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21 pages, 49312 KiB

Open AccessArticle

Effectiveness of Local Use of Green Propolis-Loaded Lipid Nanoparticles as Adjuvant Therapy to Scaling and Root Planing in the Management of Periodontitis in Rats Treated with Zoledronate

by Glauco Rodrigues Carmo Silveira, Vinícius Franzão Ganzaroli, Luan Felipe Toro, Estevão Lopes-Pereira, Leandro Lemes da Costa, João Martins de Mello-Neto, Rogério Leone Buchaim, Valdir Gouveia Garcia, Leticia Helena Theodoro, José Maurício Sforcin, Priscyla Daniely Marcato and Edilson Ervolino

Int. J. Mol. Sci. 2024, 25(22), 12443; https://doi.org/10.3390/ijms252212443 - 20 Nov 2024

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Abstract

This study assessed the effectiveness of the local use of green propolis-loaded lipid nanoparticles (GPlnp) as an adjuvant therapy to scaling and root planing (SRP) to manage experimental periodontitis (EP) in ovariectomized rats treated with zoledronate. Ten weeks before the experiment, 48 female [...] Read more.

This study assessed the effectiveness of the local use of green propolis-loaded lipid nanoparticles (GPlnp) as an adjuvant therapy to scaling and root planing (SRP) to manage experimental periodontitis (EP) in ovariectomized rats treated with zoledronate. Ten weeks before the experiment, 48 female rats were ovariectomized. On day 0, a ligature was installed in the lower first molar to induce EP. From day 0 to day 42, half of the rats were treated with vehicle (VEH), while the other half were treated with 100μg/Kg of zoledronate (ZOL). On day 14, the rats were allocated into the following groups: VEH-NLT, VEH-SRP, VEH-SRP-GPlnp, ZOL-NLT, ZOL-SRP, and ZOL-SRP-GPlnp. VEH-NLT and ZOL-NLT received no local treatment. VEH-SRP and ZOL-SRP received SRP and irrigation with physiological saline solution. VEH-SRP-GPlnp and ZOL-SRP-GPlnp received SRP and irrigation with GPlnp. A single SRP session was carried out, and four irrigation sessions were conducted (on days 14, 16, 18, and 20). On day 42, all animals were euthanized. The hemimandibles were processed for histological, histometric (percentage of total bone tissue (PTBT) and non-vital bone tissue (PNVBT)) and immunohistochemical (TNFα, IL-1β, and TRAP) analysis. VEH-SRP-GPlnp showed better tissue repair, higher PTBT, and lower immunolabeling for TNFα and IL-1β compared to the groups treated with VEH. ZOL-SRP-GPlnp showed a favorable tissue repair, with lower PNVBT, less local inflammation, and lower immunolabeling for TNFα and IL-1β compared to the groups treated with ZOL. Irrigation with GPlnp proved to be effective as an adjuvant therapy to SRP in treating EP in ovariectomized rats treated with zoledronate. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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12 pages, 5822 KiB

Open AccessArticle

Modulation of the Respiratory Epithelium Physiology by Flavonoids—Insights from 16HBEσcell Model

by Jakub Hoser, Gabriela Weglinska, Aleksandra Samsel, Kamila Maliszewska-Olejniczak, Piotr Bednarczyk and Miroslaw Zajac

Int. J. Mol. Sci. 2024, 25(22), 11999; https://doi.org/10.3390/ijms252211999 - 8 Nov 2024

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Abstract

Extensive evidence indicates that the compromise of airway epithelial barrier function is closely linked to the development of various diseases, posing a significant concern for global mortality and morbidity. Flavonoids, natural bioactive compounds, renowned for their antioxidant and anti-inflammatory properties, have been used [...] Read more.

Extensive evidence indicates that the compromise of airway epithelial barrier function is closely linked to the development of various diseases, posing a significant concern for global mortality and morbidity. Flavonoids, natural bioactive compounds, renowned for their antioxidant and anti-inflammatory properties, have been used for centuries to prevent and treat numerous ailments. Lately, a growing body of evidence suggests that flavonoids can enhance the integrity of the airway epithelial barrier. The objective of this study was to investigate the impact of selected flavonoids representing different subclasses, such as kaempferol (flavonol), luteolin (flavone), and naringenin (flavanone), on transepithelial electrical resistance (TEER), ionic currents, cells migration, and proliferation of a human bronchial epithelial cell line (16HBE14σ). To investigate the effect of selected flavonoids, MTT assay, trypan blue staining, and wound healing were assessed. Additionally, transepithelial resistance and Ussing chamber measurements were applied to investigate the impact of the flavonoids on the electrical properties of the epithelial barrier. This study showed that kaempferol, luteolin, and naringenin at micromolar concentrations were not cytotoxic to 16HBE14σ cells. Indeed, in MTT tests, a statistically significant change in cell metabolic activity for luteolin and naringenin was observed. However, our experiments showed that naringenin did not affect the proliferation of 16HBE14σ cells, while the effect of kaempferol and luteolin was inhibitory. Moreover, transepithelial electrical resistance measurements have shown that all of the flavonoids used in this study improved the epithelial integrity with the slightest effect of kaempferol and the significant impact of naringenin and luteolin. Finally, our observations suggest that luteolin increases the Cl- transport through cystic fibrosis transmembrane conductance regulator (CFTR) channel. Our findings reveal that flavonoids representing different subclasses exert distinct effects in the employed cellular model despite their similar chemical structures. In summary, our study sheds new light on the diverse effects of selected flavonoids on airway epithelial barrier function, underscoring the importance of further exploration into their potential therapeutic applications in respiratory health. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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21 pages, 9112 KiB

