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Natural Products and Human Health: Current Understanding and Application

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

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 118752

Special Issue Editors

Research Centre for Food and Nutrition, Consiglio per la Ricerca in Agricoltura e l'Analisi dell'Economia Agraria (CREA), Roma, Italy
Research Centre for Food and Nutrition, Consiglio per la Ricerca in Agricoltura e l'Analisi dell'Economia Agraria (CREA), Roma, Italy

Special Issue Information

Dear Colleagues,

Natural products (NPs) are rich source of therapeutic agents utilized in both traditional and modern medicine for treating diseases and maintaining health. For this reason, NPs are regarded as an important repository for the development of potential novel drugs.

This Special Issue aims to present novel findings documenting the pharmacological and/or biological activity of NPs products. In particular, we intend to focus on the physiological, biochemical, and molecular processes underlying the mechanism of action of NPs 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 NP metabolites will also be welcomed. Research paper on original products, extracts, and single molecules will be considered. We invite clinicians and researchers to submit relevant scientific work, in the form of either original articles, short communications or reviews, to this Special Issue of Nutrients on “Natural Products and Human Health: Current Understanding and Application”.

Dr. Raffaella Canali
Dr. Fausta Natella
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Natural Products
  • Bioactive Molecules
  • Human Health
  • Disease Prevention
  • Bioavailability
  • Metabolites
  • Molecular And Physiological Mechanism
  • Gut Microbiota

Published Papers (19 papers)

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17 pages, 8834 KiB  
Article
In Vivo Hypoglycemic Effects, Potential Mechanisms and LC-MS/MS Analysis of Dendropanax Trifidus Sap Extract
by Ahreum Lee, Yuki Sugiura, Ik-Hyun Cho, Noriko Setou, Eugene Koh, Gyun Jee Song, Seungheun Lee and Hyun-Jeong Yang
Nutrients 2021, 13(12), 4332; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13124332 - 30 Nov 2021
Cited by 2 | Viewed by 2188
Abstract
Extracts of medicinal plants have been widely used to benefit human health. Dendropanax morbiferus (DM) has been well-studied for its anti-inflammatory and anti-oxidative effects, while Dendropanax trifidus (DT) is a lesser-known ecotype phylogenetically similar to DM, which has received significantly less attention. Studies [...] Read more.
Extracts of medicinal plants have been widely used to benefit human health. Dendropanax morbiferus (DM) has been well-studied for its anti-inflammatory and anti-oxidative effects, while Dendropanax trifidus (DT) is a lesser-known ecotype phylogenetically similar to DM, which has received significantly less attention. Studies thus far have primarily focused on leaf and bark extracts of DM, and not much is yet known about the properties of either DM or DT sap. Therefore, here we performed in vivo toxicity and efficacy studies, in order to assess the biological effects of DT sap. To establish a safe dosage range, single dose or two-week daily administrations of various concentrations were performed for ICR mice. Measurements of survival ratio, body/organ weight, blood chemistry, histochemistry and Western blots were performed. A concentration of ≤0.5 mg/g DT sap was found to be safe for long-term administration. Interestingly, DT sap significantly reduced blood glucose in female mice. In addition, increasing concentrations of DT sap decreased phosphorylated (p) insulin receptor substrate (IRS)-1(ser1101)/IRS-1 in liver tissues, while increasing pAMP-activated protein kinase (AMPK)/AMPK in both the liver and spleen. To analyze its components, liquid chromatography-tandem mass spectrometry of DT sap was performed in comparison with Acer saccharum (AS) sap. Components such as estradiol, trenbolone, farnesol, dienogest, 2-hydroxyestradiol and linoleic acid were found to be highly enriched in DT sap compared to AS sap. Our results indicate DT sap exhibits hypoglycemic effects, which may be due to the abundance of the bioactive components. Full article
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24 pages, 3719 KiB  
Article
Flavonoid Phloretin Inhibits Adipogenesis and Increases OPG Expression in Adipocytes Derived from Human Bone-Marrow Mesenchymal Stromal-Cells
by Antonio Casado-Díaz, Ángel Rodríguez-Ramos, Bárbara Torrecillas-Baena, Gabriel Dorado, José Manuel Quesada-Gómez and María Ángeles Gálvez-Moreno
Nutrients 2021, 13(11), 4185; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13114185 - 22 Nov 2021
Cited by 11 | Viewed by 2539
Abstract
Phloretin (a flavonoid abundant in apple), has antioxidant, anti-inflammatory, and glucose-transporter inhibitory properties. Thus, it has interesting pharmacological and nutraceutical potential. Bone-marrow mesenchymal stem cells (MSC) have high differentiation capacity, being essential for maintaining homeostasis and regenerative capacity in the organism. Yet, they [...] Read more.
