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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (15 April 2024) | Viewed by 24443

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Prof. Dr. George Miloshev

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Institute of Molecular Biology “Roumen Tsanev”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Interests: epigenetics; chromatin; genotoxicology
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Special Issue Information

Dear Colleagues,

Natural products are made from biomolecules, compounds and extracts from plants or animals, which humans have been using for millennia. Although most natural products possess proven positive effects on human health, the appearance of some unwanted side effects cannot be entirely excluded. Therefore, data from scientific research on natural products and their applications at the molecular, cellular and organismal levels are extremely useful.

This Special Issue aims to represent high-quality, modern research and the acquired knowledge on the application of natural products.

This Special Issue calls for researchers to contribute reviews and original research reports of their recent work on the topic of the properties of natural products, as studied at the molecular, cellular or organismal level.

Subtopics may include:

Cellular metabolism of natural products;
Genotoxicity and allergenicity of natural products;
Epigenetic influence of natural products;
Natural products and aging.

Prof. Dr. George Miloshev
Guest Editor

Manuscript Submission Information

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Keywords

natural products
biomedicine
genotoxicity
epigenetics
aging

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Published Papers (10 papers)

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Research

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15 pages, 4065 KiB

Open AccessArticle

Vasorelaxant and Blood Pressure-Lowering Effects of Cnidium monnieri Fruit Ethanol Extract in Sprague Dawley and Spontaneously Hypertensive Rats

by Junkyu Park, Sujin Shin, Youngmin Bu, Ho-young Choi and Kyungjin Lee

Int. J. Mol. Sci. 2024, 25(8), 4223; https://doi.org/10.3390/ijms25084223 - 11 Apr 2024

Cited by 3 | Viewed by 1265

Abstract

Cnidium monnieri (L.) Cusson, a member of the Apiaceae family, is rich in coumarins, such as imperatorin and osthole. Cnidium monnieri fruit (CM) has a broad range of therapeutic potential that can be used in anti-bacterial, anti-cancer, and sexual dysfunction treatments. However, its efficacy in lowering blood pressure through vasodilation remains unknown. This study aimed to assess the potential therapeutic effect of CM 50% ethanol extract (CME) on hypertension and the mechanism of its vasorelaxant effect. CME (1–30 µg/mL) showed a concentration-dependent vasorelaxation on constricted aortic rings in Sprague Dawley rats induced by phenylephrine via an endothelium-independent mechanism. The vasorelaxant effect of CME was inhibited by blockers of voltage-dependent and Ca²⁺-activated K⁺ channels. Additionally, CME inhibited the vascular contraction induced by angiotensin II and CaCl₂. The main active compounds of CM, i.e., imperatorin (3–300 µM) and osthole (1–100 µM), showed a concentration-dependent vasorelaxation effect, with half-maximal effective concentration values of 9.14 ± 0.06 and 5.98 ± 0.06 µM, respectively. Orally administered CME significantly reduced the blood pressure of spontaneously hypertensive rats. Our research shows that CME is a promising treatment option for hypertension. However, further studies are required to fully elucidate its therapeutic potential. Full article

(This article belongs to the Special Issue Application of Natural Products in Biomedicine and Pharmacotherapy)

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20 pages, 4156 KiB

Open AccessArticle

Water Extracts from Industrial Hemp Waste Inhibit the Adhesion and Development of Candida Biofilm and Showed Antioxidant Activity on HT-29 Colon Cancer Cells

by Leonardo Donati, Debora Casagrande Pierantoni, Angela Conti, Eleonora Calzoni, Laura Corte, Claudio Santi, Ornelio Rosati, Gianluigi Cardinali and Carla Emiliani

Int. J. Mol. Sci. 2024, 25(7), 3979; https://doi.org/10.3390/ijms25073979 - 3 Apr 2024

