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Therapeutic Potential of Natural Compounds: Insights into Mechanisms, Molecular Docking, and Biological Activities

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

Deadline for manuscript submissions: 20 December 2024 | Viewed by 8606

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Dr. Rafał Hałasa

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Guest Editor

Department of Pharmaceutical Microbiology, Medical University of Gdańsk, 80-416 Gdańsk, Poland
Interests: antimicrobials plant secondary metabolites; plant extracts; synthetic derivatives; bacterial antibiotic resistance; antimicrobial assay; mechanism of action; clinical microbiology; diagnostic microbiology; microbial pathogenesis; hospital epidemiology

Special Issue Information

Dear Colleagues,

For centuries, folk medicine has been used to treat various ailments afflicting people and animals stemming from plants, lichens, mushrooms, etc. The accurate determination of the biological properties of chemical compounds (i.e., those responsible for the healing properties of natural products) have progressed in tandem with the development of science. Naturally occurring compounds have become the basis for modern synthetic modifications, leading to the creation of active substances with more effective mechanisms of action, improved pharmacological parameters, and low side effects. Unfortunately, new or known diseases that are resistant to current preparations have been detected.Therefore, there is a constant need to identify new compounds/mixtures of compounds that can combat new diseases,or allow us to control diseases that are immune to current treatments.

Led by Dr. Rafał Hałasa and assisted by the Topical Advisory Panel Member Dr. Katarzyna Turecka (Medical University of Gdańsk), this Special Issue is devoted to natural compounds and their derivatives, including their biological activity and mechanisms of action that may have therapeutic uses in the fight against diseases. Original research articles and reviews on these and related topics will be considered for publication in this Special Issue.

Dr. Rafał Hałasa
Guest Editor

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Keywords

natural compounds
synthetic derivatives of natural compounds
biological activity
mechanism of action
molecular docking
therapeutic potential
anticancer
antimicrobial
antiviral
anti-civilization diseases
antiobesity
antidiabetes
preventing the development of cardiovascular diseases, including myocardial infarction, hypertension and ischemic heart disease
food hypersensitivity
antiallergy

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Published Papers (8 papers)

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Research

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15 pages, 2057 KiB

Open AccessArticle

The Influence of Juglans regia L. Extract and Ellagic Acid on Oxidative Stress, Inflammation, and Bone Regeneration Biomarkers

by Alina Hanga-Farcas, Luminita Fritea, Gabriela Adriana Filip, Simona Clichici, Laura Gratiela Vicas, Vlad-Alexandru Toma, Eleonora Marian, Felicia Gabriela Gligor, Wael Abu Dayyih and Mariana Eugenia Muresan

Int. J. Mol. Sci. 2024, 25(23), 12577; https://doi.org/10.3390/ijms252312577 - 22 Nov 2024

Abstract

Bone regeneration is a highly dynamic and complex process that involves hematopoietic stem cells and mesenchymal cells, collagen fibers, non-collagenous proteins and biomolecules from extracellular matrices, and different cytokines and immune cells, as well as growth factors and hormones. Some phytochemicals due to antioxidant and anti-inflammatory effects can modulate the bone signaling pathways and improve bone healing and thus can be a good candidate for osteoregeneration. The aim of this study was to analyze the impact of Juglans regia L. extract compared to ellagic acid on bone neoformation in rats. The animals with a 5 mm calvaria defect were divided into four groups (n = 10): group 1 was treated with ellagic acid 1% (EA), group 2 was treated with Juglans regia L. extract 10% (JR), group 3 was treated with a biphasic mix of hydroxyapatite and tricalcium phosphate (Ceraform), and group 4 was treated with vehicle inert gel with carboxymethylcellulose (CMC). After 3 weeks of treatment, blood samples were collected for oxidative stress and inflammation assessment. Additionally, the receptor activator of nuclear factor kappa-Β ligand (RANKL) and hydroxyproline levels were quantified in blood. The skull samples were analyzed by scanning electron microscopy in order to detect the modifications in the four groups. The results suggested that JR extract had relevant anti-oxidant effect and bone protective activity and generated the accumulation of Ca and P, demonstrating the potential therapeutic abilities in bone regeneration. Full article

