International Journal of Molecular Sciences

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22 pages, 4569 KiB

Open AccessArticle

Ruta graveolens, but Not Rutin, Inhibits Survival, Migration, Invasion, and Vasculogenic Mimicry of Glioblastoma Cells

by Iolanda Camerino, Paola Franco, Adriana Bajetto, Stefano Thellung, Tullio Florio, Maria Patrizia Stoppelli and Luca Colucci-D’Amato

Int. J. Mol. Sci. 2024, 25(21), 11789; https://doi.org/10.3390/ijms252111789 - 2 Nov 2024

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Abstract

Glioblastoma (GBM) is the most aggressive type of brain tumor, characterized by poor outcome and limited therapeutic options. During tumor progression, GBM may undergo the process of vasculogenic mimicry (VM), consisting of the formation of vascular-like structures which further promote tumor aggressiveness and [...] Read more.

Glioblastoma (GBM) is the most aggressive type of brain tumor, characterized by poor outcome and limited therapeutic options. During tumor progression, GBM may undergo the process of vasculogenic mimicry (VM), consisting of the formation of vascular-like structures which further promote tumor aggressiveness and malignancy. The resulting resistance to anti-angiogenetic therapies urges the identification of new compounds targeting VM. Extracts of natural plants may represent potential therapeutic tools. Among these, components of Ruta graveolens water extract (RGWE) display a wide range of biological activities. To test the effect of RGWE on human GBM and rat glioma cell line VM, tube formation on a gelled matrix was monitored. Quantitative assessment of VM formation shows the clear-cut inhibitory activity of RGWE. Unlike rutin, one of the most abundant extract components, the whole RGWE strongly reduced the migration and invasion of GBM tumor cells. Moreover, RGWE induced cell death of GBM patient-derived cancer stem cells and impaired VM at sub-lethal doses. Overall, our data reveal a marked RGWE-dependent inhibition of GBM cell survival, migration, invasion, and VM formation. Thus, the clear-cut ability of RGWE to counteract GBM malignancy deserves attention, holding the promise to bring natural products to clinical use, thus uncovering new therapeutic opportunities. Full article

(This article belongs to the Special Issue Antioxidant, Anti-inflammatory, and Antiproliferative Activities of Natural Products—2nd Edition)

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26 pages, 3705 KiB

Open AccessArticle

The Green Extraction of Blueberry By-Products: An Evaluation of the Bioactive Potential of the Anthocyanin/Polyphenol Fraction

by Giorgio Capaldi, Clelia Aimone, Emanuela Calcio Gaudino, Kristina Radošević, Martina Bagović, Giorgio Grillo and Giancarlo Cravotto

Int. J. Mol. Sci. 2024, 25(20), 11032; https://doi.org/10.3390/ijms252011032 - 14 Oct 2024

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Abstract

In the context of a circular economy, this study explores the valorization of blueberry pomace (BP) as a source of bioactive compounds using sustainable extraction methods. Microwave-assisted extraction (MAE) and microwave-assisted subcritical water extraction (MASWE) were employed to obtain two distinct fractions: MAE [...] Read more.

In the context of a circular economy, this study explores the valorization of blueberry pomace (BP) as a source of bioactive compounds using sustainable extraction methods. Microwave-assisted extraction (MAE) and microwave-assisted subcritical water extraction (MASWE) were employed to obtain two distinct fractions: MAE 1° and MASWE 2°. The first extract, MAE 1°, obtained at 80 °C, had a high total anthocyanin content (21.96 mg_Cya-3-glu/g_extract), making it suitable as a natural pigment. Additionally, MAE 1° exhibited significant enzyme inhibition, particularly against α-amylase and β-glucosidase, suggesting potential anti-diabetic and anti-viral applications. The second extract, MASWE 2°, obtained at 150 °C, contained a higher total phenolic content (211.73 mg_GAE/g_extract) and demonstrated stronger antioxidant activity. MASWE 2° showed greater inhibition of acetylcholinesterase and tyrosinase, indicating its potential for use in Alzheimer’s treatment, skincare, or as a food preservative. MASWE 2° exhibited cytotoxicity against HeLa cells and effectively mitigated H₂O₂-induced oxidative stress in HaCat cells, with MAE 1° showing similar but less pronounced effects. A tested formulation combining MAE 1° and MASWE 2° extracts in a 3:2 ratio effectively enhanced anthocyanin stability, demonstrating its potential as a heat-stable pigment. The extract characteristics were compared with a conventional method (MeOH-HCl in reflux condition), and the protocol’s sustainability was assessed using several green metric tools, which provided insights into its environmental impact and efficiency. Full article

