Rh2 prevents cardiovascular dysfunction induced by Ang-II induced by decreasing JNK-regulated inflammatory responses, providing evidence for its use as an efficient regimen for HHF.
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Affiliation(s)
- Tianxiang Yu
- Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
| | - Jiachen Xu
- Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
| | - Qinyan Wang
- Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
| | - Xue Han
- Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
| | - Yu Tu
- Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Yi Wang
- Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
| | - Wu Luo
- Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Department of Cardiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
| | - Mengyang Wang
- Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Department of Pharmacology, College of Pharmacy, Beihua University, Jilin, Jilin132013, China.
| | - Guang Liang
- Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
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12
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Tang MM, Zhao ST, Li RQ, Hou W. Therapeutic mechanisms of ginseng in coronary heart disease. Front Pharmacol 2023; 14:1271029. [PMID: 37854713 PMCID: PMC10579605 DOI: 10.3389/fphar.2023.1271029] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 09/22/2023] [Indexed: 10/20/2023] Open
Abstract
Coronary heart disease (CHD) is the most common clinical manifestation of cardiovascular disease. It is characterized by myocardial ischemia, which is caused by coronary atherosclerosis. CHD is a significant global health problem with increasing prevalence every year because of significant changes in the lifestyles and diets. Ginseng is a traditional Chinese medicinal herb that has been used in food preparations and traditional medicine for several centuries. Several studies have demonstrated that ginseng improved cardiac function by normalizing blood glucose levels and decreasing blood pressure, oxidative stress, platelet aggregation, and lipid dysregulation in vivo. This review describes the current understanding of the mechanisms by which ginseng alleviates CHD, and provides a reference for the clinical development and application of ginseng as an alternative therapy for CHD.
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Affiliation(s)
| | | | | | - Wei Hou
- Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, China
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Kong J, Li L, Yuan H, Bai F, Yang K, Zhao L, Xu S. In silico discovery of potential sodium-glucose cotransporter-2 inhibitors from natural products for treatment of heart failure via molecular docking and molecular dynamics simulation approach. J Biomol Struct Dyn 2023; 41:8109-8120. [PMID: 36200619 DOI: 10.1080/07391102.2022.2130983] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 09/24/2022] [Indexed: 10/10/2022]
Abstract
Heart failure (HF) is the end stage of cardiovascular disease. Because of its complex condition and poor prognosis, HF has become an important public health problem in the world. Sodium-glucose cotransporter-2 (SGLT2) is a member of the glucose transporter family. Recently, SGLT2 inhibitors have been applied to treat HF. In this study, the main aim was to discover natural SGLT2 inhibitor from Chinese herbs through docking-based virtual screening. Totally 113 natural compounds of potential SGLT2 inhibitor were identified, which displayed docking affinity higher than six approved inhibitors (dapagliflozin (IC50 = 4.9 nM), canagliflozin (IC50 = 4.4 nM 6.7), ipragliflozin (IC50 = 7.4 nM), empagliflozin (IC50 = 3.1 nM), tofogliflozin (IC50 = 4 nM) and luseogliflozin (IC50 = 2.3 nM)) through docking-based virtual screening. Then, the top three hits (ZINC70455591, ZINC85594065 and ZINC14588133) and six known inhibitors were selected for molecular dynamics simulation and the binding free energy calculation using molecular mechanics Poisson-Boltzmann surface area to demonstrate the stability and affinity of docked complexes. These results pointed out that the three docked complexes were stabilized and the chosen compounds were tightly adhering to the binding site of SGLT2. Besides, pharmacokinetic properties of the selected compounds showed those natural compounds may be potential drug candidates. This study may be contributed to further in vitro and in vivo validation and the development of novel SGLT2 inhibitor for treating HF.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Jiwu Kong
- Drug Clinical Trial Center, Gansu Wuwei Tumor Hospital, Wuwei, Gansu, China
| | - Ling Li
- Drug Clinical Trial Center, Gansu Wuwei Tumor Hospital, Wuwei, Gansu, China
| | - Huicheng Yuan
- Drug Clinical Trial Center, Gansu Wuwei Tumor Hospital, Wuwei, Gansu, China
| | - Feng Bai
- Drug Clinical Trial Center, Gansu Wuwei Tumor Hospital, Wuwei, Gansu, China
| | - Kai Yang
- Drug Clinical Trial Center, Gansu Wuwei Tumor Hospital, Wuwei, Gansu, China
| | - Liangcun Zhao
- Drug Clinical Trial Center, Gansu Wuwei Tumor Hospital, Wuwei, Gansu, China
| | - Shaohua Xu
- Drug Clinical Trial Center, Gansu Wuwei Tumor Hospital, Wuwei, Gansu, China
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Cao X, Yao F, Zhang B, Sun X. Mitochondrial dysfunction in heart diseases: Potential therapeutic effects of Panax ginseng. Front Pharmacol 2023; 14:1218803. [PMID: 37547332 PMCID: PMC10399631 DOI: 10.3389/fphar.2023.1218803] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 07/12/2023] [Indexed: 08/08/2023] Open
Abstract
Heart diseases have a high incidence and mortality rate, and seriously affect people's quality of life. Mitochondria provide energy for the heart to function properly. The process of various heart diseases is closely related to mitochondrial dysfunction. Panax ginseng (P. ginseng), as a traditional Chinese medicine, is widely used to treat various cardiovascular diseases. Many studies have confirmed that P. ginseng and ginsenosides can regulate and improve mitochondrial dysfunction. Therefore, the role of mitochondria in various heart diseases and the protective effect of P. ginseng on heart diseases by regulating mitochondrial function were reviewed in this paper, aiming to gain new understanding of the mechanisms, and promote the clinical application of P. ginseng.
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Affiliation(s)
- Xinxin Cao
- 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
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China
- Key Laboratory of Efficacy Evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, China
| | - Fan Yao
- 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
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China
- Key Laboratory of Efficacy Evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, China
| | - Bin Zhang
- 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
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China
- Key Laboratory of Efficacy Evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, China
| | - Xiaobo Sun
- 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
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China
- Key Laboratory of Efficacy Evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, China
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Liu M, Fan M, Xu H, Liu B, Wang X, Wen F, Ji F, Ding T. A combination of Sophora flavescens alkaloids and Panax quinquefolium saponins attenuates coxsackievirus B3‑induced acute myocarditis in mice via NF‑κB signaling. Exp Ther Med 2023; 25:292. [PMID: 37206567 PMCID: PMC10189612 DOI: 10.3892/etm.2023.11991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 04/14/2023] [Indexed: 05/21/2023] Open
Abstract
Timely treatment of viral myocarditis (VMC), a form of cardiac inflammation caused by viral infections, can reduce the occurrence of dilated cardiomyopathy and sudden death. Our previous study demonstrated the anti-inflammatory and anti-fibrotic effects of KX, a combination of Sophora flavescens alkaloids and Panax quinquefolium saponins, on an autoimmune myocarditis model in vivo. The present study explored the effects of KX on coxsackievirus B3 (CVB3)-induced acute VMC in mice. Mice were randomly divided into four groups: Control, VMC, KX-high (275 mg/kg) and KX-low (138 mg/kg). Mice in the VMC, KX-high and KX-low groups received injections of CVB3 to establish the VMC model, and those in the KX-high and KX-low groups also received KX by gavage (10 ml/kg) 2 h after virus injection until euthanasia was performed on day 7 or 21. Mice in the control group received an equal KX volume of purified water. The levels of lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTn-I), IL-1β, IL-6, TNF-α and high-sensitive C-reactive protein (hs-CRP) in mouse serum was measured using ELISA. Myocardial tissue structure and degree of injury were observed using hematoxylin and eosin staining. Western blotting and reverse transcription-quantitative PCR were performed to detect the expression levels of NF-κB pathway-related mRNA and protein in myocardial tissue. The results showed that the inflammation and myocardial damage levels of the mice in the VMC group were higher at 7 days than those at 21 days. At both 7 and 21 days, KX decreased the serum CK-MB, LDH, cTn-I, IL-6, TNF-α and hs-CRP levels, and inhibited NF-κB pathway-related mRNA and protein expression in the myocardium of mice. These findings indicated that KX may reduce the inflammatory response and attenuate the pathological damage in the acute and subacute phases of CVB3-induced VMC through the NF-κB pathway.
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Affiliation(s)
- Menghui Liu
- Department of Pediatrics, Jilin Academy of Traditional Chinese Medicine, Changchun, Jilin 130012, P.R. China
- Department of Traditional Chinese Medicine, Changchun University of Traditional Chinese Medicine, Changchun, Jilin 130000, P.R. China
| | - Meiling Fan
- Department of Cardiology, The First Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin 130012, P.R. China
| | - Huibo Xu
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Traditional Chinese Medicine, Changchun, Jilin 130012, P.R. China
| | - Bo Liu
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Traditional Chinese Medicine, Changchun, Jilin 130012, P.R. China
| | - Xin Wang
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Traditional Chinese Medicine, Changchun, Jilin 130012, P.R. China
| | - Fuchun Wen
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Traditional Chinese Medicine, Changchun, Jilin 130012, P.R. China
| | - Fenglan Ji
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Traditional Chinese Medicine, Changchun, Jilin 130012, P.R. China
| | - Tao Ding
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Traditional Chinese Medicine, Changchun, Jilin 130012, P.R. China
- Correspondence to: Dr Tao Ding, Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Traditional Chinese Medicine, 155 Chuangju Street, Changchun, Jilin 130012, P.R. China
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Wei XH, Liu WJ, Jiang W, Lan TH, Pan H, Ma MY, You LZ, Shang HC. XinLi formula, a traditional Chinese decoction, alleviates chronic heart failure via regulating the interaction of AGTR1 and AQP1. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 113:154722. [PMID: 36867964 DOI: 10.1016/j.phymed.2023.154722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 02/10/2023] [Accepted: 02/18/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND XinLi formula (XLF) is a traditional Chinese medicine used in clinical practice to treat chronic heart failure (CHF) in humans, with remarkable curative effect. However, the mechanism remains unknown. PURPOSE The goal of the current investigation was to determine how XLF affected CHF in a rat model of the condition brought on by ligation of the left anterior descending coronary artery, and to investigate the underlying mechanism. STUDY DESIGN AND METHODS Cardiac function was detected by echocardiography. The contents of myocardial enzymes, Ang II, ALD, TGF-β1, and inflammatory factors were measured by ELISA. Myocardial injury and myocardial fibrosis were evaluated by HE and Masson staining. Myocardial edema was assessed by cardiac mass index and transmission electron microscopy. Using Western blot and immunohistochemistry to examining the protein expression of inflammasome, TGF-β1, AGTR1, and AQP1 in the left ventricle. Furthermore, the interaction of AGTR1 and AQP1 was evaluated by co-immunoprecipitation. RESULTS XLF attenuated myocardial enzymes and myocardial injury, and improved cardiac function in rats with CHF after myocardial infarction. It also reduced Ang II and ALD levels in CHF rats, and suppressed the expression of AGTR1 and TGF-β1, finally alleviated myocardial fibrosis. By mechanism, XLF inhibited the expression of NLRP3 inflammasome proteins, reduced the plasma contents of IL-1β, IL-18, IL-6 and TNF-α. Additionally, XLF inhibited the expression of AQP1 and the interaction of AGTR1 and AQP1, alleviating myocardial edema. The common structure of the main chemical constituents of XLF were glycoside compounds with glycosyl. CONCLUSION XLF ameliorated CHF, which was evidenced by the alleviation of myocardial fibrosis by inhibiting AGTR1/NLRP3 signal, as well as the attenuation of myocardial edema by suppressing the interaction of AGTR1 and AQP1.
