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Dipartimento di Scienze e Tecnologie Biologiche, Chimiche, Farmaceutiche (STEBICEF), Edificio 16, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy

Dr. Patrizia Bovolin

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Department of Life Sciences and Systems Biology, University of Torino, Torino, Italy

Molecular and Cellular Aspects of the Beneficial Effects of Natural Products on Chronic Diseases

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closed (31 August 2024)

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31 October 2024

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Topic Information

Dear Colleagues,

Chronic diseases account for more than 80% of deaths across the globe. They include hypertension, diabetes, cancer, and cardiovascular, kidney, respiratory, and liver diseases and are often characterized by long-term, low-grade inflammation. Chronic diseases share several common risk factors and underlying determinants, such as low physical activity, obesity, poor diet, disturbed sleep patterns, and stress. These common determinants represent opportunities for effective intervention to improve the disease trajectory toward a more favorable course. Natural products are the oldest forms of medication in human history, and bioactive molecules from natural products can still contribute to new drug development today thanks to their broad chemical and functional diversity. Over the past few decades, several studies have demonstrated that the dietary intake of vegetables, fruits, grains, and legumes rich in bioactive compounds such as flavonoids, anthocyanins, procyanidins, and several others can help combat and prevent various chronic conditions. Considering that oxidative stress and chronic inflammation are the hallmarks of several chronic diseases, promising cellular effects of various bioactive molecules are their antioxidant and anti-inflammatory actions. Other promising properties are the anti-lipogenic and anti-diabetic activities for the treatment of metabolic diseases. However, the detailed effects of bioactive natural compounds at the cellular and molecular levels remain largely unknown. The scope of this Topic is to highlight the recent advances and progress made in the mechanisms of action of bioactive natural compounds against chronic diseases. We welcome original research, reviews, and perspective articles describing in vivo, in vitro, and in silico studies. We look forward to receiving your contributions.

Prof. Dr. Claudio Luparello
Dr. Patrizia Bovolin
Topic Editors

Keywords

chronic diseases
bioactive natural compounds
cancer
metabolic syndrome
cardiovascular diseases
liver diseases
anti-lipogenic
antioxidant
anti-inflammatory
metabolomics/proteomics/transcriptomics

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomolecules biomolecules	4.8	9.4	2011	16.3 Days	CHF 2700	Submit
Cancers cancers	4.5	8.0	2009	16.3 Days	CHF 2900	Submit
Diseases diseases	2.9	0.8	2013	18.9 Days	CHF 1800	Submit
International Journal of Molecular Sciences ijms	4.9	8.1	2000	18.1 Days	CHF 2900	Submit
Nutrients nutrients	4.8	9.2	2009	17.5 Days	CHF 2900	Submit

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17 pages, 1589 KiB

Open AccessArticle

Effect of Spermidine on Endothelial Function in Systemic Lupus Erythematosus Mice

by Hyoseon Kim and Michael P. Massett

Int. J. Mol. Sci. 2024, 25(18), 9920; https://doi.org/10.3390/ijms25189920 (registering DOI) - 14 Sep 2024

Viewed by 244

Abstract

Endothelial dysfunction is common in Systemic Lupus Erythematosus (SLE), even in the absence of cardiovascular disease. Evidence suggests that impaired mitophagy contributes to SLE. Mitochondrial dysfunction is also associated with impaired endothelial function. Spermidine, a natural polyamine, stimulates mitophagy by the PINK1–parkin pathway and counters age-associated endothelial dysfunction. However, the effect of spermidine on mitophagy and vascular function in SLE has not been explored. To address this gap, 9-week-old female lupus-prone (MRL/lpr) and healthy control (MRL/MpJ) mice were randomly assigned to spermidine treatment (lpr_Spermidine and MpJ_Spermidine) for 8 weeks or as control (lpr_Control and MpJ_Control). lpr_Control mice exhibited impaired endothelial function (e.g., decreased relaxation to acetylcholine), increased markers of inflammation, and lower protein content of parkin, a mitophagy marker, in the thoracic aorta. Spermidine treatment prevented endothelial dysfunction in MRL-lpr mice. Furthermore, aortas from lpr_Spermidine mice had lower levels of inflammatory markers and higher levels of parkin. Lupus phenotypes were not affected by spermidine. Collectively, these results demonstrate the beneficial effects of spermidine treatment on endothelial function, inflammation, and mitophagy in SLE mice. These results support future studies of the beneficial effects of spermidine on endothelial dysfunction and cardiovascular disease risk in SLE. Full article

