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Current Trends of Natural Bioactive Molecules in Regulation of Cell Signaling Pathways in Different Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 13095

Special Issue Editors

Prof. Dr. Baojun Xu

E-Mail Website
Guest Editor
Food Science and Technology Program, Department of Life Sciences, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai 519087, China
Interests: phytochemicals; natural products; functional foods; human health
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Seppo Vainio

E-Mail Website
Guest Editor
Biocenter Oulu, Laboratory of Developmetnal Biology, Faculty of Biochemistry and Molecular Medicine, Borealis Biobank of Northern Finland, InfoTech, University of Oulu, Oulu, Finland
Interests: inductive signaling; control of cell fate; regeneration; morphogenesis; reprogramming
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is widely accepted that a high intake of natural bioactive molecules is associated with a decreased risk of chronic disease. According to in vitro and in vivo studies, bioactive molecules possess therapeutic potential in chronic diseases by modulating different signaling pathways. However, the molecular mechanisms behind these activities are not quite clear yet. In this Special Issue, the latest findings on the health-promoting effects of bioactive molecules, such as anti-oxidative stress, anti-cancer activity, anti-inflammatory activity, and neuroprotective activity, will be summarized. Furthermore, the cell signaling pathways (such as PI3K/Akt/mTOR, JAK/STAT, STAT3, MAPK, TNF, Notch, AMPK, Wnt/β-Catenin, mTOR, TRAIL, Fas, NF-кB, etc.) of bioactive molecules in exerting health-promoting effects will be discussed. Lastly, the underlying molecular mechanisms of how these bioactive molecules regulate their health-promoting effects will be elucidated.

Prof. Dr. Baojun Xu
Prof. Dr. Seppo Vainio
Guest Editors

Manuscript Submission Information

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Keywords

  • bioactive molecules
  • phytochemicals
  • nutrients
  • gut microbiota
  • inflammation
  • signaling pathways
  • molecular mechanisms
  • chronic diseases
  • human health

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Published Papers (4 papers)

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Research

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13 pages, 4003 KiB  
Article
Asiatic Acid Attenuates Inflammation Induced by Salmonella via Upregulating LncRNA TVX1 in Microglia
by Wenshu Zou, Jingyan Zhang, Kai Zhang, Zhiping Peng, Ruihua Xin, Lei Wang and Jianxi Li
Int. J. Mol. Sci. 2022, 23(18), 10978; https://doi.org/10.3390/ijms231810978 - 19 Sep 2022
Cited by 5 | Viewed by 2281
Abstract
Salmonella typhimurium (S.T) induces damage to the central nervous system; however, the role of Asiatic acid (AA) in this is still unknown. Microglia play a role as macrophages to recognize the invaded pathogenic microbes in the brain. The aim of this study was [...] Read more.
Salmonella typhimurium (S.T) induces damage to the central nervous system; however, the role of Asiatic acid (AA) in this is still unknown. Microglia play a role as macrophages to recognize the invaded pathogenic microbes in the brain. The aim of this study was to investigate the protective effect and mechanism of AA on the central nervous system through an in vitro model of S.T infection in microglia. We pre-treated microglia with AA before S.T infection and explored the anti-infection mechanism of AA by sequencing, quantitative reverse transcription PCR (RT-qPCR), and Western blotting. Long non-coding RNA (lncRNA) sequencing demonstrated that inflammation is a major factor in S.T infection of microglia. RT-qPCR data demonstrated that AA inhibited S.T-induced increases in the mRNA levels of the pro-inflammatory factors interleukin (IL)-1β, IL-6, and IL-18. Western blotting demonstrated that AA inhibited S.T-induced activation of the nuclear factor (NF)-κB pathway and activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome. Expression of the lncRNA TVX1 in microglia was decreased by S.T infection and increased by pretreatment with AA. Inhibition of TVX1 expression reversed the anti-inflammatory effect of AA, and overexpression of TVX1 in microglia suppressed S.T-induced inflammation. In conclusion, AA attenuated S.T-induced microglial inflammation by upregulating the expression of the lncRNA TVX1. Full article
(This article belongs to the Special Issue Current Trends of Natural Bioactive Molecules in Regulation of Cell Signaling Pathways in Different Diseases)
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11 pages, 2622 KiB  
Article
Berberine Suppresses Leukocyte Adherence by Downregulating CX3CL1 Expression and Shedding and ADAM10 in Lipopolysaccharide-Stimulated Vascular Endothelial Cells
by Yi-Hong Wu, Chen-Ying Wei, Wei-Chin Hong and Jong-Hwei Su Pang
Int. J. Mol. Sci. 2022, 23(9), 4801; https://doi.org/10.3390/ijms23094801 - 27 Apr 2022
Cited by 3 | Viewed by 2543
Abstract
Berberine exerts therapeutic effects in inflammation-associated diseases. In a lipopolysaccharide (LPS)-induced endotoxemic acute lung injury (ALI) rat model, berberine alleviated lung injury through different anti-inflammatory mechanisms; however, treatment effects on CX3CL1 expression and shedding remain to be examined. As these processes play important [...] Read more.
Berberine exerts therapeutic effects in inflammation-associated diseases. In a lipopolysaccharide (LPS)-induced endotoxemic acute lung injury (ALI) rat model, berberine alleviated lung injury through different anti-inflammatory mechanisms; however, treatment effects on CX3CL1 expression and shedding remain to be examined. As these processes play important roles in promoting the binding of leukocytes to the endothelium, the CX3CL1/CX3CR1 axis and its related pathways may serve as potential targets for the clinical treatment of ALI. The anti-inflammatory effects of berberine were investigated in LPS-stimulated rats, human umbilical cord vein endothelial cells (HUVECs), and THP-1 monocytic cells. Cx3cl1 expression in rat pulmonary tissues was examined using immunohistochemistry. CX3CL1, CX3CR1, RELA, STAT3, and ADAM10 levels were examined using Western blotting. CX3CL1 and ADAM10 mRNA levels were examined using quantitative real-time polymerase chain reaction. Soluble fractalkine levels in LPS-stimulated rats and HUVECs were examined using the enzyme-linked immunosorbent assay. Berberine significantly mitigated the LPS-induced upregulation of fractalkine and soluble fractalkine in rats and cultured HUVECs. Berberine mitigated the LPS-induced activation of the NF-κB and STAT3 signaling pathways. In THP-1 cells, berberine mitigated the LPS-induced upregulation of CX3CR1. Furthermore, the membrane expression of ADAM10 in LPS-stimulated HUVECs was suppressed by the berberine treatment. Berberine dose-dependently inhibited the LPS-induced activation of the CX3CL1/CX3CR1 axis and fractalkine shedding through ADAM10. These findings reveal a novel molecular mechanism underlying the inhibitory effect of berberine on monocyte adherence to the endothelium during inflammation. Full article
(This article belongs to the Special Issue Current Trends of Natural Bioactive Molecules in Regulation of Cell Signaling Pathways in Different Diseases)
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Review