(This article belongs to the Special Issue Antioxidant, Anti-inflammatory, and Antiproliferative Activities of Natural Products—2nd Edition)

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17 pages, 6828 KiB

Open AccessArticle

Untargeted Metabolomics Approach for the Discovery of Salinity-Related Alkaloids in a Stony Coral-Derived Fungus Aspergillus terreus

by Yayue Liu, Li Wang, Yunkai Feng, Qingnan Liao, Xiaoling Lei, Xueqiong Hu, Longjian Zhou and Yi Zhang

Int. J. Mol. Sci. 2024, 25(19), 10544; https://doi.org/10.3390/ijms251910544 - 30 Sep 2024

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Abstract

As a part of the important species that form coral reef ecosystems, stony corals have become a potential source of pharmacologically active lead compounds for an increasing number of compounds with novel chemical structures and strong biological activity. In this study, the secondary [...] Read more.

As a part of the important species that form coral reef ecosystems, stony corals have become a potential source of pharmacologically active lead compounds for an increasing number of compounds with novel chemical structures and strong biological activity. In this study, the secondary metabolites and biological activities are reported for Aspergillus terreus C21-1, an epiphytic fungus acquired from Porites pukoensis collected from Xuwen Coral Reef Nature Reserve, China. This strain was cultured in potato dextrose broth (PDB) media and rice media with different salinities based on the OSMAC strategy. The mycelial morphology and high-performance thin layer chromatographic (HPTLC) fingerprints of the fermentation extracts together with bioautography were recorded. Furthermore, an untargeted metabolomics study was performed using principal component analysis (PCA), orthogonal projection to latent structure discriminant analysis (O-PLSDA), and feature-based molecular networking (FBMN) to analyze their secondary metabolite variations. The comprehensive results revealed that the metabolite expression in A. terreus C21-1 differed significantly between liquid and solid media. The metabolites produced in liquid medium were more diverse but less numerous compared to those in solid medium. Meanwhile, the mycelial morphology underwent significant changes with increasing salinity under PDB cultivation conditions, especially in PDB with 10% salinity. Untargeted metabolomics revealed significant differences between PDB with 10% salinity and other media, as well as between liquid and solid media. FBMN analysis indicated that alkaloids, which might be produced under high salt stress, contributed largely to the differences. The biological activities results showed that six groups of crude extracts exhibited acetylcholinesterase (AChE) inhibitory activities, along with 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and antibacterial activities. The results of this study showed that the increase in salinity favored the production of unique alkaloid compounds by A. terreus C21-1. Full article

(This article belongs to the Special Issue Antioxidant, Anti-inflammatory, and Antiproliferative Activities of Natural Products—2nd Edition)

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23 pages, 3421 KiB

Open AccessArticle

Use of Guazuma ulmifolia Lam. Stem Bark Extracts to Prevent High-Fat Diet Induced Metabolic Disorders in Mice

by Elisana Lima Rodrigues, Lidiani Figueiredo Santana, Valter Aragão do Nascimento, Marcel Asato Arakaki, Claudia Andréa Lima Cardoso, Wander Fernando de Oliveira Filiú, Rita de Cássia Avellaneda Guimarães, Priscila Aiko Hiane and Karine de Cássia Freitas

Int. J. Mol. Sci. 2024, 25(16), 8889; https://doi.org/10.3390/ijms25168889 - 15 Aug 2024

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Abstract

This study aimed to evaluate the effects of supplementation with ethanolic and aqueous extracts from the bark of the stem of Guazuma ulmifolia in mice submitted to a high-fat diet as well as to evaluate the chemical composition of these extracts. The chemical [...] Read more.