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Affiliation(s)
- Xiao-Hong Wei
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China; Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou 510020, China
| | - Wen-Jing Liu
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Wei Jiang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510020, China; Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou 510020, China; Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
| | - Tao-Hua Lan
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510020, China; Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou 510020, China; Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
| | - Hai'e Pan
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Ming-Yue Ma
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Liang-Zhen You
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Hong-Cai Shang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.
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Ginsenoside Rb1 Improves Post-Cardiac Arrest Myocardial Stunning and Cerebral Outcomes by Regulating the Keap1/Nrf2 Pathway. Int J Mol Sci 2023; 24:ijms24055059. [PMID: 36902487 PMCID: PMC10003120 DOI: 10.3390/ijms24055059] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 02/02/2023] [Accepted: 02/07/2023] [Indexed: 03/09/2023] Open
Abstract
The prognosis of cardiac arrest (CA) is dismal despite the ongoing progress in cardiopulmonary resuscitation (CPR). ginsenoside Rb1 (Gn-Rb1) has been verified to be cardioprotective in cardiac remodeling and cardiac ischemia/reperfusion (I/R) injury, but its role is less known in CA. After 15 min of potassium chloride-induced CA, male C57BL/6 mice were resuscitated. Gn-Rb1 was blindly randomized to mice after 20 s of CPR. We assessed the cardiac systolic function before CA and 3 h after CPR. Mortality rates, neurological outcome, mitochondrial homeostasis, and the levels of oxidative stress were evaluated. We found that Gn-Rb1 improved the long-term survival during the post-resuscitation period but did not affect the ROSC rate. Further mechanistic investigations revealed that Gn-Rb1 ameliorated CA/CPR-induced mitochondrial destabilization and oxidative stress, partially via the activation of Keap1/Nrf2 axis. Gn-Rb1 improved the neurological outcome after resuscitation partially by balancing the oxidative stress and suppressing apoptosis. In sum, Gn-Rb1 protects against post-CA myocardial stunning and cerebral outcomes via the induction of the Nrf2 signaling pathway, which may offer a new insight into therapeutic strategies for CA.
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Hu SY, Zhou Y, Zhong SJ, Yang M, Huang SM, Li L, Li XC, Hu ZX. Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-β 1/Smad Pathway Regulation. Chin J Integr Med 2023; 29:119-126. [PMID: 35840852 DOI: 10.1007/s11655-022-2899-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/12/2022] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. METHODS Salt-sensitive (Dahl/SS) rats were fed with normal diet (0.3% NaCl) and the high-salt diet (8% NaCl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats (SS-13BN) were fed with the high-salt diet (8% NaCl) as the negative control group. After modeling, the model rats were randomly divided into heart failure (HF) group, Shenmai Injection (SMI) group and pirfenidone (PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay (ELISA), hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis. RESULTS After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were significantly reduced, and the serum NT-proBNP concentration increased significantly (all P<0.05); furthermore, the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased (P<0.05); the protein and mRNA expressions of collagen type I (Col I) were up-regulated (P<0.05), and the mRNA expressions of transforming growth factor β 1 (TGF- β 1), Smad2 and Smad3 were significantly up-regulated (P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly (P<0.05), and the mRNA expressions of Col I, TGF- β 1, Smad2 and Smad3, as well as Col I protein expression, were all significantly down-regulated (all P<0.05). CONCLUSION Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β 1/Smad signaling pathway.
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Affiliation(s)
- Si-Yuan Hu
- School of Sports Art, Hunan University of Chinese Medicine, Changsha, 410208, China.,College of Health Science, Wuhan Sports University, Wuhan, 430079, China
| | - Yao Zhou
- Department of Medicine, Hunan Traditional Chinese Medical College, Zhuzhou, Hunan Province, 412012, China
| | - Sen-Jie Zhong
- Graduate School, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Meng Yang
- Graduate School, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Shu-Min Huang
- Graduate School, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Lin Li
- Graduate School, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Xin-Chun Li
- Graduate School, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Zhi-Xi Hu
- Institute of Chinese Medicine Diagnosis, Hunan University of Chinese Medicine, Changsha, 410208, China.
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Synergistic Effects of Ginsenoside Rb3 and Ferruginol in Ischemia-Induced Myocardial Infarction. Int J Mol Sci 2022; 23:ijms232415935. [PMID: 36555577 PMCID: PMC9785845 DOI: 10.3390/ijms232415935] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/01/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
Previous research shows that ginsenoside Rb3 (G-Rb3) exhibit significant protective effects on cardiomyocytes and is considered a promising treatment for myocardial infraction (MI). However, how to improve its oral bioavailability and reduce its dosage remains to be studied. Previous studies suggest that Ferruginol (FGL) may have synergistic effects with G-Rb3. However, the underlying mechanisms remain to be explored. In this study, left anterior descending branch (LAD) coronary artery ligation or oxygen-glucose deprivation-reperfusion (OGD/R) were used to establish MI models in vivo and in vitro. Subsequently, the pharmacological effects and mechanisms of G-Rb3-FGL were explored by in vitro studies. The results showed that the G-Rb3-FGL co-treatment improved heart functions better than the G-Rb3 treatment alone in MI mice models. Meanwhile, the G-Rb3-FGL co-treatment can upregulate fatty acids oxidation (FAO) and suppress oxidative stress in the heart tissues of MI mice. In vitro studies demonstrated that the synergistic effect of G-Rb3-FGL on FAO, oxidation and inflammation was abolished by RXRα inhibitor HX531 in the H9C2 cell model. In summary, we revealed that G-Rb3 and FGL have a synergistic effect against MI. They protected cardiomyocytes by promoting FAO, inhibiting oxidative stress, and suppressing inflammation through the RXRα-Nrf2 signaling pathway.
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Chen X, Chen Y, Xie S, Wang X, Wu Y, Zhang H, Zhao Y, Jia J, Wang B, Li W, Tang J, Xiao X. The mechanism of Renshen-Fuzi herb pair for treating heart failure-Integrating a cardiovascular pharmacological assessment with serum metabolomics. Front Pharmacol 2022; 13:995796. [PMID: 36545315 PMCID: PMC9760753 DOI: 10.3389/fphar.2022.995796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 11/23/2022] [Indexed: 12/07/2022] Open
Abstract
Background: Renshen-Fuzi herb pair (RS-FZ) is often used in the clinical treatment of heart failure (HF) and has a remarkable therapeutic effect. However, the mechanism of RS-FZ for treating HF remains unclear. In our study, we explored the mechanism of RS-FZ for treating HF. Methods: Evaluation of RS-FZ efficacy by cardiovascular pharmacology. Moreover, Global metabolomics profiling of the serum was detected by UPLC-QTOF/MS. Multivariate statistics analyzed the specific serum metabolites and corresponding metabolic pathways. Combining serum metabolomics with network pharmacology, animal experiments screened and validated the critical targets of RS-FZ intervention in HF. Results: RS-FZ significantly ameliorated myocardial fibrosis, enhanced cardiac function, and reduced the serum HF marker (brain natriuretic peptide) level in rats with HF. Through topological analysis of the "Metabolite-Target-Component" interaction network, we found that 79 compounds of RS-FZ directly regulated the downstream specific serum metabolites by acting on four critical target proteins (CYP2D6, EPHX2, MAOB, and ENPP2). The immunohistochemistry results showed that RS-FZ observably improved the expression of CYP2D6 and ENPP2 proteins while decreasing the expression of EPHX2 and MAOB proteins dramatically. Conclusion: The integrated cardiovascular pharmacological assessment with serum metabolomics revealed that RS-FZ plays a crucial role in the treatment of HF by intervening in CYP2D6, EPHX2, MAOB, and ENPP2 target proteins. It provides a theoretical basis for RS-FZ for treating HF.
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Affiliation(s)
- Xiaofei Chen
- College of Medicine, Chengdu University of Chinese Medicine, Chengdu, China,Henan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, Henan Province Engineering Research Center for Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Yulong Chen
- College of Medicine, Henan University of Chinese Medicine, Zhengzhou, China
| | - Shiyang Xie
- Henan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, Henan Province Engineering Research Center for Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Xiaoyan Wang
- Henan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, Henan Province Engineering Research Center for Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Yali Wu
- Henan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, Henan Province Engineering Research Center for Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Hui Zhang
- Henan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, Henan Province Engineering Research Center for Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Ya Zhao
- Henan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, Henan Province Engineering Research Center for Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Jinhao Jia
- College of Medicine, Henan University of Chinese Medicine, Zhengzhou, China
| | - Bin Wang
- College of Medicine, Henan University of Chinese Medicine, Zhengzhou, China
| | - Weixia Li
- Henan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, Henan Province Engineering Research Center for Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China,*Correspondence: Weixia Li, ; Jinfa Tang, ; Xiaohe Xiao,
| | - Jinfa Tang
- Henan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, Henan Province Engineering Research Center for Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China,*Correspondence: Weixia Li, ; Jinfa Tang, ; Xiaohe Xiao,
| | - Xiaohe Xiao
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China,*Correspondence: Weixia Li, ; Jinfa Tang, ; Xiaohe Xiao,
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Liu L, Hu J, Mao Q, Liu C, He H, Hui X, Yang G, Qu P, Lian W, Duan L, Dong Y, Pan J, Liu Y, He Q, Li J, Wang J. Functional compounds of ginseng and ginseng-containing medicine for treating cardiovascular diseases. Front Pharmacol 2022; 13:1034870. [PMID: 36532771 PMCID: PMC9755186 DOI: 10.3389/fphar.2022.1034870] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 11/24/2022] [Indexed: 10/29/2023] Open
Abstract
Ginseng (Panax ginseng C.A.Mey.) is the dry root and rhizome of the Araliaceae ginseng plant. It has always been used as a tonic in China for strengthening the body. Cardiovascular disease is still the main cause of death in the world. Some studies have shown that the functional components of ginseng can regulate the pathological process of various cardiovascular diseases through different mechanisms, and its formulation also plays an irreplaceable role in the clinical treatment of cardiovascular diseases. Therefore, this paper elaborates the current pharmacological effects of ginseng functional components in treating cardiovascular diseases, summarizes the adverse reactions of ginseng, and sorts out the Chinese patent medicines containing ginseng formula which can treat cardiovascular diseases.
