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Metabolites
Special Issues
Plants and Plant-Based Foods for Metabolic Disease Prevention
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Plants and Plant-Based Foods for Metabolic Disease Prevention

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 14087

Special Issue Editors

Dr. Sandra Barbalho

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Guest Editor
Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), São Paulo, Brazil
Interests: inflammatory diseases; cardiovascular diseases; neurodegenerative diseases; inflammation; medicinal plants; oxidative stress
Special Issues, Collections and Topics in MDPI journals
Dr. Rosa Direito

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Guest Editor
Laboratory of Systems Integration Pharmacology, Clinical, and Regulatory Science–Research Institute for Medicines, Universidade de Lisboa (iMed.ULisboa), Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
Interests: phenolic compounds; inflammation; NCDs; drug delivery systems
Dr. Adriano Araujo

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Guest Editor
Medical School of Marilia, University of Marília, Avenue Higino Muzzi Filho 1001, Marília 15525-902, SP, Brazil
Interests: medicinal plants; cardiovascular diseases; pharmacology; toxicology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Élen Landgraf Guiguer

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Guest Editor
Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenue Higino Muzzi Filho 1001, Marília 15525-902, SP, Brazil
Interests: inflammation; oxidative stress; inflammatory bowel diseases; cardiovascular diseases; myokines; medicinal plants
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Plants have been used in the prevention and treatment of numerous human diseases since ancient times. The wide range of bioactive compounds and fibers found in plants can be related to antioxidant, anti-inflammatory, anti-proliferative and anti-neurodegeneration effects, leading to protection from common diseases in the modern world such as obesity, diabetes, hypertension, dyslipidemia, cardiovascular diseases, kidney diseases, neurodegenerative diseases and cancer. These diseases have shown exponential growth due to unhealthy lifestyle habits observed in populations in the globalized and developed world. In addition to the use of the plants and their isolated bioactive compounds, there has also been an increase in research related to the preparation of plant-based foods in an attempt to maintain these compounds even after processing. As a result, this Special Issue focuses on encouraging the development of original studies and reviews, aiming to depict the relationship between the use of plants and their derived products as sources of health and disease prevention.

Dr. Sandra M. Barbalho
Dr. Rosa Direito
Dr. Adriano Cressoni Araujo
Prof. Dr. Élen Landgraf Guiguer
Guest Editors

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Keywords

  • plants
  • plant foods
  • plant-based diet
  • medicinal plants
  • inflammation, oxidative stress
  • inflammatory diseases
  • metabolic diseases
  • neurodegenerative diseases

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Published Papers (7 papers)