Phloretin (a flavonoid abundant in apple), has antioxidant, anti-inflammatory, and glucose-transporter inhibitory properties. Thus, it has interesting pharmacological and nutraceutical potential. Bone-marrow mesenchymal stem cells (MSC) have high differentiation capacity, being essential for maintaining homeostasis and regenerative capacity in the organism. Yet, they preferentially differentiate into adipocytes instead of osteoblasts with aging. This has a negative impact on bone turnover, remodeling, and formation. We have evaluated the effects of phloretin on human adipogenesis, analyzing MSC induced to differentiate into adipocytes. Expression of adipogenic genes, as well as genes encoding OPG and RANKL (involved in osteoclastogenesis), protein synthesis, lipid-droplets formation, and apoptosis, were studied. Results showed that 10 and 20 µM phloretin inhibited adipogenesis. This effect was mediated by increasing beta-catenin, as well as increasing apoptosis in adipocytes, at late stages of differentiation. In addition, this chemical increased OPG gene expression and OPG/RANKL ratio in adipocytes. These results suggest that this flavonoid (including phloretin-rich foods) has interesting potential for clinical and regenerative-medicine applications. Thus, such chemicals could be used to counteract obesity and prevent bone-marrow adiposity. That is particularly useful to protect bone mass and treat diseases like osteoporosis, which is an epidemic worldwide. Full article
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14 pages, 4313 KiB  
Article
Mokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis
by Alaa Sirwi, Rasheed A. Shaik, Abdulmohsin J. Alamoudi, Basma G. Eid, Ahmed K. Kammoun, Sabrin R. M. Ibrahim, Gamal A. Mohamed, Hossam M. Abdallah and Ashraf B. Abdel-Naim
Nutrients 2021, 13(11), 4142; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13114142 - 19 Nov 2021
Cited by 13 | Viewed by 2226
Abstract
Doxorubicin (DOX), a common chemotherapeutic agent, suffers serious adverse effects including hepatotoxicity. Mokko lactone (ML) is a guainolide sesquiterpene with promising biological activities. The study aimed to evaluate the protection offered by ML against hepatotoxicity induced by DOX in rats. Our data indicated [...] Read more.
Doxorubicin (DOX), a common chemotherapeutic agent, suffers serious adverse effects including hepatotoxicity. Mokko lactone (ML) is a guainolide sesquiterpene with promising biological activities. The study aimed to evaluate the protection offered by ML against hepatotoxicity induced by DOX in rats. Our data indicated ML exhibited protective effects as evidenced by ameliorating the rise in serum activities of alanine transaminase, aspartate transaminase and alkaline phosphatase. This was confirmed histologically as ML prevented DOX-induced pathological alteration in liver architecture. Further, ML administration significantly prevented malondialdehyde accumulation, glutathione depletion and superoxide dismutase and catalase exhaustion. Antioxidant action of ML was associated with enhanced expression of the nuclear translocation of NF-E2-related factor 2 (Nrf2) and a lower expression of forkhead box protein O1 (FOXO1). Also, ML showed potent anti-inflammatory activities highlighted by decreased expression of interleukin 6, tumor necrosis factor α and nuclear factor κB (NF-κB). The anti-apoptotic effects of ML were associated with decreased Bax and enhanced Bcl-2 mRNA expression in liver tissues. ML caused a significant up-regulation in the expression of silent information regulator 1 (Sirt-1). Therefore, it can be concluded that ML prevents liver injury caused by DOX. This could partially be due to the ML regulatory activities on Sirt-1/FOXO1/NF-κB axis. Full article
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15 pages, 2133 KiB  
Article
Coix Seed Consumption Affects the Gut Microbiota and the Peripheral Lymphocyte Subset Profiles of Healthy Male Adults
by Minami Jinnouchi, Taisei Miyahara and Yoshio Suzuki
Nutrients 2021, 13(11), 4079; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13114079 - 15 Nov 2021
Cited by 10 | Viewed by 3181
Abstract
A systematic examination of the effects of traditional herbal medicines including their mechanisms could allow for their effective use and provide opportunities to develop new medicines. Coix seed has been suggested to promote spontaneous regression of viral skin infection. Purified oil from coix [...] Read more.
A systematic examination of the effects of traditional herbal medicines including their mechanisms could allow for their effective use and provide opportunities to develop new medicines. Coix seed has been suggested to promote spontaneous regression of viral skin infection. Purified oil from coix seed has also been suggested to increase the peripheral CD4+ lymphocytes. We, herein, attempt to shed more light on the way through which coix seed affects the human systemic immune function by hypothesizing that a central role to these changes could be played through changes in the gut microbiota. To that end, healthy adult males (n = 19) were divided into two groups; 11 of them consumed cooked coix seed (160 g per day) for 7 days (intervention), while the other eight were given no intervention. One week of coix seed consumption lead to an increase of the intestinal Faecalibacterium abundance and of the abundance (as % presence of overall peripheral lymphocytes) of CD3+CD8+ cells, CD4+ cells, CD4+CD25+ cells, and naïve/memory T cell ratio. As the relationship of microbiota and skin infection has not been clarified, our findings could provide a clue to a mechanism through which coix seed could promote the spontaneous regression of viral skin infections. Full article
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20 pages, 2450 KiB  
Article
Grifola frondosa (Maitake) Extract Reduces Fat Accumulation and Improves Health Span in C. elegans through the DAF-16/FOXO and SKN-1/NRF2 Signalling Pathways
by Paula Aranaz, Adriana Peña, Ariane Vettorazzi, María José Fabra, Antonio Martínez-Abad, Amparo López-Rubio, Joan Pera, Javier Parladé, Massimo Castellari, Fermín I. Milagro and Carlos J. González-Navarro
Nutrients 2021, 13(11), 3968; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13113968 - 07 Nov 2021
Cited by 12 | Viewed by 4066
Abstract
In recent years, food ingredients rich in bioactive compounds have emerged as candidates to prevent excess adiposity and other metabolic complications characteristic of obesity, such as low-grade inflammation and oxidative status. Among them, fungi have gained popularity for their high polysaccharide content and [...] Read more.
