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Novel Strategies in the Development of New Anti-inflammatory Drug Substances and Therapies

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 (30 November 2023) | Viewed by 16588

Special Issue Editor

Prof. Dr. Antonietta Rossi

E-Mail Website
Guest Editor
Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy
Interests: sex differences in inflammatory diseases and implications for sex-related therapy; pathobiochemistry of inflammation; molecular and biochemical pharmacology of natural and synthetic anti-inflammatory molecules
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Many inflammatory diseases are high-burden conditions for which the currently available treatment is inadequate. To date, non-steroidal anti-inflammatory drugs inhibiting prostaglandin production, represent the most important anti-inflammatory therapeutic class. Although, their use is often plagued by efficacy and safety issues, leading to very expensive and serious adverse reactions. Inflammation is a very complex pathophysiological process, involving a myriad of enzymes, mediators, and receptors, producing proinflammatory and anti-inflammatory molecules. In particular, pharmacological modulation of a single target tends to generate shunting phenomena that can compromise therapeutic efficacy. Thus, there is a clear need to develop anti-inflammatory drugs with novel mechanisms and/or multitarget action that are able to overcome the delicate balance between providing a therapeutic effect while minimizing side effects. Topics will include (but are not limited to):

  • Individuation of new targets for anti-inflammatory therapy
  • Natural products as novel therapeutic strategies
  • New synthetic compounds with anti-inflammatory proprieties.

Dr. Antonietta Rossi
Guest Editor

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Keywords

  • acute and chronic inflammatory diseases
  • multitarget therapy
  • lipid mediators
  • in vitro and in vivo studies

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Published Papers (5 papers)