(This article belongs to the Topic Molecular and Cellular Aspects of the Beneficial Effects of Natural Products on Chronic Diseases)

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Figure 1

Figure 1
Spermidine prevents endothelial dysfunction in lupus mice. Relaxation responses to increasing concentrations of ACh (A) and SNP (B) in thoracic aortas from MRL/lpr and MRL/MpJ mice with and without spermidine treatment. Values are mean ± SEM, n = 11–15 per group. BL, baseline after 70% maximal contraction with phenylephrine. * significant difference between lpr_Control and MpJ_Control, p < 0.05. # significant difference between lpr_Control and lpr_Spermidine, p < 0.05. Full article ">Figure 2
Effect of spermidine on endothelial nitric oxide synthase (eNOS). Densitometry analysis of the Western Blot and mRNA expression for p-eNOS/eNOS (A), total eNOS (B), and NOS3 (C) in thoracic and abdominal aortas from MRL/lpr and MRL/MpJ mice with and without spermidine treatment. (D) Western Blot images for phosphorylated eNOS, total eNOS, and total protein by Ponceau stain in thoracic aorta. Values are mean ± SEM. n = 3–5 mice per group. Full article ">Figure 3
Negative correlation between anti-dsDNA Ab levels and maximal responses to ACh (%). The box contains the correlation coefficient (r) and p value. Full article ">Figure 4
SLE mice have impaired mitophagy in the aorta and liver. Densitometry analysis of the Western Blot for parkin (A,B) and LC3II/I (C,D) in thoracic aortas (left: A,C) and livers (right: B,D) from MRL/lpr and MRL/MpJ mice with and without spermidine treatment. (E) Western Blot images of parkin, LC3II, LC3I, and total protein by Ponceau stain. Values are mean ± SEM, n = 3–6 mice per group. * significantly different from MpJ_Control, p < 0.05. # significantly different from lpr_Control, p < 0.05. Full article ">Figure 5
Vascular inflammatory markers are elevated in lupus mice. Densitometry analysis of the Western Blot (A) and mRNA expression (B) for Vcam1 in thoracic and abdominal aortas from MRL/lpr and MRL/MpJ mice with and without spermidine treatment. (C) Western Blot images of Vcam1 and total protein by Ponceau stain. Values are mean ± SEM. n = 4–7 mice per group. * significantly different from MpJ_Control, p < 0.05. Full article ">Figure 6
Interferon regulatory factor 1 (Irf-1) gene expression in lupus mice. mRNA expression of interferon regulatory factor 1 (Irf1) shown in the spleen (A) and liver (B) from MRL/lpr and MRL/MpJ mice with and without spermidine treatment. Values are mean ± SEM. n = 3–4 mice per group. * significantly different from MpJ_Control, p < 0.05. Full article ">

16 pages, 3625 KiB

Open AccessArticle

In Vitro Investigation of the Anti-Fibrotic Effects of 1-Phenyl-2-Pentanol, Identified from Moringa oleifera Lam., on Hepatic Stellate Cells

by Watunyoo Buakaew, Sucheewin Krobthong, Yodying Yingchutrakul, Nopawit Khamto, Pornsuda Sutana, Pachuen Potup, Yordhathai Thongsri, Krai Daowtak, Antonio Ferrante, Catherine Léon and Kanchana Usuwanthim

Int. J. Mol. Sci. 2024, 25(16), 8995; https://doi.org/10.3390/ijms25168995 - 19 Aug 2024