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Affiliation(s)
- Lanchun Liu
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jun Hu
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qiyuan Mao
- Departmen of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Chao Liu
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Haoqiang He
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiaoshan Hui
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Guang Yang
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Peirong Qu
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wenjing Lian
- Beijing University of Chinese Medicine, Beijing, China
| | - Lian Duan
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yan Dong
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Juhua Pan
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yongmei Liu
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qingyong He
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jun Li
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jie Wang
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Comprehensive chemical profiling and quantification of Shexiang Xintongning Tablets by integrating liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. ARAB J CHEM 2022. [DOI: 10.1016/j.arabjc.2022.104527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
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23
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Ginsenoside Rb1 from Panax notoginseng Suppressed TNF-α-Induced Matrix Metalloproteinase-9 via the Suppression of Double-Strand RNA-Dependent Protein Kinase (PKR)/NF-κB Pathway. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27228050. [PMID: 36432152 PMCID: PMC9692425 DOI: 10.3390/molecules27228050] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/12/2022] [Accepted: 11/16/2022] [Indexed: 11/22/2022]
Abstract
Chronic inflammation is commonly accompanied by the stimulation of matrix metalloproteinases (MMPs) production and the degradation of the extracellular matrix. The overexpression of MMP-9 (Gelatinase B) highly participates in the progression of pathetic cardiac remodeling and liver cancer metastasis. Panax notoginseng (Burkill) F. H. Chen (Sanqi), a widely used traditional Chinese medicinal herb, shows myocardial protective and anti-tumor effects. In this study, we examined the inhibitory effect of different PNG extracts on tumor necrosis factor (TNF)-α-induced MMP-9 expression in cardiac myoblast H9c2 cells. Using a bioassay-guided fractionation scheme, the most active extract was fractionated by silica gel column chromatography and high-performance liquid chromatography until an active compound was obtained. The compound was identified as Ginsenoside Rb1 by nuclear magnetic resonance. Ginsenoside Rb1 inhibited TNF-α-induced MMP-9 production in both H9c2 and liver carcinoma HepG-2 cells. Interestingly, it did not affect the MMP-2 (Gelatinase A) level and the cell proliferation of the two cell lines. The inhibitory effects of Ginsenoside Rb1 may be due to its modulation of double-strand RNA-dependent protein kinase and nuclear factor kappa B signaling pathways. The results reveal the potential use of Ginsenoside Rb1 for the treatment of inflammatory and MMP-9-related cardiac remodeling and metastasis of hepatocellular carcinomas.
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Liu M, Long X, Xu J, Chen M, Yang H, Guo X, Kang J, Ouyang Y, Luo G, Yang S, Zhou H. Hypertensive heart disease and myocardial fibrosis: How traditional Chinese medicine can help addressing unmet therapeutical needs. Pharmacol Res 2022; 185:106515. [DOI: 10.1016/j.phrs.2022.106515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/07/2022] [Accepted: 10/13/2022] [Indexed: 11/26/2022]
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Qiliqiangxin Capsule Modulates Calcium Transients and Calcium Sparks in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:9361077. [PMID: 36082183 PMCID: PMC9448542 DOI: 10.1155/2022/9361077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 07/19/2022] [Accepted: 08/06/2022] [Indexed: 12/03/2022]
Abstract
Background The therapeutic effects of Qiliqiangxin capsule (QLQX), a Chinese patent medicine, in patients with chronic heart failure are well established. However, whether QLQX modulates cardiac calcium (Ca2+) signals, which are crucial for the heart function, remains unclear. Aim of the Study. This study aimed to evaluate the role of QLQX in modulating Ca2+ signals in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Materials and Methods Fluorescence imaging was used to monitor Ca2+ signals in the cytosol and nuclei of hiPSC-CMs. For Ca2+ spark measurements, the line-scan mode of a confocal microscope was used. Results The QLQX treatment substantially decreased the frequency of spontaneous Ca2+ transients, whereas the amplitude of Ca2+ transients elicited by electrical stimulation did not change. QLQX increased the Ca2+ spark frequency in both the cytosol and nuclei without changing the sarcoplasmic reticulum Ca2+ content. Interestingly, QLQX ameliorated abnormal Ca2+ transients in CMs differentiated from hiPSCs derived from patients with long-QT syndrome. Conclusions Our findings provide the first line of evidence that QLQX directly modulates cardiac Ca2+ signals in a human cardiomyocyte model.
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26
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Zhang S, Shen Y, Liu P, Meng X, Hu D. Yangxinshi Tablet Improves Exercise Capacity for Patients with Coronary Heart Disease: Results from a Randomized, Double-Blind, Placebo-Controlled, and Multicenter Trial. Rev Cardiovasc Med 2022; 23:266. [PMID: 39076617 PMCID: PMC11266962 DOI: 10.31083/j.rcm2308266] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 06/24/2022] [Accepted: 06/30/2022] [Indexed: 07/31/2024] Open
Abstract
Objective To assess the clinical effectiveness of Yangxinshi (YXS) tablets on exercise capacity and symptoms of anxiety and depression in patients with coronary heart disease (CHD). Methods and Results A randomized, double-blind, placebo-controlled, multicenter clinical trial was performed to assess the effects of YXS tablets on exercise capacity and quality of life in patients with CHD. A total of 82 patients were included in this trial. Compared with the placebo group, the YXS group showed significant improvement in peak VO 2 (0.22 L/min vs 0.01 L/min; difference 0.1, 95% confidence interval (CI) 0.04-0.16, p = 0.000), peak Mets (0.58 vs 0.09; difference 0.3, 95% CI 0.12-0.47, p = 0.005), anaerobic threshold (AT) VO 2 (0.23 L/min vs 0.04 L/min; difference 0.12, 95% CI 0.07-0.18, p = 0.000), AT Mets (0.62 vs 0.16; difference 0.35, 95% CI 0.2-0.5, p = 0.001), and 6 minutes walking test (6MWT) (50.05 m vs 11.91 m; difference 29.92, 95% CI 18.78-41.07, p = 0.000). There were no differences in Hamilton anxiety rating scale (HAM-A score (1.97 vs 2.07; difference 2.03, 95% CI 0.99-3.06, p = 0.926) and Hamilton depression rating scale (HAM-D) score (1.06 vs 1.7; difference1.42, 95% CI 0.24-2.6, p = 0.592). Conclusions In patients with CHD, YXS tablets, compared with placebo, could improve exercise capacity, without beneficial effects on anxiety and depression symptoms.
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Affiliation(s)
- Sisi Zhang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China
| | - Yuqin Shen
- Department of Cardiovascular Medicine, Research Center for Translational Medicine, Tongji Hospital Affiliated with Shanghai Tongji University, 200065 Shanghai, China
| | - Peiliang Liu
- Department of Cardiovascular Medicine, The Jinqiu Hospital of Liaoning Province, 110067 Shenyang, Liaoning, China
| | - Xiaoping Meng
- Department of Cardiovascular Medicine and Cardiac Rehabilitation Center, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, 130000 Changchun, Jilin, China
| | - Dayi Hu
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China
- Heart Center, Peking University People's Hospital, 1000044 Beijing, China
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Liu M, Lin Y, Xu H, Li L, Ding T. Combination of Sophora flavescens alkaloids and Panax quinquefolium saponins modulates different stages of experimental autoimmune myocarditis via the NF‑κB and TGF‑β1 pathways. Exp Ther Med 2022; 24:570. [PMID: 36034755 PMCID: PMC9400131 DOI: 10.3892/etm.2022.11507] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 06/29/2022] [Indexed: 12/04/2022] Open
Abstract
Chronic cardiac inflammation and fibrosis can progress into severe forms of cardiomyopathy. Sophora flavescens alkaloids (KuShen) have been previously reported to exert anti-inflammatory effects, whereas Panax quinquefolium saponins (XiYangShen) has been shown to alleviate cardiac fibrosis. Therefore, the potential effects of their combination (KX) on different stages of autoimmune myocarditis were investigated in the present study. Mice were randomly divided into the following four groups: Control; experimental autoimmune myocarditis (EAM); KX-High (275 mg/kg); and KX-Low (138 mg/kg). A 21-day and a 60-day EAM model was established through multi-site subcutaneous injections of cardiac myosin mixed with complete Freund's adjuvant on days 0, 7, 21 and 42. Mice in the High and Low KX groups were treated by gavage (10 ml/kg) daily from day 0 (1 day before treatment) until sacrifice (day 21 or 60). Mice in the control and EAM groups received an equivalent volume of distilled water. The levels of lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTn-I), IL-1β, IL-6, TNF-α, TGF-β1, collagen type I (Col Ⅰ) and collagen type III (Col Ⅲ) were measured by ELISA in the mouse myocardial tissues or serum. Myocardial tissue structure and extent of fibrosis were visualized using H&E and Masson's staining. Western blotting and immunohistochemistry were used to measure the expression levels NF-κB and TGF-β1 pathway proteins in the myocardial tissues. The degree of inflammation in the 21-day EAM model was found to be significantly higher compared with that in the 60-day EAM model. KX significantly reduced the inflammatory response at 21 days by decreasing the expression levels of CK-MB, LDH, cTn-I, IL-1β, IL-6, TNF-α and TGF-β-activated kinase 1-binding protein 1/NF-κB pathway proteins. Myocardial fibrosis in the 60-day EAM model was also significantly worse compared with that in the 21-day EAM model. However, fibrosis was significantly delayed by treatment with KX. In addition, KX significantly decreased the expression levels of TGF-β1, Smad2, Smad4, Col I and Col III. Therefore, these data suggest that KX is beneficial for treating myocarditis by targeting multiple pathways.