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Research

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22 pages, 9142 KiB  
Article
Ethyl Acetate Extract of Cichorium glandulosum Activates the P21/Nrf2/HO-1 Pathway to Alleviate Oxidative Stress in a Mouse Model of Alcoholic Liver Disease
by Shuwen Qi, Chunzi Zhang, Junlin Yan, Xiaoyan Ma, Yewei Zhong, Wenhui Hou, Juan Zhang, Tuxia Pang and Xiaoli Ma
Metabolites 2025, 15(1), 41; https://doi.org/10.3390/metabo15010041 - 10 Jan 2025
Viewed by 1118
Abstract
Background: Alcoholic liver disease (ALD) is a significant global health concern, primarily resulting from chronic alcohol consumption, with oxidative stress as a key driver. The ethyl acetate extract of Cichorium glandulosum (CGE) exhibits antioxidant and hepatoprotective properties, but its detailed mechanism of action [...] Read more.
Background: Alcoholic liver disease (ALD) is a significant global health concern, primarily resulting from chronic alcohol consumption, with oxidative stress as a key driver. The ethyl acetate extract of Cichorium glandulosum (CGE) exhibits antioxidant and hepatoprotective properties, but its detailed mechanism of action against ALD remains unclear. This study investigates the effects and mechanisms of CGE in alleviating alcohol-induced oxidative stress and liver injury. Methods: Ultra-Performance Liquid Chromatography coupled with Quadrupole-Orbitrap Mass Spectrometry (UPLC-Q-Orbitrap-MS) was used to identify CGE components. A C57BL/6J mouse model of ALD was established via daily oral ethanol (56%) for six weeks, with CGE treatment at low (100 mg/kg) and high doses (200 mg/kg). Silibinin (100 mg/kg) served as a positive control. Liver function markers, oxidative stress indicators, and inflammatory markers were assessed. Transcriptomic and network pharmacology analyses identified key genes and pathways, validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Results: UPLC-Q-Orbitrap-MS identified 81 CGE compounds, mainly including terpenoids, flavonoids, and phenylpropanoids. CGE significantly ameliorated liver injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels and enhancing antioxidative markers such as total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) while lowering hepatic malondialdehyde (MDA) levels. Inflammation was mitigated through reduced levels of Tumor Necrosis Factor Alpha (TNF-α), Interleukin-1 Beta (IL-1β), and C-X-C Motif Chemokine Ligand 10 (CXCL-10). Transcriptomic and network pharmacology analysis revealed seven key antioxidant-related genes, including HMOX1, RSAD2, BCL6, CDKN1A, THBD, SLC2A4, and TGFβ3, validated by RT-qPCR. CGE activated the P21/Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) signaling axis, increasing P21, Nrf2, and HO-1 protein levels while suppressing Kelch-like ECH-associated Protein 1 (Keap1) expression. Conclusions: CGE mitigates oxidative stress and liver injury by activating the P21/Nrf2/HO-1 pathway and regulating antioxidant genes. Its hepatoprotective effects and multi-target mechanisms highlight CGE’s potential as a promising therapeutic candidate for ALD treatment. Full article
(This article belongs to the Special Issue Plants and Plant-Based Foods for Metabolic Disease Prevention)
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11 pages, 544 KiB  
Article
Protective Effects of a Brassica nigra Sprout Hydroalcoholic Extract on Lipid Homeostasis, Hepatotoxicity, and Nephrotoxicity in Cyclophosphamide-Induced Toxicity in Rats
by Hassan Barakat, Thamer Aljutaily, Raghad I. Alkhurayji, Huda Aljumayi, Khalid S. Alhejji and Sami O. Almutairi
Metabolites 2024, 14(12), 690; https://doi.org/10.3390/metabo14120690 - 8 Dec 2024
Viewed by 1143
Abstract
Background: Brassica nigra possesses a significant concentration of bioactive compounds and has been demonstrated to have a variety of pharmacological properties, although its sprout has not been extensively studied. Thus, the protective effects of Brassica nigra sprout hydroalcoholic extract (BNSE) on lipid [...] Read more.
Background: Brassica nigra possesses a significant concentration of bioactive compounds and has been demonstrated to have a variety of pharmacological properties, although its sprout has not been extensively studied. Thus, the protective effects of Brassica nigra sprout hydroalcoholic extract (BNSE) on lipid homeostasis, hepatotoxicity, and nephrotoxicity in cyclophosphamide (CYP)-induced toxicity in rats were examined in this study. Methods: Four experimental rat groups (n = 8 for each group) were examined as follows: NR, normal rats that received normal saline by oral gavage daily; CYP, injected with a single dose of CYP at 250 mg kg−1 intraperitoneally (i.p.) and did not receive any treatment, receiving only normal saline by oral gavage daily; CYP + BNSE250, injected with a single dose of CYP at 250 mg kg−1 i.p. and treated with BNSE at 250 