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18 pages, 3288 KiB

Open AccessArticle

Identifying Herbal Candidates and Active Ingredients Against Postmenopausal Osteoporosis Using Biased Random Walk on a Multiscale Network

by Boyun Jang, Youngsoo Kim, Jungbin Song, Young-Woo Kim and Won-Yung Lee

Int. J. Mol. Sci. 2024, 25(22), 12322; https://doi.org/10.3390/ijms252212322 - 16 Nov 2024

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Abstract

Postmenopausal osteoporosis is a major global health concern, particularly affecting aging women, and necessitates innovative treatment options. Herbal medicine, with its multi-compound, multi-target characteristics, offers a promising approach for complex diseases. In this study, we applied multiscale network and random walk-based analyses to [...] Read more.

Postmenopausal osteoporosis is a major global health concern, particularly affecting aging women, and necessitates innovative treatment options. Herbal medicine, with its multi-compound, multi-target characteristics, offers a promising approach for complex diseases. In this study, we applied multiscale network and random walk-based analyses to identify candidate herbs and their active ingredients for postmenopausal osteoporosis, focusing on their underlying mechanisms. A dataset of medicinal herbs, their active ingredients, and protein targets was compiled, and diffusion profiles were calculated to assess the propagation effects. Through correlation analysis, we prioritized herbs based on their relevance to osteoporosis, identifying the top candidates like Benincasae Semen, Glehniae Radix, Corydalis Tuber, and Houttuyniae Herba. Gene Set Enrichment Analysis (GSEA) revealed that the 49 core protein targets of these herbs were significantly associated with pathways related to inflammation, osteoclast differentiation, and estrogen metabolism. Notably, compounds such as falcarindiol from Glehniae Radix and tetrahydrocoptisine from Corydalis Tuber—previously unstudied for osteoporosis—were predicted to interact with inflammation-related proteins, including IL6, IL1B, and TNF, affecting key biological processes like apoptosis and cell proliferation. This study advances the understanding of herbal therapies for osteoporosis and offers a framework for discovering novel therapeutic agents. Full article

(This article belongs to the Special Issue Therapeutic Potential of Antioxidants in the Prevention of Human Diseases)

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19 pages, 2977 KiB

Open AccessArticle

Evaluation of the Antidiabetic Potential of Xanthone-Rich Extracts from Gentiana dinarica and Gentiana utriculosa

by Jelena Arambašić Jovanović, Dijana Krstić-Milošević, Branka Vinterhalter, Svetlana Dinić, Nevena Grdović, Aleksandra Uskoković, Jovana Rajić, Marija Đorđević, Ana Sarić, Melita Vidaković and Mirjana Mihailović

Int. J. Mol. Sci. 2024, 25(16), 9066; https://doi.org/10.3390/ijms25169066 - 21 Aug 2024

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Abstract

Despite the existence of various therapeutic approaches, diabetes mellitus and its complications have been an increasing burden of mortality and disability globally. Hence, it is necessary to evaluate the efficacy and safety of medicinal plants to support existing drugs in treating diabetes. Xanthones, [...] Read more.

Despite the existence of various therapeutic approaches, diabetes mellitus and its complications have been an increasing burden of mortality and disability globally. Hence, it is necessary to evaluate the efficacy and safety of medicinal plants to support existing drugs in treating diabetes. Xanthones, the main secondary metabolites found in Gentiana dinarica and Gentiana utriculosa, display various biological activities. In in vitro cultured and particularly in genetically transformed G. dinarica and G. utriculosa roots, there is a higher content of xanthones. The aim of this study was to investigate and compare antidiabetic properties of secondary metabolites (extracts) prepared from these two Gentiana species, cultured in vitro and genetically transformed with those collected from nature. We compare HPLC secondary metabolite profiles and the content of the main extract compounds of G. dinarica and G. utriculosa methanol extracts with their ability to scavenge DPPH free radicals and inhibit intestinal α-glucosidase in vitro. Anti-hyperglycemic activity of selected extracts was tested further in vivo on glucose-loaded Wistar rats. Our findings reveal that the most prominent radical scavenging potential and potential to control the rise in glucose level, detected in xanthone-rich extracts, were in direct correlation with an accumulation of xanthones norswertianin and norswertianin-1-O-primeveroside in G. dinarica and decussatin and decussatin-1-O-primeveroside in G. utriculosa. Full article

