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Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Phytochemicals and Human Health".

Deadline for manuscript submissions: closed (1 November 2021) | Viewed by 38083

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Prof. Dr. Assunta Pandolfi

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Department of Medical, Oral and Biotechnological Sciences, University G. d’Annunzio Chieti-Pescara, Center for Advanced Studies and Technology (CAST), 66100 Chieti, Italy
Interests: inflammation; endothelial cells; tissue regeneration; stem cells; cell differentiation; bioactive compounds; innovative cell cultures
Special Issues, Collections and Topics in MDPI journals

Dr. Domitilla Mandatori

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Department of Medical, Oral and Biotechnological Sciences, University G. d’Annunzio Chieti-Pescara, Center for Advanced Studies and Technology (CAST), 66100 Chieti, Italy
Interests: bone regeneration; bone physiology; bone cells; stem cells; tissue engineering; biomaterials; cell–material interactions; cell differentiation; 3D co-culture system; bioactive compounds

Special Issue Information

Dear Colleagues,

The constant increase in human life expectancy has significantly influenced the increase in the risk of cardiovascular and metabolic bone diseases, which may be considered as one of the most demanding global health problems.

Numerous approaches have been described to delay and possibly treat cardiometabolic disease and other age-related disorders: one of them takes account of the use of natural molecules and nutritional supplements. An extensive screening of bioactive compounds has been conducted in the last several decades, and a wide range of anti-atherosclerotic activities and osteoprotective effects have been observed, which seem to be mediated via pro-angiogenic, antioxidant, and/or anti-inflammatory pathways leading to osteoblast mineralization and osteoclast inactivation.

In particular, atherosclerotic vascular calcification in cardiovascular disease and loss of bone mineralized matrix in osteoporosis seem to be characterized by common pathophysiological molecular and cellular mechanisms potentially involved in the “bone–vascular cross talk”, which to date remain poorly investigated.

Recent findings have established that several natural compounds have potential promising and significant vascular and bone bioactivities, which may trigger the discovery of new drugs for the management of cardiovascular and metabolic bone diseases.

In this Special Issue, we encourage clinicians and researchers to contribute original research articles, short communications, and review articles that address the biochemical, physiological, and molecular processes underlying the mechanism of action of dietary bioactives in in vitro and in vivo studies related to human nutrition. The submission of studies aimed at characterizing the bioavailability and the biological effect of dietary bioactive metabolites will also be welcomed. Research papers on original products, extracts, and single molecules will be considered.

As Guest Editors, we invite you to contribute to this Special Issue on “Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases”.

Prof. Assunta Pandolfi
Dr. Domitilla Mandatori
Guest Editors

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Keywords

Dietary bioactive compounds
Cardiometabolic diseases
Metabolic bone diseases
Disease prevention
Molecular and physiological mechanisms
Human health and nutrition

Published Papers (10 papers)

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Editorial

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3 pages, 370 KiB

Open AccessEditorial

Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases

by Domitilla Mandatori and Assunta Pandolfi

Nutrients 2022, 14(12), 2459; https://doi.org/10.3390/nu14122459 - 14 Jun 2022

Viewed by 1177

Abstract

Cardiovascular and metabolic bone diseases are demanding health problems with high morbidity and mortality [...] Full article

(This article belongs to the Special Issue Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases)

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Research

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16 pages, 2871 KiB

Open AccessArticle

Three-Dimensional Co-Culture System of Human Osteoblasts and Osteoclast Precursors from Osteoporotic Patients as an Innovative Model to Study the Role of Nutrients: Focus on Vitamin K2

by Domitilla Mandatori, Letizia Penolazzi, Letizia Pelusi, Elisabetta Lambertini, Francesca Michelucci, Annamaria Porreca, Pietro Cerritelli, Caterina Pipino, Angelo Di Iorio, Danilo Bruni, Marta Di Nicola, Roberto Buda, Roberta Piva and Assunta Pandolfi