mg kg−1 by oral gavage daily for three weeks; and CYP + BNSE500, injected with a single dose of CYP at 250 mg kg−1 i.p. and treated with BNSE at 500 mg kg−1 by oral gavage daily for three weeks. Results: The results indicated a significant increase (p < 0.05) in triglyceride (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-c), and very low-density lipoprotein cholesterol (VLDL-c) levels in CYP-induced toxicity rats. The administration of BNSE at 250 and 500 mg kg−1 significantly (p < 0.05) attenuated TG, CHO, LDL-c, and VLDL-c at values comparable with the NR group. The most efficient treatment for improving the lipid profile and atherogenicity complication was BNSE at 500 mg kg−1, performing even better than 250 mg kg−1. Administrating BNSE at 250 or 500 mg kg−1 improved the liver’s function in a dose-dependent manner. Comparing the lower dose of 250 mg kg−1 of BNSE with 500 mg kg−1 showed that administrating 250 mg kg−1 attenuated alanine transaminase (ALT) by 28.92%, against 33.36% when 500 mg kg−1 was given. A similar trend was observed in aspartate aminotransferase (AST), where 19.44% was recorded for BNSE at 250 mg kg−1 and 34.93% for BNSE at 500 mg kg−1. Higher efficiency was noticed for BNSE at 250 and 500 mg kg−1 regarding alkaline phosphatase (ALP). An improvement of 38.73% for BNSE at 500 mg kg−1 was shown. The best treatment was BNSE at 500 mg kg−1, as it markedly improved liver function, such as total bilirubin (T.B.), in a dose-dependent manner. The administration of BNSE attenuated the total protein (T.P.), albumin, and globulin levels to be close to or higher than the typical values in NR rats. Conclusions: BNSE might be used for its promising hypolipidemic, hepatoprotective, and nephroprotective potential and to prevent diseases related to oxidative stress. Further research on its application in humans is highly recommended. Full article
(This article belongs to the Special Issue Plants and Plant-Based Foods for Metabolic Disease Prevention)
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13 pages, 2027 KiB  
Article
Antihypertensive Effect of Perla and Esmeralda Barley (Hordeum vulgare L.) Sprouts in an Induction Model with L-NAME In Vivo
by Abigail García-Castro, Alma D. Román-Gutiérrez, Fabiola A. Guzmán-Ortiz and Raquel Cariño-Cortés
Metabolites 2024, 14(12), 678; https://doi.org/10.3390/metabo14120678 - 3 Dec 2024
Viewed by 3693
Abstract
Background: Hypertension is one of the leading causes of premature death worldwide. Despite advances in conventional treatments, there remains a significant need for more effective and natural alternatives to control hypertension. In this context, sprouted barley extracts have emerged as a potential therapeutic [...] Read more.
Background: Hypertension is one of the leading causes of premature death worldwide. Despite advances in conventional treatments, there remains a significant need for more effective and natural alternatives to control hypertension. In this context, sprouted barley extracts have emerged as a potential therapeutic option. This study presents the evaluation of the bioactive properties of extracts from two varieties of barley germinated for different periods (3, 5, and 7 days), focusing on their potential to regulate blood pressure mechanisms. Objectives/Methods: The main objective was to assess the effects of these extracts on blood pressure regulation in N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME)-induced hypertensive rats. Renal (creatinine, urea, uric acid, and total protein) and endothelial (NOx levels) function, angiotensin-converting enzyme (ACE) I and II activity, and histopathological effects on heart and kidney tissues were evaluated. Results: In particular, Esmeralda barley extract demonstrated 83% inhibition of ACE activity in vitro. Furthermore, the combined administration of sprouted barley extract (SBE) and captopril significantly reduced blood pressure and ACE I and II activity by 22%, 81%, and 76%, respectively, after 3, 5, and 7 days of germination. The treatment also led to reductions in protein, creatinine, uric acid, and urea levels by 3%, 38%, 42%, and 48%, respectively, along with a 66% increase in plasma NO concentrations. Conclusions: This study highlights the bioactive properties of barley extracts with different germination times, emphasizing their potential health benefits as a more effective alternative to conventional antihypertensive therapies. Full article
(This article belongs to the Special Issue Plants and Plant-Based Foods for Metabolic Disease Prevention)
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21 pages, 1979 KiB  
Article
Metabolic Effects of Loquat Juice (Eriobotrya japonica Lindl Mkarkeb Variety) on Lipid Homeostasis, Liver Steatosis, and Oxidative Stress in Hyperlipidemic Mice Fed a High-Fat–High-Fructose Diet