(This article belongs to the Special Issue Therapeutic Potential of Natural Compounds: Insights into Mechanisms, Molecular Docking, and Biological Activities)

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16 pages, 5861 KiB

Open AccessArticle

Aloperine Inhibits ASFV via Regulating PRLR/JAK2 Signaling Pathway In Vitro

by Renhao Geng, Hongxia Shao, Kun Qian, Hongjun Chen and Aijian Qin

Int. J. Mol. Sci. 2024, 25(16), 9083; https://doi.org/10.3390/ijms25169083 - 21 Aug 2024

Cited by 1 | Viewed by 995

Abstract

African swine fever (ASF) has become a global pandemic due to inadequate prevention and control measures, posing a significant threat to the swine industry. Despite the approval of a single vaccine in Vietnam, no antiviral drugs against the ASF virus (ASFV) are currently available. Aloperine (ALO), a quinolizidine alkaloid extracted from the seeds and leaves of bitter beans, exhibits various biological functions, including anti-inflammatory, anti-cancer, and antiviral activities. In this study, we found that ALO could inhibit ASFV replication in MA-104, PK-15, 3D4/21, and WSL cells in a dose-dependent manner without cytotoxicity at 100 μM. Furthermore, it was verified that ALO acted on the co- and post-infection stages of ASFV by time-of-addition assay, and inhibited viral internalization rather than directly inactivating the virus. Notably, RT-qPCR analysis indicated that ALO did not exert anti-inflammatory activity during ASFV infection. Additionally, gene ontology (GO) and KEGG pathway enrichment analyses of transcriptomic data revealed that ALO could inhibit ASFV replication via the PRLR/JAK2 signaling pathway. Together, these findings suggest that ALO effectively inhibits ASFV replication in vitro and provides a potential new target for developing anti-ASFV drugs. Full article

(This article belongs to the Special Issue Therapeutic Potential of Natural Compounds: Insights into Mechanisms, Molecular Docking, and Biological Activities)

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18 pages, 4826 KiB

Open AccessArticle

Anti-Neuroinflammatory Effect of Ombuin from Rhamnus erythroxylon Pall. Leaves in LPS-Induced BV-2 Microglia by Targeting Src and Suppressing the PI3K-AKT/NF-κB Signaling Pathway

by Yanjie Bian, Nan Qiao, Suyun Han, Jixiang Gao, Xiaofang Lv, Lihuan Yuan, Linjing Zhang and Zuofu Wei

Int. J. Mol. Sci. 2024, 25(16), 8789; https://doi.org/10.3390/ijms25168789 - 13 Aug 2024

Viewed by 919

Abstract

The leaves of Rhamnus erythroxylon Pall. are widely used as tea substitutes in northwest China for their fragrant aroma, anti-irritability, and digestion-enhancing properties. Ombuin, a main flavonoid compound found in the leaves, exhibited notable anti-inflammatory and antioxidant effects. However, its potential role in treating neuroinflammatory-related diseases remains unexplored. Thus, this study aims to evaluate the anti-neuroinflammatory effects of ombuin and to explore the underlying molecular mechanisms. According to our findings, ombuin dramatically reduced the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1β, nitric oxide (NO), and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Further analysis, including transcriptomics, network pharmacology, molecular docking, and cellular heat transfer assays, revealed that Src was a direct target of ombuin. Western blot analysis showed that ombuin effectively suppressed Src phosphorylation and inhibited the downstream expressions of p-PI3K p85, p-AKT1, p-IKKα/β, p-IκBα, and nuclear factor κB (NF-κB). Meanwhile, the repression of Src significantly reversed the anti-neuroinflammatory activity of ombuin. Our results identified Src as a direct target of ombuin and implied that ombuin exerted an anti-neuroinflammatory effect by inhibiting Src phosphorylation and suppressing the activation of the PI3K-AKT and NF-κB pathways, which might provide an alternative therapeutic strategy for neurodegenerative diseases. Full article