This study aimed to evaluate the effects of supplementation with ethanolic and aqueous extracts from the bark of the stem of Guazuma ulmifolia in mice submitted to a high-fat diet as well as to evaluate the chemical composition of these extracts. The chemical composition and antioxidant potential was evaluated in aqueous and ethanolic extracts of the stem bark. The in vivo test consisted of evaluating the effects of the aqueous and ethanolic extracts of the stem bark on C57BL/6 mice receiving a high-fat diet. The animals were evaluated for weight gain, feed consumption, visceral adiposity, serum, and inflammatory and hormonal parameters. The results of the chemical analyses corroborate those obtained by the literature, which reported gallocatechin, epigallocatechin and epigallocatechin gallate. Compared with the ethanolic extract, the aqueous extract showed greater antioxidant capacity. Both extracts resulted in lower feed consumption in the animals, but they did not influence weight gain or visceral adiposity and resulted in varied changes in the lipid profile. In addition, they did not influence glucose tolerance, insulin sensitivity, or fasting blood glucose. Furthermore, the leptin levels increased, which may have contributed to satiety, but this was shown to have a negative impact on other inflammatory and hormonal parameters. Therefore, under the conditions of this study, the biologically active compounds present in the plant species Guazuma ulmifolia were not able to contribute to the treatment of metabolic changes related to the consumption of a high-fat diet. Full article

(This article belongs to the Special Issue Antioxidant, Anti-inflammatory, and Antiproliferative Activities of Natural Products—2nd Edition)

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29 pages, 927 KiB

Open AccessArticle

Comprehensive Characterization of Phytochemical Composition, Membrane Permeability, and Antiproliferative Activity of Juglans nigra Polyphenols

by Rita Osztie, Tamás Czeglédi, Sarah Ross, Bence Stipsicz, Eszter Kalydi, Szabolcs Béni, Imre Boldizsár, Eszter Riethmüller, Szilvia E. Bősze and Ágnes Alberti

Int. J. Mol. Sci. 2024, 25(13), 6930; https://doi.org/10.3390/ijms25136930 - 25 Jun 2024

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Abstract

The aim of our study was the detailed polyphenol profiling of Juglans nigra and the characterization of the membrane permeability and antiproliferative properties of its main phenolics. A total of 161 compounds were tentatively identified in J. nigra bark, leaf, and pericarp extracts [...] Read more.

The aim of our study was the detailed polyphenol profiling of Juglans nigra and the characterization of the membrane permeability and antiproliferative properties of its main phenolics. A total of 161 compounds were tentatively identified in J. nigra bark, leaf, and pericarp extracts by ultrahigh-performance liquid chromatography–high-resolution tandem mass spectrometry (UHPLC-HR-MS/MS). Eight compounds including myricetin-3-O-rhamnoside (86), quercetin-3-O-rhamnoside (106), quercetin-3-O-xyloside (74), juglone (141), 1,2,3,4-tetrahydro-7,8-dihydroxy-4-oxonaphthalen-1-yl-6-O-galloyl-glucoside (92), ellagic acid (143), gallic acid (14), and ethyl gallate (58) were isolated from J. nigra pericarp. The in vitro antiproliferative activity of the isolated compounds was investigated against three human cancer cell lines, confirming that juglone (141) inhibits cell proliferation in all of them, and has similar activity as the clinical standards. The permeability of the isolated compounds across biological membranes was evaluated by the parallel artificial membrane permeability assay (PAMPA). Both juglone (141) and ethyl-gallate (58) showed positive results in the blood–brain-barrier-specific PAMPA-BBB study. Juglone (141) also possesses logPe values which indicates that it may be able to cross both the GI and BBB membranes via passive diffusion. Full article

(This article belongs to the Special Issue Antioxidant, Anti-inflammatory, and Antiproliferative Activities of Natural Products—2nd Edition)

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15 pages, 3367 KiB

Open AccessArticle

Enhancement of Solubility, Stability, Cellular Uptake, and Bioactivity of Curcumin by Polyvinyl Alcohol

by Smee Kang, Minkyoung Kim, Hyelin Kim and Jungil Hong

Int. J. Mol. Sci. 2024, 25(11), 6278; https://doi.org/10.3390/ijms25116278 - 6 Jun 2024

Viewed by 1386

Abstract

The biological activities and related mechanisms of curcumin, a major polyphenolic compound in turmeric, the rhizome of Curcuma longa, have been extensively investigated. Due to its poor solubility in water, the analysis of curcumin’s biological activities is limited in most aqueous experimental [...] Read more.