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Affiliation(s)
- Menghui Liu
- Department of Traditional Chinese Medicine, Changchun University of Traditional Chinese Medicine, Changchun, Jilin 130000, P.R. China
| | - Yue Lin
- Department of Traditional Chinese Medicine, Changchun University of Traditional Chinese Medicine, Changchun, Jilin 130000, P.R. China
| | - Huibo Xu
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Traditional Chinese Medicine, Changchun, Jilin 130000, P.R. China
| | - Lixin Li
- Department of Pediatrics, Jilin Academy of Traditional Chinese Medicine, Changchun, Jilin 130000, P.R. China
| | - Tao Ding
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Traditional Chinese Medicine, Changchun, Jilin 130000, P.R. China
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Ni YH, Deng HF, Zhou L, Huang CS, Wang NN, Yue LX, Li GF, Yu HJ, Zhou W, Gao Y. Ginsenoside Rb1 Ameliorated Bavachin-Induced Renal Fibrosis via Suppressing Bip/eIF2α/CHOP Signaling-Mediated EMT. Front Pharmacol 2022; 13:872474. [PMID: 35873571 PMCID: PMC9304982 DOI: 10.3389/fphar.2022.872474] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 05/30/2022] [Indexed: 11/13/2022] Open
Abstract
The nephrotoxicity of Fructus Psoraleae, an effective traditional Chinese medicine for vitiligo treatment, has been reported. As one of the main toxic components in Fructus Psoraleae, bavachin (BV) was considered to be related to Fructus Psoraleae-caused adverse outcomes, but the direct evidence and molecular mechanism underlying BV-induced nephrotoxicity are not well elucidated. Therefore, this study was designed to confirm whether BV would cause toxic effects on the kidney and explore the possible mode of action. Our results demonstrated that days’ treatment with 0.5 μM BV indeed caused obvious renal fibrosis in the zebrafish kidney. The obvious E- to N-cadherin switch and the expressions of proteins promoting epithelial–mesenchymal transition (EMT) were observed in BV-treated human renal tubular epithelial and zebrafish kidneys. In addition, elevated reactive oxygen species (ROS) levels and Bip/eIF2α/CHOP-mediated endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) were caused by BV, both of which could be reversed by ROS scavenger N-acetyl-L-cysteine (NAC). Also, blocking ER stress-caused cytoplasmic Ca2+ overload with 4-PBA notably alleviated BV-induced alterations in key molecular events related to EMT and renal fibrosis. Furthermore, of the natural compounds subjected to screening, ginsenoside Rb1 significantly downregulated BV-induced ER stress by inhibiting ROS generation and following the activation of Bip/eIF2α/CHOP signaling in HK2 cells. Subsequently, BV-triggered EMT and renal fibrosis were both ameliorated by ginsenoside Rb1. In summary, our findings suggested that BV-induced ROS promoted the appearance of EMT and renal fibrosis mainly via Bip/eIF2α/CHOP-mediated ER stress. This ER stress-related toxic pathway might be a potential intervention target for BV-caused renal fibrosis, and ginsenoside Rb1 would be a promising drug against BV- or Fructus Psoraleae-induced nephrotoxicity.
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Affiliation(s)
- Yu-Hao Ni
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
| | - Hui-Fang Deng
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
| | - Lei Zhou
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China
| | - Cong-Shu Huang
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ning-Ning Wang
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Lan-Xin Yue
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
| | - Gao-Fu Li
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
| | - Hui-Jing Yu
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
| | - Wei Zhou
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
- *Correspondence: Wei Zhou, ; Yue Gao,
| | - Yue Gao
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
- *Correspondence: Wei Zhou, ; Yue Gao,
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Effect of Shenfu Injection on Differentiation of Bone Marrow Mesenchymal Stem Cells into Pacemaker-Like Cells and Improvement of Pacing Function of Sinoatrial Node. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:4299892. [PMID: 35186186 PMCID: PMC8853776 DOI: 10.1155/2022/4299892] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/16/2022] [Accepted: 01/26/2022] [Indexed: 11/17/2022]
Abstract
Sick sinus syndrome (SSS), a complex type of cardiac arrhythmia, is a major health threat to humans. Shenfu injection (SFI), a formula of traditional Chinese medicine (TCM), is effective in improving bradyarrhythmia. However, the underlying mechanism of SFI’s therapeutic effect is subject to few systematic investigations. The purpose of the present research is to examine whether SFI can boost the differentiation effectiveness of bone marrow mesenchymal stem cells (BMSCs) into pacemaker-like cells and whether the transplantation of these cells can improve the pacing function of the sinoatrial node (SAN) in a rabbit model of SSS. BMSCs from New Zealand rabbits were extracted, followed by incubation in vitro. The flow cytometry was utilized to identify the expression of CD29, CD44, CD90, and CD105 surface markers. The isolated BMSCs were treated with SFI, and the whole-cell patch-clamp method was performed to detect hyperpolarization-the activated cyclic nucleotide-gated potassium channel 4 (HCN4) channel current activation curve. The SSS rabbit model was established using the formaldehyde wet dressing method, and BMSCs treated with SFI were transplanted into the SAN of the SSS rabbit model. We detected changes in the body-surface electrocardiogram and recorded dynamic heart rate measurements. Furthermore, transplanted SFI-treated BMSCs were subjected to HE staining, TUNEL staining, qPCR, western blotting, immunofluorescence, immunohistochemistry, and enzyme-linked immunosorbent assay to study their characteristics. Our results indicate that the transplantation of SFI-treated BMSCs into the SAN of SSS rabbits improved the pacing function of the SAN. In vitro data showed that SFI induced the proliferation of BMSCs, promoted their differentiation capacity into pacemaker-like cells, and increased the HCN4 expression in BMSCs. In vivo, the transplantation of SFI treated-BMSCs preserved the function of SAN in SSS rabbits, improved the expression of the HCN4 gene and gap junction proteins (Cx43 and Cx45), and significantly upregulated the expression of cAMP in the SAN, compared to the SSS model group. In summary, the present research demonstrated that SFI might enhance the differentiation capacity of BMSCs into pacemaker-like cells, hence offering a novel approach for the development of biological pacemakers. Additionally, we confirmed the effectiveness and safety of pacemaker-like cells differentiated from BMSCs in improving the pacing function of the SAN.
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Li F, Wan SY, Hu JG, Zhang Y, Yu BY, Kou JP. Recent advances of traditional chinese medicine in the regulation of myocardial mitochondrial function. WORLD JOURNAL OF TRADITIONAL CHINESE MEDICINE 2022. [DOI: 10.4103/wjtcm.wjtcm_78_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Lin Z, Xie R, Zhong C, Huang J, Shi P, Yao H. Recent progress (2015-2020) in the investigation of the pharmacological effects and mechanisms of ginsenoside Rb 1, a main active ingredient in Panax ginseng Meyer. J Ginseng Res 2022; 46:39-53. [PMID: 35058726 PMCID: PMC8753521 DOI: 10.1016/j.jgr.2021.07.008] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 07/21/2021] [Accepted: 07/27/2021] [Indexed: 12/14/2022] Open
Abstract
Ginsenoside Rb1 (Rb1), one of the most important ingredients in Panax ginseng Meyer, has been confirmed to have favorable activities, including reducing antioxidative stress, inhibiting inflammation, regulating cell autophagy and apoptosis, affecting sugar and lipid metabolism, and regulating various cytokines. This study reviewed the recent progress on the pharmacological effects and mechanisms of Rb1 against cardiovascular and nervous system diseases, diabetes, and their complications, especially those related to neurodegenerative diseases, myocardial ischemia, hypoxia injury, and traumatic brain injury. This review retrieved articles from PubMed and Web of Science that were published from 2015 to 2020. The molecular targets or pathways of the effects of Rb1 on these diseases are referring to HMGB1, GLUT4, 11β-HSD1, ERK, Akt, Notch, NF-κB, MAPK, PPAR-γ, TGF-β1/Smad pathway, PI3K/mTOR pathway, Nrf2/HO-1 pathway, Nrf2/ARE pathway, and MAPK/NF-κB pathway. The potential effects of Rb1 and its possible mechanisms against diseases were further predicted via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and disease ontology semantic and enrichment (DOSE) analyses with the reported targets. This study provides insights into the therapeutic effects of Rb1 and its mechanisms against diseases, which is expected to help in promoting the drug development of Rb1 and its clinical applications.
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Affiliation(s)
- Zuan Lin
- Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Rongfang Xie
- Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Chenhui Zhong
- Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Jianyong Huang
- Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, China
| | - Peiying Shi
- Department of Traditional Chinese Medicine Resource and Bee Products, College of Animal Sciences (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou, China
| | - Hong Yao
- Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, China
- Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fujian Medical University, Fuzhou, China
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32
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Peng M, Liu H, Ji Q, Ma P, Niu Y, Ning S, Sun H, Pang X, Yang Y, Zhang Y, Han J, Hao G. Fufang Xueshuantong Improves Diabetic Cardiomyopathy by Regulating the Wnt/ β-Catenin Pathway. Int J Endocrinol 2022; 2022:3919161. [PMID: 36237833 PMCID: PMC9553353 DOI: 10.1155/2022/3919161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 07/02/2022] [Accepted: 08/12/2022] [Indexed: 11/30/2022] Open
Abstract
Diabetic cardiomyopathy (DCM) is one of the main complications of diabetic patients and the major reason for the high prevalence of heart failure in diabetic patients. Fufang Xueshuantong (FXST) is a traditional Chinese medicine formula commonly used in the treatment of diabetic retinopathy and stable angina pectoris. However, the role of FXST in DCM has not yet been clarified. This study was conducted to investigate the effects of FXST on diabetic myocardial lesions and reveal its molecular mechanism. The rats were intraperitoneally injected with 65 mg/kg streptozotocin (STZ) to induce diabetes mellitus (DM). DM rats were given saline or FXST. The rats in the control group were intraperitoneally injected with an equal amount of sodium citrate buffer and gavaged with saline. After 12 weeks, echocardiography, heart weight index (HWI), and myocardial pathological changes were determined. The expression of transforming growth factor-beta1 (TGF-β1), collagen I, and collagen III was examined using immunofluorescence staining and western blot. The expressions of Wnt/β-catenin signaling pathway-related proteins and mRNA were detected by western blot and real-time PCR. The results showed that FXST significantly improved cardiac function, ameliorated histopathological changes, and decreased HWI in the DM rats. FXST significantly inhibited the expression of myocardial TGF-β1, collagen I, and collagen III in DM rats. Furthermore, FXST significantly inhibited the Wnt/β-catenin pathway. Taken together, FXST has a protective effect on DCM, which might be mediated by suppressing the Wnt/β-catenin pathway.
