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Effects of Plant Extracts on Human Health

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

Deadline for manuscript submissions: closed (25 October 2024) | Viewed by 20687

Special Issue Editors


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Guest Editor
Institute of Cellular Bioelectricity (IBIOCEL): Science & Health, Departament of Biochemistry, Center of Biological Sciences, Campus Trindade, Federal University of Santa Catarina, Florianópolis 88040-900, SC, Brazil
Interests: natural compounds; diabetes; infertility; cancer; central nervous system diseases; chronic diseases; medicinal plants; pain and analgesia
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Departamento de Farmácia, Facultad de Ciencias, Universidad Nacional de Colombia, Cra. 30 45-03, Bogotá 111321, Colombia
Interests: drug delivery; pharmacokinetics; microparticles; nanoparticles; self-emulsifying delivery; extracts standardization; bioactive compounds.
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to announce a Special Issue titled "Effects of Plant Extracts on Human Health" in Nutrients. This issue aims to explore the diverse impacts of plant extracts on human health, spanning from their nutritional value to their potential therapeutic effects/nutraceuticals.

We invite researchers, scientists, and experts to contribute their original research and reviews to this Special Issue. Submissions may include, but are not limited to, studies investigating:

The bioactive compounds present in plant extracts;

The mechanisms underlying the health effects of plant extracts;

The role of plant extracts in preventing or treating various health conditions;

The potential synergistic effects of combining different plant extracts;

The impact of processing and preparation methods on the bioavailability of plant extract compounds;

The utilization of plant extracts in functional foods and nutraceuticals.

We encourage submissions that utilize diverse methodologies, including in vitro and in vivo studies, clinical trials, and meta-analyses, to provide comprehensive insights into the effects of plant extracts on human health.

We look forward to receiving your contributions and to the collective advancement of knowledge in this important area of research.

Prof. Dr. Fátima Regina Mena Barreto Silva
Prof. Dr. Diana Marcela Aragon Novoa
Guest Editors

Manuscript Submission Information

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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

  • plant extracts
  • human health
  • bioactive compounds
  • therapeutic effects
  • nutraceuticals

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Published Papers (10 papers)

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9 pages, 1337 KiB  
Article
Tryptanthrin Down-Regulates Oncostatin M by Targeting GM-CSF-Mediated PI3K-AKT-NF-κB Axis
by Na-Ra Han, Hi-Joon Park, Seong-Gyu Ko and Phil-Dong Moon
Nutrients 2024, 16(23), 4109; https://doi.org/10.3390/nu16234109 - 28 Nov 2024
Viewed by 401
Abstract
Background: Oncostatin M (OSM) is involved in several inflammatory responses. Tryptanthrin (TRYP), as a natural alkaloid, is a bioactive compound derived from indigo plants. Objectives/ Methods: The purpose of this study is to investigate the potential inhibitory activity of TRYP on OSM release [...] Read more.
Background: Oncostatin M (OSM) is involved in several inflammatory responses. Tryptanthrin (TRYP), as a natural alkaloid, is a bioactive compound derived from indigo plants. Objectives/ Methods: The purpose of this study is to investigate the potential inhibitory activity of TRYP on OSM release from neutrophils using neutrophils-like differentiated (d)HL-60 cells and neutrophils from mouse bone marrow. Results: The results showed that TRYP reduced the production and mRNA expression levels of OSM in the granulocyte–macrophage colony-stimulating factor (GM-CSF)-stimulated neutrophils-like dHL-60 cells. In addition, TRYP decreased the OSM production levels in the GM-CSF-stimulated neutrophils from mouse bone marrow. TRYP inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K), AKT, and nuclear factor (NF)-κB in the GM-CSF-stimulated neutrophils-like dHL-60 cells. Conclusions: Therefore, these results reveal for the first time that TRYP inhibits OSM release via the down-regulation of PI3K-AKT-NF-κB axis from neutrophils, presenting its potential as a therapeutic agent for inflammatory responses. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health)
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Figure 1