Viewed by 758

Abstract

Liver fibrosis, characterized by excessive extracellular matrix deposition, is driven by activated hepatic stellate cells (HSCs). Due to the limited availability of anti-fibrotic drugs, the research on therapeutic agents continues. Here we have investigated Moringa oleifera Lam. (MO), known for its various bioactive properties, for anti-fibrotic effects. This study has focused on 1-phenyl-2-pentanol (1-PHE), a compound derived from MO leaves, and its effects on LX-2 human hepatic stellate cell activation. TGF-β1-stimulated LX-2 cells were treated with MO extract or 1-PHE, and the changes in liver fibrosis markers were assessed at both gene and protein levels. Proteomic analysis and molecular docking were employed to identify potential protein targets and signaling pathways affected by 1-PHE. Treatment with 1-PHE downregulated fibrosis markers, including collagen type I alpha 1 chain (COL1A1), collagen type IV alpha 1 chain (COL4A1), mothers against decapentaplegic homologs 2 and 3 (SMAD2/3), and matrix metalloproteinase-2 (MMP2), and reduced the secretion of matrix metalloproteinase-9 (MMP-9). Proteomic analysis data showed that 1-PHE modulates the Wnt/β-catenin pathway, providing a possible mechanism for its effects. Our results suggest that 1-PHE inhibits the TGF-β1 and Wnt/β-catenin signaling pathways and HSC activation, indicating its potential as an anti-liver-fibrosis agent. Full article

(This article belongs to the Topic Molecular and Cellular Aspects of the Beneficial Effects of Natural Products on Chronic Diseases)

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Figure 1
The dose–response curves of LX-2 cell viability after treatment with varying concentrations of crude Moringa extract or 1-phenyl-2-pentanol. Full article ">Figure 2
The expression of liver fibrotic-associated genes and the MMP-9 level in crude MO extract and 1-PHE treated cells. The LX-2 cells at 2 × 105 cells/well were incubated with different concentrations of crude MO extract or 1-PHE in the presence of 10 ng/mL TGF-β1 for 48 h. The cells were harvested and the mRNA expression measured using real-time qRT-PCR. (A) The candidate liver fibrotic-associated genes, as shown above, include COL1A1, TIMP1, MMP2, SMAD2, and SMAD3. The relative gene expression was normalized to GAPDH. (B) The cell culture supernatant was collected and evaluated for the MMP-9 level. The data are presented as mean ± SD. p-value < 0.0332 (*), p-value < 0.0021 (**), p-value < 0.0002 (***), p-value < 0.0001 (****). Full article ">Figure 3
The proteomic profiling of DEPs and GO annotation analysis. In total, 1570 DEPs were identified following treatment of LX-2 cells with 1-PHE and TGF-β1 (A). Statistical thresholds (log2 fold change ≤1.5 or ≥1.5; p-value < 0.05) were applied to distinguish significantly upregulated (n = 68; red dots) and downregulated (n = 30; blue dots) proteins (B). Protein–protein interaction (PPI) network analysis demonstrated interconnectedness within the sets of upregulated and downregulated DEPs (C,D). To illuminate the potential functions of these DEPs, Gene Ontology (GO) annotation was employed, categorizing proteins by biological process, cellular component, and molecular function (E,F). Full article ">Figure 4
KEGG signaling pathway enrichment analysis of DEPs. KEGG signaling pathway enrichment analysis was performed on DEPs to elucidate the potential impact of 1-PHE on signaling pathways within LX-2 cells. Notably, Parkinson’s disease emerged as the most significantly enriched pathway associated with upregulated DEPs (A). In contrast, the renin secretion signaling pathway demonstrated the strongest enrichment among downregulated proteins (B). Intriguingly, the Wnt signaling pathway, a pathway strongly implicated in liver fibrosis and HSC activation, was also found to be downregulated (C). Downregulated genes were indicated by the color blue, while other genes within the pathway were represented by green. LRP5, LDL-receptor-related protein 5; PRKACA, protein kinase cAMP-activated catalytic subunit alpha. Full article ">Figure 5
The 2D and 3D structural characteristics of ligand-protein complexes. Specifically, the interactions between PRKACA and two ligands, 1-PHE and 3SB, were visualized (A,B). Additionally, the interaction between 1-PHE and LRP5 was investigated (C). Full article ">Figure 6
Illustration of the results of 250-nanosecond molecular dynamics simulations comparing the interactions of 1-PHE with PRKACA (A–D) and LRP5 (E–H). (A,D) present root mean square deviation (RMSD) plots, (B,F) display root mean square fluctuation (RMSF) plots, (C,G) depict numbers of hydrogen bonds, and (D,H) showcase radius of gyration (Rg) plots. Full article ">