(This article belongs to the Special Issue Therapeutic Potential of Natural Compounds: Insights into Mechanisms, Molecular Docking, and Biological Activities)

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19 pages, 5628 KiB

Open AccessArticle

An In Vitro Study on the Cytotoxic, Antioxidant, and Antimicrobial Properties of Yamogenin—A Plant Steroidal Saponin and Evaluation of Its Mechanism of Action in Gastric Cancer Cells

by Justyna Stefanowicz-Hajduk, Piotr Graczyk, Anna Hering, Magdalena Gucwa, Anna Nowak and Rafał Hałasa

Int. J. Mol. Sci. 2024, 25(9), 4627; https://doi.org/10.3390/ijms25094627 - 24 Apr 2024

Viewed by 1534

Abstract

Yamogenin is a steroidal saponin occurring in plant species such as Asparagus officinalis, Dioscorea collettii, Trigonella foenum-graecum, and Agave sp. In this study, we evaluated in vitro cytotoxic, antioxidant, and antimicrobial properties of yamogenin. The cytotoxic activity was estimated on human colon cancer HCT116, gastric cancer AGS, squamous carcinoma UM-SCC-6 cells, and human normal fibroblasts with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The amount of apoptotic and dead AGS cells after treatment with yamogenin was estimated with flow cytometry. Also, in yamogenin-treated AGS cells we investigated the reactive oxygen species (ROS) production, mitochondrial membrane depolarization, activity level of caspase-8 and -9, and gene expression at mRNA level with flow cytometry, luminometry, and RT-PCR, respectively. The antioxidant properties of yamogenin were assessed with DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays. The antimicrobial potential of the compound was estimated on Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Helicobacter pylori, Campylobacter coli, Campylobacter jejuni, Listeria monocytogenes, Lactobacillus paracasei, and Lactobacillus acidophilus bacteria strains. Yamogenin showed the strongest cytotoxic effect on AGS cells (IC₅₀ 18.50 ± 1.24 µg/mL) among the tested cell lines. This effect was significantly stronger in combinations of yamogenin with oxaliplatin or capecitabine than for the single compounds. Furthermore, yamogenin induced ROS production, depolarized mitochondrial membrane, and increased the activity level of caspase-8 and -9 in AGS cells. RT-PCR analysis revealed that this sapogenin strongly up-regulated TNFRSF25 expression at the mRNA level. These results indicate that yamogenin induced cell death via the extrinsic and intrinsic way of apoptosis. Antioxidant study showed that yamogenin had moderate in vitro potential (IC₅₀ 704.7 ± 5.9 µg/mL in DPPH and 631.09 ± 3.51 µg/mL in ABTS assay) as well as the inhibition of protein denaturation properties (with IC₅₀ 1421.92 ± 6.06 µg/mL). Antimicrobial test revealed a weak effect of yamogenin on bacteria strains, the strongest one being against S. aureus (with MIC value of 350 µg/mL). In conclusion, yamogenin may be a potential candidate for the treatment and prevention of gastric cancers. Full article

(This article belongs to the Special Issue Therapeutic Potential of Natural Compounds: Insights into Mechanisms, Molecular Docking, and Biological Activities)

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21 pages, 3717 KiB

Open AccessArticle

New Chalcone Derivatives Containing 2,4-Dichlorobenzenesulfonamide Moiety with Anticancer and Antioxidant Properties

by Anita Bułakowska, Jarosław Sławiński, Anna Hering, Magdalena Gucwa, J. Renata Ochocka, Rafał Hałasa, Łukasz Balewski and Justyna Stefanowicz-Hajduk