(This article belongs to the Special Issue Therapeutic Potential of Antioxidants in the Prevention of Human Diseases)

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12 pages, 8155 KiB

Open AccessArticle

Caffeine Protects Keratinocytes from Trichophyton mentagrophytes Infection and Behaves as an Antidermatophytic Agent

by Diogo M. da Fonseca, Lisa Rodrigues, José Sousa-Baptista, Félix Marcos-Tejedor, Marta Mota, Rodrigo A. Cunha, Chantal Fernandes and Teresa Gonçalves

Int. J. Mol. Sci. 2024, 25(15), 8303; https://doi.org/10.3390/ijms25158303 - 30 Jul 2024

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Abstract

Caffeine affords several beneficial effects on human health, acting as an antioxidant, anti-inflammatory agent, and analgesic. Caffeine is widely used in cosmetics, but its antimicrobial activity has been scarcely explored, namely against skin infection agents. Dermatophytes are the most common fungal agents of [...] Read more.

Caffeine affords several beneficial effects on human health, acting as an antioxidant, anti-inflammatory agent, and analgesic. Caffeine is widely used in cosmetics, but its antimicrobial activity has been scarcely explored, namely against skin infection agents. Dermatophytes are the most common fungal agents of human infection, mainly of skin infections. This work describes the in vitro effect of caffeine during keratinocyte infection by Trichophyton mentagrophytes, one of the most common dermatophytes. The results show that caffeine was endowed with antidermatophytic activity with a MIC, determined following the EUCAST standards, of 8 mM. Caffeine triggered a modification of the levels of two major components of the fungal cell wall, β-(1,3)-glucan and chitin. Caffeine also disturbed the ultrastructure of the fungal cells, particularly the cell wall surface and mitochondria, and autophagic-like structures were observed. During dermatophyte–human keratinocyte interactions, caffeine prevented the loss of viability of keratinocytes and delayed spore germination. Overall, this indicates that caffeine can act as a therapeutic and prophylactic agent for dermatophytosis. Full article

(This article belongs to the Special Issue Therapeutic Potential of Antioxidants in the Prevention of Human Diseases)

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20 pages, 8950 KiB

Open AccessArticle

The Scavenging Activity of Coenzyme Q₁₀ Plus a Nutritional Complex on Human Retinal Pigment Epithelial Cells

by Maria Hernandez, Sergio Recalde, Jaione Bezunartea, Maite Moreno-Orduña, Idoia Belza, Ainara Chas-Prat, Elena Perugini, Alfredo Garcia-Layana and Patricia Fernández-Robredo

Int. J. Mol. Sci. 2024, 25(15), 8070; https://doi.org/10.3390/ijms25158070 - 24 Jul 2024

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Abstract

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are common retinal diseases responsible for most blindness in working-age and elderly populations. Oxidative stress and mitochondrial dysfunction play roles in these pathogenesis, and new therapies counteracting these contributors could be of great interest. Some [...] Read more.

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are common retinal diseases responsible for most blindness in working-age and elderly populations. Oxidative stress and mitochondrial dysfunction play roles in these pathogenesis, and new therapies counteracting these contributors could be of great interest. Some molecules, like coenzyme Q₁₀ (CoQ₁₀), are considered beneficial to maintain mitochondrial homeostasis and contribute to the prevention of cellular apoptosis. We investigated the impact of adding CoQ₁₀ (Q) to a nutritional antioxidant complex (Nutrof Total^®; N) on the mitochondrial status and apoptosis in an in vitro hydrogen peroxide (H₂O₂)-induced oxidative stress model in human retinal pigment epithelium (RPE) cells. H₂O₂ significantly increased 8-OHdG levels (p < 0.05), caspase-3 (p < 0.0001) and TUNEL intensity (p < 0.01), and RANTES (p < 0.05), caspase-1 (p < 0.05), superoxide (p < 0.05), and DRP-1 (p < 0.05) levels, and also decreased IL1β, SOD2, and CAT gene expression (p < 0.05) vs. control. Remarkably, Q showed a significant recovery in IL1β gene expression, TUNEL, TNFα, caspase-1, and JC-1 (p < 0.05) vs. H₂O_2, and NQ showed a synergist effect in caspase-3 (p < 0.01), TUNEL (p < 0.0001), mtDNA, and DRP-1 (p < 0.05). Our results showed that CoQ₁₀ supplementation is effective in restoring/preventing apoptosis and mitochondrial stress-related damage, suggesting that it could be a valid strategy in degenerative processes such as AMD or DR. Full article