Cited by 3 | Viewed by 1896

Abstract

The evolution of regulatory perspectives regarding the health and nutritional properties of industrial hemp-based products (Cannabis sativa L.) has pushed research to focus on the development of new methods for both the extraction and formulation of the bioactive compounds present in hemp extracts. While the psychoactive and medicinal properties of hemp-derived cannabinoid extracts are well known, much less has been investigated on the functional and antimicrobial properties of hemp extracts. Within the hemp value chain, various agricultural wastes and by-products are generated. These materials can be valorised through eco-innovations, ultimately promoting sustainable economic development. In this study, we explored the use of waste from industrial light cannabis production for the extraction of bioactive compounds without the addition of chemicals. The five extracts obtained were tested for their antimicrobial activity on both planktonic and sessile cells of pathogenic strains of the Candida albicans, Candida parapsilosis, and Candida tropicalis species and for their antioxidant activity on HT-29 colon cancer cells under oxidative stress. Our results demonstrated that these extracts display interesting properties both as antioxidants and in hindering the development of fungal biofilm, paving the way for further investigations into the sustainable valorisation of hemp waste for different biomedical applications. Full article

(This article belongs to the Special Issue Application of Natural Products in Biomedicine and Pharmacotherapy)

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21 pages, 2174 KiB

Open AccessArticle

Extracts of Sideritis scardica and Clinopodium vulgare Alleviate Cognitive Impairments in Scopolamine-Induced Rat Dementia

by Maria Lazarova, Elina Tsvetanova, Almira Georgieva, Miroslava Stefanova, Diamara Uzunova, Petko Denev, Valya Vassileva and Krasimira Tasheva

Int. J. Mol. Sci. 2024, 25(3), 1840; https://doi.org/10.3390/ijms25031840 - 2 Feb 2024

Cited by 2 | Viewed by 1450

Abstract

Sideritis scardica Griseb. and Clinopodium vulgare L., belonging to the Lamiaceae family, are rich in terpenoids and phenolics and exhibit various pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer activities. While the memory-enhancing impacts of S. scardica are well documented, the cognitive benefits of C. vulgare remain unexplored. This study assessed the potential effect of C. vulgare on learning and memory in healthy and scopolamine (Sco)-induced memory-impaired male Wistar rats, comparing it with the effects of S. scardica. Over a 21-day period, rats orally received extracts of cultivated S. scardica (200 mg/kg) and C. vulgare (100 mg/kg), either individually or in combination, with administration starting 10 days before and continuing 11 days simultaneously with Sco injection at a dose of 2 mg/kg intraperitoneally. The results showed that both extracts effectively mitigated Sco-induced memory impairment. Their combination significantly improved recognition memory and maintained monoaminergic function. S. scardica excelled in preserving spatial working memory, while C. vulgare exhibited comparable retention of recognition memory, robust antioxidant activity and acetylcholinesterase inhibitory activity. The extracts alleviated Sco-induced downregulation of p-CREB/BDNF signaling, suggesting neuroprotective mechanisms. The extract combination positively affected most of the Sco-induced impairments, underscoring the potential for further investigation of these extracts for therapeutic development. Full article

(This article belongs to the Special Issue Application of Natural Products in Biomedicine and Pharmacotherapy)

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26 pages, 4342 KiB

Open AccessArticle

Cornelian Cherry (Cornus mas L.) Fruit Extract Lowers SREBP-1c and C/EBPα in Liver and Alters Various PPAR-α, PPAR-γ, LXR-α Target Genes in Cholesterol-Rich Diet Rabbit Model

by Maciej Danielewski, Andrzej Rapak, Angelika Kruszyńska, Małgorzata Małodobra-Mazur, Paweł Oleszkiewicz, Stanisław Dzimira, Alicja Z. Kucharska, Wojciech Słupski, Agnieszka Matuszewska, Beata Nowak, Adam Szeląg, Narcyz Piórecki, Urszula Zaleska-Dorobisz and Tomasz Sozański

Int. J. Mol. Sci. 2024, 25(2), 1199; https://doi.org/10.3390/ijms25021199 - 18 Jan 2024