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Affiliation(s)
- Meizhong Peng
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Hanying Liu
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Qingxuan Ji
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Pan Ma
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yiting Niu
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Shangqiu Ning
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Huihui Sun
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Xinxin Pang
- School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yuqian Yang
- School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yuting Zhang
- Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Jing Han
- Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Gaimei Hao
- Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
- Gansu Provincial Hospital of Traditional Chinese Medicine, Gansu, China
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Han J, Hou J, Liu Y, Liu P, Zhao T, Wang X. Using Network Pharmacology to Explore the Mechanism of Panax notoginseng in the Treatment of Myocardial Fibrosis. J Diabetes Res 2022; 2022:8895950. [PMID: 35372585 PMCID: PMC8975676 DOI: 10.1155/2022/8895950] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 05/13/2021] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE The mechanism of Panax notoginseng in treating myocardial fibrosis (MF) was investigated using network pharmacology. METHODS Effective ingredients and potential targets of Panax notoginseng were screened in relevant databases to construct a compound-target network. Targets of MF were then screened to select common targets and construct a protein-protein interaction network. This was followed by Gene Ontology and pathway enrichment analyses. Molecular docking then verified the results of network analysis. RESULTS A total of 14 effective ingredients and 119 potential targets for MF were predicted. Quercetin, beta-sitosterol, and gossypetin were speculated to be the main active ingredients. The mechanism of action may be related to AGE-RAGE, proteoglycans, and IL-17 signaling pathways. Five key targets (IL6, ALB, AKT1, TNF, and VEGFA) may be involved in the treatment of MF using Panax notoginseng. CONCLUSIONS This study embodies the complex network relationship of multicomponents, multitargets, and multipathways of Panax notoginseng in treating MF and provides a novel method for further research on this herb's mechanism.
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Affiliation(s)
- Jingxue Han
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
- Heilongjiang Academy of Chinese Medical Sciences, Harbin 150036, China
| | - Jingyi Hou
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yu Liu
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
- Heilongjiang Academy of Chinese Medical Sciences, Harbin 150036, China
| | - Peng Liu
- Shunyi Hospital, Beijing Traditional Chinese Medicine Hospital, Beijing 101300, China
| | - Tingting Zhao
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
| | - Xinwei Wang
- Heilongjiang Academy of Chinese Medical Sciences, Harbin 150036, China
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Shao-Mei W, Li-Fang Y, Li-Hong W. Traditional Chinese medicine enhances myocardial metabolism during heart failure. Biomed Pharmacother 2021; 146:112538. [PMID: 34922111 DOI: 10.1016/j.biopha.2021.112538] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 12/10/2021] [Accepted: 12/13/2021] [Indexed: 11/02/2022] Open
Abstract
The prognosis of various cardiovascular diseases eventually leads to heart failure (HF). An energy metabolism disorder of cardiomyocytes is important in explaining the molecular basis of HF; this will aid global research regarding treatment options for HF from the perspective of myocardial metabolism. There are many drugs to improve myocardial metabolism for the treatment of HF, including angiotensin receptor blocker-neprilysin inhibitor (ARNi) and sodium glucose cotransporter 2 (SGLT-2) inhibitors. Although Western medicine has made considerable progress in HF therapy, the morbidity and mortality of the disease remain high. Therefore, HF has attracted attention from researchers worldwide. In recent years, the application of traditional Chinese medicine (TCM) in HF treatment has been gradually accepted, and many studies have investigated the mechanism whereby TCM improves myocardial metabolism; the TCMs studied include Danshen yin, Fufang Danshen dripping pill, and Shenmai injection. This enables the clinical application of TCM in the treatment of HF by improving myocardial metabolism. We systematically reviewed the efficacy of TCM for improving myocardial metabolism during HF as well as the pharmacological effects of active TCM ingredients on the cardiovascular system and the potential mechanisms underlying their ability to improve myocardial metabolism. The results indicate that TCM may serve as a complementary and alternative approach for the prevention of HF. However, further rigorously designed randomized controlled trials are warranted to assess the effect of TCM on long-term hard endpoints in patients with cardiovascular disease.
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Affiliation(s)
- Wang Shao-Mei
- Cardiovascular Medicine Department, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, 158 Shangtang Road, Hangzhou 310014, Zhejiang, China
| | - Ye Li-Fang
- Cardiovascular Medicine Department, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, 158 Shangtang Road, Hangzhou 310014, Zhejiang, China
| | - Wang Li-Hong
- Cardiovascular Medicine Department, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, 158 Shangtang Road, Hangzhou 310014, Zhejiang, China.
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35
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Liu Z, Pan H, Zhang Y, Zheng Z, Xiao W, Hong X, Chen F, Peng X, Pei Y, Rong J, He J, Zou L, Wang J, Zhong J, Han X, Cao Y. Ginsenoside-Rg1 attenuates sepsis-induced cardiac dysfunction by modulating mitochondrial damage via the P2X7 receptor-mediated Akt/GSK-3β signaling pathway. J Biochem Mol Toxicol 2021; 36:e22885. [PMID: 34859534 DOI: 10.1002/jbt.22885] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 07/18/2021] [Accepted: 08/06/2021] [Indexed: 12/12/2022]
Abstract
Ginsenoside-Rg1 (G-Rg1), a saponin that is a primary component of ginseng, is effective against inflammatory diseases. The P2X purinoceptor 7 (P2X7) receptor is an ATP-gated ion channel that is predominantly expressed in immune cells and plays a key role in inflammatory processes. We investigated the role of G-Rg1 in sepsis-related cardiac dysfunction and the underlying mechanism involving the regulation of the P2X7 receptor. We detected cell viability, cytotoxicity, cellular reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) with or without G-Rg1 in lipopolysaccharide (LPS)- or hypoxia/reoxygenation (H/R)-induced H9c2 cell models of ischemia/reperfusion injury. We applied cecal ligation and puncture (CLP) to induce a mouse model of sepsis and measured the survival duration and cardiac function of CLP mice. Next, we quantified the ROS level, MMP, respiratory chain complex I-IV enzymatic activity, and mitochondrial fusion in CLP mouse heart tissues. We then investigated the role of G-Rg1 in repairing LPS-induced cell mitochondrial damage, including mitochondrial superoxidation products. The results showed that G-Rg1 inhibited LPS- or H/R-induced cardiomyocyte apoptosis, cytotoxicity, ROS levels, and mitochondrial damage. In addition, G-Rg1 prolonged the survival time of CLP mice. G-Rg1 attenuated LPS-induced superoxide production in the mitochondria of cardiomyocytes and the excessive release of cytochrome c from mitochondria into the cytoplasm. Most importantly, G-Rg1 suppressed LPS-mediated induction of proapoptotic Bax, activated Akt, induced GSK-3β phosphorylation, and balanced mitochondrial calcium levels. Overall, G-Rg1 activates the Akt/GSK-3β pathway through P2X7 receptors to inhibit sepsis-induced cardiac dysfunction and mitochondrial dysfunction.
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Affiliation(s)
- Zhengyu Liu
- Cardiology Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China.,Clinical Medicine Research Center of Heart Failure of Hunan Province, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Hongwei Pan
- Cardiology Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China.,Clinical Medicine Research Center of Heart Failure of Hunan Province, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Yixiong Zhang
- Emergency Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Zhaofen Zheng
- Cardiology Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China.,Clinical Medicine Research Center of Heart Failure of Hunan Province, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Weiwei Xiao
- Emergency Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Xiuqin Hong
- Department of Research, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Fang Chen
- Emergency Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Xiang Peng
- Clinical Medicine Research Center of Heart Failure of Hunan Province, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Yanfang Pei
- Emergency Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Jingjing Rong
- Cardiology Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China.,Clinical Medicine Research Center of Heart Failure of Hunan Province, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Jin He
- Cardiology Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China.,Clinical Medicine Research Center of Heart Failure of Hunan Province, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Lianhong Zou
- Hunan Provincial Key Laboratory of Emergency and Critical Care Metabolomics, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Jia Wang
- Department of Research, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Jie Zhong
- Department of Research, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Xiaotong Han
- Emergency Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Yan Cao
- Emergency Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
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Ke S, Wu L, Wang M, Liu D, Shi G, Zhu J, Qian X. Ginsenoside Rb1 attenuates age-associated vascular impairment by modulating the Gas6 pathway. PHARMACEUTICAL BIOLOGY 2021; 59:1369-1377. [PMID: 34629012 PMCID: PMC8510614 DOI: 10.1080/13880209.2021.1986076] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 08/21/2021] [Accepted: 09/22/2021] [Indexed: 06/13/2023]
Abstract
CONTEXT Ginsenoside Rb1 (Rb1) exerts many beneficial effects and protects against cardiovascular disease. OBJECTIVE To investigate whether Rb1 could attenuate age-related vascular impairment and identify the mechanism. MATERIALS AND METHODS Female C57BL/6J mice aged 2 and 18 months, randomly assigned to Young, Young + 20 mg/kg Rb1, Old + vehicle, Old + 10 mg/kg Rb1 and Old + 20 mg/kg Rb1 groups, were daily intraperitoneal injected with vehicle or Rb1 for 3 months. The thoracic aorta segments were used to inspect the endothelium-dependent vasorelaxation. Left thoracic aorta tissues were collected for histological or molecular expression analyses, including ageing-related proteins, markers relevant to calcification and fibrosis, and expression of Gas6/Axl. RESULTS We found that in Old + vehicle group, the expression of senescence proteins and cellular adhesion molecules were significantly increased, with worse endothelium-dependent thoracic aorta relaxation (58.35% ± 2.50%) than in Young group (88.84% ± 1.20%). However, Rb1 treatment significantly decreased the expression levels of these proteins and preserved endothelium-dependent relaxation in aged mice. Moreover, Rb1 treatment also reduced calcium deposition, collagen deposition, and the protein expression levels of collagen I and collagen III in aged mice. Furthermore, we found that the downregulation of Gas6 protein expression by 41.72% and mRNA expression by 52.73% in aged mice compared with young mice was abrogated by Rb1 treatment. But there was no significant difference on Axl expression among the groups. CONCLUSIONS Our study confirms that Rb1 could ameliorate vascular injury, suggesting that Rb1 might be a potential anti-ageing related vascular impairment agent.
