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The Effects of Natural Compounds in Cell Differentiation and Signaling...
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The Effects of Natural Compounds in Cell Differentiation and Signaling Pathways

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: closed (28 February 2022) | Viewed by 21861

Special Issue Editor

Dr. See-Hyoung Park

E-Mail Website
Guest Editor
Department of Biological and Chemical, Hongik University, Sejong, Republic of Korea
Interests: natural compounds; chemical genomics; functional foods; cosmeceuticals; cancer biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues

Phytochemicals are natural compounds produced by many kinds of plants, and their function is generally to help them thrive or thwart predators or pathogens. It is reported that there are several beneficial effects of phytochemicals on human health such as anti-cancer, anti-immune-response, anti-bacterial, and antioxidant effects. Over the last ten years, phytochemicals have been widely investigated to develop effective medicines for the treatment of various diseases because of their high efficacy and minimal side effects.

In this specific issue, we are gathering manuscripts (reviews and articles) about the regulation of cellular processes and signaling pathways by novel phytochemicals that could be applied to the development of functional foods (nutraceuticals), functional cosmetics (cosmeceuticals), and even medicines.

Dr. See-Hyoung Park
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bioactive
  • nutraceuticals
  • cosmeceuticals
  • functional foods
  • functional cosmetics
  • medicinal plants
  • signaling pathway
  • inhibitor
  • activator
  • cell differentiation

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Published Papers (5 papers)