by Imane Mokhtari, Thamer Aljutaily, Huda Aljumayi, Khadija S. Radhi, Abdulkarim S. Almutairi, Hassan Barakat, Ibrahim Khalifa, Souliman Amrani and Hicham Harnafi
Metabolites 2024, 14(11), 592; https://doi.org/10.3390/metabo14110592 - 2 Nov 2024
Viewed by 1878
Abstract
Background: Loquat fruit is consumed for its flavorful taste and a rich array of health-promoting compounds like phenolics, flavonoids, and carotenoids. This study aimed at the biochemical characterization of fresh juice from the Moroccan Mkarkeb variety of loquat and evaluating its effects on [...] Read more.
Background: Loquat fruit is consumed for its flavorful taste and a rich array of health-promoting compounds like phenolics, flavonoids, and carotenoids. This study aimed at the biochemical characterization of fresh juice from the Moroccan Mkarkeb variety of loquat and evaluating its effects on lipid homeostasis and liver steatosis in hyperlipidemic mice. Methods: The biochemical characterization followed AOAC methods. In vivo study involved hyperlipidemic mice fed a high-fat, high-fructose diet for 6 weeks and treated with loquat juice at 3.5 and 7 mL kg−1 or fenofibrate at 4 mg·kg−1. The concentrations of lipids in plasma, liver, adipose tissue, feces, and bile and blood glucose levels were quantified. Liver steatosis was visually examined and confirmed histologically, and liver injury markers (AST, ALT, ALP, LDH, and TB) were measured. Liver oxidative stress was assessed by measuring MDA content and antioxidative enzyme activities. Results: Our findings indicate that fresh loquat juice is poor in fat and protein and contains moderate sugars with a low energy value (40.82 ± 0.25 kcal/100 g). It is also rich in minerals, vitamin C, phenolic acids, flavonoids, and carotenoids. The juice effectively restored lipid metabolism by enhancing reverse cholesterol transport and lowering LDL-cholesterol, triglycerides, and the atherogenic index. The studied juice decreases blood glucose and prevents weight gain and lipid accumulation in the liver and adipose tissue. The juice prevents lipotoxicity-induced liver injury, corrects toxicity markers, and improves the liver’s morphological and histological structures. It also reduces oxidative stress by lowering MDA and activating SOD and catalase. Conclusions: The juice holds high nutritional and medicinal value, potentially preventing lipid disorders and cardiovascular issues. Full article
(This article belongs to the Special Issue Plants and Plant-Based Foods for Metabolic Disease Prevention)
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15 pages, 1920 KiB  
Article
Bioactive Compound Diversity in a Wide Panel of Sweet Potato (Ipomoea batatas L.) Cultivars: A Resource for Nutritional Food Development
by Marion Nabot, Cyrielle Garcia, Marc Seguin, Julien Ricci, Catherine Brabet and Fabienne Remize
Metabolites 2024, 14(10), 523; https://doi.org/10.3390/metabo14100523 - 26 Sep 2024
Viewed by 1165
Abstract
Objectives: This study provides an overview of the composition of the raw root flesh of a panel of 22 sweet potato (Ipomoea batatas L.) cultivars, with a focus on bioactive compounds. The large diversity of the proximate and phytochemical compositions observed between [...] Read more.
Objectives: This study provides an overview of the composition of the raw root flesh of a panel of 22 sweet potato (Ipomoea batatas L.) cultivars, with a focus on bioactive compounds. The large diversity of the proximate and phytochemical compositions observed between cultivars and within and between different flesh colors pointed out the importance of composition analysis and not only color choice for the design of foods with nutritional benefits. Methods: The nutritional composition (starch, protein, total dietary fibers) and bioactive compound composition of 22 cultivars from Reunion Island, maintained in the Vatel Biological Resource Center, were investigated. Results: Orange and purple cultivars stood out from white and yellow cultivars for their higher nutritional composition. Purple sweet potatoes were notable for their high contents of anthocyanins (55.7 to 143.4 mg/g dry weight (DW)) and phenolic compounds, in particular chlorogenic acid and ferulic acid, contributing to antioxidant activities, as well as their fiber content (14.1 ± 2.1% DW). Orange cultivars were rich in β-carotene (47.2 ± 0.7 mg/100 g DW) and to a lesser extent α-carotene (4.8 ± 1.2 mg/100 g DW). In contrast, certain white cultivars demonstrated suboptimal nutritional properties, rendering them less relevant even for applications where the lack of coloration in food is desired. Conclusions: Those characteristics enable the selection of sweet potato varieties to design food products ensuring optimal nutritional benefits and culinary versatility. Full article
(This article belongs to the Special Issue Plants and Plant-Based Foods for Metabolic Disease Prevention)
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Review