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Affiliation(s)
- Shiye Ke
- Department of Cardiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Department of Cardiology, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Lin Wu
- Department of Cardiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Min Wang
- Department of Cardiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Dinghui Liu
- Department of Cardiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Guangyao Shi
- Department of Cardiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jieming Zhu
- Department of Cardiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiaoxian Qian
- Department of Cardiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Institute of Integrated Traditional Chinese and Western Medicine, Sun Yat-Sen University, Guangzhou, China
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Shaukat A, Shaukat I, Rajput SA, Shukat R, Hanif S, Shaukat I, Zhang X, Chen C, Sun X, Ye T, Niu K, Yao Z, Shaukat S, Safdar M, Abdelrahman M, Riaz U, Zhao J, Gu X, Yang L. Ginsenoside Rb1 Mitigates Escherichia coli Lipopolysaccharide-Induced Endometritis through TLR4-Mediated NF-κB Pathway. Molecules 2021; 26:molecules26237089. [PMID: 34885671 PMCID: PMC8659231 DOI: 10.3390/molecules26237089] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 11/16/2021] [Accepted: 11/16/2021] [Indexed: 12/11/2022] Open
Abstract
Endometritis is the inflammatory response of the endometrial lining of the uterus and is associated with low conception rates, early embryonic mortality, and prolonged inter-calving intervals, and thus poses huge economic losses to the dairy industry worldwide. Ginsenoside Rb1 (GnRb1) is a natural compound obtained from the roots of Panax ginseng, having several pharmacological and biological properties. However, the anti-inflammatory properties of GnRb1 in lipopolysaccharide (LPS)-challenged endometritis through the TLR4-mediated NF-κB signaling pathway has not yet been researched. This study was planned to evaluate the mechanisms of how GnRb1 rescues LPS-induced endometritis. In the present research, histopathological findings revealed that GnRb1 ameliorated LPS-triggered uterine injury. The ELISA and RT-qPCR assay findings indicated that GnRb1 suppressed the expression level of pro-inflammatory molecules (TNF-α, IL-1β and IL-6) and boosted the level of anti-inflammatory (IL-10) cytokine. Furthermore, the molecular study suggested that GnRb1 attenuated TLR4-mediated NF-κB signaling. The results demonstrated the therapeutic efficacy of GnRb1 in the mouse model of LPS-triggered endometritis via the inhibition of the TLR4-associated NF-κB pathway. Taken together, this study provides a baseline for the protective effect of GnRb1 to treat endometritis in both humans and animals.
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Affiliation(s)
- Aftab Shaukat
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
| | - Irfan Shaukat
- Faculty of Medicine, University of Lorraine, 54052 Nancy, France;
| | - Shahid Ali Rajput
- Faculty of Veterinary and Animal Sciences, Muhammad Nawaz Shareef University of Agriculture, Multan 66000, Pakistan; or
| | - Rizwan Shukat
- Faculty of Food, Nutrition & Home Sciences, University of Agriculture, Faisalabad 38000, Pakistan;
| | - Sana Hanif
- Hubei Key Laboratory of Theory and Application of Advanced Materials Mechanics, Wuhan University of Technology, Wuhan 430070, China;
| | - Imran Shaukat
- Department of Physics, University of Agriculture, Faisalabad 38000, Pakistan;
| | - Xinxin Zhang
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
| | - Chao Chen
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
| | - Xuyang Sun
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
| | - Tingzhu Ye
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
| | - Kaifeng Niu
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
| | - Zhiqiu Yao
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
| | - Shadab Shaukat
- Department of Plant Breeding and Genetics, University of Agriculture, Faisalabad 38000, Pakistan;
| | - Muhammad Safdar
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
| | - Mohamed Abdelrahman
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
- Animal Production Department, Faculty of Agriculture, Assuit University, Asyut 71515, Egypt
| | - Umair Riaz
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
| | - Junwei Zhao
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
| | - Xiaoying Gu
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
| | - Liguo Yang
- National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China; (A.S.); (X.Z.); (C.C.); (X.S.); (T.Y.); (K.N.); (Z.Y.); (M.S.); (M.A.); (U.R.); (J.Z.); (X.G.)
- Correspondence: ; Tel.: +86-138-7105-6592
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Qin GW, Lu P, Peng L, Jiang W. Ginsenoside Rb1 Inhibits Cardiomyocyte Autophagy via PI3K/Akt/mTOR Signaling Pathway and Reduces Myocardial Ischemia/Reperfusion Injury. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2021; 49:1913-1927. [PMID: 34775933 DOI: 10.1142/s0192415x21500907] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Myocardial ischemia/reperfusion injury (MIRI) is the major cause of myocardial cell damage in acute myocardial infarction, and its treatment remains a clinical challenge. Ginsenoside Rb1 showed protective effects on the cardiovascular system; however, the underlying mechanism remains largely unclear. Effects of Ginsenoside Rb1 on rat MIRI-induced myocardial infarct size were evaluated through TTC staining. TUNEL assay and flow cytometry analysis were employed to estimate cell apoptosis. Apoptosis, autophagy and PI3K/Akt/mTOR pathway-related proteins were estimated via western blot. Expression of Beclin1 in myocardial tissues were examined by immunohistochemical analysis. Expression levels of IL-1[Formula: see text], TNF-[Formula: see text] and IL-6 were tested by enzyme-linked immunosorbent assay (ELISA). Here, we found that Ginsenoside Rb1 treatment not only alleviated MIRI in rats but also protected H9C2 cells against hypoxia/reoxygenation induced damage. Ginsenoside Rb1 abolished the MIRI-induced activation of autophagy. Meanwhile, we found that treatment of 3-MA (autophagy inhibitor) could enhance the protective effects of Ginsenoside Rb1 on H9C2 cells during H/R. Moreover, Ginsenoside Rb1 treatment resulted in the activation of the PI3K/Akt/mTOR pathway, and treatment of LY294002 (PI3K/Akt pathway repressor) abolished the protective effects of Ginsenoside Rb1 on myocardial in vitro and in vivo. Our results suggest that Ginsenoside Rb1 functions as a protector against MIRI by repressing cardiomyocyte autophagy through the PI3K/Akt/mTOR signaling pathway.
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Affiliation(s)
- Guo-Wei Qin
- Department of Science and Technology, Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, P. R. China
| | - Pan Lu
- Department of Cardiology, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, P. R. China
| | - Li Peng
- Department of Cardiology, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, P. R. China
| | - Wei Jiang
- Department of Traditional Chinese Medicine, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, P. R. China
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Saha P, Bose S, Srivastava AK, Chaudhary AA, Lall R, Prasad S. Jeopardy of COVID-19: Rechecking the Perks of Phytotherapeutic Interventions. Molecules 2021; 26:6783. [PMID: 34833873 PMCID: PMC8621307 DOI: 10.3390/molecules26226783] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/02/2021] [Accepted: 11/04/2021] [Indexed: 01/31/2023] Open
Abstract
The novel coronavirus disease (COVID-19), the reason for worldwide pandemic, has already masked around 220 countries globally. This disease is induced by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Arising environmental stress, increase in the oxidative stress level, weak immunity and lack of nutrition deteriorates the clinical status of the infected patients. Though several researches are at its peak for understanding and bringing forward effective therapeutics, yet there is no promising solution treating this disease directly. Medicinal plants and their active metabolites have always been promising in treating many clinical complications since time immemorial. Mother nature provides vivid chemical structures, which act multi-dimensionally all alone or synergistically in mitigating several diseases. Their unique antioxidant and anti-inflammatory activity with least side effects have made them more effective candidate for pharmacological studies. These medicinal plants inhibit attachment, encapsulation and replication of COVID-19 viruses by targeting various signaling molecules such as angiotensin converting enzyme-2, transmembrane serine protease 2, spike glycoprotein, main protease etc. This property is re-examined and its potency is now used to improve the existing global health crisis. This review is an attempt to focus various antiviral activities of various noteworthy medicinal plants. Moreover, its implications as prophylactic or preventive in various secondary complications including neurological, cardiovascular, acute kidney disease, liver disease are also pinpointed in the present review. This knowledge will help emphasis on the therapeutic developments for this novel coronavirus where it can be used as alone or in combination with the repositioned drugs to combat COVID-19.
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Affiliation(s)
- Priyanka Saha
- Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, WB, India; (P.S.); (S.B.); (A.K.S.)
| | - Subhankar Bose
- Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, WB, India; (P.S.); (S.B.); (A.K.S.)
| | - Amit Kumar Srivastava
- Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, WB, India; (P.S.); (S.B.); (A.K.S.)
| | - Anis Ahmad Chaudhary
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSUI), Riyadh 11623, Saudi Arabia;
| | - Rajiv Lall
- Noble Pharma, LLC, 4602 Domain Drive, Menomonie, WI 54751, USA;
| | - Sahdeo Prasad
- Noble Pharma, LLC, 4602 Domain Drive, Menomonie, WI 54751, USA;
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40
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Zhang X, Wang L, Guo R, Xiao J, Liu X, Dong M, Luan X, Ji X, Lu H. Ginsenoside Rb1 Ameliorates Diabetic Arterial Stiffening via AMPK Pathway. Front Pharmacol 2021; 12:753881. [PMID: 34712140 PMCID: PMC8546248 DOI: 10.3389/fphar.2021.753881] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 09/14/2021] [Indexed: 11/13/2022] Open
Abstract
Background and Purpose: Macrovascular complication of diabetes mellitus, characterized by increased aortic stiffness, is a major cause leading to many adverse clinical outcomes. It has been reported that ginsenoside Rb1 (Rb1) can improve glucose tolerance, enhance insulin activity, and restore the impaired endothelial functions in animal models. The aim of this study was to explore whether Rb1 could alleviate the pathophysiological process of arterial stiffening in diabetes and its potential mechanisms. Experimental Approach: Diabetes was induced in male C57BL/6 mice by administration of streptozotocin. These mice were randomly selected for treatment with Rb1 (10-60 mg/kg, i. p.) once daily for 8 weeks. Aortic stiffness was assessed using ultrasound and measurement of blood pressure and relaxant responses in the aortic rings. Mechanisms of Rb1 treatment were studied in MOVAS-1 VSMCs cultured in a high-glucose medium. Key Results: Rb1 improved DM-induced arterial stiffening and the impaired aortic compliance and endothelium-dependent vasodilation. Rb1 ameliorated DM-induced aortic remodeling characterized by collagen deposition and elastic fibers disorder. MMP2, MMP9, and TGFβ1/Smad2/3 pathways were involved in this process. In addition, Rb1-mediated improvement of arterial stiffness was partly achieved via inhibiting oxidative stress in DM mice, involving regulating NADPH oxidase. Finally, Rb1 could blunt the inhibition effects of DM on AMPK phosphorylation. Conclusion and Implications: Rb1 may represent a novel prevention strategy to alleviate collagen deposition and degradation to prevent diabetic macroangiopathy and diabetes-related complications.