Figure 1
<p>TRYP reduces OSM release. dHL-60 cells were stimulated with GM-CSF, with or without TRYP, for 4 h. (<b>a</b>) The cell viability was assessed using an MTT assay. (<b>b</b>) OSM production was examined using ELISA. (<b>c</b>) Representative images for OSM were obtained by confocal microscopy (scale bar, 10 µm). * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001.</p>
Full article ">Figure 2
<p>TRYP reduces the OSM mRNA levels. dHL-60 cells were stimulated with GM-CSF, with or without TRYP, for 30 min. OSM mRNA expression was assessed with qPCR. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>TRYP reduces the phosphorylation of PI3K. The phospho-PI3K levels were analyzed using immunoblots. Quantitative analysis of blots from three independent experiments is displayed in the right panel. *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>TRYP reduces the phosphorylation of AKT. The phospho-AKT levels were measured by WB analysis. Quantitative analysis of blots from three independent experiments is displayed in the right panel. *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>TRYP reduces the phosphorylation of NF-κB. The phospho-NF-κB levels were analyzed using immunoblots. Quantitative analysis of blots from three independent experiments is displayed in the right panel. *** <span class="html-italic">p</span> &lt; 0.001.</p>
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22 pages, 5425 KiB  
Article
Phytochemical, Cytoprotective Profiling, and Anti-Inflammatory Potential of Colchicum luteum in Rheumatoid Arthritis: An Experimental and Simulation Study
by Huda Abbasi, Maria Sharif, Peter John, Attya Bhatti, Muhammad Qasim Hayat and Qaisar Mansoor
Nutrients 2024, 16(23), 4020; https://doi.org/10.3390/nu16234020 - 24 Nov 2024
Viewed by 570
Abstract
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe pain, inflammation, and joint deformity. Currently, it affects 1% of the population, with a projection to exceed 23 million cases by 2030. Despite significant advancements, non-steroidal anti-inflammatory drugs (NSAIDs), the first [...] Read more.
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe pain, inflammation, and joint deformity. Currently, it affects 1% of the population, with a projection to exceed 23 million cases by 2030. Despite significant advancements, non-steroidal anti-inflammatory drugs (NSAIDs), the first line of treatment, are associated with a range of adverse effects. Consequently, plant-based derivatives are being utilized as an effective alternative. This study evaluates the anti-inflammatory and safety profile of Colchicum luteum hydroethanolic extract (CLHE) in comparison to NSAIDs, with a focus on COX-2 and TNFα inhibition. Methods: CLHE potential was evaluated by phytochemical screening and in vitro bioactivity assays. Toxicity profile was conducted in Human Colon Epithelial Cells (HCEC) and Balb/c mice. Anti-inflammatory potential was explored in a collagen-induced arthritic (CIA) mice model. Bioactive compounds were identified computationally from GCMS data and subjected to docking and simulation studies against COX2 and TNFα. Results: CLHE demonstrated significant antioxidant (IC-50 = 6.78 µg/mL) and anti-inflammatory (IC-50 = 97.39 µg/mL) activity. It maintained 50% cell viability at 78.5 μg/µL in HCEC cells and exhibited no toxicity at a dose of 5000 mg/kg in mice. In the CIA model, CLHE significantly reduced paw swelling, arthritic scoring, C-reactive protein levels, and spleen indices, outperforming ibuprofen. Expression analysis confirmed the downregulation of COX-2, TNFα, and MMP-9. Histopathological analysis indicated the superior efficacy of CLHE compared to ibuprofen in reducing inflammation, synovial hyperplasia, and bone erosion. Computational studies identified compound-15 (CL15), (4-(4,7-dimethoxy-1,3-benzodioxol-5-yl)-2-oxo pyrrolidine-3-carboxylic acid), a non-toxic compound with strong binding affinities to COX-2 (−12.9 KJ/mol), and TNF-α (−5.8 KJ/mol). Conclusions: The findings suggest the potential of Colchicum luteum as a safer, anti-inflammatory, and multi-targeted alternative to NSAIDs for RA treatment. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health)
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<p>Crosstalk interaction between COX-2 and TNFα in a rheumatoid arthritis joint. COX-2 leads to TNFα activation through PGE<sub>2</sub> stimulation, while TNFα simultaneously enhances COX-2 expression, creating a feedback loop that amplifies inflammation.</p>
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<p><span class="html-italic">Colchicum luteum</span> identification by (<b>a</b>) flower and stem, (<b>b</b>) corm.</p>
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<p>Biological potential of CLHE expressed as (<b>a</b>) DPPH assay: The radical scavenging potential of CLHE shows a concentration-dependent increase comparable to ibuprofen. (<b>b</b>) Protein denaturation assay: Protein denaturation inhibition activity is significantly increased with extract concentration. CLHE is a significant inhibitor of protein denaturation at 250 µg/mL (<span class="html-italic">n</span> = 3) (R<sup>2</sup> = 0.96).</p>
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<p>Cytoprotective activity of CLHE expressed as cell viability % in HCEC cells R<sup>2</sup> = 0.9 Statistical significance was determined by one-way ANOVA, followed by Bonferroni multiple comparison test where ns = non-significant and **** <span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>Anti arthritic activity of CLHE. (<b>a</b>) Experimental design, (<b>b</b>) paw edema, (<b>c</b>) arthritic index, (<b>d</b>) paw at the end of the experiment, (<b>e</b>) blood CRP levels, (<b>f</b>) spleen indices, (<b>g</b>) expression analysis of COX2, TNFα, and MMP9. Statistical significance was determined by two-way ANOVA or one-way ANOVA, wherever applicable, followed by Bonferroni multiple comparison test where * <span class="html-italic">p</span> &lt; 0.01, ** <span class="html-italic">p</span> &lt; 0.001, *** <span class="html-italic">p</span> = 0.0001 **** <span class="html-italic">p</span> &lt; 0.0001 represents control group vs. disease control group and ## <span class="html-italic">p</span> &lt; 0.001, ### <span class="html-italic">p</span> = 0.0001 and #### <span class="html-italic">p</span> &lt; 0.0001 represents disease control group vs. treatment groups.</p>
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<p>H&amp;E-stained tissue of the tarsal joint of CIA Balb/c mice. (<b>a</b>–<b>c</b>) Group 1: (<b>a</b>) inflammation, (<b>b</b>) immune cell infiltration and synovial hyperplasia, (<b>c</b>) bone erosion represented by black arrows. (<b>d</b>–<b>f</b>) Group 2: (<b>d</b>) inflammation, (<b>e</b>) immune cell infiltration and synovial hyperplasia, (<b>f</b>) bone erosion represented by black arrows. (<b>g</b>–<b>i</b>) Group 3: (<b>g</b>) inflammation, (<b>h</b>) immune cell infiltration and synovial hyperplasia, (<b>i</b>) bone erosion represented by black arrows. (<b>j</b>–<b>l</b>). Group 4: (<b>j</b>) inflammation, (<b>k</b>) immune cell infiltration and synovial hyperplasia, (<b>l</b>) bone erosion represented by black arrows. Figures were scaled to 100 µm and original magnifications were 20× and 40×. (<b>m</b>) Histopathological scoring; statistical significance was determined by one-way ANOVA, followed by Bonferroni multiple comparison test where *** <span class="html-italic">p</span> = 0.0001, **** <span class="html-italic">p</span> &lt; 0.0001 represents control group vs. disease control group and # <span class="html-italic">p</span> &lt; 0.01, ## <span class="html-italic">p</span> &lt; 0.001, ### <span class="html-italic">p</span> = 0.0001 and #### <span class="html-italic">p</span> &lt; 0.0001 represents disease control group vs. treatment groups where ns = non-significant.</p>
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<p>Bioactive natural compounds identified in CHLE through GC-MS from CL01 to CL15.</p>
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<p>ProTox 3.0 indicating safety of CL15 in all parameters except slight immunotoxicity (<span class="html-italic">p</span> = 0.7).</p>
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<p>Molecular interaction of CL15 with (<b>a</b>) COX-2 and (<b>b</b>) TNFα.</p>
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<p>Molecular dynamics simulation graphically representing (<b>a</b>) RMSD, (<b>b</b>) RoG, (<b>c</b>) H-bond, and (<b>d</b>) MMGBPSA, where red represents complex 1 and black represents complex 2.</p>
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<p>Conformational change and structural rotation of (<b>a</b>) complex 1 and (<b>b</b>) complex 2.</p>
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14 pages, 7075 KiB  
Article
Lysimachia mauritiana Lam. Extract Alleviates Airway Inflammation Induced by Particulate Matter Plus Diesel Exhaust Particles in Mice
by Yoon-Young Sung, Seung-Hyung Kim, Won-Kyung Yang, Heung Joo Yuk, Mi-Sun Kim and Dong-Seon Kim
Nutrients 2024, 16(21), 3732; https://doi.org/10.3390/nu16213732 - 31 Oct 2024
Viewed by 556
Abstract
Exposure to air pollution poses a risk to human respiratory health, and a preventive and therapeutic remedy against fine dust-induced respiratory disease is needed. Background/Objectives: The respiratory-protective effects of Lysimachia mauritiana (LM) against airway inflammation were evaluated in a mouse model exposed to [...] Read more.