Nutrients 2021, 13(8), 2823; https://doi.org/10.3390/nu13082823 - 17 Aug 2021

Cited by 7 | Viewed by 2899

Abstract

Several natural compounds, such as vitamin K2, have been highlighted for their positive effects on bone metabolism. It has been proposed that skeletal disorders, such as osteoporosis, may benefit from vitamin K2-based therapies or its regular intake. However, further studies are needed to better clarify the effects of vitamin K2 in bone disorders. To this aim, we developed in vitro a three-dimensional (3D) cell culture system one step closer to the bone microenvironment based on co-culturing osteoblasts and osteoclasts precursors obtained from bone specimens and peripheral blood of the same osteoporotic patient, respectively. Such a 3-D co-culture system was more informative than the traditional 2-D cell cultures when responsiveness to vitamin K2 was analyzed, paving the way for data interpretation on single patients. Following this approach, the anabolic effects of vitamin K2 on the osteoblast counterpart were found to be correlated with bone turnover markers measured in osteoporotic patients’ sera. Overall, our data suggest that co-cultured osteoblasts and osteoclast precursors from the same osteoporotic patient may be suitable to generate an in vitro 3-D experimental model that potentially reflects the individual’s bone metabolism and may be useful to predict personal responsiveness to nutraceutical or drug molecules designed to positively affect bone health. Full article

(This article belongs to the Special Issue Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases)

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16 pages, 2757 KiB

Open AccessArticle

Pro-Osteogenic Properties of Violina pumpkin (Cucurbita moschata) Leaf Extracts: Data from In Vitro Human Primary Cell Cultures

by Elisabetta Lambertini, Letizia Penolazzi, Giulia Pellielo, Caterina Pipino, Assunta Pandolfi, Serena Fiorito, Francesco Epifano, Salvatore Genovese and Roberta Piva

Nutrients 2021, 13(8), 2633; https://doi.org/10.3390/nu13082633 - 30 Jul 2021

Cited by 3 | Viewed by 2795

Abstract

Traditional medicines rely mainly on use of plant extracts to mitigate or treat a wide range of disorders, including those that affect skeletal homeostasis. In this study, we investigated for the first time the potential pro-osteogenic effects of hexane, acetone and methanol extracts of the leaves of Cucurbita moschata, a very popular pumpkin cultivar in Western countries. We found that in Cucurbita moschata leaves, there are acetone-extractable substances—in particular, fatty acids such as 13-OH-9Z,11E,15E-octadecatrienoic acid (PU-13OH-FA), which is capable of both stimulating the function of human primary osteoblasts, which are responsible for bone formation, and inhibiting the differentiation of human osteoclasts, which are responsible for bone resorption. This dual effect was monitored by analyzing Runx2 expression, deposition of mineralized matrix, ALP activity, TRAP and actin ring staining respectively. This study suggests that bioactive chemicals from Cucurbita moschata leaves are potentially suitable as therapeutics for managing metabolic bone disorders such as osteoporosis and rheumatoid arthritis, and promoting tissue healing and functional recovery after bone fractures. The data we obtained increase knowledge on the biological activities of Cucurbita moschata, and in particular underline the potential benefits of consuming leaves which are a part of the plant currently little considered in the Western world. Full article

(This article belongs to the Special Issue Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases)

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21 pages, 2741 KiB

Open AccessArticle

Protective Effects Induced by a Hydroalcoholic Allium sativum Extract in Isolated Mouse Heart

by Lucia Recinella, Annalisa Chiavaroli, Fabrizio Masciulli, Caterina Fraschetti, Antonello Filippi, Stefania Cesa, Francesco Cairone, Era Gorica, Marinella De Leo, Alessandra Braca, Alma Martelli, Vincenzo Calderone, Giustino Orlando, Claudio Ferrante, Luigi Menghini, Simonetta Cristina Di Simone, Serena Veschi, Alessandro Cama, Luigi Brunetti and Sheila Leone