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Affiliation(s)
- Xinyu Zhang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lei Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Rong Guo
- Department of Cardiology, Ji'an Municipal Center People's Hospital, Ji'an, China
| | - Jie Xiao
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaoling Liu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Mei Dong
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaorong Luan
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaoping Ji
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Huixia Lu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Dr. Gilbert Hung Ginseng Laboratory, Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong, Hong Kong, SAR China
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Zhang J, Luo D, Li F, Li Z, Gao X, Qiao J, Wu L, Li M. Ginsenoside Rg3 Alleviates Antithyroid Cancer Drug Vandetanib-Induced QT Interval Prolongation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:3520034. [PMID: 34659631 PMCID: PMC8516564 DOI: 10.1155/2021/3520034] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 08/31/2021] [Indexed: 12/14/2022]
Abstract
Inhibition of human ether-a-go-go-related gene (hERG) potassium channel is responsible for acquired long QT syndromes, which leads to life-threatening cardiac arrhythmia. A multikinase inhibitor, vandetanib, prolongs the progression-free survival time in advanced medullary thyroid cancer. However, vandetanib has been reported to induce significant QT interval prolongation, which limits its clinical application. Some studies have showed that ginsenoside Rg3 decelerated hERG K(+) channel tail current deactivation. Therefore, in this study, we aim to confirm whether ginsenoside Rg3 targeting hERG K(+) channel could be used to reverse the vandetanib-induced QT interval prolongation. Electrocardiogram (ECG) and monophasic action potential (MAP) were recorded using electrophysiology signal sampling and analysis system in Langendorff-perfused rabbit hearts. The current clamp mode of the patch-clamp technique was used to record transmembrane action potential. The whole-cell patch-clamp technique was used to record the hERG K+ current. In Langendorff-perfused hearts, vandetanib prolonged the QT interval in a concentration-dependent manner with an IC50 of 1.96 μmol/L. In human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), vandetanib significantly prolonged the action potential duration at 50%, 70%, and 90% repolarization (APD50, APD70, and APD90). In stable transfected human hERG gene HEK293 cells, vandetanib caused concentrate-dependent inhibition in the step and tail currents of hERG. As expected, ginsenoside Rg3 relieved vandetanib-induced QT interval prolongation in Langendorff-perfused heart and reversed vandetanib-induced APD prolongation in hiPSC-CMs. Furthermore, ginsenoside Rg3 alleviated vandetanib-induced hERG current inhibition and accelerated the process of the channel activation. Ginsenoside Rg3 may be a promising cardioprotective agent against vandetanib-induced QT interval prolongation through targeting hERG channel. These novel findings highlight the therapeutic potential of ginsenoside to prevent vandetanib-induced cardiac arrhythmia.
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Affiliation(s)
- Juan Zhang
- Key Laboratory of Medical Electrophysiology of Ministry of Education, Medical Electrophysiology Key Lab of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
| | - Dan Luo
- Key Laboratory of Medical Electrophysiology of Ministry of Education, Medical Electrophysiology Key Lab of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
| | - Fang Li
- Key Laboratory of Medical Electrophysiology of Ministry of Education, Medical Electrophysiology Key Lab of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
| | - Zhiyi Li
- Key Laboratory of Medical Electrophysiology of Ministry of Education, Medical Electrophysiology Key Lab of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
| | - Xiaoli Gao
- Key Laboratory of Medical Electrophysiology of Ministry of Education, Medical Electrophysiology Key Lab of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
| | - Jie Qiao
- Key Laboratory of Medical Electrophysiology of Ministry of Education, Medical Electrophysiology Key Lab of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
| | - Lin Wu
- Key Laboratory of Medical Electrophysiology of Ministry of Education, Medical Electrophysiology Key Lab of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
- Department of Cardiology, Peking University First Hospital, Beijing, China
| | - Miaoling Li
- Key Laboratory of Medical Electrophysiology of Ministry of Education, Medical Electrophysiology Key Lab of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
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42
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Mohammadi Pour P, Farzaei MH, Soleiman Dehkordi E, Bishayee A, Asgary S. Therapeutic targets of natural products for the management of cardiovascular symptoms of coronavirus disease 2019. Phytother Res 2021; 35:5417-5426. [PMID: 34110678 DOI: 10.1002/ptr.7172] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 03/01/2021] [Accepted: 04/09/2021] [Indexed: 12/14/2022]
Abstract
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first occurred in China in December 2019 and subsequently spread all over the world with cardiovascular, renal, and pulmonary symptoms. Therefore, recognizing and treating the cardiovascular sign and symptoms that caused by coronavirus disease 2019 (COVID-19) can be effective in reducing patient mortality. To control the COVID-19-related cardiovascular symptoms, natural products are considered one of the promising choices as complementary medicine. Scientists are struggling to discover new antiviral agents specific to this virus. In this review, the natural products for management of cardiovascular symptoms of COVID-19 are categorized into three groups: (a) natural products with an impact on angiotensin II type 1 receptor; (b) natural products that inhibit angiotensin-converting enzyme activity; and (c) natural products that mimic adenosine activity. All these natural products should undergo clinical investigations to test their efficacy, safety, and toxicity in the treatment of cardiovascular symptoms of COVID-19. This article summarizes agents with potential efficacy against COVID-19-related cardiovascular symptoms.
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Affiliation(s)
- Pardis Mohammadi Pour
- Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ebrahim Soleiman Dehkordi
- Medical Plants Research Center, Basic Health Science, Shahrekord University of Medical Science, Shahrekord, Iran
| | - Anupam Bishayee
- Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Sedigheh Asgary
- Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
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43
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Junior AG, Tolouei SEL, Dos Reis Lívero FA, Gasparotto F, Boeing T, de Souza P. Natural Agents Modulating ACE-2: A Review of Compounds with Potential against SARS-CoV-2 Infections. Curr Pharm Des 2021; 27:1588-1596. [PMID: 33459225 DOI: 10.2174/1381612827666210114150607] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 12/02/2020] [Accepted: 12/14/2020] [Indexed: 01/08/2023]
Abstract
One of the biggest challenges of public health worldwide is reducing the number of events and deaths related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The angiotensinconverting enzyme 2 (ACE-2), a carboxypeptidase that degrades angiotensin II into angiotensin 1-7, has been identified as a potent receptor for SARS-CoV-2. In the last decades, ACE inhibition has assumed a central role in reducing cardiovascular and renal events. However, with the advent of COVID-19, attention has been turned to ACE-2 as a possible target to reduce virus binding to different human cells. This review aims to discuss recent developments related to the medicinal properties of natural compounds as ACE/ACE-2 inhibitors, which should be highlighted in the future development of studies looking for modulators in SARS-CoV-2 infection. Data show that bioactive compounds isolated from several natural products act by inhibiting ACE/ACE-2, which changes the entire axis of this system. Of the compounds addressed in this review, 7 phenolic compounds, including quercetin, curcumin, naringenin, luteolin, hesperidin, mangiferin, and gallic acid showed binding affinity with molecular ACE-2 target in silico, and 1, esculetin, decreased ACE-2 expression in vivo. Regarding terpenoids and alkaloids, nimbin, withaferin A, andrographolide, zingiberene and, berberine, piperine and thebaine, respectively, showed a binding affinity with molecular ACE-2 target in silico. These findings reinforce the need for future preclinical and clinical studies on these compounds and specific inhibitory effects on ACE-2 of all the other compounds described herein only as nonspecific ACE inhibitors. It is important to mention that some natural compounds such as magnolol, resveratrol, rosmarinic acid, tanshinone IIA, and nicotine have also demonstrated the potential to increase the activity or expression of ACE-2, and could therefore aggravate SARS-CoV-2 infection.
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Affiliation(s)
- Arquimedes Gasparotto Junior
- Laboratory of Electrophysiology and Cardiovascular Pharmacology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil
| | - Sara Emília Lima Tolouei
- Laboratory of Reproductive Toxicology, Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil
| | - Francislaine Aparecida Dos Reis Lívero
- Laboratory of Preclinical Research of Natural Products, Post-Graduate Program in Medicinal Plants and Phytotherapeutics in Basic Attention, Paranaense University, Umuarama, PR, Brazil
| | - Francielli Gasparotto
- Cesumar Institute of Science, Technology and Innovation (ICETI), University Center of Maringa, Maringa, PR, Brazil
| | - Thaise Boeing
- School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil
| | - Priscila de Souza
- Postgraduate Program in Pharmaceutical Sciences, University of Vale do Itajai, Itajai, SC, Brazil
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44
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Wang S, Cui Y, Xiong M, Li M, Wang P, Cui J, Du X, Chen Y, Zhang T. Dual Activity of Ginsenoside Rb1 in Hypertrophic Cardiomyocytes and Activated Macrophages: Implications for the Therapeutic Intervention of Cardiac Hypertrophy. J Inflamm Res 2021; 14:1789-1806. [PMID: 33981156 PMCID: PMC8108398 DOI: 10.2147/jir.s310633] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 04/15/2021] [Indexed: 11/23/2022] Open
Abstract
Purpose Owing to the important mechanistic implications in the pathogenesis of cardiac hypertrophy and heart failure, inflammation has been proposed as a druggable target for the treatment of cardiac hypertrophy and heart failure. Ginseng is a widely used medicinal herb for the treatment of cardiovascular disorders. As one of the major chemical components of ginseng, ginsenoside Rb1 (Rb1) contributes to the cardiovascular effects of ginseng. Meanwhile, anti-inflammatory activity of Rb1 has also been documented. The current work aims to further delineate the pharmacological implications of Rb1 in the treatment of cardiac hypertrophy. Methods Angiotensin II (Ang II) infusion mouse model was adopted to investigate the effects of Rb1 on cardiac hypertrophic remodeling and associated inflammation in vivo. Furthermore, the mechanisms of actions of Rb1 in modulating the hypertrophic and inflammatory responses were investigated in cardiomyocytes and macrophages, respectively. Results Rb1 mitigates Ang II-induced cardiac hypertrophy, cardiac inflammation and systemic inflammation in vivo. In cardiomyocytes, Rb1 directly counteracts the pro-hypertrophic effects of Ang II and phenylephrine and maintains the mitochondrial function. In lipopolysaccharide (LPS)-stimulated macrophages, Rb1 decreases the phosphorylation of mitogen-activated protein kinases (MAPKs) and mitogen-activated protein kinase kinase 1/2 (MEK1/2) and reduces the production of inflammation mediators such as interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF). Rb1 also suppresses the expression of pro-hypertrophic microRNA-155 (miR-155) in LPS- or Ang II-stimulated macrophages. Furthermore, in activated macrophages, miR-155 is in part accountable for the suppressive effect of Rb1 on the production of IL-6, an inflammation mediator with pro-hypertrophic functions in the heart. Conclusion The work here provides novel experimental evidence supporting the notion that Rb1 protects against cardiac hypertrophy in part through suppressing the inflammatory mechanisms that promotes the pathological remodeling of the heart.