13 pages, 1992 KiB

Open AccessArticle

Inhibitive Mechanism of Loquat Flower Isolate on Tyrosinase Activity and Melanin Synthesis in Mouse Melanoma B16 Cells

by Qianqian Chen, Wenyang Tao, Jianfeng Wang, Jingrui Li, Meiyu Zheng, Yinying Liu, Shengmin Lu and Zhongxiang Fang

Biomolecules 2024, 14(8), 895; https://doi.org/10.3390/biom14080895 - 24 Jul 2024

Viewed by 592

Abstract

Melanin naturally exists in organisms and is synthetized by tyrosinase (TYR); however, its over-production may lead to aberrant pigmentation and skin conditions. Loquat (Eriobotrya japonica (Thunb.) Lindl.) flowers contain a variety of bioactive compounds, while studies on their suppressive capabilities against melanin synthesis are limited. Loquat flower isolate product (LFP) was obtained by ethanol extraction and resin purification, and its inhibitory efficiency against TYR activity was investigated by enzyme kinetics and multiple spectroscopy analyses. In addition, the impact of LFP on melanin synthesis-related proteins’ expression in mouse melanoma B16 cells was analyzed using Western blotting. HPLC-MS/MS analysis indicated that LFP was composed of 137 compounds, of which 12 compounds, including flavonoids (quercetin, isorhamnoin, p-coumaric acid, etc.) and cinnamic acid and its derivatives, as well as benzene and its derivatives, might have TYR inhibitory activities. LFP inhibited TYR activity in a concentration-dependent manner with its IC50 value being 2.8 mg/mL. The inhibition was an anti-competitive one through altering the enzyme’s conformation rather than chelating copper ions at the active center. LFP reduced the expression of TYR, tyrosinase-related protein (TRP) 1, and TRP2 in melanoma B16 cells, hence inhibiting the synthesis of melanin. The research suggested that LFP had the potential to reduce the risks of hyperpigmentation caused by tyrosinase and provided a foundation for the utilization of loquat flower as a natural resource in the development of beauty and aging-related functional products. Full article

(This article belongs to the Topic Molecular and Cellular Aspects of the Beneficial Effects of Natural Products on Chronic Diseases)

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Figure 1
Inhibitory effects of LFP (A) and kojic acid (B) on in vitro activities of tyrosinase and LFP’s effect on the reaction rate of tyrosinase (C) and its Lineweaver–Burk curves (D). v on the ordinate and [E] and [S] on the abscissa refer to the reaction rate, tyrosinase concentration, and substrate (L-DOPA) concentration, respectively. Full article ">Figure 2
Effects of different concentrations of Cu2+ on the ultraviolet-visible spectra of LFP (A) and the comparison on the Fourier transform infrared spectra of tyrosinase and its mixture with LFP (B). Full article ">Figure 3
Effect of different concentrations of LFP on the fluorescence intensity of tyrosinase (A), the relative fluorescence intensity changed with LFP concentrations (B), and Stern–Volmer curve graphs of fluorescence quenching of tyrosinase by LFP (C). F0 and F represent the fluorescence intensity of TYR in the absence and presence of LFP, respectively, and [Q] means the concentration of the quencher (LFP). Full article ">Figure 4
Effect of LFP on the cell viability (A), TYR activities (B), and melanin contents (C) in mouse melanoma B16 cells. * and ** indicate p < 0.05 and p < 0.01, respectively, compared with the blank control. Full article ">Figure 5
Effects of LFP and kojic acid on TYR (A), TRP1 (B), and TRP2 (C) expressions in mouse melanoma B16 cells and the combined electrophoregrams of three related proteins after different treatments (D). The numbers on the abscissas and the electrophoregrams represent groups of the blank control (without LFP, 1), 50 μg/mL LFP treatment (2), 100 μg/mL LFP treatment (3), and 25 μg/mL kojic acid (4). *, **, ***, and **** indicate the significant difference levels at p < 0.05, p < 0.01, p < 0.001, and p < 0.0001, respectively. Full article ">