Open AccessArticle

Melittin Inhibits Colorectal Cancer Growth and Metastasis by Ac-Tivating the Mitochondrial Apoptotic Pathway and Suppressing Epithelial–Mesenchymal Transition and Angiogenesis

by Kangli Wang, Lingchen Tao, Meifei Zhu, Xinyu Yu, Yuanyuan Lu, Bin Yuan and Fuliang Hu

Int. J. Mol. Sci. 2024, 25(21), 11686; https://doi.org/10.3390/ijms252111686 - 30 Oct 2024

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Abstract

Melittin has previously been found to have a positive effect on colorectal cancer (CRC) treatment, one of the most difficult-to-treat malignancies, but the mechanism by which this effect occurs remains unclear. We evaluated melittin’s pro-apoptotic and anti-metastatic effects on CRC in vitro and [...] Read more.

Melittin has previously been found to have a positive effect on colorectal cancer (CRC) treatment, one of the most difficult-to-treat malignancies, but the mechanism by which this effect occurs remains unclear. We evaluated melittin’s pro-apoptotic and anti-metastatic effects on CRC in vitro and in vivo. The results showed that melittin-induced mitochondrial ROS bursts decreased ΔΨm, inhibited Bcl-2 expression, and increased Bax expression in both cells and tumor tissues. This led to increased mitochondrial membrane permeability and the release of pro-apoptotic factors, particularly the high expression of Cytochrome C, initiating the apoptosis program. Additionally, through wound-healing and transwell assays, melittin inhibited the migration and invasion of CRC cells. In vivo, the anti-metastatic effect of melittin was also verified in a lung metastasis mouse model. Western blotting and immunohistochemistry analysis indicated that melittin suppressed the expression of MMPs and regulated the expression of crucial EMT markers and related transcription factors, thereby inhibiting EMT. Furthermore, the melittin disrupts neovascularization, ultimately inhibiting the metastasis of CRC. In conclusion, melittin exerts anti-CRC effects by promoting apoptosis and inhibiting metastasis, providing a theoretical basis for further research on melittin as a targeted therapeutic agent for CRC. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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18 pages, 1224 KiB

Open AccessArticle

Effect of Sprouting, Fermentation and Cooking on Antioxidant Content and Total Antioxidant Activity in Quinoa and Amaranth

by Martina Vento, Clara Maria Della Croce, Lorenza Bellani, Eliana Lanfranca Tassi, Maria Cristina Echeverria and Lucia Giorgetti

Int. J. Mol. Sci. 2024, 25(20), 10972; https://doi.org/10.3390/ijms252010972 - 12 Oct 2024

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Abstract

The study of different processing techniques, such as sprouting, cooking and fermentation, can help to develop new products for human health. In this work, raw, cooked and fermented seeds and germinated seeds of Chenopodium quinoa Willd. var. Tunkahuan and Amaranthus caudatus L. var. [...] Read more.

The study of different processing techniques, such as sprouting, cooking and fermentation, can help to develop new products for human health. In this work, raw, cooked and fermented seeds and germinated seeds of Chenopodium quinoa Willd. var. Tunkahuan and Amaranthus caudatus L. var. Alegrìa were compared for the content of antioxidant molecules, total antioxidant capacity and mineral elements. Fermentation was induced spontaneously, with the yeast Saccharomyces cerevisiae, with the bacterium Lactobacillus plantarum and with both microorganisms, for 24 and 48 h. The increase in antioxidant molecules and antioxidant activity was induced by germination, by 24 h of spontaneous fermentation (polyphenols and flavonoids) and by 24 h of L. plantarum fermentation (total antioxidant activity) for both species. Germinated seeds of the two plants showed higher values in respect to seeds of macroelements and microelements. No genotoxic but rather protective effects were determined for seed and germinated seed extracts using the D7 strain of S. cerevisiae, a good tool for the evaluation of protection from oxidative damage induced by radical oxygen species (ROS) in cells and tissues. Therefore, the two varieties could be very suitable for their use in human diet and in supplements, especially as germinated seeds or as fermented foods. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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15 pages, 288 KiB