Nutrients 2021, 13(7), 2332; https://doi.org/10.3390/nu13072332 - 8 Jul 2021

Cited by 16 | Viewed by 3108

Abstract

The aim of the present study was to investigate the possible protective effects of a garlic hydroalcoholic extract on the burden of oxidative stress and inflammation occurring on mouse heart specimens exposed to E. coli lipopolysaccharide (LPS), which is a well-established inflammatory stimulus. Headspace solid-phase microextraction combined with the gas chromatography–mass spectrometry (HS-SPME/GC–MS) technique was applied to determine the volatile fraction of the garlic powder, and the HS-SPME conditions were optimized for each of the most representative classes of compounds. CIEL*a*b* colorimetric analyses were performed on the powder sample at the time of delivery, after four and after eight months of storage at room temperature in the dark, to evaluate the color changing. Freshly prepared hydroalcoholic extract was also evaluated in its color character. Furthermore, the hydroalcoholic extract was analyzed through GC–MS. The extract was found to be able to significantly inhibit LPS-induced prostaglandin (PG) E₂ and 8-iso-PGF_2α levels, as well as mRNA levels of cyclooxygenase (COX)-2, interleukin (IL)-6, and nuclear factor-kB (NF-kB), in heart specimens. Concluding, our findings showed that the garlic hydroalcoholic extract exhibited cardioprotective effects on multiple inflammatory and oxidative stress pathways. Full article

(This article belongs to the Special Issue Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases)

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13 pages, 1774 KiB

Open AccessArticle

Myoinositol Reduces Inflammation and Oxidative Stress in Human Endothelial Cells Exposed In Vivo to Chronic Hyperglycemia

by Maria Pompea Antonia Baldassarre, Pamela Di Tomo, Giorgia Centorame, Assunta Pandolfi, Natalia Di Pietro, Agostino Consoli and Gloria Formoso

Nutrients 2021, 13(7), 2210; https://doi.org/10.3390/nu13072210 - 27 Jun 2021

Cited by 17 | Viewed by 3682

Abstract

Myo-inositol (Myo) improves insulin resistance, glucose metabolism, and helps gestational diabetes (GDM) management. GDM is associated with a pro-inflammatory state and increased oxidative stress, which are both involved in vascular damage in diabetes. Our aim was to study Myo anti-inflammatory/antioxidant potential effects on an in vitro model of human umbilical vein endothelial cells (HUVECs). To this end, monocyte cell adhesion to HUVECs, adhesion molecule membrane exposure, and oxidative stress levels were determined in cells from control (C-) and GDM women treated during pregnancy either with diet only (GD-) or with diet plus Myo (GD+Myo). To deeply study the vascular effects of Myo, the same evaluations were performed in C- and GD-HUVECs following 48 h in vitro stimulation with Myo. Notably, we first observed that GD-HUVECs obtained from women assuming Myo supplementation exhibited a significantly decreased number of monocytes that adhered to endothelial cells, less adhesion molecule exposure, and lower intracellular reactive oxygen species (ROS) levels in the basal state as compared to GD-HUVECs obtained from women treated by diet only. This Myo anti-inflammatory/antioxidant effect was confirmed by 48 h in vitro stimulation of GD-HUVECs as compared to controls. Altogether, these results strongly suggest that Myo may exert protective actions against chronic inflammation induced by endothelial dysfunction in diabetes. Full article

(This article belongs to the Special Issue Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases)

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14 pages, 636 KiB

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Dietary Polyphenol Intake Is Associated with Biological Aging, a Novel Predictor of Cardiovascular Disease: Cross-Sectional Findings from the Moli-Sani Study

by Simona Esposito, Alessandro Gialluisi, Simona Costanzo, Augusto Di Castelnuovo, Emilia Ruggiero, Amalia De Curtis, Mariarosaria Persichillo, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, Marialaura Bonaccio and on behalf of the Investigators for the Moli-Sani Study

