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Effects of Natural Products in the Context of Cardiometabolic Disease

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 October 2016) | Viewed by 138046

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Prof. Dr. Atanas G. Atanasov

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Ludwig Boltzmann Institute for Digital Health and Patient Safety, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria
Interests: molecular medicine; digital health; open innovation; biotechnology; natural products; science communication; molecular pharmacology
Special Issues, Collections and Topics in MDPI journals

Dr. Karel Šmejkal

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Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Brno, Czech Republic
Interests: phytochemistry; pharmacognosy; bioactivity; anti-inflammatory effect; animicrobial effect
Special Issues, Collections and Topics in MDPI journals

Dr. Elke Heiss

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Guest Editor

Department of Pharmacognosy, University of Vienna, Vienna, Austria
Interests: natural products; mode of action; cellular stress response; bioenergetics, metabolic and redox homeostasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiometabolic diseases, including, among others, atherosclerosis, diabetes type 2, and liver steatosis, are the main cause of morbidity and mortality in the world. An accumulating body of evidence indicates that some naturally occurring molecules, partly present in diet or traditional medicinal plants, are able to modulate the initiation or the progression of this group of disorders.

This Special Issue aims at summarizing current developments in the targeted area of research. We, therefore, encourage submission of reviews or original research papers studying in vitro or in vivo the action of natural molecules on cellular signaling pathways, proteins, or physiological reactions relevant for cardiometabolic disease.

Adj. Prof. Dr. Atanas G. Atanasov
Assoc. Prof. Dr. Karel Šmejkal
Ass. Prof. PD Dr. Elke Heiss
Guest Editors

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Keywords

natural products
cardiovascular disease
drug discovery
pharmacology
metabolic disease
diabetes
metabolism
inflammation
cell signaling

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Related Special Issue

Bioactive Molecules and Their Mechanisms of Action in Molecules (20 articles)

Published Papers (11 papers)

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Editorial

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164 KiB

Open AccessEditorial

Does a Graphical Abstract Bring More Visibility to Your Paper?

by Eva-Maria Pferschy-Wenzig, Ulrich Pferschy, Dongdong Wang, Andrei Mocan and Atanas G. Atanasov

Molecules 2016, 21(9), 1247; https://doi.org/10.3390/molecules21091247 - 18 Sep 2016

Cited by 36 | Viewed by 31293

Abstract

A graphical abstract (GA) represents a piece of artwork that is intended to summarize the main findings of an article for readers at a single glance. Many publishers currently encourage authors to supplement their articles with GAs, in the hope that such a convenient visual summary will facilitate readers with a clearer outline of papers that are of interest and will result in improved overall visibility of the respective publication. To test this assumption, we statistically compared publications with or without GA published in Molecules between March 2014 and March 2015 with regard to several output parameters reflecting visibility. Contrary to our expectations, manuscripts published without GA performed significantly better in terms of PDF downloads, abstract views, and total citations than manuscripts with GA. To the best of our knowledge, this is the first empirical study on the effectiveness of GA for attracting attention to scientific publications. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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Research

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3643 KiB

Open AccessArticle

Effect of Phenolic Compounds from Elderflowers on Glucose- and Fatty Acid Uptake in Human Myotubes and HepG2-Cells

by Giang Thanh Thi Ho, Eili Tranheim Kase, Helle Wangensteen and Hilde Barsett

Molecules 2017, 22(1), 90; https://doi.org/10.3390/molecules22010090 - 6 Jan 2017

Cited by 25 | Viewed by 9382

Abstract

Type 2 diabetes (T2D) is manifested by progressive metabolic impairments in tissues such as skeletal muscle and liver, and these tissues become less responsive to insulin, leading to hyperglycemia. In the present study, stimulation of glucose and oleic acid uptake by elderflower extracts, constituents and metabolites were tested in vitro using the HepG2 hepatocellular liver carcinoma cell line and human skeletal muscle cells. Among the crude extracts, the 96% EtOH extract showed the highest increase in glucose and oleic acid uptake in human skeletal muscle cells and HepG2-cells. The flavonoids and phenolic acids contained therein were potent stimulators of glucose and fatty acid uptake in a dose-dependent manner. Most of the phenolic constituents and several of the metabolites showed high antioxidant activity and showed considerably higher α-amylase and α-glucosidase inhibition than acarbose. Elderflower might therefore be valuable as a functional food against diabetes. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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2351 KiB

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Riboflavin Reduces Pro-Inflammatory Activation of Adipocyte-Macrophage Co-culture. Potential Application of Vitamin B2 Enrichment for Attenuation of Insulin Resistance and Metabolic Syndrome Development

by Agnieszka Irena Mazur-Bialy and Ewa Pocheć

Molecules 2016, 21(12), 1724; https://doi.org/10.3390/molecules21121724 - 15 Dec 2016

