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Natural Organic Compounds: Cellular Pathways and Effects
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Natural Organic Compounds: Cellular Pathways and Effects

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

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 12599

Special Issue Editor

Prof. Dr. Clara Balsano

E-Mail Website
Guest Editor
Department of Life, Health and Environmental Sciences-MESVA, School of Emergency-Urgency Medicine, University of L’Aquila, 67100 L’Aquila, Italy
Interests: metabolic syndrome; hepatocarcinoma; MASLD; NAFLD; MAFLD; obesity; liver steatosis; nutrition; autoimmune hepatitis; transition biometal; digital health; HBV and HCV infective diseases

Special Issue Information

Dear Colleagues,

Natural organic compounds are essential for human life. Efforts are needed to understand the signaling pathways influenced by natural organic compounds, mainly because they have great potential for the treatment of a wide range of pathologies. A large number of studies indicate that a variety of natural compounds, such as curcumin, green tea, olive oil, oleuropein, folate, copper, selenium, and isoflavones show a wide range of anti-inflammatory, anti-oxidant, and anti-tumoral properties, via targeting a sequence of cellular and molecular pathways. Natural compounds further contribute to the prevention or treatment of various pathologies interacting with powerful molecules, such as microRNAs and exosomes. Finally, they also have important effects on mitochondria functions, which play an important role in the pathogenesis of many pathologies (e.g., cardiovascular, neurological, inflammatory, metabolic, and cancer diseases).

Natural organic compounds, because they target multiple molecules, enhance their efficacy through synergistic interactions, and are not associated with adverse effects, as many pharmacological agents are, have specific applications for the prevention and treatment of a large number of chronic diseases.

This Special Issue will be focalized on the targeting of organic natural compounds to the subcellular compartments, one of the most promising trends in modern molecular pharmacology.

Prof. Dr. Clara Balsano
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

  • Natural compounds
  • Nutraceuticals
  • Intracellular pathways
  • Mitochondrial dysfunction
  • Metabolic, inflammatory, and stress alterations
  • Targeted therapy

Published Papers (4 papers)