Exposure to air pollution poses a risk to human respiratory health, and a preventive and therapeutic remedy against fine dust-induced respiratory disease is needed. Background/Objectives: The respiratory-protective effects of Lysimachia mauritiana (LM) against airway inflammation were evaluated in a mouse model exposed to a fine dust mixture of diesel exhaust particles and particulate matter with a diameter of less than 10 µm (PM10D). Methods: To induce airway inflammation, PM10D was intranasally injected into BALB/c mice three times a day for 12 days, and LM extracts were given orally once per day. The immune cell subtypes, histopathology, and expression of inflammatory mediators were analyzed from the bronchoalveolar lavage fluid (BALF) and lungs. Results: LM alleviated the accumulation of neutrophils and the number of inflammatory cells in the lungs and the BALF of the PM10D-exposed mice. LM also reduced the release of inflammatory mediators (MIP-2, IL-17, IL-1α, CXCL1, TNF-α, MUC5AC, and TRP receptor channels) in the BALF and lungs. Lung histopathology was used to examine airway inflammation and the accumulation of collagen fibers and inflammatory cells after PM10D exposure and showed that LM administration improved this inflammation. Furthermore, LM extract inhibited the MAPK and NF-κB signaling pathway in the lungs and improved expectoration activity through an increase in phenol red release from the trachea. Conclusions: LM alleviated PM10D-exposed neutrophilic airway inflammation by suppressing MAPK/NF-κB activation. This study indicates that LM extract may be an effective therapeutic agent against inflammatory respiratory diseases. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health)
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Figure 1
<p>Chemical structure of mauritianin (MT). Comparison of UPLC DAD chromatograms of the 50% ethanol extract from <span class="html-italic">Lysimachia mauritiana</span> (<b>A</b>), MS (<b>B</b>), and MS/MS (<b>C</b>) data for the qualitative analysis of major chemical constituents. The UPLC chromatogram was acquired at 265 nm.</p>
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<p>Experimental setup and the effect of <span class="html-italic">Lysimachia mauritiana</span> extract on total and immune cell numbers in a model of airway inflammation induced by particulate matter with a diameter less than 10 µm plus diesel exhaust particles (PM10D) [<a href="#B13-nutrients-16-03732" class="html-bibr">13</a>]. (<b>A</b>) Experimental setup; (<b>B</b>) neutrophils in bronchoalveolar lavage fluid (BALF) cytospin (magnification: 200×); total numbers of (<b>C</b>) BALF cells and (<b>D</b>) lung cells. N = 6/group. ### <span class="html-italic">p</span> &lt; 0.001 vs. normal. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 vs. PM10D control (CTL).</p>
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<p>Effect of <span class="html-italic">Lysimachia mauritiana</span> extract on (<b>A</b>) the number of white blood cells (WBCs) and (<b>B</b>,<b>C</b>) WBC differential cell counting. N = 6/group. ### <span class="html-italic">p</span> &lt; 0.001 vs. normal. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001 vs. particulate matter with a diameter less than 10 µm plus diesel exhaust particles (PM10D) control (CTL).</p>
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<p>Effect of <span class="html-italic">Lysimachia mauritiana</span> extract on the release of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) in a model of airway inflammation induced by particulate matter with a diameter less than 10 µm plus diesel exhaust particles (PM10D). BALF production of (<b>A</b>) IL-1α, (<b>B</b>) CXCL1, (<b>C</b>) TNF-α, (<b>D</b>) IL-17, and (<b>E</b>) MIP-2 (n = 6/group). ## <span class="html-italic">p</span> &lt; 0.01 and ### <span class="html-italic">p</span> &lt; 0.001 vs. normal. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 vs. PM10D control (CTL).</p>
Full article ">Figure 5
<p>Effect of <span class="html-italic">Lysimachia mauritiana</span> extract on lung histopathology. (<b>A</b>) Hematoxylin and eosin (H and E) staining and Masson’s trichrome (MT) staining of the lung tissue of mice with airway inflammation induced by particulate matter with a diameter less than 10 µm plus diesel exhaust particles (PM10D) (magnification: 200×) (n = 6). (<b>B</b>) Histopathological cell damage. ### <span class="html-italic">p</span> &lt; 0.001 vs. normal., ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001 vs. PM10D control (CTL).</p>
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<p>Effect of <span class="html-italic">Lysimachia mauritiana</span> extract on the mRNA expression of airway inflammation–related genes in the lung tissue of mice with airway inflammation induced by particulate matter with a diameter less than 10 µm plus diesel exhaust particles (PM10D). mRNA expression levels of (<b>A</b>) TRPA1, (<b>B</b>) MUC5AC, (<b>C</b>) CXCL1, (<b>D</b>) TRPV1, (<b>E</b>) TNF-α, and (<b>F</b>) MIP-2 (n = 6). ## <span class="html-italic">p</span> &lt; 0.01 and ### <span class="html-italic">p</span> &lt; 0.001 vs. normal. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 vs. PM10D control (CTL).</p>
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<p>Effect of <span class="html-italic">Lysimachia mauritiana</span> extract on mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling induced by particulate matter with a diameter less than 10 µm plus diesel exhaust particles (PM10D) in the lung tissue of mice with PM10D-induced airway inflammation. (<b>A</b>) Protein expression of phospho-ERK, ERK, phospho-p38, p38, phospho-JNK, JNK, phospho-p65, p65, and β-actin. (<b>B</b>) Quantitative analysis of each protein band using ImageJ (n = 3). # <span class="html-italic">p</span> &lt; 0.05 and ## <span class="html-italic">p</span> &lt; 0.01vs. normal. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 vs. PM10D control (CTL).</p>
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<p>Effect of <span class="html-italic">Lysimachia mauritiana</span> extract on phenol red secretion in ICR mice. The amount of phenol red secretion in the airways was measured by injecting 5% phenol red into mice treated with Levosol (positive control) or LM extract for 3 days. N = 12/group. # <span class="html-italic">p</span> &lt; 0.05 vs. normal, and * <span class="html-italic">p</span> &lt; 0.05 vs. control.</p>
Full article ">
21 pages, 11740 KiB  
Article
Network Pharmacology Combined with Experimental Validation to Investigate the Mechanism of the Anti-Hyperuricemia Action of Portulaca oleracea Extract
by Yiming Zhang, Shengying Zhu, Yueming Gu, Yanjing Feng and Bo Gao
Nutrients 2024, 16(20), 3549; https://doi.org/10.3390/nu16203549 - 19 Oct 2024
Viewed by 1296
Abstract
Background/Objectives: Hyperuricemia (HUA) is a common metabolic disease caused by purine metabolic disorders in the body. Portulaca oleracea L. (PO) is an edible wild vegetable. Methods: In this study, the regulatory effect of PO on HUA and its potential mechanism were initially elucidated [...] Read more.
Background/Objectives: Hyperuricemia (HUA) is a common metabolic disease caused by purine metabolic disorders in the body. Portulaca oleracea L. (PO) is an edible wild vegetable. Methods: In this study, the regulatory effect of PO on HUA and its potential mechanism were initially elucidated through network pharmacology and experimental validation. Results: The results showed that PO from Sichuan province was superior to the plant collected from other habitats in inhibiting xanthine oxidase (XOD) activity. Berberine and stachydrine were isolated and identified from PO for the first time by UPLC-Q-Exactive Orbitrap MS. The potential molecular targets and related signaling pathways were predicted by network pharmacology and molecular docking techniques. Molecular docking showed that berberine had strong docking activity with XOD, and the results of in vitro experiments verified this prediction. Through experimental analysis of HUA mice, we found that PO can reduce the production of uric acid (UA) in the organism by inhibiting XOD activity. On the other hand, PO can reduce the body ‘s reabsorption of urate and aid in its excretion out of the body by inhibiting the urate transporter proteins (GLUT9, URAT1) and promoting the high expression of urate excretory protein (ABCG2). The results of H/E staining showed that, compared with the positive drug (allopurinol and benzbromarone) group, there was no obvious renal injury in the middle- and high-dose groups of PO extract. Conclusions: In summary, our findings reveal the potential of wild plant PO as a functional food for the treatment of hyperuricemia. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health)
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Figure 1
<p>(<b>A</b>) Photograph of the aerial parts of <span class="html-italic">Portulaca Oleracea</span>. (<b>B</b>) Mechanism map of purine metabolism and uric acid excretion pathway (Created in bioRender). (<b>C</b>) Inhibitory effect of PO extracts from different producing areas on XOD, in vitro.</p>
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<p>PO component analysis by UPLC-Q-Orbitrap MS. (<b>A</b>) Total ion chromatogram (TIC). (<b>B</b>) LC-MS chromatograms of the stachydrine (RT: 2.37) and berberine (RT: 3.41) standards. (<b>C</b>) LC-MS chromatograms of the stachydrine (RT: 2.36) and berberine (RT: 3.41) in the sample. (<b>D</b>) LC-MS chromatograms of the stachydrine ion channel (<b>left</b>) and MS2 spectra (<b>right</b>) for the separated sample. (<b>E</b>) Ion channel chromatogram (<b>left</b>) and MS2 spectra (<b>right</b>) of berberine in the separated sample.</p>
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<p>PPI network of PO active-compound targets. (<b>A</b>) Venn diagram of active compounds in PO and intersection targets in HUA. (<b>B</b>) Potential-target PPI network diagram. (<b>C</b>) Component–target–pathway network diagram for PO in the treatment of HUA.</p>
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<p>(<b>A</b>) GO function annotation. (<b>B</b>) KEGG pathway enrichment analysis. (<b>C</b>) Visualization of berberine and XOD molecular docking results. The white structure represents the ABCG2 protein, the yellow structure represents the active compound, and the green structure represents the binding site between the two. The value represents the binding affinity, and the unit is kcal/mol.</p>
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<p>Serum levels of UA and XOD in mice after intragastric administration. (<b>A</b>) Serum uric acid level in mice after intragastric administration. (<b>B</b>) The level of XOD in serum of mice after intragastric administration. <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 compared with the control group. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001, compared with the model group. ns (no significance).</p>