14 pages, 1868 KiB

Open AccessArticle

Investigating the Antifibrotic Effects of β-Citronellol on a TGF-β1-Stimulated LX-2 Hepatic Stellate Cell Model

by Watunyoo Buakaew, Sucheewin Krobthong, Yodying Yingchutrakul, Pachuen Potup, Yordhathai Thongsri, Krai Daowtak, Antonio Ferrante and Kanchana Usuwanthim

Biomolecules 2024, 14(7), 800; https://doi.org/10.3390/biom14070800 - 5 Jul 2024

Viewed by 1040

Abstract

Liver fibrosis, a consequence of chronic liver damage or inflammation, is characterized by the excessive buildup of extracellular matrix components. This progressive condition significantly raises the risk of severe liver diseases like cirrhosis and hepatocellular carcinoma. The lack of approved therapeutics underscores the urgent need for novel anti-fibrotic drugs. Hepatic stellate cells (HSCs), key players in fibrogenesis, are promising targets for drug discovery. This study investigated the anti-fibrotic potential of Citrus hystrix DC. (KL) and its bioactive compound, β-citronellol (β-CIT), in a human HSC cell line (LX-2). Cells exposed to TGF-β1 to induce fibrogenesis were co-treated with crude KL extract and β-CIT. Gene expression was analyzed by real-time qRT-PCR to assess fibrosis-associated genes (ACTA2, COL1A1, TIMP1, SMAD2). The release of matrix metalloproteinase 9 (MMP-9) was measured by ELISA. Proteomic analysis and molecular docking identified potential signaling proteins and modeled protein–ligand interactions. The results showed that both crude KL extract and β-CIT suppressed HSC activation genes and MMP-9 levels. The MAPK signaling pathway emerged as a potential target of β-CIT. This study demonstrates the ability of KL extract and β-CIT to inhibit HSC activation during TGF-β1-induced fibrogenesis, suggesting a promising role of β-CIT in anti-hepatic fibrosis therapies. Full article

(This article belongs to the Topic Molecular and Cellular Aspects of the Beneficial Effects of Natural Products on Chronic Diseases)

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Figure 1
Dose–response curve of crude KL extract and β-citronellol on viability of the LX-2 cells. Full article ">Figure 2
Crude KL extract and β-CIT attenuate the expression of hepatic-fibrosis-associated genes and mitigate MMP-9 production in LX-2 cells challenged with TGF-β1. Following a 24 h co-treatment protocol, mRNA was extracted and subjected to real-time qRT-PCR analysis. Expression levels were normalized to the housekeeping gene GAPDH (A), revealing a marked downregulation of fibrosis-related genes. Furthermore, a statistically significant reduction in MMP-9 levels was observed in the cell culture supernatant (B). Statistical significance was denoted as follows: p < 0.0332 (*), p < 0.0002 (***), p < 0.0001 (****). Full article ">Figure 3
The functional enrichment analysis of DEPs. Quantitative LC-MS/MS analysis yielded a total of 1570 differentially expressed proteins (DEPs) (A). Volcano plots visually demonstrated the upregulated (n = 125, red) and downregulated (n = 65, green) proteins within this dataset (B). To elucidate potential functional relationships, protein–protein interaction (PPI) network analyses were performed separately for the upregulated (C) and downregulated (D) protein subsets. Gene ontology (GO) annotations illuminated key biological processes associated with both upregulated (E) and downregulated (F) DEPs. Full article ">Figure 4
The KEGG analysis of DEPs. Amongst the most significantly enriched KEGG signaling pathways, differential protein expression patterns emerged (upregulated: A; downregulated: B). Notably, the MAPK signaling pathway exhibited a pronounced association with downregulated proteins (C; indicated in blue). Full article ">Figure 5
The 2D and 3D structures of candidate target proteins and β-CIT interaction. Full article ">