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Research

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16 pages, 33869 KiB  
Article
(20S) Ginsenoside Rh2 Exerts Its Anti-Tumor Effect by Disrupting the HSP90A-Cdc37 System in Human Liver Cancer Cells
by Chen Chen, Yu-Shi Wang, En-Ting Zhang, Gang-Ao Li, Wen-Yuan Liu, Yang Li and Ying-Hua Jin
Int. J. Mol. Sci. 2021, 22(23), 13170; https://doi.org/10.3390/ijms222313170 - 06 Dec 2021
Cited by 14 | Viewed by 3022
Abstract
(20S) ginsenoside Rh2 (G-Rh2), a major bioactive metabolite of ginseng, effectively inhibits the survival and proliferation of human liver cancer cells. However, its molecular targets and working mechanism remain largely unknown. Excitingly, we screened out heat shock protein 90 alpha (HSP90A), a key [...] Read more.
(20S) ginsenoside Rh2 (G-Rh2), a major bioactive metabolite of ginseng, effectively inhibits the survival and proliferation of human liver cancer cells. However, its molecular targets and working mechanism remain largely unknown. Excitingly, we screened out heat shock protein 90 alpha (HSP90A), a key regulatory protein associated with liver cancer, as a potential target of (20S) G-Rh2 by phage display analysis and mass spectrometry. The molecular docking and thermal shift analyses demonstrated that (20S) G-Rh2 directly bound to HSP90A, and this binding was confirmed to inhibit the interaction between HSP90A and its co-chaperone, cell division cycle control protein 37 (Cdc37). It is well-known that the HSP90A-Cdc37 system aids in the folding and maturation of cyclin-dependent kinases (CDKs). As expected, CDK4 and CDK6, the two G0-G1 phase promoting kinases as well as CDK2, a key G1-S phase transition promoting kinase, were significantly downregulated with (20S) G-Rh2 treatment, and these downregulations were mediated by the proteasome pathway. In the same condition, the cell cycle was arrested at the G0-G1 phase and cell growth was inhibited significantly by (20S) G-Rh2 treatment. Taken together, this study for the first time reveals that (20S) G-Rh2 exerts its anti-tumor effect by targeting HSP90A and consequently disturbing the HSP90A-Cdc37 chaperone system. HSP90A is frequently overexpressed in human hepatoma cells and the higher expression is closely correlated to the poor prognosis of liver cancer patients. Thus, (20S) G-Rh2 might become a promising alternative drug for liver cancer therapy. Full article
(This article belongs to the Special Issue Natural Organic Compounds: Cellular Pathways and Effects)
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16 pages, 6847 KiB  
Article
(20S) Ginsenoside Rh2 Inhibits STAT3/VEGF Signaling by Targeting Annexin A2
by Yu-Shi Wang, Chen Chen, Shi-Yin Zhang, Yang Li and Ying-Hua Jin
Int. J. Mol. Sci. 2021, 22(17), 9289; https://doi.org/10.3390/ijms22179289 - 27 Aug 2021
Cited by 12 | Viewed by 2610
Abstract
Signal transducers and activators of transcription 3 (STAT3) acts as a transcriptional signal transducer, converting cytokine stimulation into specific gene expression. In tumor cells, aberrant activation of the tyrosine kinase pathway leads to excessive and continuous activation of STAT3, which provides further signals [...] Read more.
Signal transducers and activators of transcription 3 (STAT3) acts as a transcriptional signal transducer, converting cytokine stimulation into specific gene expression. In tumor cells, aberrant activation of the tyrosine kinase pathway leads to excessive and continuous activation of STAT3, which provides further signals for tumor cell growth and surrounding angiogenesis. In this process, the tumor-associated protein Annexin A2 interacts with STAT3 and promotes Tyr705 phosphorylation and STAT3 transcriptional activation. In this study, we found that (20S) ginsenoside Rh2 (G-Rh2), a natural compound inhibitor of Annexin A2, inhibited STAT3 activity in HepG2 cells. (20S) G-Rh2 interfered with the interaction between Annexin A2 and STAT3, and inhibited Tyr705 phosphorylation and subsequent transcriptional activity. The inhibitory activity of STAT3 leaded to the negative regulation of the four VEGFs, which significantly reduced the enhanced growth and migration ability of HUVECs in co-culture system. In addition, (20S)G-Rh2 failed to inhibit STAT3 activity in cells overexpressing (20S)G-Rh2 binding-deficient Annexin A2-K301A mutant, further proving Annexin A2-mediated inhibition of STAT3 by (20S)G-Rh2. These results indicate that (20S)G-Rh2 is a potent inhibitor of STAT3, predicting the potential activity of (20S)G-Rh2 in targeted therapy applications. Full article
(This article belongs to the Special Issue Natural Organic Compounds: Cellular Pathways and Effects)
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13 pages, 2284 KiB  
Article
Kahweol Exerts Skin Moisturizing Activities by Upregulating STAT1 Activity
by Hongxi Chen, Mohammad Amjad Hossain, Jong-Hoon Kim and Jae Youl Cho
Int. J. Mol. Sci. 2021, 22(16), 8864; https://doi.org/10.3390/ijms22168864 - 18 Aug 2021
Cited by 7 | Viewed by 2416
Abstract
Kahweol is a diterpene present in coffee. Until now, several studies have shown that kahweol has anti-inflammatory and anti-angiogenic functions. Due to the limited research available about skin protection, this study aims to discern the potential abilities of kahweol and the possible regulation [...] Read more.
Kahweol is a diterpene present in coffee. Until now, several studies have shown that kahweol has anti-inflammatory and anti-angiogenic functions. Due to the limited research available about skin protection, this study aims to discern the potential abilities of kahweol and the possible regulation targets. First, the cytotoxicity of kahweol was checked by 3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay, while 2,20-azino-bis (3ethylbenzothiazoline-6-sulphonic acid) diammonium salt and 1-diphenyl-2-picryl-hydrazyl were used to examine the radical scavenging ability. Polymerase chain reaction analysis was performed to explore the proper time points and doses affecting skin hydration and barrier-related genes. Luciferase assay and Western blotting were used to explore the possible transcription factors. Finally, fludarabine (a STAT1 inhibitor) was chosen to discern the relationship between skin-moisturizing factors and STAT1. We found that HaCaT cells experienced no toxicity from kahweol, and kahweol displayed moderate radical scavenging ability. Moreover, kahweol increased the outcome of HAS1, HAS2, occludin, and TGM-1 from six hours in a dose-dependent manner as well as the activation of STAT1 from six hours. Additionally, kahweol recovered the suppression of HAS2, STAT1-mediated luciferase activity, and HA secretion, which was all downregulated by fludarabine. In this study, we demonstrated that kahweol promotes skin-moisturizing activities by upregulating STAT1. Full article
(This article belongs to the Special Issue Natural Organic Compounds: Cellular Pathways and Effects)
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Review

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14 pages, 706 KiB  
Review
It Is High Time Physicians Thought of Natural Products for Alleviating NAFLD. Is There Sufficient Evidence to Use Them?
by Giovanni Tarantino, Clara Balsano, Silvano Junior Santini, Giovanni Brienza, Irma Clemente, Benedetta Cosimini and Gaia Sinatti
Int. J. Mol. Sci. 2021, 22(24), 13424; https://doi.org/10.3390/ijms222413424 - 14 Dec 2021
Cited by 65 | Viewed by 3940
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease all over the world due to the obesity pandemic; currently, therapeutic options for NAFLD are scarce, except for diet recommendations and physical activity. NAFLD is characterized by excessive accumulation of [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease all over the world due to the obesity pandemic; currently, therapeutic options for NAFLD are scarce, except for diet recommendations and physical activity. NAFLD is characterized by excessive accumulation of fat deposits (>5%) in the liver with subsequent inflammation and fibrosis. Studies in the literature show that insulin resistance (IR) may be considered as the key mechanism in the onset and progression of NAFLD. Recently, using natural products as an alternative approach in the treatment of NAFLD has drawn growing attention among physicians. In this review, the authors present the most recent randomized controlled trials (RCTs) and lines of evidence from animal models about the efficacy of nutraceutics in alleviating NAFLD. Among the most studied substances in the literature, the following molecules were chosen because of their presence in the literature of both clinical and preclinical studies: spirulina, oleuropein, garlic, berberine, resveratrol, curcumin, ginseng, glycyrrhizin, coffee, cocoa powder, epigallocatechin-3-gallate, and bromelain. Full article
(This article belongs to the Special Issue Natural Organic Compounds: Cellular Pathways and Effects)
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