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Research

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13 pages, 4369 KiB  
Article
Anti-Inflammatory Effects of Alphitolic Acid Isolated from Agrimonia coreana Nakai Extracts Are Mediated via the Inhibition of ICRAC Activity in T Cells
by Su Jin Park, Jin Seok Lee, Yu Ran Nam, Ji Min Lee, Dae-Won Ki, Bong-Sik Yun, Seong Woo Choi, Nhung Thi Hong Van, Joo Hyun Nam, Hyun Jong Kim and Woo Kyung Kim
Int. J. Mol. Sci. 2023, 24(24), 17309; https://doi.org/10.3390/ijms242417309 - 9 Dec 2023
Cited by 2 | Viewed by 1767
Abstract
Agrimonia pilosa Ledeb., an important medicinal herb in traditional East Asian medicine, is primarily used to treat abdominal pain, dysentery, and hemostasis. There are ten other reported species of Agrimonia plants, including Agrimonia coreana Nakai—a naturally growing species in South Korea—and Agrimonia eupatoria [...] Read more.
Agrimonia pilosa Ledeb., an important medicinal herb in traditional East Asian medicine, is primarily used to treat abdominal pain, dysentery, and hemostasis. There are ten other reported species of Agrimonia plants, including Agrimonia coreana Nakai—a naturally growing species in South Korea—and Agrimonia eupatoria Linn. Although recent studies have isolated numerous active constituents and investigated their effects, the medicinal utility of this herb is not yet fully explored. Through patch-clamp recording, a previous study reported that Agrimonia plant extracts inhibit the function of Ca2+ release-activated Ca2+ channels (CRACs). Herein, we aimed to identify and isolate the main compounds in A. coreana responsible for CRAC inhibition while assessing the anti-inflammatory effects mediated by this inhibition. We demonstrated for the first time that alphitolic acid isolated from A. coreana has a dose-dependent inhibitory effect on CRAC activity and, thus, an inhibitory effect on intracellular calcium increase. Furthermore, analysis of human CD4+ T cell proliferation via the carboxyfluorescein diacetate succinimidyl ester method revealed that alphitolic acid inhibited T cell proliferation in a concentration-dependent manner. Our findings provide a theoretical basis for the potential therapeutic use of alphitolic acid in the treatment of inflammatory diseases. Full article
(This article belongs to the Special Issue Novel Strategies in the Development of New Anti-inflammatory Drug Substances and Therapies)
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19 pages, 5215 KiB  
Article
Beneficial Effects of Astragalus membranaceus (Fisch.) Bunge Extract in Controlling Inflammatory Response and Preventing Asthma Features
by Danilo D’Avino, Ida Cerqua, Hammad Ullah, Michele Spinelli, Rita Di Matteo, Elisabetta Granato, Raffaele Capasso, Lucianna Maruccio, Armando Ialenti, Maria Daglia, Fiorentina Roviezzo and Antonietta Rossi
Int. J. Mol. Sci. 2023, 24(13), 10954; https://doi.org/10.3390/ijms241310954 - 30 Jun 2023
Cited by 43 | Viewed by 3742
Abstract
Astragalus membranaceus (Fisch.) Bunge root is used as herbal medicine for its immunomodulating activities in Chinese medicine. Recently, beneficial properties of A. membranaceus on allergic diseases have been proposed. Here we investigated the role of a commercial extract of A. membranaceus, standardized [...] Read more.
Astragalus membranaceus (Fisch.) Bunge root is used as herbal medicine for its immunomodulating activities in Chinese medicine. Recently, beneficial properties of A. membranaceus on allergic diseases have been proposed. Here we investigated the role of a commercial extract of A. membranaceus, standardized to 16% polysaccharides, in regulating the immune-inflammatory response in vitro and in vivo and its therapeutic application in asthma. A. membranaceus extract inhibited prostaglandin E2 and leukotriene C4 production in stimulated J774 and peritoneal macrophages, respectively. The extract also reduced interlukin-1β, tumor necrosis factor-α, and nitrite production, affecting inducible nitric oxide synthase expression. In vivo experiments confirmed the anti-inflammatory properties of A. membranaceus, as evident by a reduction in zymosan-induced peritoneal cellular infiltration and pro-inflammatory mediator production. The efficacy of A. membranaceus extract in modulating the immune response was confirmed in a model of allergic airway inflammation. Extracts improve lung function by inhibiting airway hyperresponsiveness, airway remodeling, and fibrosis. Its anti-asthmatic effects were further sustained by inhibition of the sensitization process, as indicated by a reduction of ovalbumin-induced IgE levels and the mounting of a Th2 immune response. In conclusion, our data demonstrate the anti-inflammatory properties of the commercial extract of A. membranaceus and its beneficial effects on asthma feature development. Full article
(This article belongs to the Special Issue Novel Strategies in the Development of New Anti-inflammatory Drug Substances and Therapies)
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17 pages, 3816 KiB  
Article
Ceria Nanoparticles Alleviated Osteoarthritis through Attenuating Senescence and Senescence-Associated Secretory Phenotype in Synoviocytes
by Xunshan Ren, Huangming Zhuang, Fuze Jiang, Yuelong Zhang and Panghu Zhou
Int. J. Mol. Sci. 2023, 24(5), 5056; https://doi.org/10.3390/ijms24055056 - 6 Mar 2023
Cited by 10 | Viewed by 3297
Abstract
Accumulation of senescent cells is the prominent risk factor for osteoarthritis (OA), accelerating the progression of OA through a senescence-associated secretory phenotype (SASP). Recent studies emphasized the existence of senescent synoviocytes in OA and the therapeutic effect of removing senescent synoviocytes. Ceria nanoparticles [...] Read more.
Accumulation of senescent cells is the prominent risk factor for osteoarthritis (OA), accelerating the progression of OA through a senescence-associated secretory phenotype (SASP). Recent studies emphasized the existence of senescent synoviocytes in OA and the therapeutic effect of removing senescent synoviocytes. Ceria nanoparticles (CeNP) have exhibited therapeutic effects in multiple age-related diseases due to their unique capability of ROS scavenging. However, the role of CeNP in OA remains unknown. Our results revealed that CeNP could inhibit the expression of senescence and SASP biomarkers in multiple passaged and hydrogen-peroxide-treated synoviocytes by removing ROS. In vivo, the concentration of ROS in the synovial tissue was remarkably suppressed after the intra-articular injection of CeNP. Likewise, CeNP reduced the expression of senescence and SASP biomarkers as determined by immunohistochemistry analysis. The mechanistic study showed that CeNP inactivated the NFκB pathway in senescent synoviocytes. Finally, safranin O–fast green staining showed milder destruction of articular cartilage in the CeNP-treated group compared with the OA group. Overall, our study suggested that CeNP attenuated senescence and protected cartilage from degeneration via scavenging ROS and inactivating the NFκB signaling pathway. This study has potentially significant implications in the field of OA as it provides a novel strategy for OA treatment. Full article
(This article belongs to the Special Issue Novel Strategies in the Development of New Anti-inflammatory Drug Substances and Therapies)
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13 pages, 1667 KiB  
Communication
Influence of Cucurbiturils on the Production of Reactive Oxygen Species by T- and B-Lymphocytes, Platelets and Red Blood Cells
by Alina A. Aktanova, Olga S. Boeva, Margarita Sh. Barkovskaya, Ekaterina A. Kovalenko and Ekaterina A. Pashkina
Int. J. Mol. Sci. 2023, 24(2), 1441; https://doi.org/10.3390/ijms24021441 - 11 Jan 2023
Cited by 3 | Viewed by 1976
Abstract
Reactive oxygen species (ROS) are highly reactive chemical molecules containing oxygen. ROS play an important role in signaling and cell homeostasis at low and moderate concentrations. ROS could be a cause of damage to proteins, nucleic acids, lipids, membranes and organelles at high [...] Read more.
Reactive oxygen species (ROS) are highly reactive chemical molecules containing oxygen. ROS play an important role in signaling and cell homeostasis at low and moderate concentrations. ROS could be a cause of damage to proteins, nucleic acids, lipids, membranes and organelles at high concentrations. There are a lot of cells that can produce ROS to maintain functional activity. It is known that metal nanoparticles can increase production of ROS in cells. However, the effect of cucurbiturils on ROS production is still unknown. In our study, we evaluated production of ROS by the immune (T-, B-lymphocytes, NK-cells) and non-immune cells (red blood cells, platelets), as well as tumor cells line (1301, K562) after treatment with cucurbiturils in vitro. Assessment of reactive oxide species (ROS) were provided by using dihydrorhodamine 123 (DHR 123). Fluorescence intensity and percentage DHR123 were measured by flow cytometry. Platelets, erythrocytes and activated T-helpers were changed the level of ROS production in response to stimulation with cucurbiturils. It was found that the percentage of these ROS-producing cells was reduced by cucurbiturils. Thus, cucurbiturils may affect the production of ROS by cells, but further research is needed in this area. Full article
(This article belongs to the Special Issue Novel Strategies in the Development of New Anti-inflammatory Drug Substances and Therapies)
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Review