Open AccessArticle

Efficient Production of 4’-Hydroxydihydrochalcones Using Non-Conventional Yeast Strains

by Paweł Chlipała, Julia Bienia, Marcelina Mazur, Monika Dymarska and Tomasz Janeczko

Int. J. Mol. Sci. 2024, 25(19), 10735; https://doi.org/10.3390/ijms251910735 - 5 Oct 2024

Cited by 1 | Viewed by 1051

Abstract

The quest for novel therapeutic agents has rekindled interest in natural products, particularly those derived from biotransformation processes. Dihydrochalcones, a class of plant secondary metabolites, exhibit a range of pharmacological properties. Chalcone and dihydrochalcone compounds with the characteristic 4’-hydroxy substitution are present in [...] Read more.

The quest for novel therapeutic agents has rekindled interest in natural products, particularly those derived from biotransformation processes. Dihydrochalcones, a class of plant secondary metabolites, exhibit a range of pharmacological properties. Chalcone and dihydrochalcone compounds with the characteristic 4’-hydroxy substitution are present in ‘dragon’s blood’ resin, known for its traditional medicinal uses and complex composition, making the isolation of these compounds challenging. This study investigates the efficient production of 4′-hydroxydihydrochalcones using non-conventional yeast strains. We evaluated the biotransformation efficiency of various 4′-hydroxychalcone substrates utilizing yeast strains such as Yarrowia lipolytica KCh 71, Saccharomyces cerevisiae KCh 464, Rhodotorula rubra KCh 4 and KCh 82, and Rhodotorula glutinis KCh 242. Our findings revealed that Yarrowia lipolytica KCh 71, Rhodotorula rubra KCh 4 and KCh 82, and Rhodotorula glutinis KCh 242 exhibited the highest conversion efficiencies, exceeding 98% within one hour for most substrates. The position of methoxy substituents in the chalcone ring significantly influenced hydrogenation efficiency. Moreover, we observed isomerization of trans-4′-hydroxy-2-methoxychalcone to its cis isomer, catalyzed by light exposure. This study underscores the potential of using yeast strains for the sustainable and efficient production of dihydrochalcones, providing a foundation for developing new therapeutic agents and nutraceuticals. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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18 pages, 2443 KiB

Open AccessArticle

Biological Properties of the Mucus and Eggs of Helix aspersa Müller as a Potential Cosmetic and Pharmaceutical Raw Material: A Preliminary Study

by Anna Herman, Patrycja Wińska, Małgorzata Białek and Andrzej P. Herman

Int. J. Mol. Sci. 2024, 25(18), 9958; https://doi.org/10.3390/ijms25189958 - 15 Sep 2024

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Abstract

In recent years, snail mucus (SM) has become popular as an active ingredient in cosmetic and pharmaceutical products. In turn, snail eggs (SEs) also seem to be a promising active compound, but the biological activities of SEs are significantly less known. Therefore, our [...] Read more.

In recent years, snail mucus (SM) has become popular as an active ingredient in cosmetic and pharmaceutical products. In turn, snail eggs (SEs) also seem to be a promising active compound, but the biological activities of SEs are significantly less known. Therefore, our preliminary study aimed to compare the biological activities of the SEs and SM of Helix aspersa Müller. The metabolomic analysis (LC–MS technique), determination of the antimicrobial activity (agar diffusion test, broth microdilution methods), antioxidant activity (ABTS assay), cytotoxicity assay (MTT), and proapoptotic properties (flow cytometry) of the SEs and SM were evaluated. It was found that the SEs and SM contain 8005 and 7837 compounds, respectively. The SEs showed antibacterial activity against S. aureus (MIC 12.5 mg/mL) and P. aeruginosa (MIC 3.12 mg/mL). The EC50 estimation of the antioxidant activity is 89.64 mg/mL and above 100 mg/mL for the SEs and SM, respectively. The SEs also inhibited the cell proliferation of cancer cell lines (HCT-116, MCF-7, HT-29) more strongly compared to the SM. The highest proportion of apoptotic cells in HCT-116 was observed. The reach composition of the compounds in the SEs and SM may be crucial for the creation of new cosmetic and pharmaceutical raw materials with different biological activities. However, further extended studies on the biological activities of H. aspersa-delivered materials are still necessary. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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15 pages, 16273 KiB

Open AccessArticle

Xanthoxylin Attenuates Lipopolysaccharide-Induced Lung Injury through Modulation of Akt/HIF-1α/NF-κB and Nrf2 Pathways

by Fu-Chao Liu, Yuan-Han Yang, Chia-Chih Liao and Hung-Chen Lee

Int. J. Mol. Sci. 2024, 25(16), 8742; https://doi.org/10.3390/ijms25168742 - 10 Aug 2024

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Abstract

Xanthoxylin, a bioactive phenolic compound extracted from the traditional herbal medicine Penthorum Chinense Pursh, is renowned for its anti-inflammatory effects. While previous studies have highlighted the anti-inflammatory and antioxidant properties of Xanthoxylin, its precise mechanisms, particularly concerning immune response and organ protection, [...] Read more.