Cited by 4 | Viewed by 2063

Abstract

Cornelian cherry (Cornus mas L.) fruits, abundant in iridoids and anthocyanins, are natural products with proven beneficial impacts on the functions of the cardiovascular system and the liver. This study aims to assess and compare whether and to what extent two different doses of resin-purified cornelian cherry extract (10 mg/kg b.w. or 50 mg/kg b.w.) applied in a cholesterol-rich diet rabbit model affect the levels of sterol regulatory element-binding protein 1c (SREBP-1c) and CCAAT/enhancer binding protein α (C/EBPα), and various liver X receptor-α (LXR-α), peroxisome proliferator-activated receptor-α (PPAR-α), and peroxisome proliferator-activated receptor-γ (PPAR-γ) target genes. Moreover, the aim is to evaluate the resistive index (RI) of common carotid arteries (CCAs) and aortas, and histopathological changes in CCAs. For this purpose, the levels of SREBP-1c, C/EBPα, ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), fatty acid synthase (FAS), endothelial lipase (LIPG), carnitine palmitoyltransferase 1A (CPT1A), and adiponectin receptor 2 (AdipoR2) in liver tissue were measured. Also, the levels of lipoprotein lipase (LPL), visceral adipose tissue-derived serine protease inhibitor (Vaspin), and retinol-binding protein 4 (RBP4) in visceral adipose tissue were measured. The RI of CCAs and aortas, and histopathological changes in CCAs, were indicated. The oral administration of the cornelian cherry extract decreased the SREBP-1c and C/EBPα in both doses. The dose of 10 mg/kg b.w. increased ABCA1 and decreased FAS, CPT1A, and RBP4, and the dose of 50 mg/kg b.w. enhanced ABCG1 and AdipoR2. Mitigations in atheromatous changes in rabbits’ CCAs were also observed. The obtained outcomes were compared to the results of our previous works. The beneficial results confirm that cornelian cherry fruit extract may constitute a potentially effective product in the prevention and treatment of obesity-related disorders. Full article

(This article belongs to the Special Issue Application of Natural Products in Biomedicine and Pharmacotherapy)

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17 pages, 1131 KiB

Open AccessArticle

Yolkin, a Polypeptide Complex from Egg Yolk, Affects Cytokine Levels and Leukocyte Populations in Broiler Chicken Blood and Lymphoid Organs after In Ovo Administration

by Marianna Szczypka, Magdalena Lis, Maciej Kuczkowski, Kamila Bobrek, Aleksandra Pawlak, Aleksandra Zambrowicz, Andrzej Gaweł and Bożena Obmińska-Mrukowicz

Int. J. Mol. Sci. 2023, 24(24), 17494; https://doi.org/10.3390/ijms242417494 - 14 Dec 2023

Cited by 2 | Viewed by 1279

Abstract

Yolkin is a polypeptide complex isolated from hen egg yolk that exhibits immunomodulating properties. The aim of the present study was to determine whether in-ovo-delivered yolkin affects leukocyte populations and cytokine levels in broiler chickens. The experiment was carried out on eggs from Ross 308 broiler breeder birds. Yolkin was administered in ovo on the 18th day of incubation, once, at the following three doses: 1, 10, or 100 µg/egg. The immunological parameters were assessed in 1-, 7-, 14-, 21-, 28-, 35-, and 42-day-old birds kept under farming conditions and routinely vaccinated. The leukocyte populations were determined in the thymus, spleen, and blood. The cytokine (IL-1β, IL-2, IL-6, and IL-10) levels were determined in the plasma of the broiler chickens. Each experimental group included eight birds. The most pronounced effect of yolkin was an increase in the population of T cells, both CD4⁺ and CD8⁺, mainly in the blood. This effect on the lymphocyte subsets may be valuable regarding chicken immune responses, mainly against T-dependent antigens, during infection or after vaccination. Full article

(This article belongs to the Special Issue Application of Natural Products in Biomedicine and Pharmacotherapy)

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22 pages, 1733 KiB

Open AccessArticle

Haberlea rhodopensis Extract Tunes the Cellular Response to Stress by Modulating DNA Damage, Redox Components, and Gene Expression

by Dessislava Staneva, Neli Dimitrova, Borislav Popov, Albena Alexandrova, Milena Georgieva and George Miloshev

Int. J. Mol. Sci. 2023, 24(21), 15964; https://doi.org/10.3390/ijms242115964 - 4 Nov 2023