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<p>Serum levels of SCr and BUN in mice after intragastric administration. (<b>A</b>) The level of SCr in serum of mice after intragastric administration. (<b>B</b>) The level of BUN in serum of mice after intragastric administration. <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 compared with the control group. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001, compared with the model group. ns (no significance).</p>
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<p>H/E-stained pathological sections of mouse kidney tissue (400×).</p>
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<p>(<b>A</b>) Western Blot analysis of kidney tissues after drug administration in each group of mice. (<b>B</b>) ABCG2 protein expression level. (<b>C</b>) GLUT9 protein expression level. (<b>D</b>) URAT1 protein expression level. <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 compared with the control group. * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01, compared with the model. ns (no significance).</p>
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<p>IHC analysis of renal tissues after drug administration in each group of mice (200×). (<b>A</b>) ABCG2 protein IHC expression level. (<b>B</b>) GLUT9 protein IHC expression level. (<b>C</b>) URAT1 protein IHC expression level. <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. control. * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001, vs. model. Positive area values were analyzed by Image.</p>
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16 pages, 3717 KiB  
Article
The Protective Effects of an Aged Black Garlic Water Extract on the Prostate
by Maria Loreta Libero, Antonio J. Montero-Hidalgo, Lucia Recinella, Raúl M. Luque, Daniele Generali, Alessandra Acquaviva, Giustino Orlando, Claudio Ferrante, Luigi Menghini, Simonetta Cristina Di Simone, Nilofar Nilofar, Annalisa Chiavaroli, Luigi Brunetti and Sheila Leone
Nutrients 2024, 16(17), 3025; https://doi.org/10.3390/nu16173025 - 7 Sep 2024
Viewed by 2248
Abstract
Chronic inflammation is a recognized risk factor for various cancers, including prostate cancer (PCa). We aim to explore the potential protective effects of aged black garlic extract (ABGE) against inflammation-induced prostate damage and its impact on prostate cancer cell lines. We used an [...] Read more.
Chronic inflammation is a recognized risk factor for various cancers, including prostate cancer (PCa). We aim to explore the potential protective effects of aged black garlic extract (ABGE) against inflammation-induced prostate damage and its impact on prostate cancer cell lines. We used an ex vivo model of inflammation induced by Escherichia coli lipopolysaccharide (LPS) on C57BL/6 male mouse prostate specimens to investigate the anti-inflammatory properties of ABGE. The gene expression levels of pro-inflammatory biomarkers (COX-2, NF-κB, and TNF-α, IL-6) were measured. Additionally, we evaluated ABGE’s therapeutic effects on the prostate cancer cell lines through in vitro functional assays, including colony formation, tumorsphere formation, migration assays, and phosphorylation arrays to assess the signaling pathways (MAPK, AKT, JAK/STAT, and TGF-β). ABGE demonstrated significant anti-inflammatory and antioxidant effects in preclinical models, partly attributed to its polyphenolic content, notably catechin and gallic acid. In the ex vivo model, ABGE reduced the gene expression levels of COX-2, NF-κB, TNF-α, and IL-6. The in vitro studies showed that ABGE inhibited cell proliferation, colony and tumorsphere formation, and cell migration in the prostate cancer cells, suggesting its potential as a therapeutic agent. ABGE exhibits promising anti-inflammatory and anti-cancer properties, supporting further investigation into ABGE as a potential agent for managing inflammation and prostate cancer. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health)
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<p>Effects of aged black garlic water extract (ABGE) (10–1000 μg/mL) on LPS-induced <span class="html-italic">cyclooxygenase</span> (<span class="html-italic">COX</span>)<span class="html-italic">-2</span> (<b>a</b>), <span class="html-italic">nuclear factor kappa</span> (<span class="html-italic">NF-κ</span>) <span class="html-italic">B</span> (<b>b</b>), <span class="html-italic">tumor necrosis factor</span> (<span class="html-italic">TNF)-α</span> (<b>c</b>), and <span class="html-italic">interleukin</span> (<span class="html-italic">IL)-6</span> (<b>d</b>) gene expression (RQ, relative quantification) in mouse prostate specimens. Data shown are means ± SEM of two independent experiments with triplicate determinations. ANOVA, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.005; and *** <span class="html-italic">p</span> &lt; 0.001 vs. LPS.</p>
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<p>Effects of aged black garlic water extract (ABGE) on cell proliferation of control prostate (PNT-2) (<b>a</b>), androgen-dependent (LNCaP) (<b>b</b>), and androgen-independent (PC-3) (<b>c</b>) prostate cancer (PCa) cells. Cell proliferation and growth were evaluated by resazurin reagent after incubation for 24, 48, and 72 h of PNT-2, LNCaP, and PC-3 cell lines with ABGE at different concentrations (10, 100, 500, and 1000 µg/mL) or vehicle. Data shown are means ± SEM of 3 independent experiments with 3 replicates of each condition. ANOVA, * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> = 0.001, **** <span class="html-italic">p</span> &lt; 0.0001 vs. vehicle.</p>
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<p>Effects of aged black garlic water extract (ABGE) on colony formation of LNCaP (<b>a</b>) and PC-3 (<b>b</b>) cell lines in response to ABGE at 1000 µg/mL or vehicle. Data shown are means ± SEM of 3 independent experiments with 3 replicates of each condition. ANOVA, **** <span class="html-italic">p</span> &lt; 0.0001 vs. vehicle.</p>
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<p>Effects of aged black garlic water extract (ABGE) on tumor spheroid formation of LNCaP (<b>a</b>,<b>a.1</b>) and PC-3 (<b>b</b>,<b>b.1</b>) cell line with ABGE at 1000 µg/mL or vehicle. Data shown are means ± SEM of 3 independent experiments with 3 replicates of each condition. ANOVA, * <span class="html-italic">p</span> &lt; 0.05 vs. vehicle.</p>
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<p>Effects of aged black garlic water extract (ABGE) on migration of PC-3 cell line with ABGE at 1000 µg/mL or vehicle for 24 h. Data shown are means ± SEM of 3 independent experiments with 3 replicates of each condition. ANOVA, **** <span class="html-italic">p</span> &lt; 0.0001 vs. vehicle.</p>
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<p>Effects of aged black garlic water extract (ABGE) in combination to LPS on cell proliferation of androgen-independent PC-3 cells. Cell proliferation was evaluated by resazurin reagent after incubation for 24, 48, and 72 h of PC-3 cell line with ABGE at 1000 µg/mL or vehicle. Data shown are means ± SEM of 3 independent experiments with 3 replicates of each condition. ANOVA, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.005 vs. vehicle. ANOVA, # <span class="html-italic">p</span> &lt; 0.05, ## <span class="html-italic">p</span> &lt; 0.005 vs. ABGE.</p>
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<p>The MAPK signaling pathway in the phosphoprotein array in response to 24 h treatment of 1000 µg/mL ABGE. The log2 Fold Change in the phosphorylation protein level in comparison with that for the control condition (threshold: log2 Fold Change = 0.2).</p>
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<p>The AKT signaling pathway in the phosphoprotein array in response to 24 h treatment of 1000 µg/mL ABGE. The log2 Fold Change in the phosphorylation protein level in comparison with that for the control condition (threshold: log2 Fold Change = 0.2).</p>
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<p>The JAK/STAT signaling pathway in the phosphoprotein array in response to 24 h treatment of 1000 µg/mL ABGE. The log2 Fold Change in the phosphorylation protein level in comparison with that for the control condition (threshold: log2 Fold Change = 0.2).</p>
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<p>The TGF-β pathway in the phosphoprotein array in response to 24 h treatment of 1000 µg/mL ABGE. The log2 Fold Change in the phosphorylation protein level in comparison with that for the control condition (threshold: log2 Fold Change = 0.2).</p>
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14 pages, 3650 KiB  
Article
Effects of Castanopsis echinocarpa on Sensorineural Hearing Loss via Neuronal Gene Regulation
by Isabel Rodriguez, Youn Hee Nam, Sung Woo Shin, Gyeong Jin Seo, Na Woo Kim, Wanlapa Nuankaew, Do Hoon Kim, Yu Hwa Park, Hwa Yeon Lee, Xi Hui Peng, Bin Na Hong and Tong Ho Kang
Nutrients 2024, 16(16), 2716; https://doi.org/10.3390/nu16162716 - 15 Aug 2024
Viewed by 941
Abstract
Sensorineural hearing loss (SNHL), characterized by damage to the inner ear or auditory nerve, is a prevalent auditory disorder. This study explores the potential of Castanopsis echinocarpa (CAE) as a therapeutic agent for SNHL. In vivo experiments were conducted using zebrafish and mouse [...] Read more.
Sensorineural hearing loss (SNHL), characterized by damage to the inner ear or auditory nerve, is a prevalent auditory disorder. This study explores the potential of Castanopsis echinocarpa (CAE) as a therapeutic agent for SNHL. In vivo experiments were conducted using zebrafish and mouse models. Zebrafish with neomycin-induced ototoxicity were treated with CAE, resulting in otic hair cell protection with an EC50 of 0.49 µg/mL and a therapeutic index of 1020. CAE treatment improved auditory function and protected cochlear sensory cells in a mouse model after noise-induced hearing loss (NIHL). RNA sequencing of NIHL mouse cochleae revealed that CAE up-regulates genes involved in neurotransmitter synthesis, secretion, transport, and neuronal survival. Real-time qPCR validation showed that NIHL decreased the mRNA expression of genes related to neuronal function, such as Gabra1, Gad1, Slc32a1, CaMK2b, CaMKIV, and Slc17a7, while the CAE treatment significantly elevated these levels. In conclusion, our findings provide strong evidence that CAE protects against hearing loss by promoting sensory cell protection and enhancing the expression of genes critical for neuronal function and survival. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health)