Xanthoxylin, a bioactive phenolic compound extracted from the traditional herbal medicine Penthorum Chinense Pursh, is renowned for its anti-inflammatory effects. While previous studies have highlighted the anti-inflammatory and antioxidant properties of Xanthoxylin, its precise mechanisms, particularly concerning immune response and organ protection, remain underexplored. This study aimed to elucidate the effects of Xanthoxylin on inflammation and associated signaling pathways in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced via intratracheal administration of LPS, followed by intraperitoneal injections of Xanthoxylin at doses of 1, 2.5, 5, and 10 mg/kg, administered 30 min post-LPS exposure. Lung tissues were harvested for analysis 6 h after LPS challenge. Xanthoxylin treatment significantly mitigated lung tissue damage, pathological alterations, immune cell infiltration, and the production of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Additionally, Xanthoxylin modulated the expression of key proteins in the protein kinase B (Akt)/hypoxia-inducible factor 1-alpha (HIF-1α)/nuclear factor-kappa B (NF-κB) signaling pathway, as well as nuclear factor erythroid 2-related factor 2 (Nrf2) and oxidative markers such as superoxide dismutase (SOD) and malondialdehyde (MDA) in the context of LPS-induced injury. This study demonstrates that Xanthoxylin exerts protective and anti-inflammatory effects by down-regulating and inhibiting the Akt/HIF-1α/NF-κB pathways, suggesting its potential as a therapeutic target for the prevention and treatment of ALI or acute respiratory distress syndrome (ARDS). Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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36 pages, 7923 KiB

Open AccessArticle

The Ethyl Acetate Extract of Phyllanthus emblica L. Alleviates Diabetic Nephropathy in a Murine Model of Diabetes

by Cheng-Hsiu Lin and Chun-Ching Shih

Int. J. Mol. Sci. 2024, 25(12), 6686; https://doi.org/10.3390/ijms25126686 - 18 Jun 2024

Cited by 1 | Viewed by 1336

Abstract

Oil-Gan is the fruit of the genus Phyllanthus emblica L. The fruits have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN [...] Read more.

Oil-Gan is the fruit of the genus Phyllanthus emblica L. The fruits have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN throughout the disease course. The primary aim of this study was to examine the protective effects (including analyses of urine and blood, and inflammatory cytokine levels) and mechanisms of the ethyl acetate extract of P. emblica (EPE) on db/db mice, an animal model of diabetic nephropathy; the secondary aim was to examine the expression levels of p- protein kinase Cα (PKCα)/t-PKCα in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-β1 (TGF-β1) by Western blot analyses. Eight db/m mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included a vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. The administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing 3 (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. A histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-β1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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16 pages, 4357 KiB

Open AccessArticle

Effects of 3-(4-Hydroxy-3-methoxyphenyl)propionic Acid on Enhancing Grip Strength and Inhibiting Protein Catabolism Induced by Exhaustive Exercise

by Yishan Tong, Jiapeng Huang, Shuo Wang, Riyo Awa, Takashi Tagawa, Ziwei Zhang, Tiehan Cao, Haruki Kobori and Katsuhiko Suzuki

Int. J. Mol. Sci. 2024, 25(12), 6627; https://doi.org/10.3390/ijms25126627 - 16 Jun 2024

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Abstract

3-(4-Hydroxy-3-methoxyphenyl)propionic acid (HMPA), also known as dihydroferulic acid, is a hydroxycinnamic acid derivative that can be derived from the microbial transformation of dietary polyphenols or naturally obtained from fermented foods. Although numerous studies have documented its antioxidant and anti-obesity effects, the effect of [...] Read more.