Nutrients 2021, 13(5), 1701; https://doi.org/10.3390/nu13051701 - 17 May 2021

Cited by 13 | Viewed by 4135

Abstract

Biological aging, or the discrepancy between biological and chronological age of a subject (Δage), has been associated with a polyphenol-rich Mediterranean diet and represents a new, robust indicator of cardiovascular disease risk. We aimed to disentangle the relationship of dietary polyphenols and total antioxidant capacity with Δage in a cohort of Italians. A cross-sectional analysis was performed on a sub-cohort of 4592 subjects (aged ≥ 35 y; 51.8% women) from the Moli-sani Study (2005–2010). Food intake was recorded by a 188-item food-frequency questionnaire. The polyphenol antioxidant content (PAC)-score was constructed to assess the total dietary content of polyphenols. Total antioxidant capacity was measured in foods by these assays: trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) and ferric reducing-antioxidant power (FRAP). A deep neural network, based on 36 circulating biomarkers, was used to compute biological age and the resulting Δage, which was tested as outcome in multivariable-adjusted linear regressions. Δage was inversely associated with the PAC-score (β = −0.31; 95%CI −0.39, −0.24) but not with total antioxidant capacity of the diet. A diet rich in polyphenols, by positively contributing to deceleration of the biological aging process, may exert beneficial effects on the long-term risk of cardiovascular disease and possibly of bone health. Full article

(This article belongs to the Special Issue Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases)

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17 pages, 4011 KiB

Open AccessArticle

Sasa quelpaertensis Leaf Extract Ameliorates Dyslipidemia, Insulin Resistance, and Hepatic Lipid Accumulation in High-Fructose-Diet-Fed Rats

by Jeong Yong Park, Mi Gyeong Jang, Jung Min Oh, Hee Chul Ko, Sung-Pyo Hur, Jae-Won Kim, Songyee Baek and Se-Jae Kim

Nutrients 2020, 12(12), 3762; https://doi.org/10.3390/nu12123762 - 7 Dec 2020

Cited by 3 | Viewed by 2378

Abstract

Background: Increased dietary fructose consumption is closely associated with lipid and glucose metabolic disorders. Sasa quelpaertensis Nakai possesses various health-promoting properties, but there has been no research on its protective effect against fructose-induced metabolic dysfunction. In this study, we investigated the effects of S. quelpaertensis leaf extract (SQE) on metabolic dysfunction in high-fructose-diet-fed rats. Methods: Animals were fed a 46% carbohydrate diet, a 60% high-fructose diet, or a 60% high-fructose diet with SQE (500 mg/kg of body weight (BW)/day) in drinking water for 16 weeks. Serum biochemical parameters were measured and the effects of SQE on hepatic histology, protein expression, and transcriptome profiles were investigated. Results: SQE improved dyslipidemia and insulin resistance induced in high-fructose-diet-fed rats. SQE ameliorated the lipid accumulation and inflammatory response in liver tissues by modulating the expressions of key proteins related to lipid metabolism and antioxidant response. SQE significantly enriched the genes related to the metabolic pathway, namely, the tumor necrosis factor (TNF) signaling pathway and the PI3K-Akt signaling pathway. Conclusions: SQE could effectively prevent dyslipidemia, insulin resistance, and hepatic lipid accumulation by regulation of metabolism-related gene expressions, suggesting its role as a functional ingredient to prevent lifestyle-related metabolic disorders. Full article

(This article belongs to the Special Issue Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases)

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14 pages, 20620 KiB

Open AccessArticle

Scopolin Attenuates Osteoporotic Bone Loss in Ovariectomized Mice

by Eunkuk Park, Jeonghyun Kim, Hyun-Seok Jin, Chun Whan Choi, Tae Hyun Choi, Sangho Choi, Dam Huh and Seon-Yong Jeong

Nutrients 2020, 12(11), 3565; https://doi.org/10.3390/nu12113565 - 20 Nov 2020

Cited by 11 | Viewed by 2201

Abstract

Bone remodeling is a renewal process regulated by bone synthesis (osteoblasts) and bone destruction (osteoclasts). A previous study demonstrated that Lycii radicis cortex (LRC) extract inhibited ovariectomized (OVX)-induced bone loss in mice. This study investigated the anti-osteoporotic effects of bioactive constituent(s) from the LRC extract. The effective compound(s) were screened, and a single compound, scopolin, which acts as a phytoalexin, was chosen as a candidate component. Scopolin treatment enhanced alkaline phosphatase activity and increased mineralized nodule formation in MC3T3-E1 pre-osteoblastic cells. However, osteoclast differentiation in primary-cultured monocytes was reduced by treatment with scopolin. Consistently, scopolin treatment increased osteoblast differentiation in the co-culture of monocytes (osteoclasts) and MC3T3-E1 (osteoblast) cells. Scopolin treatment prevented bone mineral density loss in OVX-induced osteoporotic mice. These results suggest that scopolin could be a therapeutic bioactive constituent for the treatment and prevention of osteoporosis. Full article