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<p>CAE’s efficacy on otic hair cell protection after neomycin-induced ototoxicity in zebrafish model. (<b>A</b>) Number of otic hair cells in the untreated group (NM) and the treated groups (0.5, 1, 5, and 10 µg/mL of CAE). (<b>B</b>) Fluorescence images of otic hair cells in the normal (NOR), control (NM), and treated groups. Hair cells were stained with YO-PRO-1 at 0.1%. Data are presented as means ± SEM. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 (control vs. treated groups). <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 (normal vs. control group). <span class="html-italic">n</span> = 10 per group.</p>
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<p>Dose–response curves and therapeutic index of CAE. (<b>A</b>) The EC<sub>50</sub> value of CAE in neomycin (NM)-induced ototoxicity was defined as 0.497 µg/mL. (<b>B</b>) The LC<sub>50</sub> value of zebrafish embryos exposed to CAE for 48 h was defined as 500 µg/mL. (<b>C</b>) The therapeutic index (TI) of CAE was calculated to be 1020, indicating a high level of drug safety. Data are presented as means ± SEM. Conc. = concentration; EC<sub>50</sub> = 50% effective concentration; LC<sub>50</sub> = 50% lethal concentration. <span class="html-italic">n</span> = 10 per group for EC<sub>50</sub>; <span class="html-italic">n</span> = 20 per group for LC<sub>50</sub>.</p>
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<p>Toxicity evaluation of CAE based on zebrafish embryo testing. Data represent 48 h of exposure. (<b>A</b>) Hatching rate of zebrafish embryos exposed to CAE at varying concentrations: 10–1000 µg/mL. (<b>B</b>) Heartbeat rate (beats per minute) of zebrafish treated with CAE at varying concentrations: 10–400 µg/mL. (<b>C</b>) Body length of zebrafish treated with CAE at varying concentrations: 10–400 µg/mL. Data are presented as means ± SEM. <span class="html-italic">n</span> = 20 per group.</p>
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<p>Effects of CAE on auditory function in NIHL mouse model. No-treatment (NIHL) and CAE-treated groups were compared. Auditory brainstem response (ABR) threshold shifts with click stimulus (<b>A</b>), 8 kHz tone burst (<b>B</b>), and 16 kHz tone burst (<b>C</b>) in mouse model at 10 days (10 D) and 20 days (20 D) after noise insult. Data are presented as means ± SEM. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 (NIHL group vs. CAE-treated groups). CAE 100, 100 mg/kg; CAE 300, 300 mg/kg; CAE 500, 500 mg/kg. <span class="html-italic">n</span> = 10 per group.</p>
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<p>CAE alleviated cochlear hair cell damage in NIHL mice. (<b>A</b>) Outer hair cell (OHC) survival in 1 mm segments from the apex, middle, and base of the cochlea (<span class="html-italic">n</span> = 6 per group). (<b>B</b>) Fluorescence images of the outer (OHC) and inner (IHC) hair cells at the apex, middle, and base of the cochlea by Rhodamine phalloidin staining. Scale bar = 50 µm. <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 (normal group vs. NIHL group). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 (NIHL group vs. CAE-treated group). NOR = normal. CAE 100, 100 mg/kg. White triangles indicate the locations where the loss of outer hair cells occurred.</p>
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<p>Differential gene expression induced by CAE treatment in the cochlea of NIHL mice (<span class="html-italic">n</span> = 3 per group) using Reactome Pathway analysis. Heat map based on RNA-seq analysis of gene expression in the mouse cochlea and Venn diagram showing the overlap of RNA-seq results for the regulated gene set of CAE vs. NIHL group. Genes were categorized into CAE-induced and CAE-repressed groups. Of the total genes, 211 were significantly altered by CAE treatment (false discovery rate (FDR) adjusted Q &lt; 0.01, |fold change| ≥ 2.0).</p>
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<p>Functional categorization of genes up-regulated by CAE 100 mg/kg using Reactome Pathway analysis (<span class="html-italic">n</span> = 3 per group). Heat map generated from RNA-seq data showing gene sets involved in transmission across chemical synapses (<span class="html-italic">p</span> value 8.74 × 10<sup>−21</sup>; Q value 1.21 × 10<sup>−18</sup>; Enrichment score 101.5087) and the neuronal system (<span class="html-italic">p</span> value 2.92 × 10<sup>−22</sup>; Q value 8.09 × 10<sup>−20</sup>; Enrichment score 110.3959).</p>
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<p>Changes in the expression of neuronal function-related genes in NIHL mice treated with CAE 100 mg/kg. Gene expression changes were evaluated by qPCR 20 days after noise insult. The effects of CAE treatment on genes related to inhibitory synaptic transmission (<b>A</b>–<b>C</b>), neuronal survival (<b>D</b>,<b>E</b>), and synaptic function (<b>E</b>,<b>F</b>) are shown. Data are presented as means ± SEM. <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 (NOR group vs. NIHL group); ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 (NIHL group vs. CAE-treated group). NOR = normal.</p>
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10 pages, 3551 KiB  
Article
Selaginella tamariscina Ethanol Extract Attenuates Influenza A Virus Infection by Inhibiting Hemagglutinin and Neuraminidase
by Won-Kyung Cho, Hee-Jeong Choi and Jin Yeul Ma
Nutrients 2024, 16(14), 2377; https://doi.org/10.3390/nu16142377 - 22 Jul 2024
Viewed by 1014
Abstract
Selaginella tamariscina is a perennial plant that is used for diverse diseases. This study investigated whether Selaginella tamariscina has an antiviral effect against influenza A virus (IAV) infection. We used green fluorescent protein (GFP)-tagged influenza A virus (IAV) to examine the effect of [...] Read more.
Selaginella tamariscina is a perennial plant that is used for diverse diseases. This study investigated whether Selaginella tamariscina has an antiviral effect against influenza A virus (IAV) infection. We used green fluorescent protein (GFP)-tagged influenza A virus (IAV) to examine the effect of Selaginella tamariscina ethanol extract (STE) on influenza viral infection. Fluorescence microscopy and flow cytometry showed that STE potently represses GFP expression by the virus, dose-dependently. STE significantly inhibited the expression of the IAV M2, NP, HA, NA, NS1, and PB2 proteins. Time-of-addition and hemagglutination inhibition assays showed that STE has an inhibitory effect on hemagglutinin and viral binding on the cells at an early infection time. In addition, STE exerted a suppressive effect on the neuraminidase activity of the H1N1 and H3N2 IAVs. Furthermore, dose-dependently, STE inhibited the cytopathic effect induced by H3N2, as well as by H1N1 IAV. Especially in the presence of 200 µg/mL STE, the cytopathic effect was completely blocked. Our findings suggest that STE has antiviral efficacy against IAV infection; thus, it could be developed as a natural IAV inhibitor. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health)
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<p>Cytotoxicity and antiviral effect of <span class="html-italic">Selaginella tamariscina</span> ethanol extract (STE) in RAW 264.7 cells. (<b>A</b>) The toxicity of STE in the cells was evaluated using a CCK-8 assay. The data represent the mean ± SD from three independent experiments. The unpaired Student <span class="html-italic">t</span>-test was used to assess the statistical significance. * <span class="html-italic">P</span> &lt; 0.5, ** <span class="html-italic">P</span> &lt; 0.05, and *** <span class="html-italic">P</span> &lt; 0.005, compared with the untreated control. (<b>B</b>,<b>C</b>) The cells were cotreated with PR8-GFP IAV and STE. The effect of STE on PR8-GFP IAV infection was evaluated by comparing GFP expression using a fluorescence microscope (<b>B</b>) and FACS analysis (<b>C</b>). The data represent the mean ± SD from three independent experiments. The unpaired Student <span class="html-italic">t</span>-test was used to assess the statistical significance. ** <span class="html-italic">P</span> &lt; 0.005, and *** <span class="html-italic">P</span> &lt; 0.0005, compared with the virus-infected control.</p>
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<p>STE protects the cells from the cytopathic effect induced by H1N1 (<b>A</b>) and H3N2 (<b>B</b>) influenza virus infection. STE at the indicated concentrations or medium (mock) was mixed with H1N1 or H3N2 IAV before infection of the cells. The cells infected with the mixture were incubated until the cytopathic effect formed. The cell viability was determined via a CCK-8 assay. The data represent the mean ± SD from three independent experiments. The unpaired Student <span class="html-italic">t</span>-test was used to assess the statistical significance. * <span class="html-italic">P</span> &lt; 0.05, ** <span class="html-italic">P</span> &lt; 0.005; NS, no significance.</p>
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<p>STE suppresses IAV protein expression. STE and PR8-GFP IAV were incubated for 1 h at 4 °C. The cells were coinfected with the mixture for 24 h at 37 °C. The cells were fixed and detected with antibodies against IAV proteins, including M2, NP, NS1, NA, HA, and PB2 (red color). To detect the nuclei, the cells were stained with Hoechst 33342 (blue color). The co-localization images of red viral proteins and blue nuclei were captured using a fluorescence microscope.</p>