3-(4-Hydroxy-3-methoxyphenyl)propionic acid (HMPA), also known as dihydroferulic acid, is a hydroxycinnamic acid derivative that can be derived from the microbial transformation of dietary polyphenols or naturally obtained from fermented foods. Although numerous studies have documented its antioxidant and anti-obesity effects, the effect of HMPA on muscle function remains unknown. This study investigated the effects of HMPA on muscle strength and exercise endurance capacity. Mice were orally administered low and high doses of HMPA for 14 days and subjected to grip force and treadmill exhaustion tests to evaluate muscle function. Our results showed that HMPA-administered groups significantly enhanced absolute grip strength (p = 0.0256) and relative grip strength (p = 0.0209), and low-dose HMPA decreased the plasma level of blood urea nitrogen after exercise (p = 0.0183), but HMPA did not affect endurance performance. Low-dose HMPA administration increased Myf5 expression in sedentary mice (p = 0.0106), suggesting that low-dose HMPA may promote muscle development. Additionally, HMPA improved hepatic glucose and lipid metabolism, and inhibited muscular lipid metabolism and protein catabolism, as indicated by changes in mRNA expression levels of related genes. These findings suggest that HMPA may be a promising dietary supplement for muscle health and performance. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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11 pages, 809 KiB

Open AccessArticle

Antibacterial Effect of Spanish Honeys of Different Botanical Origins against Staphylococcus epidermidis

by Vanesa Núñez-Gómez, Marta San Mateo, Lorena Sánchez-Martínez and María Jesús Periago

Int. J. Mol. Sci. 2024, 25(12), 6590; https://doi.org/10.3390/ijms25126590 - 15 Jun 2024

Viewed by 789

Abstract

Honey is traditionally used for its medicinal properties attributed to its antibacterial and antioxidant effects. It is considered a natural alternative to conventional antibiotics. This effect has been attributed to their physico-chemical properties, as various chemical parameters can synergistically influence this effect. The [...] Read more.

Honey is traditionally used for its medicinal properties attributed to its antibacterial and antioxidant effects. It is considered a natural alternative to conventional antibiotics. This effect has been attributed to their physico-chemical properties, as various chemical parameters can synergistically influence this effect. The aim of this study is to assess Spanish honeys of diverse botanical origins for their antibacterial efficacy against Staphylococcus epidermidis, correlating their physico-chemical attributes, (poly)phenol content, and antioxidant activity. The methods included colour determination via two methodologies, acidity, pH, moisture content, and sugar concentration. (Poly)phenol content was quantified using the Folin-Ciocalteau method, while antioxidant activity was evaluated via the FRAP method. Subsequently, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against S. epidermidis were investigated with different concentrations of honeys. The results revealed a direct relationship between honey darkness, (poly)phenol concentration, antioxidant activity, and antibacterial efficacy. Darker honeys exhibited higher (poly)phenol levels, greater antioxidant activity, and consequently, lower MIC and MBC values, showing enhanced antibacterial properties. These findings underscore the potential of honey as a therapeutic agent against S. epidermidis, particularly in wound healing applications to avoid infection. Further research into honey’s multifaceted properties is warranted to unveil novel therapeutic avenues in healthcare. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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14 pages, 2656 KiB

Open AccessArticle

Generation of Porcine and Rainbow Trout 3D Intestinal Models and Their Use to Investigate Astaxanthin Effects In Vitro

by Sharon Arcuri, Georgia Pennarossa, Rolando Pasquariello, Madhusha Prasadani, Fulvio Gandolfi and Tiziana A. L. Brevini

Int. J. Mol. Sci. 2024, 25(11), 5966; https://doi.org/10.3390/ijms25115966 - 29 May 2024

Cited by 2 | Viewed by 891

Abstract

Astaxanthin (AST) is a natural compound derived from shellfish, microorganisms, and algae, with several healthy properties. For this reason, it is widely used in the diet of humans and animals, such as pigs, broilers, and fish, where its addition is related to its [...] Read more.

Astaxanthin (AST) is a natural compound derived from shellfish, microorganisms, and algae, with several healthy properties. For this reason, it is widely used in the diet of humans and animals, such as pigs, broilers, and fish, where its addition is related to its pigmenting properties. Moreover, AST’s ability to reduce free radicals and protect cells from oxidative damage finds application during the weaning period, when piglets are exposed to several stressors. To better elucidate the mechanisms involved, here we generate ad hoc pig and rainbow trout in vitro platforms able to mimic the intestinal mucosa. The morphology is validated through histological and molecular analysis, while functional properties of the newly generated intestinal barriers, both in porcine and rainbow trout models, are demonstrated by measuring trans-epithelial electrical resistance and analyzing permeability with fluorescein isothiocyanate–dextran. Exposure to AST induced a significant upregulation of antioxidative stress markers and a reduction in the transcription of inflammation-related interleukins. Altogether, the present findings demonstrate AST’s ability to interact with the molecular pathways controlling oxidative stress and inflammation both in the porcine and rainbow trout species and suggest AST’s positive role in prevention and health. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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22 pages, 4138 KiB

Open AccessArticle

Mechanochemical Approach to Obtaining a Multicomponent Fisetin Delivery System Improving Its Solubility and Biological Activity

by Natalia Rosiak, Ewa Tykarska and Judyta Cielecka-Piontek

Int. J. Mol. Sci. 2024, 25(7), 3648; https://doi.org/10.3390/ijms25073648 - 25 Mar 2024

Cited by 3 | Viewed by 1351

Abstract

In this study, binary amorphous solid dispersions (ASDs, fisetin-Eudragit^®) and ternary amorphous solid inclusions (ASIs, fisetin-Eudragit^®-HP-β-cyclodextrin) of fisetin (FIS) were prepared by the mechanochemical method without solvent. The amorphous nature of FIS in ASDs and ASIs was confirmed using [...] Read more.