(This article belongs to the Special Issue Therapeutic Potential of Antioxidants in the Prevention of Human Diseases)

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12 pages, 1452 KiB

Open AccessArticle

The Effect of a Ketogenic Diet versus Mediterranean Diet on Clinical and Biochemical Markers of Inflammation in Patients with Obesity and Psoriatic Arthritis: A Randomized Crossover Trial

by Vaia Lambadiari, Pelagia Katsimbri, Aikaterini Kountouri, Emmanouil Korakas, Argyro Papathanasi, Eirini Maratou, George Pavlidis, Loukia Pliouta, Ignatios Ikonomidis, Sofia Malisova, Dionysios Vlachos and Evangelia Papadavid

Int. J. Mol. Sci. 2024, 25(5), 2475; https://doi.org/10.3390/ijms25052475 - 20 Feb 2024

Cited by 5 | Viewed by 9045

Abstract

The effect of different diet patterns on psoriasis (PSO) and psoriatic arthritis (PSA) is unknown. Τhe aim of our study was to evaluate the effectiveness of a Mediterranean diet (MD) and Ketogenic diet (KD), in patients with PSO and PSA. Twenty-six patients were [...] Read more.

The effect of different diet patterns on psoriasis (PSO) and psoriatic arthritis (PSA) is unknown. Τhe aim of our study was to evaluate the effectiveness of a Mediterranean diet (MD) and Ketogenic diet (KD), in patients with PSO and PSA. Twenty-six patients were randomly assigned to start either with MD or KD for a period of 8 weeks. After a 6-week washout interval, the two groups were crossed over to the other type of diet for 8 weeks. At the end of this study, MD and KD resulted in significant reduction in weight (p = 0.002, p < 0.001, respectively), in BMI (p = 0.006, p < 0.001, respectively), in waist circumference (WC) (p = 0.001, p < 0.001, respectively), in total fat mass (p = 0.007, p < 0.001, respectively), and in visceral fat (p = 0.01, p < 0.001, respectively), in comparison with baseline. After KD, patients displayed a significant reduction in the Psoriasis Area and Severity Index (PASI) (p = 0.04), Disease Activity Index of Psoriatic Arthritis (DAPSA) (p = 0.004), interleukin (IL)-6 (p = 0.047), IL-17 (p = 0.042), and IL-23 (p = 0.037), whereas no significant differences were observed in these markers after MD (p > 0.05), compared to baseline. The 22-week MD–KD diet program in patients with PSO and PSA led to beneficial results in markers of inflammation and disease activity, which were mainly attributed to KD. Full article

(This article belongs to the Special Issue Therapeutic Potential of Antioxidants in the Prevention of Human Diseases)

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13 pages, 4768 KiB

Open AccessArticle

β-Carotene Supplementation Improves Pancreas Function during Moderate Ethanol Consumption: Initial Characterization from a Morphological Overview

by Cristian Sandoval, Angeles Vera, Katherine Birditt, Karina Godoy, Florencia Carmine, José Caamaño and Jorge Farías

Int. J. Mol. Sci. 2024, 25(2), 1219; https://doi.org/10.3390/ijms25021219 - 19 Jan 2024

Cited by 1 | Viewed by 1279

Abstract

Alcohol is believed to harm acinar cells, pancreatic ductal epithelium, and pancreatic stellate cells. After giving ethanol and/or β-carotene to C57BL/6 mice, our goal was to evaluate their biochemistry, histology, and morpho-quantitative features. There were six groups of C57BL/6 mice: 1. Group C [...] Read more.