Cited by 42 | Viewed by 9631

Abstract

Due to the progressive increase in the incidence of obese and overweight individuals, cardiometabolic syndrome has become a worldwide pandemic in recent years. Given the immunomodulatory properties of riboflavin, the current study was performed to investigate the potency of riboflavin in reducing obesity-related inflammation, which is the main cause of insulin resistance, diabetes mellitus 2 or arteriosclerosis. We determined whether pretreatment with a low dose of riboflavin (10.4–1000 nM) affected the pro-inflammatory activity of adipocyte-macrophage co-culture (3T3 L1-RAW 264.7) following lipopolysaccharide stimulation (LPS; 100 ng/mL) which mimics obesity-related inflammation. The apoptosis of adipocytes and macrophages as well as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1beta (IL-1β), monocyte chemotactic protein 1 (MCP-1), high-mobility group box 1 (HMGB1), transforming growth factor–beta 1 (TGFβ), interleukin 10 (IL-10), inducible nitric oxide synthase (iNOS), nitric oxide (NO), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1) expression and release, macrophage migration and adipokines (adiponectin and leptin) were determined. Our results indicated an efficient reduction in pro-inflammatory factors (TNFα, IL-6, MCP-1, HMGB1) upon culture with riboflavin supplementation (500–1000 nM), accompanied by elevation in anti-inflammatory adiponectin and IL-10. Moreover, macrophage migration was reduced by the attenuation of chemotactic MCP-1 release and degradation of the extracellular matrix by MMP-9. In conclusion, riboflavin effectively inhibits the pro-inflammatory activity of adipocyte and macrophage co-cultures, and therefore we can assume that its supplementation may reduce the likelihood of conditions associated with the mild inflammation linked to obesity. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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2660 KiB

Open AccessArticle

Salidroside Suppresses HUVECs Cell Injury Induced by Oxidative Stress through Activating the Nrf2 Signaling Pathway

by Yao Zhu, Ya-Jie Zhang, Wei-Wei Liu, Ai-Wu Shi and Ning Gu

Molecules 2016, 21(8), 1033; https://doi.org/10.3390/molecules21081033 - 9 Aug 2016

Cited by 69 | Viewed by 7888

Abstract

Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Salidroside (SAL), one of the main effective constituents of Rhodiola rosea, has been reported to suppress oxidative stress-induced cardiomyocyte injury and necrosis by promoting transcription of nuclear factor E2-related factor 2 (Nrf2)-regulated genes such as heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase (quinone1) (NQO1). However, it has not been indicated whether SAL might ameliorate endothelial injury induced by oxidative stress. Here, our study demonstrated that SAL might suppress HUVEC cell injury induced by oxidative stress through activating the Nrf2 signaling pathway. The results of our study indicated that SAL decreased the levels of intercellular reactive oxygen species (ROS) and malondialdehyde (MDA), and improved the activities of superoxide dismutase (SOD) and catalase (CAT), resulting in protective effects against oxidative stress-induced cell damage in HUVECs. It suppressed oxidative stress damage by inducing Nrf2 nuclear translocation and activating the expression of Nrf2-regulated antioxidant enzyme genes such as HO-1 and NQO1 in HUVECs. Knockdown of Nrf2 with siRNA abolished the cytoprotective effects against oxidative stress, decreased the expression of Nrf2, HO-1, and NQO1, and inhibited the nucleus translocation of Nrf2 in HUVECs. This study is the first to demonstrate that SAL suppresses HUVECs cell injury induced by oxidative stress through activating the Nrf2 signaling pathway. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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4483 KiB

Open AccessArticle

Qingxuan Jiangya Decoction Reverses Vascular Remodeling by Inducing Vascular Smooth Muscle Cell Apoptosis in Spontaneously Hypertensive Rats

by Fei Xiao, Fei He, Hongwei Chen, Shan Lin, Aling Shen, Youqin Chen, Jianfeng Chu and Jun Peng

Molecules 2016, 21(7), 956; https://doi.org/10.3390/molecules21070956 - 22 Jul 2016

Cited by 18 | Viewed by 7158

Abstract

Qingxuan Jiangya Decoction (QXJYD), a traditional Chinese medicine formula prescribed by academician Ke-ji Chen, has been used in China to clinically treat hypertension for decades of years. However, the molecular mechanisms of its action remain largely unknown. In this study, we examined the therapeutic efficacy of QXJYD against elevated systolic blood pressure in the spontaneously hypertensive rat (SHR) model, and investigated the underlying molecular mechanisms. We found that oral administration of QXJYD significantly reduced the elevation of systolic blood pressure in SHR but had no effect on body weight change. Additionally, QXJYD treatment significantly decreased the media thickness and ratio of media thickness/lumen diameter in the carotid arteries of SHR. Moreover, QXJYD remarkably promoted apoptosis of vascular smooth muscle cells and reduced the expression of anti-apoptotic B-cell leukemia/lymphoma 2. Furthermore, QXJYD significantly decreased the plasma Angiotensin II level in SHR. Collectively, our findings suggest that reversing vascular remodeling via inducing VSMC apoptosis could be one of the mechanisms whereby QXJYD treats hypertension. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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3517 KiB