In this study, binary amorphous solid dispersions (ASDs, fisetin-Eudragit^®) and ternary amorphous solid inclusions (ASIs, fisetin-Eudragit^®-HP-β-cyclodextrin) of fisetin (FIS) were prepared by the mechanochemical method without solvent. The amorphous nature of FIS in ASDs and ASIs was confirmed using XRPD (X-ray powder diffraction). DSC (Differential scanning calorimetry) confirmed full miscibility of multicomponent delivery systems. FT-IR (Fourier-transform infrared analysis) confirmed interactions that stabilize FIS’s amorphous state and identified the functional groups involved. The study culminated in evaluating the impact of amorphization on water solubility and conducting in vitro antioxidant assays: 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)—ABTS, 2,2-diphenyl-1-picrylhydrazyl—DPPH, Cupric Reducing Antioxidant Capacity—CUPRAC, and Ferric Reducing Antioxidant Power—FRAP and in vitro neuroprotective assays: inhibition of acetylcholinesterase—AChE and butyrylcholinesterase—BChE. In addition, molecular docking allowed for the determination of possible bonds and interactions between FIS and the mentioned above enzymes. The best preparation turned out to be ASI_30_EPO (ASD fisetin-Eudragit^® containing 30% FIS in combination with HP-β-cyclodextrin), which showed an improvement in apparent solubility (126.5 ± 0.1 µg∙mL⁻¹) and antioxidant properties (ABTS: IC₅₀ = 10.25 µg∙mL⁻¹, DPPH: IC₅₀ = 27.69 µg∙mL⁻¹, CUPRAC: IC_0.5 = 9.52 µg∙mL⁻¹, FRAP: IC_0.5 = 8.56 µg∙mL⁻¹) and neuroprotective properties (inhibition AChE: 39.91%, and BChE: 42.62%). Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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15 pages, 2970 KiB

Open AccessArticle

Vitexicarpin Induces Apoptosis and Inhibits Metastatic Properties via the AKT-PRAS40 Pathway in Human Osteosarcoma

by Hyung-Mun Yun, Hyun Sook Kwon, Joon Yeop Lee and Kyung-Ran Park

Int. J. Mol. Sci. 2024, 25(7), 3582; https://doi.org/10.3390/ijms25073582 - 22 Mar 2024

Cited by 3 | Viewed by 1396

Abstract

Osteosarcoma, which has poor prognosis after metastasis, is the most common type of bone cancer in children and adolescents. Therefore, plant-derived bioactive compounds are being actively developed for cancer therapy. Artemisia apiacea Hance ex Walp. is a traditional medicinal plant native to Eastern [...] Read more.

Osteosarcoma, which has poor prognosis after metastasis, is the most common type of bone cancer in children and adolescents. Therefore, plant-derived bioactive compounds are being actively developed for cancer therapy. Artemisia apiacea Hance ex Walp. is a traditional medicinal plant native to Eastern Asia, including China, Japan, and Korea. Vitexicarpin (Vitex), derived from A. apiacea, has demonstrated analgesic, anti-inflammatory, antitumour, and immunoregulatory properties; however, there are no published studies on Vitex isolated from the aerial parts of A. apiacea. Thus, this study aimed to evaluate the antitumour activity of Vitex against human osteosarcoma cells. In the present study, Vitex (>99% purity) isolated from A. apiacea induced significant cell death in human osteosarcoma MG63 cells in a dose- and time-dependent manner; cell death was mediated by apoptosis, as evidenced by the appearance of cleaved-PARP, cleaved-caspase 3, anti-apoptotic proteins (Survivin and Bcl-2), pro-apoptotic proteins (Bax), and cell cycle-related proteins (Cyclin D1, Cdk4, and Cdk6). Additionally, a human phosphokinase array proteome profiler revealed that Vitex suppressed AKT-dependent downstream kinases. Further, Vitex reduced the phosphorylation of PRAS40, which is associated with autophagy and metastasis, induced autophagosome formation, and suppressed programmed cell death and necroptosis. Furthermore, Vitex induced antimetastatic activity by suppressing the migration and invasion of MMP13, which is the primary protease that degrades type I collagen for tumour-induced osteolysis in bone tissues and preferential metastasis sites. Taken together, our results suggest that Vitex is an attractive target for treating human osteosarcoma. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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16 pages, 1434 KiB

