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Advances in Pharmacology of Prostaglandins
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Advances in Pharmacology of Prostaglandins

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 8203

Special Issue Editors

Dr. Federica Finetti

E-Mail Website
Guest Editor
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, SI, Italy
Interests: antioxidant; anti-inflammatory; antitumoral and antiangiogenic potential of natural compounds; their semisynthetic derivatives and/or analogs produced by metabolic engineering and evaluation of their potential biomedical and nutraceutical applications; molecular mechanisms underlying cerebral cavernous malformation (CCM) with particular focus on the study of physiopathological functions of KRIT1 protein and its functional interactions
Special Issues, Collections and Topics in MDPI journals
Dr. Lorenza Trabalzini

E-Mail Website
Guest Editor
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, SI, Italy
Interests: antioxidant; anti-inflammatory; antitumoral activity; natural compounds; nutraceutical applications; cerebral cavernous malformation; KRIT1
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Prostaglandins are products of polyunsaturated fatty acid metabolism, particularly arachidonic acid released from membrane phospholipids through the action of phospholipase A2 in response to a variety of chemical, physical, and neurohormonal factors. Arachidonic acid is rapidly metabolized to oxygenated products by two distinct enzymatic pathways: cyclooxygenase and lipoxygenase. The intermediate cyclooxygenase products are converted to primary prostaglandins. The generation of various prostaglandins varies from tissue to tissue and exerts a broad spectrum of effects, including cardiovascular, respiratory, gastrointestinal and neuromodulatory. In addition, prostaglandins regulate pain, uterus and urinary bladder contraction, fever, and important physiopathological processes, including inflammation and cancer progression. Many diseases result from the imbalanced or increased production of prostaglandins. Pharmacological modulation of prostaglandin levels represents a fundamental weapon in the treatment of several pathological conditions, and the development of new specific and selective drugs with low side effects is a goal of pharmacological research.

Suitable topics include but are not limited to the development of new cyclooxygenase inhibitors, the discovery of cyclooxygenase inhibitors, the pharmacological modulation of prostaglandins levels, the identification of prostaglandin synthase inhibitors, and the pharmacological characterization of specific prostaglandin receptor agonists or antagonists.

Dr. Federica Finetti
Dr. Lorenza Trabalzini
Guest Editors

Manuscript Submission Information

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Keywords

  • anti-inflammatory drugs
  • prostaglandin level modulators
  • agonists and antagonists of prostaglandin receptors
  • chronic inflammatory diseases
  • cardiovascular diseases
  • neuroinflammation
  • autoimmune diseases
  • gastrointestinal diseases
  • respiratory tract
  • cancer

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Published Papers (4 papers)