In recent years, food ingredients rich in bioactive compounds have emerged as candidates to prevent excess adiposity and other metabolic complications characteristic of obesity, such as low-grade inflammation and oxidative status. Among them, fungi have gained popularity for their high polysaccharide content and other bioactive components with beneficial activities. Here, we use the C. elegans model to investigate the potential activities of a Grifola frondosa extract (GE), together with the underlying mechanisms of action. Our study revealed that GE represents an important source of polysaccharides and phenolic compounds with in vitro antioxidant activity. Treatment with our GE extract, which was found to be nongenotoxic through a SOS/umu test, significantly reduced the fat content of C. elegans, decreased the production of intracellular ROS and aging–lipofuscin pigment, and increased the lifespan of nematodes. Gene expression and mutant analyses demonstrated that the in vivo anti-obesity and antioxidant activities of GE were mediated through the daf-2/daf-16 and skn-1/nrf-2 signalling pathways, respectively. Taken together, our results suggest that our GE extract could be considered a potential functional ingredient for the prevention of obesity-related disturbances. Full article
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12 pages, 5038 KiB  
Article
Effect of Geumgwe-Sinkihwan on Renal Dysfunction in Ischemia/Reperfusion-Induced Acute Renal Failure Mice
by Byung Hyuk Han, Hyeon Kyoung Lee, Se Hoon Jang, Ai Lin Tai, Youn Jae Jang, Jung Joo Yoon, Hye Yoom Kim, Ho Sub Lee, Yun Jung Lee and Dae Gill Kang
Nutrients 2021, 13(11), 3859; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13113859 - 28 Oct 2021
Cited by 1 | Viewed by 1935
Abstract
Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure (ARF). Geumgwe-sinkihwan (GSH) was recorded in a traditional Chines medical book named “Bangyakhappyeon” in 1884. GSH has been used for treatment for patients with diabetes and glomerulonephritis caused by deficiency of [...] Read more.
Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure (ARF). Geumgwe-sinkihwan (GSH) was recorded in a traditional Chines medical book named “Bangyakhappyeon” in 1884. GSH has been used for treatment for patients with diabetes and glomerulonephritis caused by deficiency of kidney yang and insufficiency of kidney gi. Here we investigate the effects of GSH in mice model of ischemic acute kidney injury. The mice groups are as follows; sham group: C57BL6 male mice, I/R group: C57BL6 male mice with I/R surgery, GSH low group: I/R + 100 mg/kg/day GSH, and GSH high group: I/R + 300 mg/kg/day GSH. Ischemia was induced by clamping both renal arteries and reperfusion. Mice were orally given GSH (100 and 300 mg/kg/day) during 3 days after surgery. Treatment with GSH significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen levels. Treatment with GSH reduced neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), specific renal injury markers. GSH also reduced the periodic acid–Schiff and picro sirius red staining intensity in kidney of I/R group. Western blot and real-time RT-qPCR analysis demonstrated that GSH decreased protein and mRNA expression levels of the inflammatory cytokines in I/R-induced ARF mice. Moreover, GSH inhibited protein and mRNA expression of inflammasome-related protein including NLRP3 (NOD-like receptor pyrin domain-containing protein 3, cryoprin), ASC (Apoptosis-associated speck-like protein containing a CARD), and caspase-1. These findings provided evidence that GSH ameliorates renal injury including metabolic dysfunction and inflammation via the inhibition of NLRP3-dependent inflammasome in I/R-induced ARF mice. Full article
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32 pages, 5726 KiB  
Article
Plant-Derived and Dietary Hydroxybenzoic Acids—A Comprehensive Study of Structural, Anti-/Pro-Oxidant, Lipophilic, Antimicrobial, and Cytotoxic Activity in MDA-MB-231 and MCF-7 Cell Lines
by Monika Kalinowska, Ewelina Gołębiewska, Grzegorz Świderski, Sylwia Męczyńska-Wielgosz, Hanna Lewandowska, Anna Pietryczuk, Adam Cudowski, Aleksander Astel, Renata Świsłocka, Mariola Samsonowicz, Anna Barbara Złowodzka, Waldemar Priebe and Włodzimierz Lewandowski
Nutrients 2021, 13(9), 3107; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13093107 - 04 Sep 2021
Cited by 30 | Viewed by 4966
Abstract
Seven derivatives of plant-derived hydroxybenzoic acid (HBA)—including 2,3-dihydroxybenzoic (2,3-DHB, pyrocatechuic), 2,4-dihydroxybenzoic (2,4-DHB, β-resorcylic), 2,5-dihydroxybenzoic (2,5-DHB, gentisic), 2,6-dihydroxybenzoic (2,6-DHB, γ-resorcylic acid), 3,4-dihydroxybenzoic (3,4-DHB, protocatechuic), 3,5-dihydroxybenzoic (3,5-DHB, α-resorcylic), and 3,4,5-trihydroxybenzoic (3,4,5-THB, gallic) acids—were studied for their structural and biological properties. Anti-/pro-oxidant properties were evaluated by [...] Read more.