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20 pages, 1044 KiB  
Review
Role of Oxidative Stress in Peyronie’s Disease: Biochemical Evidence and Experiences of Treatment with Antioxidants
by Gianni Paulis, Giovanni De Giorgio and Luca Paulis
Int. J. Mol. Sci. 2022, 23(24), 15969; https://doi.org/10.3390/ijms232415969 - 15 Dec 2022
Cited by 16 | Viewed by 5199
Abstract
Background: Peyronie’s disease (PD) is a chronic inflammatory condition affecting adult males, involving the tunica albuginea of the corpora cavernosa of the penis. PD is frequently associated with penile pain, erectile dysfunction, and a secondary anxious–depressive state. The etiology of PD has not [...] Read more.
Background: Peyronie’s disease (PD) is a chronic inflammatory condition affecting adult males, involving the tunica albuginea of the corpora cavernosa of the penis. PD is frequently associated with penile pain, erectile dysfunction, and a secondary anxious–depressive state. The etiology of PD has not yet been completely elucidated, but local injury is generally recognized to be a triggering factor. It has also been widely proven that oxidative stress is an essential, decisive component in all inflammatory processes, whether acute or chronic. Current conservative medical treatment comprises oral substances, penile injections, and physical therapy. Aim: This article intends to show how antioxidant therapy is able to interfere with the pathogenetic mechanisms of the disease. Method: This article consists of a synthetic narrative review of the current scientific literature on antioxidant therapy for this disease. Results: The good results of the antioxidant treatment described above also prove that the doses used were adequate and the concentrations of the substances employed did not exceed the threshold at which they might have interacted negatively with the mechanisms of the redox regulation of tissue. Conclusions: We believe new, randomized, controlled studies are needed to confirm the efficacy of treatment with antioxidants. However, we consider the experiences of antioxidant treatment which can already be found in the literature useful for the clinical practice of urologists in the treatment of this chronic inflammatory disease. Full article
(This article belongs to the Special Issue Novel Strategies in the Development of New Anti-inflammatory Drug Substances and Therapies)
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