Alcohol is believed to harm acinar cells, pancreatic ductal epithelium, and pancreatic stellate cells. After giving ethanol and/or β-carotene to C57BL/6 mice, our goal was to evaluate their biochemistry, histology, and morpho-quantitative features. There were six groups of C57BL/6 mice: 1. Group C (control), 2. Group LA (low-dose alcohol), 3. Group MA (moderate-dose alcohol), 4. Group B (β-carotene), 5. Group LA + B (low-dose alcohol combined with β-carotene), and 6. Group MA + B (moderate-dose alcohol combined with β-carotene). After the animals were euthanized on day 28, each specimen’s pancreatic tissue was taken. Lipase, uric acid, and amylase were assessed using biochemical assessment. Furthermore, the examination of the pancreatic structure was conducted using Ammann’s fibrosis scoring system. Finally, the morpho-quantitative characteristics of the pancreatic islets and acinar cells were determined. In the serum of the MA + B group, there were higher amounts of total amylase (825.953 ± 193.412 U/L) and lower amounts of lipase (47.139 ± 6.099 U/L) (p < 0.05). Furthermore, Ammann’s fibrosis punctuation in the pancreas revealed significant variations between the groups (p < 0.001). Finally, the stereological analysis of pancreatic islets showed that the groups were different (p < 0.001). These findings suggest that antioxidant treatments might help decrease the negative effects of ethanol exposure in animal models. Full article

(This article belongs to the Special Issue Therapeutic Potential of Antioxidants in the Prevention of Human Diseases)

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Review

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21 pages, 1096 KiB

Open AccessReview

Flavonoids and Their Role in Preventing the Development and Progression of MAFLD by Modifying the Microbiota

by Aneta Sokal-Dembowska, Sara Jarmakiewicz-Czaja and Rafał Filip

Int. J. Mol. Sci. 2024, 25(20), 11187; https://doi.org/10.3390/ijms252011187 - 17 Oct 2024

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Abstract

With the increasing prevalence and serious health consequences of metabolic-associated fatty liver disease (MAFLD), early diagnosis and intervention are key to effective treatment. Recent studies highlight the important role of dietary factors, including the use of flavonoids, in improving liver health. These compounds [...] Read more.

With the increasing prevalence and serious health consequences of metabolic-associated fatty liver disease (MAFLD), early diagnosis and intervention are key to effective treatment. Recent studies highlight the important role of dietary factors, including the use of flavonoids, in improving liver health. These compounds possess anti-inflammatory, antioxidant, and liver-protective properties. Flavonoids have been shown to affect the gut microbiota, which plays a key role in liver function and disease progression. Therefore, their role in preventing the development and progression of MAFLD through modulation of the microbiome seems to be of interest. This narrative review aims to consolidate the current evidence on the effects of selected flavonoids on MAFLD progression, their potential mechanisms of action, and the implications for the development of personalized dietary interventions for the management of liver disease. Full article

(This article belongs to the Special Issue Therapeutic Potential of Antioxidants in the Prevention of Human Diseases)

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30 pages, 11699 KiB

Open AccessReview

The Bioactivity and Phytochemicals of Muscari comosum (Leopoldia comosa), a Plant of Multiple Pharmacological Activities

by Varun Jaiswal and Hae-Jeung Lee

Int. J. Mol. Sci. 2024, 25(5), 2592; https://doi.org/10.3390/ijms25052592 - 23 Feb 2024

Cited by 2 | Viewed by 1770

Abstract

Leopoldia comosa (LC), popularly known as Muscari comosum, spontaneously grows in the Mediterranean region and its bulbs are used as a vegetable. Traditionally, they are also used to treat various diseases and conditions, which has inspired the study of the pharmacological activities [...] Read more.

Leopoldia comosa (LC), popularly known as Muscari comosum, spontaneously grows in the Mediterranean region and its bulbs are used as a vegetable. Traditionally, they are also used to treat various diseases and conditions, which has inspired the study of the pharmacological activities of different parts of LC. These studies revealed the numerous biological properties of LC including antioxidant, anti-inflammatory, anti-diabetes, anti-obesity, anti-cancer, anti-Alzheimer’s disease, antibacterial, and immune stimulant. High antioxidant activity compared to other non-cultivated plants, and the potential role of antioxidant activity in other reported activities make LC an excellent candidate to be developed as an antioxidant plant against important associated diseases. The presence of a diverse class of phytochemicals (n = 85), especially flavonoids and homoisoflavones, in LC, also imparts significance to the nutraceutical candidature of the plant. However, limited animal studies and the lack of a directional approach have limited the further design of effective clinical studies for the development of LC. The current study is the first attempt to comprehensively compile information regarding the phytochemicals and pharmacological activities of LC, emphasize the targets/markers targeted by LC, important in other activities, and also highlight the current gaps and propose possible bridges for the development of LC as a therapeutic and/or supplement against important diseases. Full article

(This article belongs to the Special Issue Therapeutic Potential of Antioxidants in the Prevention of Human Diseases)

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