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<p>STE affects the virus attachment and entry and directly kills the virus at an early phase. The cells were cotreated with STE (100 µg/mL) and PR8-GFP IAV (10 MOI) to examine the effect of STE on viral attachment, entry, or virucidal stage. The detailed time-of-addition methods were described in the Materials and Methods Section. The images of GFP-expressing cells were obtained using brightfield and fluorescence microscopy (<b>A</b>). The cells fixed with paraformaldehyde were analyzed by flow cytometry (<b>B</b>). The data represent the mean ± SD from three independent experiments. The unpaired Student <span class="html-italic">t</span>-test was used to assess the statistical significance. ** <span class="html-italic">P</span> &lt; 0.005, *** <span class="html-italic">P</span> &lt; 0.0005; NS, no significance.</p>
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<p>STE reduces the HA unit of influenza viruses (<b>A</b>,<b>B</b>). The cells were cotreated with STE at the indicated concentrations and H1N1 IAV for 24 h at 37 °C. The 2-fold serially diluted supernatants and chicken RBC cells were mixed in round 96-well plates for 1 h at room temperature. The red circle indicates hemagglutination (HA) units.</p>
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<p>STE dose-dependently represses the neuraminidase activities of H1N1 and H3N2 IAVs. Serially diluted STE (<b>A</b>) or oseltamivir carboxylate (<b>B</b>) was mixed with H1N1 or H3N2 IAV in 96-well black plates. The detailed neuraminidase activity assay was described in materials and methods. The data represent the mean ± SD from three independent experiments. The unpaired Student <span class="html-italic">t</span>-test was used to assess the statistical significance. * <span class="html-italic">P</span> &lt; 0.05, ** <span class="html-italic">P</span> &lt; 0.005, and *** <span class="html-italic">P</span> &lt; 0.0005, compared with the H1N1 virus-infected group. <sup>#</sup> <span class="html-italic">P</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">P</span> &lt; 0.005, and <sup>###</sup> <span class="html-italic">P</span> &lt; 0.0005, compared with the H3N2 virus-infected group.</p>
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12 pages, 1726 KiB  
Article
Antithrombotic Effect of Oil from the Pulp of Bocaiúva—Acrocomia aculeata (Jacq.) Lodd. ex Mart. (Arecaceae)
by Isabelly Teixeira Espinoça, Denise Caroline Luiz Soares Basilio, Anna Júlia Papa de Araujo, Rafael Seiji Nakano Ota, Kamylla Fernanda Souza de Souza, Nadla Soares Cassemiro, Davi Campos Lagatta, Edgar Julian Paredes-Gamero, Maria Lígia Rodrigues Macedo, Denise Brentan Silva, Janaina de Cássia Orlandi Sardi, Danilo Wilhelm-Filho, Ana Cristina Jacobowski and Eduardo Benedetti Parisotto
Nutrients 2024, 16(13), 2024; https://doi.org/10.3390/nu16132024 - 26 Jun 2024
Viewed by 1524
Abstract
The study aimed to evaluate the antithrombotic action of Acrocomia aculeata pulp oil (AAPO) in natura, in an in vitro experimental model. AAPO was obtained by solvent extraction, and its chemical characterization was performed by gas chromatography coupled to a mass spectrometer (GC-MS). [...] Read more.
The study aimed to evaluate the antithrombotic action of Acrocomia aculeata pulp oil (AAPO) in natura, in an in vitro experimental model. AAPO was obtained by solvent extraction, and its chemical characterization was performed by gas chromatography coupled to a mass spectrometer (GC-MS). In vitro toxicity was evaluated with the Trypan Blue exclusion test and in vivo by the Galleria mellonella model. ADP/epinephrine-induced platelet aggregation after treatment with AAPO (50, 100, 200, 400, and 800 μg/mL) was evaluated by turbidimetry, and coagulation was determined by prothrombin activity time (PT) and activated partial thromboplastin time (aPTT). Platelet activation was measured by expression of P-selectin on the platelet surface by flow cytometry and intraplatelet content of reactive oxygen species (ROS) by fluorimetry. The results showed that AAPO has as major components such as oleic acid, palmitic acid, lauric acid, caprylic acid, and squalene. AAPO showed no toxicity in vitro or in vivo. Platelet aggregation decreased against agonists using treatment with different concentrations of AAPO. Oil did not interfere in PT and aPTT. Moreover, it expressively decreased ROS-induced platelet activation and P-selectin expression. Therefore, AAPO showed antiplatelet action since it decreased platelet activation verified by the decrease in P-selectin expression as well as in ROS production. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health)
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<p>Toxicity in human platelets and systemic in <span class="html-italic">G. mellonella</span>. (<b>A</b>) Percentage (%) of human platelet viability obtained in PRP treated with <span class="html-italic">Acrocomia aculeata</span> (AAPO) pulp oil at different concentrations (50, 100, 200, 400, and 800 μg/mL); negative control (NC): vehicle (DMSO, 0.6%) and positive control (PC): Triton X100 (1%). (***) indicates statistical difference with <span class="html-italic">p</span> &lt; 0.001 compared to NC. (<b>B</b>) In vivo systemic toxicity in <span class="html-italic">G. mellonella</span> model treated with different concentrations (50, 100, 400, and 800 μg/mL) of AAPO. The percentage of survival was evaluated for 72 h; negative control (NC): saline and positive control: DMSO (100%). Difference estimates in survival were compared using a <span class="html-italic">p</span> &lt; 0.05 log-rank test.</p>
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<p>Effect of AAPO on platelet aggregation induced by ADP and epinephrine. Percentage (%) of platelet aggregation at different concentrations of AAPO (50, 100, 200, 400, and 800 μg/mL), induced by ADP (30 μM) (<b>A</b>,<b>B</b>) and epinephrine (5 μg/mL) (<b>C</b>,<b>D</b>) for 5 and 10 min, respectively; negative control—NC (DMSO 0.6%) and positive control—PC (Ticlopidine 10 μM). (***) The statistical difference with <span class="html-italic">p</span> &lt; 0.001 compared to negative control (NC). (#) The statistical difference with <span class="html-italic">p</span> &lt; 0.001 compared to positive control (PC).</p>
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<p>Expression of platelet surface P-selectin after exposure of platelets to AAPO. (<b>A</b>) Representative dot plots generated by FlowJo software. The gate shows the platelet population. (<b>B</b>) Representative dot plot showing a platelet-positive population (CD42b-FITC). (<b>C</b>) Representative histograms showing the activation of platelets incubated with AAPO and stimulated by ADP (30 μM) for 5 min. Activated platelets were labeled with CD42b-FITC (5 μL) and CD62P (CD62P-PE, 5 μL) and kept in the dark for 15 min. (<b>D</b>) Mean fluorescence intensity (MFI) of CD62P-PE expressed on the membrane of activated platelets treated with different concentrations of AAPO (50, 100, 200, 400, and 800 μg/mL). DMSO (0.6%): negative control; ADP (30 μM): positive control. Three independent experiments were performed. (***) The statistical difference with <span class="html-italic">p</span> &lt; 0.001 compared to negative control. (##) The statistical difference with <span class="html-italic">p</span> &lt; 0.01 and (###) statistical difference with <span class="html-italic">p</span> &lt; 0.001 compared to ADP group.</p>
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<p>Intraplatelet content of ROS in AAPO-treated platelets. Intraplatelet ROS content after 30 min of incubation with DCFH-DA (10 µM), in platelets treated with 50, 100, 200, 400, and 800 μg/mL of <span class="html-italic">A. aculeata</span> pulp oil (AAPO) or controls; negative control—NC (DMSO 0.6%) and positive control—PC (hydrogen peroxide, H<sub>2</sub>O<sub>2</sub>). (***) The statistical difference with <span class="html-italic">p</span> &lt; 0.001 compared to negative control (NC). (#) The statistical difference with <span class="html-italic">p</span> &lt; 0.001 compared to positive control (PC).</p>
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14 pages, 2167 KiB  
Article
Antidiabetic Effect of Passiflora ligularis Leaves in High Fat-Diet/Streptozotocin-Induced Diabetic Mice
by Diana P. Rey, Sandra M. Echeverry, Ivonne H. Valderrama, Ingrid A. Rodriguez, Luis F. Ospina, Fatima Regina Mena Barreto Silva and Marcela Aragón
Nutrients 2024, 16(11), 1669; https://doi.org/10.3390/nu16111669 - 29 May 2024
Viewed by 1246
Abstract
Type 2 diabetes mellitus (T2DM) is a major global public health concern, prompting the ongoing search for new treatment options. Medicinal plants have emerged as one such alternative. Our objective was to evaluate the antidiabetic effect of an extract from the leaves of [...] Read more.
Type 2 diabetes mellitus (T2DM) is a major global public health concern, prompting the ongoing search for new treatment options. Medicinal plants have emerged as one such alternative. Our objective was to evaluate the antidiabetic effect of an extract from the leaves of Passiflora ligularis (P. ligularis). For this purpose, T2DM was first induced in mice using a high-fat diet and low doses of streptozotocin. Subsequently, an aqueous extract or an ethanolic extract of P. ligularis leaves was administered for 21 days. The following relevant results were found: fasting blood glucose levels were reduced by up to 41%, and by 29% after an oral glucose overload. The homeostasis model assessment of insulin resistance (HOMA-IR) was reduced by 59%. Histopathologically, better preservation of pancreatic tissue was observed. Regarding oxidative stress parameters, there was an increase of up to 48% in superoxide dismutase (SOD), an increase in catalase (CAT) activity by 35% to 80%, and a decrease in lipid peroxidation (MDA) by 35% to 80% in the liver, kidney, or pancreas. Lastly, regarding the lipid profile, triglycerides (TG) were reduced by up to 30%, total cholesterol (TC) by 35%, and low-density lipoproteins (LDL) by up to 32%, while treatments increased high-density lipoproteins (HDL) by up to 35%. With all the above, we can conclude that P. ligularis leaves showed antihyperglycemic, hypolipidemic, and antioxidant effects, making this species promising for the treatment of T2DM. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health)
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Figure 1