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Research

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20 pages, 8607 KiB  
Article
Artemisinin Attenuates Amyloid-Induced Brain Inflammation and Memory Impairments by Modulating TLR4/NF-κB Signaling
by Xia Zhao, Xiaosu Huang, Chao Yang, Yizhou Jiang, Wenshu Zhou and Wenhua Zheng
Int. J. Mol. Sci. 2022, 23(11), 6354; https://doi.org/10.3390/ijms23116354 - 6 Jun 2022
Cited by 28 | Viewed by 4219
Abstract
The abnormal immune response is an early change in the pathogenesis of Alzheimer’s disease (AD). Microglial activation is a crucial regulator of the immune response, which contributes to progressive neuronal injury by releasing neurotoxic products. Therefore, finding effective drugs to regulate microglial homeostasis [...] Read more.
The abnormal immune response is an early change in the pathogenesis of Alzheimer’s disease (AD). Microglial activation is a crucial regulator of the immune response, which contributes to progressive neuronal injury by releasing neurotoxic products. Therefore, finding effective drugs to regulate microglial homeostasis and neuroinflammation has become a new AD treatment strategy. Artemisinin has potent anti-inflammatory and immune activities. However, it is unclear whether Artemisinin contributes to the regulation of microglial activation, thereby improving AD pathology. This study found that Artemisinin significantly reduced amyloid beta-peptide 1–42 (Aβ1–42)-induced increases in nitric oxide and reactive oxygen species and inflammatory factors in BV2 cells. In addition, Artemisinin inhibited the migration of microglia and prevented the expansion of the inflammatory cascade. The mechanical studies showed Artemisinin inhibited neuroinflammation and exerted neuroprotective effects by regulating the Toll-like receptor 4 (TLR4)/Nuclear factor-kappa B (NF-κB) signaling pathway. Similar results were obtained in AD model mice, in which Artemisinin administration attenuated Aβ1–42-induced neuroinflammation and neuronal injury, reversing spatial learning and memory deficits. The anti-inflammatory effect of Artemisinin is also accompanied by the activation of the TLR4/NF-κB signaling pathway in the animal model. Our results indicate that Artemisinin attenuated Aβ1–42-induced neuroinflammation and neuronal injury by stimulating the TLR4/NF-κB signaling pathway. These findings suggest that Artemisinin is a potential therapeutic agent for AD. Full article
(This article belongs to the Special Issue The Effects of Natural Compounds in Cell Differentiation and Signaling Pathways)
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15 pages, 6409 KiB  
Article
Epigallocatechin Gallate Protects against Hypoxia-Induced Inflammation in Microglia via NF-κB Suppression and Nrf-2/HO-1 Activation
by So-Ra Kim, Kyung-Joo Seong, Won-Jae Kim and Ji-Yeon Jung
Int. J. Mol. Sci. 2022, 23(7), 4004; https://doi.org/10.3390/ijms23074004 - 4 Apr 2022
Cited by 51 | Viewed by 4774
Abstract
Hypoxia-induced neuroinflammation in stroke, neonatal hypoxic encephalopathy, and other diseases subsequently contributes to neurological damage and neuronal diseases. Microglia are the primary neuroimmune cells that play a crucial role in cerebral inflammation. Epigallocatechin gallate (EGCG) has a protective antioxidant and anti-inflammatory effects against [...] Read more.
Hypoxia-induced neuroinflammation in stroke, neonatal hypoxic encephalopathy, and other diseases subsequently contributes to neurological damage and neuronal diseases. Microglia are the primary neuroimmune cells that play a crucial role in cerebral inflammation. Epigallocatechin gallate (EGCG) has a protective antioxidant and anti-inflammatory effects against neuroinflammation. However, the effects of EGCG on hypoxia-induced inflammation in microglia and the underlying mechanism remain unclear. In this study, we investigated whether EGCG might have a protective effect against hypoxia injury in microglia by treatment with CoCl2 to establish a hypoxic model of BV2 microglia cells following EGCG pre-treatment. An exposure of cells to CoCl2 caused an increase in inflammatory mediator interleukin (IL)-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 expression, which were significantly ameliorated by EGCG via inhibition of NF-κB pathway. In addition, EGCG attenuated the expression of hypoxia-inducible factor (HIF)-1α and the generation of ROS in hypoxic BV2 cells. Furthermore, the suppression of hypoxia-induced IL-6 production by EGCG was mediated via the inhibition of HIF-1α expression and the suppression of ROS generation in BV2 cells. Notably, EGCG increased the Nrf-2 levels and HO-1 levels in the presence of CoCl2. Additionally, EGCG suppressed hypoxia-induced apoptosis of BV2 microglia with cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3. In summary, EGCG protects microglia from hypoxia-induced inflammation and oxidative stress via abrogating the NF-κB pathway as well as activating the Nrf-2/HO-1 pathway. Full article
(This article belongs to the Special Issue The Effects of Natural Compounds in Cell Differentiation and Signaling Pathways)
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13 pages, 2321 KiB  
Article
The Apoptotic Effect of Caffeic or Chlorogenic Acid on the C32 Cells That Have Simultaneously Been Exposed to a Static Magnetic Field
by Magdalena Kimsa-Dudek, Agnieszka Synowiec-Wojtarowicz, Agata Krawczyk, Agnieszka Kosowska, Małgorzata Kimsa-Furdzik and Tomasz Francuz
Int. J. Mol. Sci. 2022, 23(7), 3859; https://doi.org/10.3390/ijms23073859 - 31 Mar 2022
Cited by 6 | Viewed by 2026
Abstract
The induction of apoptosis is one of the main goals of the designed anti-cancer therapies. In recent years, increased attention has been paid to the physical factors such as magnetic fields and to the natural bioactive compounds and the possibilities using them in [...] Read more.
The induction of apoptosis is one of the main goals of the designed anti-cancer therapies. In recent years, increased attention has been paid to the physical factors such as magnetic fields and to the natural bioactive compounds and the possibilities using them in medicine. Hence, the aim of this study was to evaluate the anti-tumor effect of caffeic or chlorogenic acid in combination with a moderate-strength static magnetic field on C32 melanoma cells by assessing the effect of both factors on the apoptotic process. The apoptosis of the C32 cells was evaluated using a flow cytometry analysis. The expression of the apoptosis-associated genes was determined using the RT-qPCR technique. The caspase activity and the concentration of the oxidative damage markers were also measured. It was found that phenolic acids and a static magnetic field trigger the apoptosis of the C32 cells and also affect the expression of the genes encoding the apoptosis regulatory proteins. In conclusion, our study indicated that both of the phenolic acids and a static magnetic field can be used supportively in the treatment of melanoma and that caffeic acid is more pro-apoptotic than chlorogenic acid. Full article
(This article belongs to the Special Issue The Effects of Natural Compounds in Cell Differentiation and Signaling Pathways)
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16 pages, 4028 KiB  
Article
Hyperforin and Myrtucommulone Derivatives Act as Natural Modulators of Wnt/β-Catenin Signaling in HCT116 Colon Cancer Cells
by Aneliya Knauthe, Sonnhild Mittag, Laura Bloch, Kai Frederik Albring, Martin Schmidt, Oliver Werz and Otmar Huber
Int. J. Mol. Sci. 2022, 23(6), 2984; https://doi.org/10.3390/ijms23062984 - 10 Mar 2022
Cited by 6 | Viewed by 2329
Abstract
The therapeutic activities of natural plant extracts have been well known for centuries. Many of them, in addition to antiviral and antibiotic effects, turned out to have anti-tumor activities by targeting different signaling pathways. The canonical Wnt pathway represents a major tumorigenic pathway [...] Read more.
The therapeutic activities of natural plant extracts have been well known for centuries. Many of them, in addition to antiviral and antibiotic effects, turned out to have anti-tumor activities by targeting different signaling pathways. The canonical Wnt pathway represents a major tumorigenic pathway deregulated in numerous tumor entities, including colon cancer. Here, we investigated the acylphloroglucinols hyperforin (HF) from St. John’s wort (Hypericum perforatum L.) and myrtucommulone A (MC A) from myrtle (Myrtus communis) and semi-synthetic derivatives thereof (HM 177, HM 297, HM298) for their effects on Wnt/β-catenin signaling. None of these substances revealed major cytotoxicity on STF293 embryonic kidney and HCT116 colon carcinoma cells at concentrations up to 10 μM. At this concentration, HF and HM 177 showed the strongest effect on cell proliferation, whereas MC A and HM 177 most prominently inhibited anchorage-independent growth of HCT116 cells. Western blot analyses of active β-catenin and β-catenin/TCF reporter gene assays in STF293 cells revealed inhibitory activities of HF, MC A and HM 177. In line with this, the expression of endogenous Wnt target genes, Axin and Sp5, in HCT116 cells was significantly reduced. Our data suggest that the acylphloroglucinols hyperforin, myrtucommulone A and its derivative HM 177 represent potential new therapeutic agents to inhibit Wnt/β-catenin signaling in colon cancer. Full article
(This article belongs to the Special Issue The Effects of Natural Compounds in Cell Differentiation and Signaling Pathways)
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Review