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Clematichinenoside (AR) Attenuates Hypoxia/Reoxygenation-Induced H9c2 Cardiomyocyte Apoptosis via a Mitochondria-Mediated Signaling Pathway

by Haiyan Ding, Rong Han, Xueshan Chen, Weirong Fang, Meng Liu, Xuemei Wang, Qin Wei, Nandani Darshika Kodithuwakku and Yunman Li

Molecules 2016, 21(6), 683; https://doi.org/10.3390/molecules21060683 - 30 May 2016

Cited by 13 | Viewed by 8789

Abstract

Mitochondria-mediated cardiomyocyte apoptosis is involved in myocardial ischemia/reperfusion (MI/R) injury. Clematichinenoside (AR) is a triterpenoid saponin isolated from the roots of Clematis chinensis with antioxidant and anti-inflammatory cardioprotection effects against MI/R injury, yet the anti-apoptotic effect and underlying mechanisms of AR in MI/R injury remain unclear. We hypothesize that AR may improve mitochondrial function to inhibit MI/R-induced cardiomyocyte apoptosis. In this study, we replicated an in vitro H9c2 cardiomyocyte MI/R model by hypoxia/reoxygenation (H/R) treatment. The viability of H9c2 cardiomyocytes was determined by MTT assay; apoptosis was evaluated by flow cytometry and TUNEL experiments; mitochondrial permeability transition pore (mPTP) opening was analyzed by a calcein-cobalt quenching method; and mitochondrial membrane potential (ΔΨm) was detected by JC-1. Moreover, we used western blots to determine the mitochondrial cytochrome c translocation to cytosolic and the expression of caspase-3, Bcl-2, and Bax proteins. These results showed that the application of AR decreased the ratio of apoptosis and the extent of mPTP opening, but increased ΔΨm. AR also inhibited H/R-induced release of mitochondrial cytochrome c and decreased the expression of the caspase-3, Bax proteins. Conversely, it remarkably increased the expression of Bcl-2 protein. Taken together, these results revealed that AR protects H9c2 cardiomyocytes against H/R-induced apoptosis through mitochondrial-mediated apoptotic signaling pathway. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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2464 KiB

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Agrimonia eupatoria L. and Cynara cardunculus L. Water Infusions: Comparison of Anti-Diabetic Activities

by Anika Kuczmannová, Andrea Balažová, Eva Račanská, Miroslava Kameníková, Silvia Fialová, Jaroslav Majerník, Milan Nagy, Peter Gál and Pavel Mučaji

Molecules 2016, 21(5), 564; https://doi.org/10.3390/molecules21050564 - 28 Apr 2016

Cited by 31 | Viewed by 7169

Abstract

Diabetes mellitus (DM) is frequently diagnosed at a time when patients already suffer from several cardiovascular complications. Our previously published data (Molecules 201520 (11): 20538-50) on the anti-oxidative properties of Agrimonia eupatoria L. (AE) and Cynara cardunculus L. (CC) prompted us to extend the available evidence on their possible protective activities on selected DM-related parameters in a streptozotocin-induced DM rat model and in a series of in vitro experiments. Male rats were divided into four groups: control group, untreated diabetic group, AE and CC treated diabetic groups. During a five-week period, changes in blood glucose and body weight were monitored. Then, rats were sacrificed and subjected to the assessment of changes in the reactivity of aortas and measurement of butyrylcholinesterase activity. To complete the panel of experiments, α-glucosidase activity was assessed in vitro. Our results demonstrate that both tested extracts exert similar anti-diabetic activities. However, better anti-oxidant activity of the A. eupatoria extract indicates its higher clinical potential in the prevention and/or adjuvant therapy of developing cardiovascular complications related to DM and diseases associated with oxidative stress. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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4446 KiB

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The Chemical Composition of Achillea wilhelmsii C. Koch and Its Desirable Effects on Hyperglycemia, Inflammatory Mediators and Hypercholesterolemia as Risk Factors for Cardiometabolic Disease

by Elian Khazneh, Petra Hřibová, Jan Hošek, Pavel Suchý, Peter Kollár, Gabriela Pražanová, Jan Muselík, Zuzana Hanaková, Jiří Václavík, Michał Miłek, Jaroslav Legáth and Karel Šmejkal

Molecules 2016, 21(4), 404; https://doi.org/10.3390/molecules21040404 - 25 Mar 2016