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Affiliation(s)
- Shihua Wang
- Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Yimeng Cui
- Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Minqi Xiong
- Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.,Clinical Research Institute of Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Mei Li
- Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Peiwei Wang
- Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.,Clinical Research Institute of Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Jingang Cui
- Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.,Clinical Research Institute of Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Xiaoye Du
- Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.,Clinical Research Institute of Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Yu Chen
- Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.,Clinical Research Institute of Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People's Republic of China.,Laboratory of Clinical and Molecular Pharmacology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Teng Zhang
- Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.,Clinical Research Institute of Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People's Republic of China
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He Y, Huang W, Zhang C, Chen L, Xu R, Li N, Wang F, Han L, Yang M, Zhang D. Energy metabolism disorders and potential therapeutic drugs in heart failure. Acta Pharm Sin B 2021; 11:1098-1116. [PMID: 34094822 PMCID: PMC8144890 DOI: 10.1016/j.apsb.2020.10.007] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 08/27/2020] [Accepted: 09/07/2020] [Indexed: 02/07/2023] Open
Abstract
Heart failure (HF) is a global public health problem with high morbidity and mortality. A large number of studies have shown that HF is caused by severe energy metabolism disorders, which result in an insufficient heart energy supply. This deficiency causes cardiac pump dysfunction and systemic energy metabolism failure, which determine the development of HF and recovery of heart. Current HF therapy acts by reducing heart rate and cardiac preload and afterload, treating the HF symptomatically or delaying development of the disease. Drugs aimed at cardiac energy metabolism have not yet been developed. In this review, we outline the main characteristics of cardiac energy metabolism in healthy hearts, changes in metabolism during HF, and related pathways and targets of energy metabolism. Finally, we discuss drugs that improve cardiac function via energy metabolism to provide new research ideas for the development and application of drugs for treating HF.
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Zhang X, Lv S, Zhang W, Jia Q, Wang L, Ding Y, Yuan P, Zhu Y, Liu L, Li Y, Zhang J. Shenmai injection improves doxorubicin cardiotoxicity via miR-30a/Beclin 1. Biomed Pharmacother 2021; 139:111582. [PMID: 33895525 DOI: 10.1016/j.biopha.2021.111582] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 04/01/2021] [Accepted: 04/02/2021] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Shenmai Injection (SMI) has been widely used in the treatment of cardiovascular diseases and can reduce side effects when combined with chemotherapy drugs. However, the potential protective mechanism of SMI on the cardiotoxicity caused by anthracyclines has not been clear. METHODS We used network pharmacology methods to collect the compound components in SMI and myocardial injury targets, constructed a 'drug-disease' target interaction network relationship diagram, and screened the core targets to predict the potential mechanism of SMI in treating cardiotoxicity of anthracyclines. In addition, the rat model of doxorubicin cardiotoxicity was induced by injecting doxorubicin through the tail vein. The rats were randomized in the model group, miR-30a agomir group, SMI low-dose group, SMI high-dose group，and the control group. The cardiac ultrasound was used to evaluate the structure and function of the rat heart. HE staining was used to observe the pathological changes of the rat myocardium. Transmission electron microscopy was used to observe myocardial autophagosomes. The expression of miR-30a and Beclin 1 mRNA in the rat myocardium was detected by RT-qPCR. Western Blot detected the expression of LC3-II/LC3-I and p62 protein. RESULTS The network pharmacological analysis found that SMI could act synergistically through multiple targets and multiple pathways, which might exert a myocardial protective effect through PI3K-Akt signaling pathways and cancer microRNAs. In vivo, compared with the control group, the treatment group could improve the cardiac structure and function, and reduce myocardial pathological damage and the number of autophagosomes. The expression of miR-30a in the myocardium of rats in miR-30a agomir group and SMI group increased (P < 0.01)，Beclin 1 mRNA was decreased (P < 0.01)，LC3-Ⅱ/LC3-I protein was decreased (P < 0.01 or P < 0.05)，and p62 protein was increased (P < 0.01 or P < 0.05). CONCLUSIONS SMI has the characteristics of multi-component, multi-target, and multi-pathway. It can inhibit myocardial excessive autophagy by regulating the expression of miR-30a/Beclin 1 and alleviate the myocardial injury induced by doxorubicin.
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Affiliation(s)
- Xiaonan Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Shichao Lv
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin Key Laboratory of Traditional Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Wanqin Zhang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Qiujin Jia
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Lirong Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Yuejia Ding
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Peng Yuan
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Yaping Zhu
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Longtao Liu
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
| | - Yanyang Li
- Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
| | - Junping Zhang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
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Xiao H, Chen J, Duan L, Li S. Role of emerging vitamin K‑dependent proteins: Growth arrest‑specific protein 6, Gla‑rich protein and periostin (Review). Int J Mol Med 2021; 47:2. [PMID: 33448308 PMCID: PMC7834955 DOI: 10.3892/ijmm.2020.4835] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 10/21/2020] [Indexed: 01/27/2023] Open
Abstract
Vitamin K‑dependent proteins (VKDPs) are a group of proteins that need vitamin K to conduct carboxylation. Thus far, scholars have identified a total of 17 VKDPs in the human body. In this review, we summarize three important emerging VKDPs: Growth arrest‑specific protein 6 (Gas 6), Gla‑rich protein (GRP) and periostin in terms of their functions in physiological and pathological conditions. As examples, carboxylated Gas 6 and GRP effectively protect blood vessels from calcification, Gas 6 protects from acute kidney injury and is involved in chronic kidney disease, GRP contributes to bone homeostasis and delays the progression of osteoarthritis, and periostin is involved in all phases of fracture healing and assists myocardial regeneration in the early stages of myocardial infarction. However, periostin participates in the progression of cardiac fibrosis, idiopathic pulmonary fibrosis and airway remodeling of asthma. In addition, we discuss the relationship between vitamin K, VKDPs and cancer, and particularly the carboxylation state of VKDPs in cancer.
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Affiliation(s)
- Huiyu Xiao
- Department of Physiology, Dalian Medical University, Dalian, Liaoning 116044
| | - Jiepeng Chen
- Sungen Bioscience Co., Ltd., Shantou, Guangdong 515071, P.R. China
| | - Lili Duan
- Sungen Bioscience Co., Ltd., Shantou, Guangdong 515071, P.R. China
| | - Shuzhuang Li
- Department of Physiology, Dalian Medical University, Dalian, Liaoning 116044
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Sarhene M, Ni JY, Duncan ES, Liu Z, Li S, Zhang J, Guo R, Gao S, Gao X, Fan G. Ginsenosides for cardiovascular diseases; update on pre-clinical and clinical evidence, pharmacological effects and the mechanisms of action. Pharmacol Res 2021; 166:105481. [PMID: 33549726 DOI: 10.1016/j.phrs.2021.105481] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 01/20/2021] [Accepted: 02/02/2021] [Indexed: 12/14/2022]
Abstract
Cardiovascular disease (CVD) remains the major cause of death worldwide, accounting for almost 31% of the global mortality annually. Several preclinical studies have indicated that ginseng and the major bioactive ingredient (ginsenosides) can modulate several CVDs through diverse mechanisms. However, there is paucity in the translation of such experiments into clinical arena for cardiovascular ailments due to lack of conclusive specific pathways through which these activities are initiated and lack of larger, long-term well-structured clinical trials. Therefore, this review elaborates on current pharmacological effects of ginseng and ginsenosides in the cardiovascular system and provides some insights into the safety, toxicity, and synergistic effects in human trials. The review concludes that before ginseng, ginsenosides and their preparations could be utilized in the clinical treatment of CVDs, there should be more preclinical studies in larger animals (like the guinea pig, rabbit, dog, and monkey) to find the specific dosages, address the toxicity, safety and synergistic effects with other conventional drugs. This could lead to the initiation of large-scale, long-term well-structured randomized, and placebo-controlled clinical trials to test whether treatment is effective for a longer period and test the efficacy against other conventional therapies.
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Affiliation(s)
- Michael Sarhene
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Jing Yu Ni
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Esi Sophia Duncan
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Zhihao Liu
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Sheng Li
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Jing Zhang
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Rui Guo
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Shan Gao
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiumei Gao
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Guanwei Fan
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China.
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Dong Z, Dai H, Feng Z, Liu W, Gao Y, Liu F, Zhang Z, Zhang N, Dong X, Zhao Q, Zhou X, Du J, Liu B. Mechanism of herbal medicine on hypertensive nephropathy (Review). Mol Med Rep 2021; 23:234. [PMID: 33537809 PMCID: PMC7893801 DOI: 10.3892/mmr.2021.11873] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 12/30/2020] [Indexed: 12/11/2022] Open
Abstract
Hypertensive nephropathy is the most common complication of hypertension, and is one of the main causes of end-stage renal disease (ESRD) in numerous countries. The basic pathological feature of hypertensive nephropathy is arteriolosclerosis followed by renal parenchymal damage. The etiology of this disease is complex, and its pathogenesis is mainly associated with renal hemodynamic changes and vascular remodeling. Despite the increased knowledge on the pathogenesis of hypertensive nephropathy, the current clinical treatment methods are still not effective in preventing the development of the disease to ESRD. Herbal medicine, which is used to relieve symptoms, can improve hypertensive nephropathy through multiple targets. Since there are few clinical studies on the treatment of hypertensive nephropathy with herbal medicine, this article aims to review the progress on the basic research on the treatment of hypertensive nephropathy with herbal medicine, including regulation of the renin angiotensin system, inhibition of sympathetic excitation, antioxidant stress and anti-inflammatory protection of endothelial cells, and improvement of obesity-associated factors. Herbal medicine with different components plays a synergistic and multi-target role in the treatment of hypertensive nephropathy. The description of the mechanism of herbal medicine in the treatment of hypertensive nephropathy will contribute towards the progress of modern medicine.
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Affiliation(s)
- Zhaocheng Dong
- Beijing Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
| | - Haoran Dai
- Shunyi Branch, Beijing Traditional Chinese Medicine Hospital, Beijing 101300, P.R. China
| | - Zhandong Feng
- Beijing Chinese Medicine Hospital Pinggu Hospital, Beijing 101200, P.R. China
| | - Wenbin Liu
- Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, P.R. China
| | - Yu Gao
- Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, P.R. China
| | - Fei Liu
- Beijing Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
| | - Zihan Zhang
- Beijing Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
| | - Na Zhang
- Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, P.R. China
| | - Xuan Dong
- Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, P.R. China
| | - Qihan Zhao
- Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, P.R. China
| | - Xiaoshan Zhou
- Beijing Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
| | - Jieli Du
- Beijing Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
| | - Baoli Liu
- Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, P.R. China
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50
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Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: Pharmacology and mechanisms. Biomed Pharmacother 2020; 132:110915. [DOI: 10.1016/j.biopha.2020.110915] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 10/05/2020] [Accepted: 10/17/2020] [Indexed: 12/16/2022] Open
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