Open AccessArticle

Caffeic Acid Phosphanium Derivatives: Potential Selective Antitumor, Antimicrobial and Antiprotozoal Agents

by Miloš Lukáč, Lívia Slobodníková, Martin Mrva, Aneta Dušeková, Mária Garajová, Martin Kello, Dominika Šebová, Martin Pisárčik, Marián Kojnok, Andrej Vrták, Elena Kurin and Silvia Bittner Fialová

Int. J. Mol. Sci. 2024, 25(2), 1200; https://doi.org/10.3390/ijms25021200 - 18 Jan 2024

Cited by 1 | Viewed by 1390

Abstract

Caffeic acid (CA) is one of the most abundant natural compounds present in plants and has a broad spectrum of beneficial pharmacological activities. However, in some cases, synthetic derivation of original molecules can expand their scope. This study focuses on the synthesis of [...] Read more.

Caffeic acid (CA) is one of the most abundant natural compounds present in plants and has a broad spectrum of beneficial pharmacological activities. However, in some cases, synthetic derivation of original molecules can expand their scope. This study focuses on the synthesis of caffeic acid phosphanium derivatives with the ambition of increasing their biological activities. Four caffeic acid phosphanium salts (CAPs) were synthesized and tested for their cytotoxic, antibacterial, antifungal, and amoebicidal activity in vitro, with the aim of identifying the best area for their medicinal use. CAPs exhibited significantly stronger cytotoxic activity against tested cell lines (HeLa, HCT116, MDA-MB-231 MCF-7, A2058, PANC-1, Jurkat) in comparison to caffeic acid. Focusing on Jurkat cells (human leukemic T cell lymphoma), the IC₅₀ value of CAPs ranged from 0.9 to 8.5 μM while IC₅₀ of CA was >300 μM. Antimicrobial testing also confirmed significantly higher activity of CAPs against selected microbes in comparison to CA, especially for Gram-positive bacteria (MIC 13–57 μM) and the yeast Candida albicans (MIC 13–57 μM). The anti-Acanthamoeba activity was studied against two pathogenic Acanthamoeba strains. In the case of A. lugdunensis, all CAPs revealed a stronger inhibitory effect (EC₅₀ 74–3125 μM) than CA (>10⁵ µM), while in A. quina strain, the higher inhibition was observed for three derivatives (EC₅₀ 44–291 μM). The newly synthesized quaternary phosphanium salts of caffeic acid exhibited selective antitumor action and appeared to be promising antimicrobial agents for topical application, as well as potential molecules for further research. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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45 pages, 3284 KiB

Open AccessReview

Unveiling the Therapeutic Potential of Folate-Dependent One-Carbon Metabolism in Cancer and Neurodegeneration

by Ana Filipa Sobral, Andrea Cunha, Vera Silva, Eva Gil-Martins, Renata Silva and Daniel José Barbosa

Int. J. Mol. Sci. 2024, 25(17), 9339; https://doi.org/10.3390/ijms25179339 - 28 Aug 2024

Viewed by 2457

Abstract

Cellular metabolism is crucial for various physiological processes, with folate-dependent one-carbon (1C) metabolism playing a pivotal role. Folate, a B vitamin, is a key cofactor in this pathway, supporting DNA synthesis, methylation processes, and antioxidant defenses. In dividing cells, folate facilitates nucleotide biosynthesis, [...] Read more.

Cellular metabolism is crucial for various physiological processes, with folate-dependent one-carbon (1C) metabolism playing a pivotal role. Folate, a B vitamin, is a key cofactor in this pathway, supporting DNA synthesis, methylation processes, and antioxidant defenses. In dividing cells, folate facilitates nucleotide biosynthesis, ensuring genomic stability and preventing carcinogenesis. Additionally, in neurodevelopment, folate is essential for neural tube closure and central nervous system formation. Thus, dysregulation of folate metabolism can contribute to pathologies such as cancer, severe birth defects, and neurodegenerative diseases. Epidemiological evidence highlights folate’s impact on disease risk and its potential as a therapeutic target. In cancer, antifolate drugs that inhibit key enzymes of folate-dependent 1C metabolism and strategies targeting folate receptors are current therapeutic options. However, folate’s impact on cancer risk is complex, varying among cancer types and dietary contexts. In neurodegenerative conditions, including Alzheimer’s and Parkinson’s diseases, folate deficiency exacerbates cognitive decline through elevated homocysteine levels, contributing to neuronal damage. Clinical trials of folic acid supplementation show mixed outcomes, underscoring the complexities of its neuroprotective effects. This review integrates current knowledge on folate metabolism in cancer and neurodegeneration, exploring molecular mechanisms, clinical implications, and therapeutic strategies, which can provide crucial information for advancing treatments. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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20 pages, 2002 KiB

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Plant-Based HSP90 Inhibitors in Breast Cancer Models: A Systematic Review

by Ilham Zarguan, Sonia Ghoul, Lamiae Belayachi and Abdelaziz Benjouad

Int. J. Mol. Sci. 2024, 25(10), 5468; https://doi.org/10.3390/ijms25105468 - 17 May 2024

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Abstract

Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets is more necessary than ever to tackle this pathology. Heat-Shock Protein 90 (HSP90), a chaperone protein, is implicated in breast [...] Read more.

Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets is more necessary than ever to tackle this pathology. Heat-Shock Protein 90 (HSP90), a chaperone protein, is implicated in breast cancer pathogenesis, rendering it an appealing target. Looking for alternative approach such as Plant-based compounds and natural HSP90 inhibitors offer promising prospects for innovative therapeutic strategies. This study aims to identify plant-based compounds with anticancer effects on breast cancer models and elucidate their mechanism of action in inhibiting the HSP90 protein. A systematic review was conducted and completed in January 2024 and included in vitro, in vivo, and in silico studies that investigated the effectiveness of plant-based HSP90 inhibitors tested on breast cancer models. Eleven studies were included in the review. Six plants and 24 compounds from six different classes were identified and proved to be effective against HSP90 in breast cancer models. The studied plant extracts showed a dose- and time-dependent decrease in cell viability. Variable IC50 values showed antiproliferative effects, with the plant Tubocapsicum anomalum demonstrating the lowest value. Withanolides was the most studied class. Fennel, Trianthema portulacastrum, and Spatholobus suberectus extracts were shown to inhibit tumor growth and angiogenesis and modulate HSP90 expression as well as its cochaperone interactions in breast cancer mouse models. The identified plant extracts and compounds were proven effective against HSP90 in breast cancer models, and this inhibition showed promising effects on breast cancer biology. Collectively, these results urge the need of further studies to better understand the mechanism of action of HSP90 inhibitors using comparable methods for preclinical observations. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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23 pages, 1689 KiB

Open AccessReview

Therapeutic Potential of Chlorogenic Acid in Chemoresistance and Chemoprotection in Cancer Treatment

by Nicole Cortez, Cecilia Villegas, Viviana Burgos, Leandro Ortiz, Jaime R. Cabrera-Pardo and Cristian Paz

Int. J. Mol. Sci. 2024, 25(10), 5189; https://doi.org/10.3390/ijms25105189 - 10 May 2024

Cited by 1 | Viewed by 1543

Abstract

Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors’ resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic [...] Read more.

Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors’ resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals effectively. This review is a summary of current information about CGA, including its natural sources, biosynthesis, metabolism, toxicology, role in combatting chemoresistance, and protective effects against chemotherapy-induced toxicity. It also emphasizes the potential of CGA as a pharmacological adjuvant in cancer treatment with drugs such as 5-fluorouracil, cisplatin, oxaliplatin, doxorubicin, regorafenib, and radiotherapy. By analyzing more than 140 papers from PubMed, Google Scholar, and SciFinder, we hope to find the therapeutic potential of CGA in improving cancer therapy. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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22 pages, 1914 KiB

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Oxidative Stress: The Role of Antioxidant Phytochemicals in the Prevention and Treatment of Diseases

by Adele Muscolo, Oliva Mariateresa, Torello Giulio and Russo Mariateresa

Int. J. Mol. Sci. 2024, 25(6), 3264; https://doi.org/10.3390/ijms25063264 - 13 Mar 2024

Cited by 32 | Viewed by 6677

Abstract

Oxidative stress, characterized by an imbalance favouring oxidants over antioxidants, is a key contributor to the development of various common diseases. Counteracting these oxidants is considered an effective strategy to mitigate the levels of oxidative stress in organisms. Numerous studies have indicated an [...] Read more.

Oxidative stress, characterized by an imbalance favouring oxidants over antioxidants, is a key contributor to the development of various common diseases. Counteracting these oxidants is considered an effective strategy to mitigate the levels of oxidative stress in organisms. Numerous studies have indicated an inverse correlation between the consumption of vegetables and fruits and the risk of chronic diseases, attributing these health benefits to the presence of antioxidant phytochemicals in these foods. Phytochemicals, present in a wide range of foods and medicinal plants, play a pivotal role in preventing and treating chronic diseases induced by oxidative stress by working as antioxidants. These compounds exhibit potent antioxidant, anti-inflammatory, anti-aging, anticancer, and protective properties against cardiovascular diseases, diabetes mellitus, obesity, and neurodegenerative conditions. This comprehensive review delves into the significance of these compounds in averting and managing chronic diseases, elucidating the key sources of these invaluable elements. Additionally, it provides a summary of recent advancements in understanding the health benefits associated with antioxidant phytochemicals. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

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