Cited by 24 | Viewed by 8389

Abstract

This study was done to identify the content compounds of Achillea wilhelmsii (A. wilhelmsii) and to evaluate its hypoglycemic and anti-hypercholesterolemic activity and effect on inflammatory mediators. The extracts and fractions of A. wilhelmsii were thoroughly analyzed using high performance liquid chromatography (HPLC), and the total content of phenols and flavonoids was determined. The hypoglycemic activity was evaluated in vivo using alloxan-induced diabetic mice. The effect upon inflammatory mediators was evaluated in vitro using the human monocytic leukemia cell line (THP-1). The anti-hypercholesterolemic activity was evaluated in vitro using the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase assay kit. The water extract (WE)-treated group showed the highest reduction in the fasting blood glucose levels (FBGL). The chloroform fraction (CF) and ethyl acetate fraction (EAF) both showed a significant ability to reduce the secretion of tumor necrosis factor alpha (TNF-α). The EAF, however, also attenuated the levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The CF showed the most significant 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibition activity. The five main compounds in the CF were isolated and identified. Out of the five compounds in the CF, 1β,10β-epoxydesacetoxymatricarin (CP1) and leucodin (CP2) showed the highest anti-hypercholesterolemic potential. A molecular docking study provided corresponding results. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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Review

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2196 KiB

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Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents

by Chang-Ik Choi

Molecules 2016, 21(9), 1136; https://doi.org/10.3390/molecules21091136 - 27 Aug 2016

Cited by 88 | Viewed by 14617

Abstract

Diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions, leading to the development of life-threatening complications. Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia, weight gain, and hepato-renal toxicity, have increased demand for the discovery of novel, safer antidiabetic drugs. Since the important roles of the sodium-glucose cotransporter 2 (SGLT2) for glucose homeostasis in the kidney were recently elucidated, pharmacological inhibition of SGLT2 has been considered a promising therapeutic target for the treatment of type 2 diabetes. Since the discovery of the first natural SGLT2 inhibitor, phlorizin, several synthetic glucoside analogs have been developed and introduced into the market. Furthermore, many efforts to find new active constituents with SGLT2 inhibition from natural products are still ongoing. This review introduces the history of research on the development of early-generation SGLT2 inhibitors, and recent progress on the discovery of novel candidates for SGLT2 inhibitor from several natural products that are widely used in traditional herbal medicine. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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Open AccessReview

Kazakh Ziziphora Species as Sources of Bioactive Substances

by Karel Šmejkal, Milan Malaník, Karlygash Zhaparkulova, Zuriyadda Sakipova, Liliya Ibragimova, Galya Ibadullaeva and Milan Žemlička

Molecules 2016, 21(7), 826; https://doi.org/10.3390/molecules21070826 - 25 Jun 2016

Cited by 25 | Viewed by 9262

Abstract

Ziziphora species represent the prototypical example of the Lamiaceae family. The phytochemicals present in Ziziphora include monoterpenic essential oils, triterpenes and phenolic substances belonging to the flavonoids. In Kazakh traditional medicine, Ziziphora species possess several medicinal uses. In particular, Z. bungeana Lam. and Z. clinopodioides Lam. are used for the treatment of illnesses related to the cardiovascular system or to combat different infections. Unfortunately, the majority of the information about the complex Ziziphora species is only available in Russian and Chinese language, therefore, we decided gather all available information on Kazakhstan Ziziphora, namely its content compounds, medicinal uses and published patents, to draw the attention of scientists to this very interesting plant with high medicinal potential. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

1020 KiB

Open AccessReview

Natural Products to Counteract the Epidemic of Cardiovascular and Metabolic Disorders

by Birgit Waltenberger, Andrei Mocan, Karel Šmejkal, Elke H. Heiss and Atanas G. Atanasov

Molecules 2016, 21(6), 807; https://doi.org/10.3390/molecules21060807 - 22 Jun 2016

Cited by 142 | Viewed by 22934

Abstract

Natural products have always been exploited to promote health and served as a valuable source for the discovery of new drugs. In this review, the great potential of natural compounds and medicinal plants for the treatment or prevention of cardiovascular and metabolic disorders, global health problems with rising prevalence, is addressed. Special emphasis is laid on natural products for which efficacy and safety have already been proven and which are in clinical trials, as well as on plants used in traditional medicine. Potential benefits from certain dietary habits and dietary constituents, as well as common molecular targets of natural products, are also briefly discussed. A glimpse at the history of statins and biguanides, two prominent representatives of natural products (or their derivatives) in the fight against metabolic disease, is also included. The present review aims to serve as an “opening” of this special issue of Molecules, presenting key historical developments, recent advances, and future perspectives outlining the potential of natural products for prevention or therapy of cardiovascular and metabolic disease. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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