Seven derivatives of plant-derived hydroxybenzoic acid (HBA)—including 2,3-dihydroxybenzoic (2,3-DHB, pyrocatechuic), 2,4-dihydroxybenzoic (2,4-DHB, β-resorcylic), 2,5-dihydroxybenzoic (2,5-DHB, gentisic), 2,6-dihydroxybenzoic (2,6-DHB, γ-resorcylic acid), 3,4-dihydroxybenzoic (3,4-DHB, protocatechuic), 3,5-dihydroxybenzoic (3,5-DHB, α-resorcylic), and 3,4,5-trihydroxybenzoic (3,4,5-THB, gallic) acids—were studied for their structural and biological properties. Anti-/pro-oxidant properties were evaluated by using DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS•+ (2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), FRAP (ferric-reducing antioxidant power), CUPRAC (cupric-reducing antioxidant power), and Trolox oxidation assays. Lipophilicity was estimated by means of experimental (HPLC) and theoretical methods. The antimicrobial activity against Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis), Salmonella enteritidis (S. enteritidis), and Candida albicans (C. albicans) was studied. The cytotoxicity of HBAs in MCF-7 and MDA-MB-231 cell lines was estimated. Moreover, the structure of HBAs was studied by means of experimental (FTIR, 1H, and 13C NMR) and quantum chemical DFT methods (the NBO and CHelpG charges, electrostatic potential maps, and electronic parameters based on the energy of HOMO and LUMO orbitals). The aromaticity of HBA was studied based on the calculated geometric and magnetic aromaticity indices (HOMA, Aj, BAC, I6, NICS). The biological activity of hydroxybenzoic acids was discussed in relation to their geometry, the electronic charge distribution in their molecules, their lipophilicity, and their acidity. Principal component analysis (PCA) was used in the statistical analysis of the obtained data and the discussion of the dependency between the structure and activity (SAR: structure–activity relationship) of HBAs. This work provides valuable information on the potential application of hydroxybenzoic acids as bioactive components in dietary supplements, functional foods, or even drugs. Full article
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25 pages, 5441 KiB  
Article
Gardenia Jasminoides Ameliorates Antibiotic-Associated Aggravation of DNCB-Induced Atopic Dermatitis by Restoring the Intestinal Microbiome Profile
by Hyo In Kim, Se Hyang Hong, Seo Yeon Lee, Jin Mo Ku, Min Jeong Kim and Seong-Gyu Ko
Nutrients 2021, 13(4), 1349; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13041349 - 18 Apr 2021
Cited by 13 | Viewed by 3124
Abstract
The intestinal microbiome is considered one of the key regulators of health. Accordingly, the severity of atopic dermatitis (AD) is mediated by the skin and intestinal microbiome environment. In this study, while evaluating the aggravation in AD symptoms by the antibiotics cocktail (ABX)-induced [...] Read more.
The intestinal microbiome is considered one of the key regulators of health. Accordingly, the severity of atopic dermatitis (AD) is mediated by the skin and intestinal microbiome environment. In this study, while evaluating the aggravation in AD symptoms by the antibiotics cocktail (ABX)-induced depletion of the intestinal microbiome, we sought to verify the effect of Gardenia jasminoides (GJ), a medicinal herb used for inflammatory diseases, on AD regarding its role on the intestinal microbiome. To verify the aggravation in AD symptoms induced by the depletion of the intestinal microbiome, we established a novel mouse model by administrating an ABX to create a microbiome-free environment in the intestine, and then applied 2,4-dinitrochlorobenzene (DNCB) to induce an AD-like skin inflammatory response. While ABX treatment aggravated AD-like symptoms, the 2-week administration of GJ improved these pathological changes. DNCB application upregulated immune cell count and serum cytokine expression, which were alleviated by GJ. Moreover, pathological alterations by antibiotics and DNCB, including histological damage of the intestine and the intestinal expression of IL-17, were recovered in GJ-treated mice. The beneficial effect of GJ was due to the restoration of the intestinal microbiome composition. Overall, we suggest GJ as a potential therapeutic agent for AD due to its regulation of the intestinal microbiome. Full article
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14 pages, 2251 KiB  
Article
Shikonin Derivatives from Onsoma visianii Decrease Expression of Phosphorylated STAT3 in Leukemia Cells and Exert Antitumor Activity
by Zeljko Todorovic, Jelena Milovanovic, Dragana Arsenijevic, Nenad Vukovic, Milena Vukic, Aleksandar Arsenijevic, Predrag Djurdjevic, Marija Milovanovic and Nebojsa Arsenijevic
Nutrients 2021, 13(4), 1147; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13041147 - 31 Mar 2021
Cited by 6 | Viewed by 2300
Abstract
Antitumor effects of shikonins on chronic lymphocytic leukemia (CLL) and B-cell prolymphocytic leukemia (B-PLL) are mostly unexplored. The antitumor activity of shikonins, isolated from Onosma visianii Clem (Boraginaceae), in BCL1, mouse CLL cells and JVM-13, human B-PLL cells was explored in [...] Read more.