23 pages, 5402 KiB

Open AccessArticle

Antimelanoma Effects of Alchemilla vulgaris: A Comprehensive In Vitro and In Vivo Study

by Sanja Jelača, Ivan Jovanovic, Dijana Bovan, Sladjana Pavlovic, Nevena Gajovic, Duško Dunđerović, Zora Dajić-Stevanović, Aleksandar Acović, Sanja Mijatović and Danijela Maksimović-Ivanić

Diseases 2024, 12(6), 125; https://doi.org/10.3390/diseases12060125 - 8 Jun 2024

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Abstract

Due to the rich ethnobotanical and growing evidence-based medicine records, the Alchemillae herba, i.e., the upper parts of the Lady’s mantle (Alchemilla vulgaris L.), was used for the assessment of antimelanoma activity. The ethanolic extract of A. vulgaris strongly suppressed the viability of B16F1, B16F10, 518A2, and Fem-X cell lines. In contrast to the in vitro study, where the B16F1 cells were more sensitive to the treatment than the more aggressive counterpart B16F10, the results obtained in vivo using the corresponding syngeneic murine model were quite the opposite. The higher sensitivity of B16F10 tumors in vivo may be attributed to a more complex response to the extract compared to one triggered in vitro. In addition, the strong immunosuppressive microenvironment in the B16F1 model is impaired by the treatment, as evidenced by enhanced antigen-presenting potential of dendritic cells, influx and activity of CD4⁺ T and CD8⁺ T lymphocytes, decreased presence of T regulatory lymphocytes, and attenuation of anti-inflammatory cytokine production. All these effects are supported by the absence of systemic toxicity. A. vulgaris extract treatment results in a sustained and enhanced ability to reduce melanoma growth, followed by the restoration of innate and adopted antitumor immunity without affecting the overall physiology of the host. Full article

(This article belongs to the Topic Molecular and Cellular Aspects of the Beneficial Effects of Natural Products on Chronic Diseases)