Int. J. Mol. Sci. 2024, 25(1), 274; https://doi.org/10.3390/ijms25010274 - 24 Dec 2023

Cited by 2 | Viewed by 1633

Abstract

Chalcones and their derivatives, both natural and synthetic, exhibit diverse biological activities. In this study, we focused on designing and synthesizing (E)-2,4-dichloro-N-(4-cinnamoylphenyl)-5-methylbenzenesulfonamides 4–8 with the following two pharmacophore groups: 2,4-dichlorobenzenesulfonamide and chalcone. The obtained compounds displayed notable anticancer effects on various human cancer cells, such as cervical HeLa, acute promyelocytic leukemia HL-60, and gastric adenocarcinoma AGS, when assessed with the MTT test. The activity of all compounds against cancer cells was significant, and the obtained IC₅₀ values were in the range of 0.89–9.63 µg/mL. Among all the tested compounds, derivative 5 showed the highest activity on the AGS cell line. Therefore, it was tested for cell cycle inhibition, induction of mitochondrial membrane depolarization, and activation of caspase-8 and -9. These results showed that this compound strongly arrested the cell cycle in the subG0 phase, depolarized the mitochondrial membrane, and activated caspase-8 and -9. Similar to the anticancer effects, all the obtained compounds 4–8 were also assessed for their antioxidant activity. The highest antiradical effect was demonstrated for derivative 5, which was able to inhibit DPPH and ABTS radicals. All examined compounds showed dose-dependent activity against neutrophil elastase. Notably, derivatives 7 and 8 demonstrated inhibitory properties similar to oleanolic acid, with IC₅₀ values of 25.61 ± 0.58 and 25.73 ± 0.39 µg/mL, respectively. To determine the antibacterial activity of derivatives 4–8, the minimum bacteriostatic concentration (MIC) values were estimated (>500 µg/mL for all the tested bacterial strains). The findings demonstrate the substantial potential of sulfonamide-based chalcone 5 as a promising drug in anticancer therapy. Full article

(This article belongs to the Special Issue Therapeutic Potential of Natural Compounds: Insights into Mechanisms, Molecular Docking, and Biological Activities)

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Review

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35 pages, 1381 KiB

Open AccessReview

Nutraceuticals as Modulators of Molecular Placental Pathways: Their Potential to Prevent and Support the Treatment of Preeclampsia

by Patrycja Bukowska, Michalina Bralewska, Tadeusz Pietrucha and Agata Sakowicz

Int. J. Mol. Sci. 2024, 25(22), 12167; https://doi.org/10.3390/ijms252212167 - 13 Nov 2024

Viewed by 352

Abstract

Preeclampsia (PE) is a serious condition characterized by new-onset hypertension and proteinuria or organ dysfunction after the 20th week of gestation, making it a leading cause of maternal and fetal mortality worldwide. Despite extensive research, significant gaps remain in understanding the mechanisms underlying PE, contributing to the ineffectiveness of current prevention and treatment strategies. Consequently, premature cesarean sections often become the primary intervention to safeguard maternal and fetal health. Emerging evidence indicates that placental insufficiency, driven by molecular disturbances, plays a central role in the development of PE. Additionally, the maternal microbiome may be implicated in the pathomechanism of preeclampsia by secreting metabolites that influence maternal inflammation and oxidative stress, thereby affecting placental health. Given the limitations of pharmaceuticals during pregnancy due to potential risks to fetal development and concerns about teratogenic effects, nutraceuticals may provide safer alternatives. Nutraceuticals are food products or dietary supplements that offer health benefits beyond basic nutrition, including plant extracts or probiotics. Their historical use in traditional medicine has provided valuable insights into their safety and efficacy, including for pregnant women. This review will examine how the adoption of nutraceuticals can enhance dysregulated placental pathways, potentially offering benefits in the prevention and treatment of preeclampsia. Full article