Cited by 3 | Viewed by 2360

Abstract

Ionizing radiation (IR) and reactive oxygen species (ROS)-induced oxidative stress can cause damage to cellular biomolecules, including DNA, proteins, and lipids. These harmful effects can compromise essential cellular functions and significantly raise the risk of metabolic dysfunction, accumulation of harmful mutations, genome instability, cancer, accelerated cellular senescence, and even death. Here, we present an investigation of HeLa cancer cells’ early response to gamma IR (γ-IR) and oxidative stress after preincubation of the cells with natural extracts of the resurrection plant Haberlea rhodopensis. In light of the superior protection offered by plant extracts against radiation and oxidative stress, we investigated the cellular defence mechanisms involved in such protection. Specifically, we sought to evaluate the molecular effects of H. rhodopensis extract (HRE) on cells subjected to genotoxic stress by examining the components of the redox pathway and quantifying the transcription levels of several critical genes associated with DNA repair, cell cycle regulation, and apoptosis. The influence of HRE on genome integrity and the cell cycle was also studied via comet assay and flow cytometry. Our findings demonstrate that HREs can effectively modulate the cellular response to genotoxic and oxidative stress within the first two hours following exposure, thereby reducing the severity of such stress. Furthermore, we observed the specificity of genoprotective HRE doses depending on the source of the applied genotoxic stress. Full article

(This article belongs to the Special Issue Application of Natural Products in Biomedicine and Pharmacotherapy)

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18 pages, 4179 KiB

Open AccessArticle

Water Extract of Capsella bursa-pastoris Mitigates Doxorubicin-Induced Cardiotoxicity by Upregulating Antioxidant Enzymes

by Yuhui Jeong, Sun-Ho Lee, Jangho Lee, Min-Sun Kim, Yu-Geon Lee, Jin-Taek Hwang, Sang-Yoon Choi, Ho-Geun Yoon, Tae-Gyu Lim, Seung-Hyun Lee and Hyo-Kyoung Choi

Int. J. Mol. Sci. 2023, 24(21), 15912; https://doi.org/10.3390/ijms242115912 - 2 Nov 2023

Cited by 4 | Viewed by 2207

Abstract

Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of Capsella bursa-pastoris (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death. Superoxide dismutase (SOD) levels, reactive oxygen species (ROS) production, and oxygen consumption rate were measured in H9c2 cells. C57BL/6 mice were treated with DOX and CBW to assess their impact on various cardiac parameters. Human-induced pluripotent stem-cell-derived cardiomyocytes were also used to investigate DOX-induced electrophysiological changes and the potential ameliorative effects of CBW. UPLC-TQ/MS analysis identified seven flavonoids in CBW, with luteolin-7-O-glucoside and isoorientin as the major compounds. CBW inhibited DOX-induced death of H9c2 rat cardiomyocytes but did not affect DOX-induced death of MDA-MB-231 human breast cancer cells. CBW increased SOD levels in a dose-dependent manner, reducing ROS production and increasing the oxygen consumption rate in H9c2 cells. The heart rate, RR interval, QT, and ST prolongation remarkably recovered in C57BL/6 mice treated with the combination of DOX and CBW compared to those in mice treated with DOX alone. Administration of CBW with DOX effectively alleviated collagen accumulation, cell death in mouse heart tissues, and reduced the levels of creatinine kinase (CK) and lactate dehydrogenase (LDH) in serum. Furthermore, DOX-induced pathological electrophysiological features in human-induced pluripotent stem-cell-derived cardiomyocytes were ameliorated by CBW. CBW may prevent DICT by stabilizing SOD and scavenging ROS. The presence of flavonoids, particularly luteolin-7-O-glucoside and isoorientin, in CBW may contribute to its protective effects. These results suggest the potential of CBW as a traditional therapeutic option to mitigate DOX-induced cardiotoxicity. Full article

(This article belongs to the Special Issue Application of Natural Products in Biomedicine and Pharmacotherapy)

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17 pages, 4607 KiB

Open AccessArticle

Photoprotective Effects of Dendrobium nobile Lindl. Polysaccharides against UVB-Induced Oxidative Stress and Apoptosis in HaCaT Cells

by Yunluan Long, Wuji Wang, Yanyan Zhang, Fanpan Du, Shiqian Zhang, Zheng Li, Jiang Deng and Jingjie Li

Int. J. Mol. Sci. 2023, 24(7), 6120; https://doi.org/10.3390/ijms24076120 - 24 Mar 2023