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Figure 1

Figure 1
A. vulgaris extract decreases melanoma cell viability in vitro and suppresses tumor cell growth in vivo. B16F1 and B16F10 cells were treated with a wide range of concentrations of A. vulgaris extract and viability assays (MTT and SRB) were performed after 72 h. All data are presented as mean ± SD from one representative out of three independent experiments and statistically significant were considered p values less than 0.05, compared to controls (upper panel). Primary tumors were induced by sc. inoculation of B16F1 or B16F10 cells into C57BL/6 mice and treated with 50 mg/kg of A. vulgaris extract (n = 10 animals per group). For evaluation of statistical significance between groups in in vivo experiments, the non-parametric Mann–Whitney test was used (lower panel). * p < 0.05; *** p < 0.001. Full article ">Figure 2
A. vulgaris extract exhibits different modes of action on B16F1 and B16F10 cell lines. Cells were treated with an IC50 dose of A. vulgaris extract for 72 h. Cellular proliferation (CFSE), apoptosis (Ann/PI), and autophagy (AO) were detected by corresponding staining followed by flow cytometry analysis (A). Data are presented as mean ± SD from three independent experiments. B16F1 cell viability after combined treatment with A. vulgaris extract and autophagy inhibitor 3-MA (1 mM) was assessed by SRB assay (B), * p < 0.05; ** p < 0.01; *** p < 0.001 compared to control and ### p < 0.001 comparing to A. vulgaris extract treatment. Cellular senescence was analyzed using FDG staining (C), while production of ROS/RNS species was detected by redox sensitive dye (DHR123) (D) and subsequent flowcytometric evaluation. Full article ">Figure 2 Cont.
A. vulgaris extract exhibits different modes of action on B16F1 and B16F10 cell lines. Cells were treated with an IC50 dose of A. vulgaris extract for 72 h. Cellular proliferation (CFSE), apoptosis (Ann/PI), and autophagy (AO) were detected by corresponding staining followed by flow cytometry analysis (A). Data are presented as mean ± SD from three independent experiments. B16F1 cell viability after combined treatment with A. vulgaris extract and autophagy inhibitor 3-MA (1 mM) was assessed by SRB assay (B), * p < 0.05; ** p < 0.01; *** p < 0.001 compared to control and ### p < 0.001 comparing to A. vulgaris extract treatment. Cellular senescence was analyzed using FDG staining (C), while production of ROS/RNS species was detected by redox sensitive dye (DHR123) (D) and subsequent flowcytometric evaluation. Full article ">Figure 3
Representative micrographs of the most significant histopathological alterations noted in the B16F1 and B16F10 models. (A) H/E staining, scale bar 200 µm. Black stars are areas of tumor necrosis. (B) PCNA immunoexpression (green) in melanoma tissue of control animals (left) and animals treated with A. vulgaris extract (right). Scale bar 25 µm. The apoptotic area is surrounded by a white interrupted line. Full article ">Figure 4
A. vulgaris extract alters the number and phenotype of immunocompetent cells in the spleen of tumor-bearing mice. The percentages of CD11c+MHCII+ (A), CD11c+MHCII+CD86+ (B), CD3+CD8+PD-1+ (C), CD3+CD8+perforin+ (D), CD3+CD4+IFN-γ+ (E), CD3+CD4+IL-10+ (F), CD4+CD25+Foxp3+ (G) cells in spleen were examined and presented in form of graphs and representative flow cytometry data (FACS) plots. In the experimental group, tumor-bearing mice were treated with A. vulgaris extract (i.p. 50 mg/kg in two cycles of 5 days with a break of two days), while the control group consisted of tumor-bearing mice treated with vehicle. Data are presented as means ± SEM of three individual experiments, each carried out with six mice per experimental group. Statistical significance was tested by Mann–Whitney rank-sum test or Student’s unpaired t-test and log-rank test where appropriate. * p < 0.05; ** p < 0.01; *** p < 0.001. Full article ">Figure 5
A. vulgaris extract enhances potent antitumor immune response in tumor microenvironment. The percentage of CD11c+ (A), CD11c+CD40+ (B), CD8+CD107a+ (C), CD8+perforin+ (D), CD4+TNF-α+ (E), CD4+IL-10+ (F), CD4+CD25+Foxp3+ (G), were analyzed and presented in form of graphs and representative flow cytometry data (FACS) plots. In the experimental group, tumor-bearing mice were treated with A. vulgaris extract (i.p. 50 mg/kg in two cycles of 5 days with a break of two days), while the control group consisted of tumor-bearing mice treated with a vehicle. Data are presented as means ± SEM of three individual experiments, each carried out with six mice per experimental group. Statistical significance was tested by Mann–Whitney rank-sum test or Student’s unpaired t-test and log-rank test where appropriate. ** p < 0.01; *** p < 0.001. Full article ">Figure 6
Representative micrographs of the most significant histopathological alterations of kidney (A) and liver (B) were noted in B16F1 and B16F10 models. Black arrows point to dilated venules. Scale bar 200 µm. Black arrowheads delineate immature kidney tissue on the right from mature on the left. White arrowheads show foci of inflammatory infiltrates in liver tissue. White arrows mark vacuolated hepatocytes. Black stars reveal extramedullary hematopoiesis. All pictures are H/E stained and 200× magnified. Full article ">