Antitumor effects of shikonins on chronic lymphocytic leukemia (CLL) and B-cell prolymphocytic leukemia (B-PLL) are mostly unexplored. The antitumor activity of shikonins, isolated from Onosma visianii Clem (Boraginaceae), in BCL1, mouse CLL cells and JVM-13, human B-PLL cells was explored in this study. The cytotoxicity of shikonin derivatives was measured by an MTT test. Cell death, proliferation, cell cycle, and expression of molecules that control these processes were analyzed by flow cytometry. Expression of STAT3-regulated genes was analyzed by real-time q-RT-PCR (Quantitative Real-Time Polymerase Chain Reaction). The antitumor effects of shikonin derivatives in vivo were analyzed, using flow cytometry, by detection of leukemia cells in the peripheral blood and spleens of mice intravenously injected with BCL1 cells. The two most potent derivatives, isobutyrylshikonin (IBS) and α-methylbutyrylshikonin (MBS), induced cell cycle disturbances and apoptosis, inhibited proliferation, and decreased expression of phospho-STAT3 and downstream-regulated molecules in BCL1 and JVM-13 cells. IBS and MBS decreased the percentage of leukemia cells in vivo. The link between the decrease in phosphorylated STAT3 by MBS and IBS and BCL1 cell death was confirmed by detection of enhanced cell death after addition of AG490, an inhibitor of Jak2 kinase. It seems that IBS and MBS, by decreasing STAT3 phosphorylation, trigger apoptosis, inhibit cell proliferation, and attenuate leukemia cell stemness. Full article
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14 pages, 2428 KiB  
Article
Plant-Derived Trans-β-Caryophyllene Boosts Glucose Metabolism and ATP Synthesis in Skeletal Muscle Cells through Cannabinoid Type 2 Receptor Stimulation
by Federica Geddo, Susanna Antoniotti, Giulia Querio, Iris Chiara Salaroglio, Costanzo Costamagna, Chiara Riganti and Maria Pia Gallo
Nutrients 2021, 13(3), 916; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13030916 - 12 Mar 2021
Cited by 8 | Viewed by 2492
Abstract
Skeletal muscle plays a pivotal role in whole-body glucose metabolism, accounting for the highest percentage of glucose uptake and utilization in healthy subjects. Impairment of these key functions occurs in several conditions including sedentary lifestyle and aging, driving toward hyperglycemia and metabolic chronic [...] Read more.
Skeletal muscle plays a pivotal role in whole-body glucose metabolism, accounting for the highest percentage of glucose uptake and utilization in healthy subjects. Impairment of these key functions occurs in several conditions including sedentary lifestyle and aging, driving toward hyperglycemia and metabolic chronic diseases. Therefore, strategies pointed to improve metabolic health by targeting skeletal muscle biochemical pathways are extremely attractive. Among them, we focused on the natural sesquiterpene and cannabinoid type 2 (CB2) receptor agonist Trans-β-caryophyllene (BCP) by analyzing its role in enhancing glucose metabolism in skeletal muscle cells. Experiments were performed on C2C12 myotubes. CB2 receptor membrane localization in myotubes was assessed by immunofluorescence. Within glucose metabolism, we evaluated glucose uptake (by the fluorescent glucose analog 2-NBDG), key enzymes of both glycolytic and oxidative pathways (by spectrophotometric assays and metabolic radiolabeling) and ATP production (by chemiluminescence-based assays). In all experiments, CB2 receptor involvement was tested with the CB2 antagonists AM630 and SR144528. Our results show that in myotubes, BCP significantly enhances glucose uptake, glycolytic and oxidative pathways, and ATP synthesis through a CB2-dependent mechanism. Giving these outcomes, CB2 receptor stimulation by BCP could represent an appealing tool to improve skeletal muscle glucose metabolism, both in physiological and pathological conditions. Full article
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11 pages, 3549 KiB  
Article
Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches
by Jayeong Hwang, Kumju Youn, Gyutae Lim, Jinhyuk Lee, Dong Hyun Kim and Mira Jun
Nutrients 2021, 13(1), 254; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13010254 - 17 Jan 2021
Cited by 7 | Viewed by 3623
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease conceptualized as a clinical-biological neurodegenerative construct where amyloid-beta pathophysiology is supposed to play a role. The loss of cognitive functions is mostly characterized by the rapid hydrolysis of acetylcholine by cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterase [...] Read more.