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Research

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17 pages, 1903 KiB  
Article
Noradrenaline and Adrenoreceptors Are Involved in the Regulation of Prostaglandin I2 Production in the Porcine Endometrium after Experimentally Induced Inflammation
by Barbara Jana, Jarosław Całka, Aneta Andronowska, Aleksandra Mówińska, Krzysztof Witek and Katarzyna Palus
Int. J. Mol. Sci. 2024, 25(12), 6313; https://doi.org/10.3390/ijms25126313 - 7 Jun 2024
Viewed by 603
Abstract
Endometritis is a common disease in animals, leading to disruption of reproductive processes and economic losses. Noradrenergic control of prostaglandin (PG)I2 formation by inflamed endometrium is unknown. We determined the involvement of α1-, α2- and β-adrenoreceptors (ARs) in noradrenaline-influenced PGI synthase (PGIS) protein [...] Read more.
Endometritis is a common disease in animals, leading to disruption of reproductive processes and economic losses. Noradrenergic control of prostaglandin (PG)I2 formation by inflamed endometrium is unknown. We determined the involvement of α1-, α2- and β-adrenoreceptors (ARs) in noradrenaline-influenced PGI synthase (PGIS) protein abundance and PGI2 release from porcine (1) endometrial explants with Escherichia coli (E. coli)-induced inflammation in vivo, and (2) E. coli lipopolysaccharide (LPS)-treated endometrial epithelial cells. Experiment 1. E. coli suspension (E. coli group) or saline (CON group) was injected into the uterine horns. In both groups, noradrenaline increased endometrial PGIS abundance and PGI2 release versus the control values, and it was higher in the E. coli group than in the CON group. In the CON group, a noradrenaline stimulating effect on both parameters takes place through α1D-, α2C- and β2-ARs. In the E. coli group, noradrenaline increased PGIS abundance and PGI2 release via α1A-, α2(B,C)- and β(1,2)-ARs, and PGI2 release also by α2A-ARs. Experiment 2. LPS and noradrenaline augmented the examined parameters in endometrial epithelial cells versus the control value. In LPS-treated cells, β(1,2)-ARs mediate in noradrenaline excitatory action on PGIS protein abundance and PGI2 release. β3-ARs also contribute to PGI2 release. Under inflammatory conditions, noradrenaline via ARs increases PGI2 synthesis and release from the porcine endometrium, including epithelial cells. Our findings suggest that noradrenaline may indirectly affect processes regulated by PGI2 in the inflamed uterus. Full article
(This article belongs to the Special Issue Advances in Pharmacology of Prostaglandins)
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15 pages, 3534 KiB  
Article
The Presence of TGFβ3 in Human Ovarian Intrafollicular Fluid and Its Involvement in Thromboxane Generation in Follicular Granulosa Cells through a Canonical TGFβRI, Smad2/3 Signaling Pathway and COX-2 Induction
by Tsung-Hsuan Lai, Hsuan-Ting Chen, Pi-Hui Wu and Wen-Bin Wu
Int. J. Mol. Sci. 2024, 25(10), 5558; https://doi.org/10.3390/ijms25105558 - 20 May 2024
Cited by 1 | Viewed by 877
Abstract
Ovarian follicular fluid (FF) has a direct impact on oocyte quality, playing key roles in fertilization, implantation, and early embryo development. In our recent study, we found FF thromboxane (TX) to be a novel factor inversely correlated with oocyte maturation and identified thrombin, [...] Read more.
Ovarian follicular fluid (FF) has a direct impact on oocyte quality, playing key roles in fertilization, implantation, and early embryo development. In our recent study, we found FF thromboxane (TX) to be a novel factor inversely correlated with oocyte maturation and identified thrombin, transforming growth factor β (TGFβ), TNF-α, and follicular granulosa cells (GCs) as possible contributors to FF TX production. Therefore, this study sought to investigate the role of TGFβ3 in regulating TX generation in human ovarian follicular GCs. TGFβ3 was differentially and significantly present in the FF of large and small follicles obtained from IVF patients with average concentrations of 68.58 ± 12.38 and 112.55 ± 14.82 pg/mL, respectively, and its levels were correlated with oocyte maturity. In an in vitro study, TGFβ3 induced TX generation/secretion and the converting enzyme-COX-2 protein/mRNA expression both in human HO23 and primary cultured ovarian follicular GCs. While TGFβRI and Smad2/3 signaling was mainly required for COX-2 induction, ERK1/2 appeared to regulate TX secretion. The participation of Smad2/3 and COX-2 in TGFβ3-induced TX generation/secretion could be further supported by the observations that Smad2/3 phosphorylation and nuclear translocation and siRNA knockdown of COX-2 expression compromised TX secretion in GCs challenged with TGFβ3. Taken together, the results presented here first demonstrated that FF TGFβ3 levels differ significantly in IVF patients’ large preovulatory and small mid-antral follicles and are positively associated with oocyte maturation. TGFβ3 can provoke TX generation by induction of COX-2 mRNA/protein via a TGFβR-related canonical Smad2/3 signaling pathway, and TX secretion possibly by ERK1/2. These imply that TGFβ3 is one of the inducers for yielding FF TX in vivo, which may play a role in folliculogenesis and oocyte maturation. Full article
(This article belongs to the Special Issue Advances in Pharmacology of Prostaglandins)
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16 pages, 3882 KiB  
Article
Fluorinated Benzofuran and Dihydrobenzofuran as Anti-Inflammatory and Potential Anticancer Agents
by Abeer J. Ayoub, Ghewa A. El-Achkar, Sandra E. Ghayad, Layal Hariss, Razan H. Haidar, Leen M. Antar, Zahraa I. Mallah, Bassam Badran, René Grée, Ali Hachem, Eva Hamade and Aida Habib
Int. J. Mol. Sci. 2023, 24(12), 10399; https://doi.org/10.3390/ijms241210399 - 20 Jun 2023
Cited by 3 | Viewed by 2035
Abstract
Benzofuran and 2,3-dihydrobenzofuran scaffolds are heterocycles of high value in medicinal chemistry and drug synthesis. Targeting inflammation in cancer associated with chronic inflammation is a promising therapy. In the present study, we investigated the anti-inflammatory effects of fluorinated benzofuran and dihydrobenzofuran derivatives in [...] Read more.
Benzofuran and 2,3-dihydrobenzofuran scaffolds are heterocycles of high value in medicinal chemistry and drug synthesis. Targeting inflammation in cancer associated with chronic inflammation is a promising therapy. In the present study, we investigated the anti-inflammatory effects of fluorinated benzofuran and dihydrobenzofuran derivatives in macrophages and in the air pouch model of inflammation, as well as their anticancer effects in the human colorectal adenocarcinoma cell line HCT116. Six of the nine compounds suppressed lipopolysaccharide-stimulated inflammation by inhibiting the expression of cyclooxygenase-2 and nitric oxide synthase 2 and decreased the secretion of the tested inflammatory mediators. Their IC50 values ranged from 1.2 to 9.04 µM for interleukin-6; from 1.5 to 19.3 µM for Chemokine (C-C) Ligand 2; from 2.4 to 5.2 µM for nitric oxide; and from 1.1 to 20.5 µM for prostaglandin E2. Three novel synthesized benzofuran compounds significantly inhibited cyclooxygenase activity. Most of these compounds showed anti-inflammatory effects in the zymosan-induced air pouch model. Because inflammation may lead to tumorigenesis, we tested the effects of these compounds on the proliferation and apoptosis of HCT116. Two compounds with difluorine, bromine, and ester or carboxylic acid groups inhibited the proliferation by approximately 70%. Inhibition of the expression of the antiapoptotic protein Bcl-2 and concentration-dependent cleavage of PARP-1, as well as DNA fragmentation by approximately 80%, were described. Analysis of the structure–activity relationship suggested that the biological effects of benzofuran derivatives are enhanced in the presence of fluorine, bromine, hydroxyl, and/or carboxyl groups. In conclusion, the designed fluorinated benzofuran and dihydrobenzofuran derivatives are efficient anti-inflammatory agents, with a promising anticancer effect and a combinatory treatment in inflammation and tumorigenesis in cancer microenvironments. Full article
(This article belongs to the Special Issue Advances in Pharmacology of Prostaglandins)
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Review