Cited by 9 | Viewed by 2475

Abstract

Acute ultraviolet (UV)-B radiation is the major external factor causing photodamage. In this study, we aimed to determine the effects of Dendrobium nobile Lindl. polysaccharides (DNPs) on photodamage in HaCaT keratinocytes after UVB irradiation and the underlying mechanisms. We found that DNPs significantly attenuated the decline in the viability and proliferation of HaCaT cells after UVB irradiation. Moreover, DNPs scavenged reactive oxygen species (ROS), improved the activities of endogenous antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, and reduced the levels of malondialdehyde, while partially attenuating cell cycle arrest, suggesting their antioxidant and anti-apoptotic properties. The mitogen-activated protein kinase (MAPK) pathway was found to be important for the attenuation of UVB-induced photodamage in the HaCaT cells. Furthermore, DNPs exerted cytoprotective effects by downregulating UVB-induced ROS-mediated phosphorylation of MAPKs, including p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase, and by inhibiting p53 expression as well as the apoptotic cascade response. Therefore, DNPs ameliorated UVB-induced oxidative damage and apoptosis in HaCaT cells via the regulation of MAPKs. Our findings thus highlight the Dendrobium nobile Lindl polysaccharides as promising therapeutic candidates for UVB-induced photodamage. Full article

(This article belongs to the Special Issue Application of Natural Products in Biomedicine and Pharmacotherapy)

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Review

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17 pages, 4902 KiB

Open AccessReview

Drug Development from Natural Products Based on the Pathogenic Mechanism of Asthma

by Min-Hee Kim, Chun-Sik Bae, So-Hyeon Bok, Hyo-Seung Choi, Taeho Ahn, Seung-Sik Cho and Dae-Hun Park

Int. J. Mol. Sci. 2023, 24(15), 12469; https://doi.org/10.3390/ijms241512469 - 5 Aug 2023

Cited by 3 | Viewed by 2173

Abstract

Asthma is a chronic inflammatory disease of the pulmonary system associated with many wheeze-to-sleep apnea complications that may lead to death. In 2019, approximately 262 million patients suffered from asthma, and 455 thousand died from the disease worldwide. It is a more severe health problem in children and older adults, and as the aging of society intensifies, the problem will continue to worsen. Asthma inducers can be classified as indoor and outdoor allergens and can cause asthma due to their repeated invasion. There are several theories about asthma occurrence, such as the imbalance between Th1 and Th2, inflammation in the pulmonary system, and the abnormal apoptosis/cell proliferation of cells related to asthma. Although there are many medications for asthma, as it is an incurable disease, the purpose of the drugs is only to suppress the symptoms. The current drugs can be divided into relievers and controllers; however, as they have many adverse effects, such as immune suppression, growth retardation, promotion of cataracts, hyperactivity, and convulsions, developing new asthma drugs is necessary. Although natural products can have adverse effects, the development of asthma drugs from natural products may be beneficial, as some have anti-asthmatic effects such as immune modulation, anti-inflammation, and/or apoptosis modulation. Full article

(This article belongs to the Special Issue Application of Natural Products in Biomedicine and Pharmacotherapy)

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34 pages, 3130 KiB

Open AccessReview

Blackberries and Mulberries: Berries with Significant Health-Promoting Properties

by Mariana S. Martins, Ana C. Gonçalves, Gilberto Alves and Luís R. Silva

Int. J. Mol. Sci. 2023, 24(15), 12024; https://doi.org/10.3390/ijms241512024 - 27 Jul 2023

Cited by 18 | Viewed by 5938

Abstract

Blackberries and mulberries are small and perishable fruits that provide significant health benefits when consumed. In reality, both are rich in phytochemicals, such as phenolics and volatile compounds, and micronutrients, such as vitamins. All the compounds are well-known thanks to their medicinal and pharmacological properties, namely antioxidant, anti-inflammatory, anti-cancer, antiviral, and cardiovascular properties. Nevertheless, variables such as genotype, production conditions, fruit ripening stage, harvesting time, post-harvest storage, and climate conditions influence their nutritional composition and economic value. Given these facts, the current review focuses on the nutritional and chemical composition, as well as the health benefits, of two blackberry species (Rubus fruticosus L., and Rubus ulmifolius Schott) and one mulberry species (Morus nigra L.). Full article

(This article belongs to the Special Issue Application of Natural Products in Biomedicine and Pharmacotherapy)

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