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14 pages, 1050 KiB  
Review
Anticancer and Anti-Metastatic Role of Thymoquinone: Regulation of Oncogenic Signaling Cascades by Thymoquinone
by Ammad Ahmad Farooqi, Rukset Attar and Baojun Xu
Int. J. Mol. Sci. 2022, 23(11), 6311; https://doi.org/10.3390/ijms23116311 - 5 Jun 2022
Cited by 7 | Viewed by 3380
Abstract
Cancer is a life-threatening and multifaceted disease. Pioneering research works in the past three decades have mechanistically disentangled intertwined signaling networks which play contributory roles in carcinogenesis and metastasis. Phenomenal strides have been made in leveraging our scientific knowledge altogether to a new [...] Read more.
Cancer is a life-threatening and multifaceted disease. Pioneering research works in the past three decades have mechanistically disentangled intertwined signaling networks which play contributory roles in carcinogenesis and metastasis. Phenomenal strides have been made in leveraging our scientific knowledge altogether to a new level of maturity. Rapidly accumulating wealth of information has underlined a myriad of transduction cascades which can be pharmaceutically exploited for cancer prevention/inhibition. Natural products serve as a treasure trove and compel interdisciplinary researchers to study the cancer chemopreventive roles of wide-ranging natural products in cell culture and preclinical studies. Experimental research related to thymoquinone has gradually gained momentum because of the extra-ordinary cancer chemopreventive multifunctionalities of thymoquinone. In this mini-review, we provide an overview of different cell signaling cascades reported to be regulated by thymoquinone for cancer chemoprevention. Essentially, thymoquinone efficacy has also been notably studied in animal models, which advocates for a rationale-based transition of thymoquinone from the pre-clinical pipeline to clinical trials. Full article
(This article belongs to the Special Issue Current Trends of Natural Bioactive Molecules in Regulation of Cell Signaling Pathways in Different Diseases)
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13 pages, 1252 KiB  
Review
Regulation of Cell-Signaling Pathways by Berbamine in Different Cancers
by Ammad Ahmad Farooqi, Ru Wen, Rukset Attar, Simona Taverna, Ghazala Butt and Baojun Xu
Int. J. Mol. Sci. 2022, 23(5), 2758; https://doi.org/10.3390/ijms23052758 - 2 Mar 2022
Cited by 13 | Viewed by 3525
Abstract
Natural product research is a cornerstone of the architectural framework of clinical medicine. Berbamine is a natural, potent, pharmacologically active biomolecule isolated from Berberis amurensis. Berbamine has been shown to modulate different oncogenic cell-signaling pathways in different cancers. In this review, we [...] Read more.
Natural product research is a cornerstone of the architectural framework of clinical medicine. Berbamine is a natural, potent, pharmacologically active biomolecule isolated from Berberis amurensis. Berbamine has been shown to modulate different oncogenic cell-signaling pathways in different cancers. In this review, we comprehensively analyze how berbamine modulates deregulated pathways (JAK/STAT, CAMKII/c-Myc) in various cancers. We systematically analyze how berbamine induces activation of the TGF/SMAD pathway for the effective inhibition of cancer progression. We also summarize different nanotechnological strategies currently being used for proficient delivery of berbamine to the target sites. Berbamine has also been reported to demonstrate potent anti-cancer and anti-metastatic effects in tumor-bearing mice. The regulation of non-coding RNAs by berbamine is insufficiently studied, and future studies must converge on the identification of target non-coding RNAs. A better understanding of the regulatory role of berbamine in the modulation of non-coding RNAs and cell-signaling pathways will be advantageous in the effective translation of laboratory findings to clinically effective therapeutics. Full article
(This article belongs to the Special Issue Current Trends of Natural Bioactive Molecules in Regulation of Cell Signaling Pathways in Different Diseases)
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