Alzheimer’s disease (AD) is a neurodegenerative disease conceptualized as a clinical-biological neurodegenerative construct where amyloid-beta pathophysiology is supposed to play a role. The loss of cognitive functions is mostly characterized by the rapid hydrolysis of acetylcholine by cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, both enzymes are responsible for non-catalytic actions such as interacting with amyloid β peptide (Aβ) which further leads to promote senile plaque formation. In searching for a natural cholinesterase inhibitor, the present study focused on two isocoumarines from hydrangea, thunberginol C (TC) and hydrangenol 8-O-glucoside pentaacetate (HGP). Hydrangea-derived compounds were demonstrated to act as dual inhibitors of both AChE and BChE. Furthermore, the compounds exerted selective and non-competitive mode of inhibition via hydrophobic interaction with peripheral anionic site (PAS) of the enzymes. Overall results demonstrated that these natural hydrangea-derived compounds acted as selective dual inhibitors of AChE and BChE, which provides the possibility of potential source of new type of anti-cholinesterases with non-competitive binding property with PAS. Full article
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13 pages, 3375 KiB  
Article
Allyl Isothiocyanate Protects Acetaminophen-Induced Liver Injury via NRF2 Activation by Decreasing Spontaneous Degradation in Hepatocyte
by Min Woo Kim, Ju-Hee Kang, Hyun Jin Jung, Se Yong Park, Thu Han Le Phan, Hee Namgung, Seung-Yong Seo, Yeo Sung Yoon and Seung Hyun Oh
Nutrients 2020, 12(11), 3585; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12113585 - 23 Nov 2020
Cited by 16 | Viewed by 3303
Abstract
Acetaminophen (APAP) is one of the most frequently prescribed analgesic and anti-pyretic drugs. However, APAP-induced hepatotoxicity is a major cause of acute liver failure globally. While the therapeutic dose is safe, an overdose of APAP produces an excess of the toxic metabolite N [...] Read more.
Acetaminophen (APAP) is one of the most frequently prescribed analgesic and anti-pyretic drugs. However, APAP-induced hepatotoxicity is a major cause of acute liver failure globally. While the therapeutic dose is safe, an overdose of APAP produces an excess of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), subsequently resulting in hepatotoxicity. Allyl isothiocyanate (AITC), a bioactive molecule in cruciferous plants, is reported to exert various biological effects, including anti-inflammatory, anti-cancer, and anti-microbial effects. Notably, AITC is known for activating nuclear factor erythroid 2-related factor 2 (NRF2), but there is limited evidence supporting the beneficial effects on hepatocytes and liver, where AITC is mainly metabolized. We applied a mouse model in the current study to investigate whether AITC protects the liver against APAP-induced injury, wherein we observed the protective effects of AITC. Furthermore, NRF2 nuclear translocation and the increase of target genes by AITC treatment were confirmed by in vitro experiments. APAP-induced cell damage was attenuated by AITC via an NRF2-dependent manner, and rapid NRF2 activation by AITC was attributed to the elevation of NRF2 stability by decreasing its spontaneous degradation. Moreover, liver tissues from our mouse experiment revealed that AITC increases the expression of heme oxygenase-1 (HO-1), an NRF2 target gene, confirming the potential of AITC as a hepatoprotective agent that induces NRF2 activation. Taken together, our results indicate the potential of AITC as a natural-product-derived NRF2 activator targeting the liver. Full article
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20 pages, 2324 KiB  
Article
Assessing the Intestinal Permeability and Anti-Inflammatory Potential of Sesquiterpene Lactones from Chicory
by Melanie S. Matos, José D. Anastácio, J. William Allwood, Diogo Carregosa, Daniela Marques, Julie Sungurtas, Gordon J. McDougall, Regina Menezes, Ana A. Matias, Derek Stewart and Cláudia Nunes dos Santos
Nutrients 2020, 12(11), 3547; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12113547 - 19 Nov 2020
Cited by 15 | Viewed by 4496
Abstract
Cichorium intybus L. has recently gained major attention due to large quantities of health-promoting compounds in its roots, such as inulin and sesquiterpene lactones (SLs). Chicory is the main dietary source of SLs, which have underexplored bioactive potential. In this study, we assessed [...] Read more.
Cichorium intybus L. has recently gained major attention due to large quantities of health-promoting compounds in its roots, such as inulin and sesquiterpene lactones (SLs). Chicory is the main dietary source of SLs, which have underexplored bioactive potential. In this study, we assessed the capacity of SLs to permeate the intestinal barrier to become physiologically available, using in silico predictions and in vitro studies with the well-established cell model of the human intestinal mucosa (differentiated Caco-2 cells). The potential of SLs to modulate inflammatory responses through modulation of the nuclear factor of activated T-cells (NFAT) pathway was also evaluated, using a yeast reporter system. Lactucopicrin was revealed as the most permeable chicory SL in the intestinal barrier model, but it had low anti-inflammatory potential. The SL with the highest anti-inflammatory potential was 11β,13-dihydrolactucin, which inhibited up to 54% of Calcineurin-responsive zinc finger (Crz1) activation, concomitantly with the impairment of the nuclear accumulation of Crz1, the yeast orthologue of human NFAT. Full article
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13 pages, 3118 KiB  
Article
St. John’s Wort Suppresses Growth in Triple-Negative Breast Cancer Cell Line MDA-MB-231 by Inducing Prodeath Autophagy and Apoptosis
by Mikyoung You, Young-Hyun Lee, Hwa-Jin Kim, Ji Hyun Kook and Hyeon-A Kim
Nutrients 2020, 12(10), 3175; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12103175 - 17 Oct 2020
Cited by 8 | Viewed by 2663
Abstract
The rational regulation of programmed cell death by means of autophagy and apoptosis has been considered a potential treatment strategy for cancer. We demonstrated the inhibitory effect of St. John’s Wort (SJW) on growth in the triple-negative breast cancer (TNBC) cell line and [...] Read more.