The biological activities and related mechanisms of curcumin, a major polyphenolic compound in turmeric, the rhizome of Curcuma longa, have been extensively investigated. Due to its poor solubility in water, the analysis of curcumin’s biological activities is limited in most aqueous experimental systems. In the present study, the effects of polyvinyl alcohol (PVA), a dietary-compatible vehicle, on the solubility, stability, cellular uptake, and bioactivities of curcumin were investigated. Curcumin solubility was improved significantly by PVA; the color intensity of curcumin aqueous solution in the presence of PVA increased concentration-dependently with its peak shift to a shorter wavelength. Improved suspension stability and photostability of curcumin in an aqueous solution were also observed in the presence of PVA, even at 62.5 μg/mL. The scavenging activities of curcumin against DPPH, ABTS, AAPH radicals, and nitric oxide were enhanced significantly in the presence of PVA. PVA at 250 μg/mL also significantly enhanced the cytotoxic activity of curcumin against both HCT 116 colon cancer and INT 407 (HeLa-derived) embryonic intestinal cells by reducing the IC₅₀ from 16 to 11 μM and 25 to 15 μM, respectively. PVA improved the cellular uptake of curcumin in a concentration-dependent manner in INT 407 cells; it increased the cellular levels more effectively at lower curcumin treatment concentrations. The present results indicate that PVA improves the solubility and stability of curcumin, and changes in these chemical behaviors of curcumin in aqueous systems by PVA could enhance the bioavailability and pharmacological efficacy of curcumin. Full article

(This article belongs to the Special Issue Antioxidant, Anti-inflammatory, and Antiproliferative Activities of Natural Products—2nd Edition)

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Review

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14 pages, 2044 KiB

Open AccessReview

Melanin as a Photothermal Agent in Antimicrobial Systems

by Arianna Menichetti, Dario Mordini and Marco Montalti

Int. J. Mol. Sci. 2024, 25(16), 8975; https://doi.org/10.3390/ijms25168975 - 18 Aug 2024

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Abstract

Bacterial infection is one of the most problematic issues for human health and the resistance of bacteria to traditional antibiotics is a matter of huge concern. Therefore, research is focusing on the development of new strategies to efficiently kill these microorganisms. Recently, melanin [...] Read more.

Bacterial infection is one of the most problematic issues for human health and the resistance of bacteria to traditional antibiotics is a matter of huge concern. Therefore, research is focusing on the development of new strategies to efficiently kill these microorganisms. Recently, melanin is starting to be investigated for this purpose. Indeed, this very versatile material presents outstanding photothermal properties, already studied for photothermal therapy, which can be very useful for the light-induced eradication of bacteria. In this review, we present antibacterial melanin applications based on the photothermal effect, focusing both on the single action of melanin and on its combination with other antibacterial systems. Melanin, also thanks to its biocompatibility and ease of functionalization, has been demonstrated to be easily applicable as an antimicrobial agent, especially for the treatment of local infections. Full article

(This article belongs to the Special Issue Antioxidant, Anti-inflammatory, and Antiproliferative Activities of Natural Products—2nd Edition)

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52 pages, 8424 KiB

Open AccessReview

Natural Guardians: Natural Compounds as Radioprotectors in Cancer Therapy

by Anna Stasiłowicz-Krzemień, Anna Gościniak, Dorota Formanowicz and Judyta Cielecka-Piontek

Int. J. Mol. Sci. 2024, 25(13), 6937; https://doi.org/10.3390/ijms25136937 - 25 Jun 2024

Cited by 2 | Viewed by 1389

Abstract

Cancer remains a significant global health challenge, with millions of deaths attributed to it annually. Radiotherapy, a cornerstone in cancer treatment, aims to destroy cancer cells while minimizing harm to healthy tissues. However, the harmful effects of irradiation on normal cells present a [...] Read more.

Cancer remains a significant global health challenge, with millions of deaths attributed to it annually. Radiotherapy, a cornerstone in cancer treatment, aims to destroy cancer cells while minimizing harm to healthy tissues. However, the harmful effects of irradiation on normal cells present a formidable obstacle. To mitigate these effects, researchers have explored using radioprotectors and mitigators, including natural compounds derived from secondary plant metabolites. This review outlines the diverse classes of natural compounds, elucidating their roles as protectants of healthy cells. Furthermore, the review highlights the potential of these compounds as radioprotective agents capable of enhancing the body’s resilience to radiation therapy. By integrating natural radioprotectors into cancer treatment regimens, clinicians may improve therapeutic outcomes while minimizing the adverse effects on healthy tissues. Ongoing research in this area holds promise for developing complementary strategies to optimize radiotherapy efficacy and enhance patient quality of life. Full article

(This article belongs to the Special Issue Antioxidant, Anti-inflammatory, and Antiproliferative Activities of Natural Products—2nd Edition)

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