Figure 1
<p>Chromatographic profile of aqueous extract of <span class="html-italic">Passiflora ligularis</span> leaves (blue) and an ethanol fraction of <span class="html-italic">Passiflora ligularis</span> leaves (pink) at 350 nm. Chromatographic signal 1 corresponds to isoquercetin, signal 2 corresponds to astragalin, and signal 3 corresponds to chrysin. The analytical method used was previously described in the methodology section.</p>
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<p>Difference between day 0 and 7, 14, and 21 days in blood glucose levels (BGLs) of the experimental mice. Normoglycemic (blue), vehicle (red), metformin 250 mg/kg (purple), aqueous extract 500 mg/kg (yellow), ethanol fraction 250 mg/kg (green). Data are expressed as mean ± SEM, <span class="html-italic">n</span> = 6 animals per group. Two-way ANOVA post-test Bonferroni; **** <span class="html-italic">p</span> &lt; 0.0001 with respect to the vehicle group.</p>
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<p>Oral glucose overload test. Normoglycemic (blue), vehicle (red), metformin 250 mg/kg (purple), aqueous extract of <span class="html-italic">P. ligularis</span> 500 mg/kg (yellow), ethanol fraction of <span class="html-italic">P. ligularis</span> 250 mg/kg (green). Data are expressed as mean ± SEM, <span class="html-italic">n</span> = 6 animals per group. Two-way ANOVA post-test Bonferroni; **** <span class="html-italic">p</span> &lt; 0.0001 with respect to the vehicle group.</p>
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<p>Photomicrographs of pancreatic tissues from different experimental groups were stained by hematoxylin and eosin (H&amp;E) and examined with magnifying power (40×). (<b>a</b>) Normoglycemic group, (<b>b</b>) Vehicle, (<b>c</b>) Metformin, (<b>d</b>) Aqueous extract of <span class="html-italic">P. ligularis</span>, (<b>e</b>) Ethanol fraction of <span class="html-italic">P. ligularis</span>. Arrows show the presence of Langerhans islets.</p>
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<p>Effect of <span class="html-italic">P. ligularis</span> on oxidative stress parameters. Normoglycemic (blue), vehicle (red), metformin 250 mg/kg (purple), aqueous extract of <span class="html-italic">P. ligularis</span> 500 mg/kg (yellow), ethanol fraction of <span class="html-italic">P. ligularis</span> 250 mg/kg (green). SOD activity: (<b>a</b>) liver, (<b>b</b>) kidney, (<b>c</b>) pancreas; CAT activity: (<b>d</b>) liver, (<b>e</b>) kidney, (<b>f</b>) pancreas; MDA levels: (<b>g</b>) liver, (<b>h</b>) kidney, (<b>i</b>) pancreas. Data are expressed as mean ± SEM, <span class="html-italic">n</span> = 6 animals per group. One-way ANOVA post-test Dunnet; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 and **** <span class="html-italic">p</span> &lt; 0.0001 with respect to the vehicle group.</p>
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Review