17 pages, 2334 KiB

Open AccessArticle

Chemical Characterization, Free Radical Scavenging, and Cellular Antioxidant Properties of the Egadi Island Endemic Brassica macrocarpa Guss Leaf Extract

by Adele Cicio, Noemi Aloi, Stefania Sut, Valeria Longo, Francesca Terracina, Stefano Dall’Acqua, Maria Grazia Zizzo, Maurizio Bruno, Vincenzo Ilardi, Paolo Colombo, Claudio Luparello and Rosa Serio

Biomolecules 2024, 14(6), 636; https://doi.org/10.3390/biom14060636 - 29 May 2024

Viewed by 985

Abstract

The genus Brassica is an important source of food in the Mediterranean diet with documented nutritional and medicinal properties. However, few studies have investigated the phytochemical composition and the biological activity of wild Sicilian taxa. Thus, we aimed to study the chemical profile and the antioxidant potential, in vitro and in LPS-stimulated RAW 264.7 cells, of a methanolic extract of leaves of wild Brassica macrocarpa Guss (B. macrocarpa) (Egadi Islands; Sicily-Italy). B. macrocarpa methanolic extract showed a large amount of glucosinolates and different phenolic compounds. It exhibited antioxidant activity in the DPPH assay and in LPS-stimulated RAW 264.7 cells, being able to reduce NO and ROS levels and NOS2 mRNA expression. Our study demonstrated that Sicilian B. macrocarpa methanolic extract, in LPS-stimulated macrophages, efficiently counteracts oxidative stress and displays radical scavenging activity. Future studies are required to identify the contribution of the single phytocomponents, to characterize the action mechanism, and to reveal possible applications in human health. Full article

(This article belongs to the Topic Molecular and Cellular Aspects of the Beneficial Effects of Natural Products on Chronic Diseases)

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20 pages, 8590 KiB

Open AccessArticle

A Lombard Variety of Sweet Pepper Regulating Senescence and Proliferation: The Voghera Pepper

by Fabrizio De Luca, Federica Gola, Alberto Azzalin, Claudio Casali, Ludovica Gaiaschi, Gloria Milanesi, Riccardo Vicini, Paola Rossi and Maria Grazia Bottone

Nutrients 2024, 16(11), 1681; https://doi.org/10.3390/nu16111681 - 29 May 2024

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Abstract

Aging and its related disorders are important issues nowadays and the first cause of this physio-pathological condition is the overproduction of ROS. Ascorbic acid is an antioxidant mediator and its anti-aging proprieties are well known. Our previous data demonstrated that Voghera sweet pepper (VP), a distinctive type of pepper cultivated in Italy, is particularly rich in ascorbic acid. Based on these data, the anti-aging effect mediated by extracts of the edible part of VP was evaluated on an in vitro model of both young and old Normal Human Diploid Fibroblasts (NHDF). Using phase contrast microscopy, we observed that VP may help cells in the maintenance of physiological morphology during aging. Cytofluorimetric analyses revealed that VP extracts led to an increase in DNA synthesis and percentage of living cells, linked to a consequent increase in mitotic events. This hypothesis is supported by the enhancement of PCNA expression levels observed in old, treated fibroblasts, corroborating the idea that this extract could recover a young phenotype in adult fibroblasts, confirmed by the study of p16 and p53 expression levels and TEM analyses. Based on these results, we may suppose that VP can lead to the partial recovery of “young-like” phenotypes in old fibroblasts. Full article

(This article belongs to the Topic Molecular and Cellular Aspects of the Beneficial Effects of Natural Products on Chronic Diseases)

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Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomolecules biomolecules	4.8	9.4	2011	16.3 Days	CHF 2700
Cancers cancers	4.5	8.0	2009	16.3 Days	CHF 2900
Diseases diseases	2.9	0.8	2013	18.9 Days	CHF 1800
International Journal of Molecular Sciences ijms	4.9	8.1	2000	18.1 Days	CHF 2900
Nutrients nutrients	4.8	9.2	2009	17.5 Days	CHF 2900

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Molecular and Cellular Aspects of the Beneficial Effects of Natural Products on Chronic Diseases

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