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34 pages, 3911 KiB  
Review
Polyphenols, Alkaloids, and Terpenoids Against Neurodegeneration: Evaluating the Neuroprotective Effects of Phytocompounds Through a Comprehensive Review of the Current Evidence
by Enzo Pereira de Lima, Lucas Fornari Laurindo, Vitor Cavallari Strozze Catharin, Rosa Direito, Masaru Tanaka, Iris Jasmin Santos German, Caroline Barbalho Lamas, Elen Landgraf Guiguer, Adriano Cressoni Araújo, Adriana Maria Ragassi Fiorini and Sandra Maria Barbalho
Metabolites 2025, 15(2), 124; https://doi.org/10.3390/metabo15020124 - 13 Feb 2025
Cited by 5 | Viewed by 2517
Abstract
Neurodegenerative diseases comprise a group of chronic, usually age-related, disorders characterized by progressive neuronal loss, deformation of neuronal structure, or loss of neuronal function, leading to a substantially reduced quality of life. They remain a significant focus of scientific and clinical interest due [...] Read more.
Neurodegenerative diseases comprise a group of chronic, usually age-related, disorders characterized by progressive neuronal loss, deformation of neuronal structure, or loss of neuronal function, leading to a substantially reduced quality of life. They remain a significant focus of scientific and clinical interest due to their increasing medical and social importance. Most neurodegenerative diseases present intracellular protein aggregation or their extracellular deposition (plaques), such as α-synuclein in Parkinson’s disease and amyloid beta (Aβ)/tau aggregates in Alzheimer’s. Conventional treatments for neurodegenerative conditions incur high costs and are related to the development of several adverse effects. In addition, many patients are irresponsive to them. For these reasons, there is a growing tendency to find new therapeutic approaches to help patients. This review intends to investigate some phytocompounds’ effects on neurodegenerative diseases. These conditions are generally related to increased oxidative stress and inflammation, so phytocompounds can help prevent or treat neurodegenerative diseases. To achieve our aim to provide a critical assessment of the current literature about phytochemicals targeting neurodegeneration, we reviewed reputable databases, including PubMed, EMBASE, and COCHRANE, seeking clinical trials that utilized phytochemicals against neurodegenerative conditions. A few clinical trials investigated the effects of phytocompounds in humans, and after screening, 13 clinical trials were ultimately included following PRISMA guidelines. These compounds include polyphenols (flavonoids such as luteolin and quercetin, phenolic acids such as rosmarinic acid, ferulic acid, and caffeic acid, and other polyphenols like resveratrol), alkaloids (such as berberine, huperzine A, and caffeine), and terpenoids (such as ginkgolides and limonene). The gathered evidence underscores that quercetin, caffeine, ginkgolides, and other phytochemicals are primarily anti-inflammatory, antioxidant, and neuroprotective, counteracting neuroinflammation, neuronal oxidation, and synaptic dysfunctions, which are crucial aspects of neurodegenerative disease intervention in various included conditions, such as Alzheimer’s and other dementias, depression, and neuropsychiatric disorders. In summary, they show that the use of these compounds is related to significant improvements in cognition, memory, disinhibition, irritability/lability, aberrant behavior, hallucinations, and mood disorders. Full article
(This article belongs to the Special Issue Plants and Plant-Based Foods for Metabolic Disease Prevention)
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22 pages, 813 KiB  
Review
Exploring the Impact of Catechins on Bone Metabolism: A Comprehensive Review of Current Research and Future Directions
by Iris Jasmin Santos German, Sandra Maria Barbalho, Jesus Carlos Andreo, Tereza Lais Menegucci Zutin, Lucas Fornari Laurindo, Victória Dogani Rodrigues, Adriano Cressoni Araújo, Elen Landgraf Guiguer, Rosa Direito, Karina Torres Pomini and André Luis Shinohara
Metabolites 2024, 14(10), 560; https://doi.org/10.3390/metabo14100560 - 18 Oct 2024
Cited by 3 | Viewed by 1638
Abstract
Background/Objectives: Degenerative musculoskeletal diseases represent a global health problem due to the progressive deterioration of affected individuals. As a bioactive compound, catechins have shown osteoprotective properties by stimulating osteoblastic cells and inhibiting bone resorption. Thus, this review aimed to address the mechanism of [...] Read more.
Background/Objectives: Degenerative musculoskeletal diseases represent a global health problem due to the progressive deterioration of affected individuals. As a bioactive compound, catechins have shown osteoprotective properties by stimulating osteoblastic cells and inhibiting bone resorption. Thus, this review aimed to address the mechanism of action of catechins on bone tissue. Methods: The search was applied to PubMed without limitations in date, language, or article type. Fifteen articles matched the topic and objective of this review. Results: EGCG (epigallocatechin gallate) and epicatechin demonstrated action on the osteogenic markers RANKL, TRAP, and NF-κβ and expression of BMPs and ALP, thus improving the bone microarchitecture. Studies on animals showed the action of EGCG in increasing calcium and osteoprotegerin levels, in addition to regulating the transcription factor NF-ATc1 associated with osteoclastogenesis. However, it did not show any effect on osteocalcin and RANK. Regarding human studies, EGCG reduced the risk of fracture in a dose-dependent manner. In periodontal tissue, EGCG reduced IL-6, TNF, and RANKL in vitro and in vivo. Human studies showed a reduction in periodontal pockets, gingival index, and clinical attachment level. The action of EGCG on membranes and hydrogels showed biocompatible and osteoinductive properties on the microenvironment of bone tissue by stimulating the expression of osteogenic growth factors and increasing osteocalcin and alkaline phosphate levels, thus promoting new bone formation. Conclusions: EGCG stimulates cytokines related to osteogenes, increasing bone mineral density, reducing osteoclastogenesis factors, and showing great potential as a therapeutic strategy for reducing the risk of bone fractures. Full article
(This article belongs to the Special Issue Plants and Plant-Based Foods for Metabolic Disease Prevention)
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