The rational regulation of programmed cell death by means of autophagy and apoptosis has been considered a potential treatment strategy for cancer. We demonstrated the inhibitory effect of St. John’s Wort (SJW) on growth in the triple-negative breast cancer (TNBC) cell line and xenografted mice and its target mechanism concerning autophagic and apoptotic cell death. SJW ethanol extract (SJWE) inhibited proliferation in a dose-dependent manner. SJWE treatment dramatically increased autophagy flux and apoptosis compared with the control. The autophagy inhibitor, 3-methyladenine (3-MA), reversed the SJWE-induced inhibition of cell proliferation and regulation of autophagy and apoptosis, indicating that SJWE induced apoptosis through prodeath autophagy. Furthermore, SJWE inhibited tumor growth and induced autophagy and apoptosis in the tumor of MDA-MB-231 xenografted athymic nude mice. Our results indicate that SJWE might have great potential as a new anticancer therapy for triple-negative breast cancer by inducing prodeath autophagy and apoptosis. Full article
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15 pages, 1015 KiB  
Article
Research Quality-Based Multivariate Modeling for Comparison of the Pharmacological Effects of Black and Red Ginseng
by Dong-Kyu Lee, Seongoh Park, Nguyen Phuoc Long, Jung Eun Min, Hyung Min Kim, Eugine Yang, Seul Ji Lee, Johan Lim and Sung Won Kwon
Nutrients 2020, 12(9), 2590; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12092590 - 26 Aug 2020
Cited by 10 | Viewed by 2983
Abstract
Black ginseng has various pharmacological activities, but only few studies have compared its pharmacological effects with those of red ginseng. We conducted an integrative systematic literature evaluation and developed a non-inferiority test based on the multivariate modeling approach to compare the pharmacological effects [...] Read more.
Black ginseng has various pharmacological activities, but only few studies have compared its pharmacological effects with those of red ginseng. We conducted an integrative systematic literature evaluation and developed a non-inferiority test based on the multivariate modeling approach to compare the pharmacological effects of red ginseng and black ginseng. We searched reported studies on the pharmaceutical effects and composition of ginsenosides and assigned numeric scores using nonlinear principal component analysis, based on discretization measures for the included publications. Downstream weighted linear regression models were constructed to study the eight major biological activities that are generally known to be exhibited by red ginseng. Our statistical model, based on available ordinal information gathered from previous literature, helped in comparing the overlapping effects of black ginseng. Black ginseng showed antioxidant effects comparable to those of red ginseng; however, this variant was inferior to red ginseng in enhancing immunity, relieving fatigue, alleviating depression/anxiety, decreasing body fat, and reducing blood pressure. We have showed a cost-efficient method to indirectly evaluate the biological effects of ginseng products using data from published articles. This method can also be used to compare the nutritional and medicinal value of herbal medicines that share similar compositions of bioactive compounds. Full article
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Review

Jump to: Research

60 pages, 11088 KiB  
Review
Black Cumin (Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety
by Md. Abdul Hannan, Md. Ataur Rahman, Abdullah Al Mamun Sohag, Md. Jamal Uddin, Raju Dash, Mahmudul Hasan Sikder, Md. Saidur Rahman, Binod Timalsina, Yeasmin Akter Munni, Partha Protim Sarker, Mahboob Alam, Md. Mohibbullah, Md. Nazmul Haque, Israt Jahan, Md. Tahmeed Hossain, Tania Afrin, Md. Mahbubur Rahman, Md. Tahjib-Ul-Arif, Sarmistha Mitra, Diyah Fatimah Oktaviani, Md Kawsar Khan, Ho Jin Choi, Il Soo Moon and Bonglee Kimadd Show full author list remove Hide full author list
Nutrients 2021, 13(6), 1784; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13061784 - 24 May 2021
Cited by 105 | Viewed by 53152
Abstract
Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin (Nigella sativa L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific [...] Read more.
Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin (Nigella sativa L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries. The pleiotropic pharmacological effects of black cumin, and its main bioactive component thymoquinone (TQ), have been manifested by their ability to attenuate oxidative stress and inflammation, and to promote immunity, cell survival, and energy metabolism, which underlie diverse health benefits, including protection against metabolic, cardiovascular, digestive, hepatic, renal, respiratory, reproductive, and neurological disorders, cancer, and so on. Furthermore, black cumin acts as an antidote, mitigating various toxicities and drug-induced side effects. Despite significant advances in pharmacological benefits, this miracle herb and its active components are still far from their clinical application. This review begins with highlighting the research trends in black cumin and revisiting phytochemical profiles. Subsequently, pharmacological attributes and health benefits of black cumin and TQ are critically reviewed. We overview molecular pharmacology to gain insight into the underlying mechanism of health benefits. Issues related to pharmacokinetic herb–drug interactions, drug delivery, and safety are also addressed. Identifying knowledge gaps, our current effort will direct future research to advance potential applications of black cumin and TQ in health and diseases. Full article
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37 pages, 3696 KiB  
Review
The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer
by Getinet M. Adinew, Equar Taka, Patricia Mendonca, Samia S. Messeha and Karam F. A. Soliman
Nutrients 2021, 13(4), 1212; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13041212 - 07 Apr 2021
Cited by 28 | Viewed by 5520
Abstract
Triple- negative breast cancer (TNBC) incidence rate has regularly risen over the last decades and is expected to increase in the future. Finding novel treatment options with minimum or no toxicity is of great importance in treating or preventing TNBC. Flavonoids are new [...] Read more.