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19 pages, 327 KiB  
Review
Ashwagandha’s Multifaceted Effects on Human Health: Impact on Vascular Endothelium, Inflammation, Lipid Metabolism, and Cardiovascular Outcomes—A Review
by Michał Wiciński, Anna Fajkiel-Madajczyk, Zuzanna Kurant, Sara Liss, Paweł Szyperski, Monika Szambelan, Bartłomiej Gromadzki, Iga Rupniak, Maciej Słupski and Iwona Sadowska-Krawczenko
Nutrients 2024, 16(15), 2481; https://doi.org/10.3390/nu16152481 - 31 Jul 2024
Cited by 1 | Viewed by 9723
Abstract
Withania somnifera, commonly known as Ashwagandha, has been popular for many years. Numerous studies have shown that the extract of this plant, due to its wealth of active substances, can induce anti-inflammatory, neuroprotective, immunomodulatory, hepatoprotective, cardioprotective, anti-diabetic, adaptogenic, anti-arthritic, anti-stress, and antimicrobial [...] Read more.
Withania somnifera, commonly known as Ashwagandha, has been popular for many years. Numerous studies have shown that the extract of this plant, due to its wealth of active substances, can induce anti-inflammatory, neuroprotective, immunomodulatory, hepatoprotective, cardioprotective, anti-diabetic, adaptogenic, anti-arthritic, anti-stress, and antimicrobial effects. This review examines the impact of Ashwagandha extract on the vascular endothelium, inflammation, lipid metabolism, and cardiovascular outcomes. Studies have shown that Ashwagandha extracts exhibit an anti-angiogenic effect by inhibiting vascular endothelial growth factor (VEGF)-induced capillary sprouting and formation by lowering the mean density of microvessels. Furthermore, the results of numerous studies highlight the anti-inflammatory role of Ashwagandha extract, as the action of this plant causes a decrease in the expression of pro-inflammatory cytokines. Interestingly, withanolides, present in Ashwagandha root, have shown the ability to inhibit the differentiation of preadipocytes into adipocytes. Research results have also proved that W. somnifera demonstrates cardioprotective effects due to its antioxidant properties and reduces ischemia/reperfusion-induced apoptosis. It seems that this plant can be successfully used as a potential treatment for several conditions, mainly those with increased inflammation. More research is needed to elucidate the exact mechanisms by which the substances contained in W. somnifera extracts can act in the human body. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health)
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