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18 pages, 820 KiB  
Review
Arachidonic Acid Pathways and Male Fertility: A Systematic Review
by Malvina Hoxha, Arcangelo Barbonetti and Bruno Zappacosta
Int. J. Mol. Sci. 2023, 24(9), 8207; https://doi.org/10.3390/ijms24098207 - 3 May 2023
Cited by 4 | Viewed by 2761
Abstract
Arachidonic acid (AA) is a polyunsaturated fatty acid that is involved in male fertility. Human seminal fluid contains different prostaglandins: PGE (PGE1 and PGE2), PGF2α, and their specific 19-hydroxy derivatives, 18,19-dehydro derivatives of PGE1 and PGE2 [...] Read more.
Arachidonic acid (AA) is a polyunsaturated fatty acid that is involved in male fertility. Human seminal fluid contains different prostaglandins: PGE (PGE1 and PGE2), PGF2α, and their specific 19-hydroxy derivatives, 18,19-dehydro derivatives of PGE1 and PGE2. The objective of this study is to synthesize the available literature of in vivo animal studies and human clinical trials on the association between the AA pathway and male fertility. PGE is significantly decreased in the semen of infertile men, suggesting the potential for exploitation of PGE agonists to improve male fertility. Indeed, ibuprofen can affect male fertility by promoting alterations in sperm function and standard semen parameters. The results showed that targeting the AA pathways could be an attractive strategy for the treatment of male fertility. Full article
(This article belongs to the Special Issue Advances in Pharmacology of Prostaglandins)
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