(This article belongs to the Special Issue Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases)

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15 pages, 3572 KiB

Open AccessArticle

Protective Effect of Vitis labrusca Leaves Extract on Cardiovascular Dysfunction through HMGB1-TLR4-NFκB Signaling in Spontaneously Hypertensive Rats

by Hye Yoom Kim, Mi Hyeon Hong, Jung Joo Yoon, Dae Sung Kim, Se Won Na, Youn Jae Jang, Yun Jung Lee, Dae Gill Kang and Ho Sub Lee

Nutrients 2020, 12(10), 3096; https://doi.org/10.3390/nu12103096 - 11 Oct 2020

Cited by 13 | Viewed by 3066

Abstract

The Vitis labrusca is a grapevine that has antioxidant, neuroprotective, hepatoprotective, and anticarcinogenic activity. However, the effect of Vitis labrusca leaves on the cardiovascular system is yet to be ascertained. The present study was designed to investigate the effects of Vitis labrusca leaves extract (HP1) on cardiovascular remodeling in spontaneously hypertensive rats. Experiments were performed in rats and were randomly divided into the following groups: Wistar Kyoto rat (WKY), normal control group; spontaneously hypertensive rats (SHR), negative control group; SHR + Losa, positive control group (losartan, 10 mg/kg/daily, AT₁ receptor blocker) and SHR + HP1 (100 mg/kg/daily). HP1 was orally administered daily for 4 weeks. The HP1 treatment significantly improved blood pressure, electrocardiographic parameters, and echocardiogram parameters compared to hypertensive rats. Additionally, the left ventricular (LV) remodeling and LV dysfunction were significantly improved in HP1-treated hypertensive rats. Furthermore, an increase in fibrotic area has been observed in hypertensive rats compared with WKY. However, administration of HP1 significantly attenuated cardiac fibrosis in hypertensive rats. Moreover, HP1 suppressed the expression of high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), receptor for advanced glycation end products (RAGE), and extracellular signal-regulated kinases (ERK1/2) induced by hypertensive rats, resulting in improved vascular remodeling. Therefore, these results suggest that HP1 can improve the cardiovascular remodeling in hypertensive rats, and the mechanisms may be related to the suppressive effect of HP1 on HMGB1-TLR4-NFκB signaling in the cardiovascular system. Thus, the protective role of the traditional herbal medicine HP1 may provide new insights into the development of therapeutic drugs on the development of hypertensive cardiovascular dysfunction. Full article

(This article belongs to the Special Issue Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases)

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Review

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Open AccessFeature PaperReview

The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification

by Domitilla Mandatori, Letizia Pelusi, Valeria Schiavone, Caterina Pipino, Natalia Di Pietro and Assunta Pandolfi

Nutrients 2021, 13(4), 1222; https://doi.org/10.3390/nu13041222 - 7 Apr 2021

Cited by 31 | Viewed by 11452

Abstract

Osteoporosis (OP) and vascular calcification (VC) represent relevant health problems that frequently coexist in the elderly population. Traditionally, they have been considered independent processes, and mainly age-related. However, an increasing number of studies have reported their possible direct correlation, commonly defined as “bone-vascular crosstalk”. Vitamin K2 (VitK2), a family of several natural isoforms also known as menaquinones (MK), has recently received particular attention for its role in maintaining calcium homeostasis. In particular, VitK2 deficiency seems to be responsible of the so-called “calcium paradox” phenomenon, characterized by low calcium deposition in the bone and its accumulation in the vessel wall. Since these events may have important clinical consequences, and the role of VitK2 in bone-vascular crosstalk has only partially been explained, this review focuses on its effects on the bone and vascular system by providing a more recent literature update. Overall, the findings reported here propose the VitK2 family as natural bioactive molecules that could be able to play an important role in the prevention of bone loss and vascular calcification, thus encouraging further in-depth studies to achieve its use as a dietary food supplement. Full article

(This article belongs to the Special Issue Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases)

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Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases

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