(This article belongs to the Special Issue Therapeutic Potential of Natural Compounds: Insights into Mechanisms, Molecular Docking, and Biological Activities)

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19 pages, 1005 KiB

Open AccessReview

Activation of Nrf2 and FXR via Natural Compounds in Liver Inflammatory Disease

by Marta Belka, Aleksandra Gostyńska-Stawna, Maciej Stawny and Violetta Krajka-Kuźniak

Int. J. Mol. Sci. 2024, 25(20), 11213; https://doi.org/10.3390/ijms252011213 - 18 Oct 2024

Viewed by 847

Abstract

Liver inflammation is frequently linked to oxidative stress and dysregulation of bile acid and fatty acid metabolism. This review focuses on the farnesoid X receptor (FXR), a critical regulator of bile acid homeostasis, and its interaction with the nuclear factor erythroid 2-related factor 2 (Nrf2), a key modulator of cellular defense against oxidative stress. The review explores the interplay between FXR and Nrf2 in liver inflammatory diseases, highlighting the potential therapeutic effects of natural FXR agonists. Specifically, compounds such as auraptene, cafestol, curcumin, fargesone A, hesperidin, lycopene, oleanolic acid, resveratrol, rutin, ursolic acid, and withaferin A are reviewed for their ability to modulate both the FXR and Nrf2 pathways. This article discusses their potential to alleviate liver inflammation, oxidative stress, and damage in diseases such as metabolic-associated fatty liver disease (MAFLD), cholestatic liver injury, and viral hepatitis. In addition, we address the molecular mechanisms driving liver inflammation, including oxidative stress, immune responses, and bile acid accumulation, while also summarizing relevant experimental models. This review emphasizes the promising therapeutic potential of targeting both the Nrf2 and FXR pathways using natural compounds, paving the way for future treatments for liver diseases. Finally, the limitations of the clinical application were indicated, and further research directions were proposed. Full article

(This article belongs to the Special Issue Therapeutic Potential of Natural Compounds: Insights into Mechanisms, Molecular Docking, and Biological Activities)

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41 pages, 3391 KiB

Open AccessReview

A Comprehensive Review of Molecular Mechanisms, Pharmacokinetics, Toxicology and Plant Sources of Juglanin: Current Landscape and Future Perspectives

by Magdalena Rutkowska, Martyna Witek and Monika A. Olszewska

Int. J. Mol. Sci. 2024, 25(19), 10323; https://doi.org/10.3390/ijms251910323 - 25 Sep 2024

Viewed by 998

Abstract

Juglanin (kaempferol 3-O-α-L-arabinofuranoside) is a flavonol glycoside occurring in many plants, including its commercial sources Juglans regia, Polygonum aviculare and Selliguea hastata. Recent extensive studies have explored the potential of using juglanin in various pathological conditions, including cardiovascular disorders, central nervous and skeletal system disorders, metabolic syndrome, hepatic injury, and cancers. The results indicated a wide range of effects, like anti-inflammatory, anti-oxidant, anti-fibrotic, anti-thrombotic, anti-angiogenic, hepatoprotective, hypolipidemic, hypoglycemic, anti-apoptotic (normal cells), and pro-apoptotic (cancer cells). The health-promoting properties of juglanin can be attributed to its influence on many signaling pathways, associated with SIRT1, AMPK, Nrf2, STING, TLR4, MAPKs, NF-κB, AKT, JAK, and their downstream genes. This review primarily summarizes the current knowledge of molecular mechanisms, pharmacokinetics, biocompatibility, and human use safety of juglanin. In addition, the most promising new plant sources and other existing challenges and prospects have also been reviewed and discussed, aiming to provide direction and rationale for the further development and broader pharmaceutical application of juglanin. Full article

(This article belongs to the Special Issue Therapeutic Potential of Natural Compounds: Insights into Mechanisms, Molecular Docking, and Biological Activities)

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