Triple- negative breast cancer (TNBC) incidence rate has regularly risen over the last decades and is expected to increase in the future. Finding novel treatment options with minimum or no toxicity is of great importance in treating or preventing TNBC. Flavonoids are new attractive molecules that might fulfill this promising therapeutic option. Flavonoids have shown many biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In addition to their anticancer effects by arresting the cell cycle, inducing apoptosis, and suppressing cancer cell proliferation, flavonoids can modulate non-coding microRNAs (miRNAs) function. Several preclinical and epidemiological studies indicate the possible therapeutic potential of these compounds. Flavonoids display a unique ability to change miRNAs’ levels via different mechanisms, either by suppressing oncogenic miRNAs or activating oncosuppressor miRNAs or affecting transcriptional, epigenetic miRNA processing in TNBC. Flavonoids are not only involved in the regulation of miRNA-mediated cancer initiation, growth, proliferation, differentiation, invasion, metastasis, and epithelial-to-mesenchymal transition (EMT), but also control miRNAs-mediated biological processes that significantly impact TNBC, such as cell cycle, immune system, mitochondrial dysregulation, modulating signaling pathways, inflammation, and angiogenesis. In this review, we highlighted the role of miRNAs in TNBC cancer progression and the effect of flavonoids on miRNA regulation, emphasizing their anticipated role in the prevention and treatment of TNBC. Full article
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20 pages, 2444 KiB  
Review
Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers
by Robert Kubina, Marcello Iriti and Agata Kabała-Dzik
Nutrients 2021, 13(3), 845; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13030845 - 05 Mar 2021
Cited by 41 | Viewed by 4151
Abstract
Flavonols are ones of the most common phytochemicals found in diets rich in fruit and vegetables. Research suggests that molecular functions of flavonoids may bring a number of health benefits to people, including the following: decrease inflammation, change disease activity, and alleviate resistance [...] Read more.
Flavonols are ones of the most common phytochemicals found in diets rich in fruit and vegetables. Research suggests that molecular functions of flavonoids may bring a number of health benefits to people, including the following: decrease inflammation, change disease activity, and alleviate resistance to antibiotics as well as chemotherapeutics. Their antiproliferative, antioxidant, anti-inflammatory, and antineoplastic activity has been proved. They may act as antioxidants, while preventing DNA damage by scavenging reactive oxygen radicals, reinforcing DNA repair, disrupting chemical damages by induction of phase II enzymes, and modifying signal transduction pathways. One of such research areas is a potential effect of flavonoids on the risk of developing cancer. The aim of our paper is to present a systematic review of antineoplastic activity of flavonols in general. Special attention was paid to selected flavonols: fisetin, kaempferol, and quercetin in preclinical and in vitro studies. Study results prove antiproliferative and proapoptotic properties of flavonols with regard to head and neck cancer. However, few study papers evaluate specific activities during various processes associated with cancer progression. Moreover, an attempt was made to collect the majority of substantive studies on bioactive potential of the selected flavonols, especially with regard to modulation of a range of signal transduction pathways that participate in cancer development. Full article
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18 pages, 3764 KiB  
Review
Rhinacanthus nasutus “Tea” Infusions and the Medicinal Benefits of the Constituent Phytochemicals
by James Michael Brimson, Mani Iyer Prasanth, Dicson Sheeja Malar, Sirikalaya Brimson and Tewin Tencomnao
Nutrients 2020, 12(12), 3776; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12123776 - 09 Dec 2020
Cited by 17 | Viewed by 7403
Abstract
Rhinacanthus nasutus (L.) Kurz (Acanthaceae) (Rn) is an herbaceous shrub native to Thailand and much of South and Southeast Asia. It has several synonyms and local or common names. The root of Rn is used in Thai traditional medicine to treat [...] Read more.
Rhinacanthus nasutus (L.) Kurz (Acanthaceae) (Rn) is an herbaceous shrub native to Thailand and much of South and Southeast Asia. It has several synonyms and local or common names. The root of Rn is used in Thai traditional medicine to treat snake bites, and the roots and/or leaves can be made into a balm and applied to the skin for the treatment of skin infections such as ringworm, or they may be brewed to form an infusion for the treatment of inflammatory disorders. Rn leaves are available to the public for purchase in the form of “tea bags” as a natural herbal remedy for a long list of disorders, including diabetes, skin diseases (antifungal, ringworm, eczema, scurf, herpes), gastritis, raised blood pressure, improved blood circulation, early-stage tuberculosis antitumor activity, and as an antipyretic. There have been many studies investigating the roles of Rn or compounds isolated from the herb regarding diseases such as Alzheimer’s and other neurodegenerative diseases, cancer, diabetes and infection with bacteria, fungi or viruses. There have, however, been no clinical trials to confirm the efficacy of Rn in the treatment of any of these disorders, and the safety of these teas over long periods of consumption has never been tested. This review assesses the recent research into the role of Rn and its constituent compounds in a range of diseases. Full article
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