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19 pages, 844 KiB  
Review
Modulation of Nrf2 and NF-κB Signaling Pathways by Naturally Occurring Compounds in Relation to Cancer Prevention and Therapy. Are Combinations Better Than Single Compounds?
by Violetta Krajka-Kuźniak and Wanda Baer-Dubowska
Int. J. Mol. Sci. 2021, 22(15), 8223; https://doi.org/10.3390/ijms22158223 - 30 Jul 2021
Cited by 58 | Viewed by 6988
Abstract
Nrf2 (nuclear factor erythroid 2-related factor 2) and NF-κB (nuclear factor–kappa B) signaling pathways play a central role in suppressing or inducing inflammation and angiogenesis processes. Therefore, they are involved in many steps of carcinogenesis through cooperation with multiple signaling molecules and pathways. [...] Read more.
Nrf2 (nuclear factor erythroid 2-related factor 2) and NF-κB (nuclear factor–kappa B) signaling pathways play a central role in suppressing or inducing inflammation and angiogenesis processes. Therefore, they are involved in many steps of carcinogenesis through cooperation with multiple signaling molecules and pathways. Targeting both transcription factors simultaneously may be considered an equally important strategy for cancer chemoprevention and therapy. Several hundreds of phytochemicals, mainly edible plant and vegetable components, were shown to activate Nrf2 and mediate antioxidant response. A similar number of phytochemicals was revealed to affect NF-κB. While activation of Nrf2 and inhibition of NF-κB may protect normal cells against cancer initiation and promotion, enhanced expression and activation in cancer cells may lead to resistance to conventional chemo- or radiotherapy. Most phytochemicals, through different mechanisms, activate Nrf2, but others, such as luteolin, can act as inhibitors of both Nrf2 and NF-κB. Despite many experimental data confirming the above mechanisms currently, limited evidence exists demonstrating such activity in humans. Combinations of phytochemicals resembling that in a natural food matrix but allowing higher concentrations may improve their modulating effect on Nrf2 and NF-κB and ultimately cancer prevention and therapy. This review presents the current knowledge on the effect of selected phytochemicals and their combinations on Nrf2 and NF-κB activities in the above context. Full article
(This article belongs to the Special Issue The Effects of Natural Compounds in Cell Differentiation and Signaling Pathways)
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