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Search Results (163)

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Keywords = COX-1/5-LOX

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17 pages, 2498 KiB  
Article
Lemongrass Alleviates Primary Dysmenorrhea Symptoms by Reducing Oxidative Stress and Inflammation and Relaxing the Uterine Muscles
by Sheikh Safeena Sidiq, Qaiser Jabeen, QurratUlAin Jamil, Muhammad Saeed Jan, Iram Iqbal, Fatima Saqib, Mohammed Aufy and Shahid Muhammad Iqbal
Antioxidants 2025, 14(7), 838; https://doi.org/10.3390/antiox14070838 - 8 Jul 2025
Viewed by 431
Abstract
Primary dysmenorrhea (PD) is characterized by lower abdominal spasms and painful cramps during menstruation in females with a normal pelvic anatomy. Cymbopogon citratus (DC.) Stapf, commonly known as lemongrass, is consumed in the form of herbal tea around the world. It has been [...] Read more.
Primary dysmenorrhea (PD) is characterized by lower abdominal spasms and painful cramps during menstruation in females with a normal pelvic anatomy. Cymbopogon citratus (DC.) Stapf, commonly known as lemongrass, is consumed in the form of herbal tea around the world. It has been traditionally used for menstrual disorders in several communities. This study aims to evaluate the traditional use of C. citratus for its efficacy in alleviating the symptoms of PD. C. citratus extract (CcE) was chemically characterized using HPLC and GCMS, which indicated the presence of several phenolic compounds and long-chain fatty acids. The anti-inflammatory activity of CcE was assessed by COX-I, COX-II, and 5-LOX enzyme inhibition with IC50 values of 143.7, 91.7, and 61.5 µg/mL, respectively, and showed good total antioxidant capacity and free radical scavenging activity. PD was induced in female Wistar rats by administering estradiol valerate followed by oxytocin to induce PD symptoms. CcE efficacy was assessed at 30, 100, and 300 mg/kg concentrations and compared with ibuprofen. CcE 300 mg/kg reduced abdominal contortions and inflammation in the rat uterus. The inflammatory (COX-II, TNFα and IL-10) and oxidative stress (TAC, TOS, MDA and SOD) markers in uterine tissue homogenate were also improved. An in vivo analgesic assessment through hot-plate, tail-flick, and acetic acid-induced writhing assays showed good analgesic activity by CcE, while ex vivo experiments described tocolytic effects in rat uterine muscles. CcE alleviates PD by its antioxidant, anti-inflammatory, analgesic, and tocolytic effects. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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12 pages, 697 KiB  
Article
Dietary Gluten-Free Regimen Does Not Affect the Suppression of the Inflammatory Response in the Arachidonic Acid Cascade in Hashimoto’s Disease
by Małgorzata Szczuko, Lidia Kwiatkowska, Urszula Szczuko, Leon Rudak, Karina Ryterska, Anhelli Syrenicz, Jakub Pobłocki and Arleta Drozd
Int. J. Mol. Sci. 2025, 26(13), 6507; https://doi.org/10.3390/ijms26136507 - 6 Jul 2025
Viewed by 509
Abstract
The incidence of Hashimoto’s disease (HD) increases with age and in people who have other autoimmune diseases. It is characterized by lymphocytic infiltration, fibrosis, and atrophy of the thyroid parenchyma with the simultaneous presence of thyroid peroxidase antibodies (ATPO) and/or thyroglobulin antibodies (ATG). [...] Read more.
The incidence of Hashimoto’s disease (HD) increases with age and in people who have other autoimmune diseases. It is characterized by lymphocytic infiltration, fibrosis, and atrophy of the thyroid parenchyma with the simultaneous presence of thyroid peroxidase antibodies (ATPO) and/or thyroglobulin antibodies (ATG). Eicosanoids are formed via the cyclooxygenase (COX), lipoxygenase (LOX), and monooxygenase (CYP450) pathways with arachidonic acid (ARA), resulting in the production of epoxyeicosatrienoic acids (EETs) or hydroxyeicosatetraenoic acids (HETEs). These eicosanoids can act in an autocrine or paracrine manner on target cells. This study aimed to examine whether a gluten-free diet (GFD) can modulate the enzymatic pathways of the pro-inflammatory ARA cascade. The study material consisted of serum samples from Caucasian female patients with HD aged 18–55 years. Participants were enrolled in the study based on the presence of an ultrasound characteristic of HD, and elevated serum levels of anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies. Patients with confirmed celiac disease did not participate in the study. A total of 78 samples were analyzed, with 39 collected after 3 months of following a GFD. Eicosanoids (thromboxane B2, prostaglandin E2, leukotriene B4, and 16R-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (16-RS HETE)) were extracted using high-performance liquid chromatography. The contribution of leukotriene (LTB) was analyzed in the LOX pathway, prostaglandins (PGE2) and thromboxane (TXB2) were selected for the involvement of the COX pathway, and 16RS HETE was used for the CYP450 pathway. All parameters were analyzed before and after a 3-month dietary intervention that included a gluten-free diet. In the obtained results, only one mediator, leukotriene B4, was significant (p < 0.05). The mean level on the initial visit was 0.202 ± 0.11 (SD), while it was 0.421 ± 0.27 (SD) on the subsequent visit, indicating a significant increase in its level after implementing a GFD. Although there was a trend in the CYP 450 pathway of decreased 16-RS HETE, the presented correlations show that thromboxane B4 and 16RS-HETE were positively correlated with the body mass and body fat mass of the examined patients. There was a trend in the CYP 450 pathway of decreased 16-RS HETE after GFD. Thromboxane B4 and 16RS-HETE levels before GFD were positively correlated with the body mass and body fat mass of the examined patients. A gluten-free diet in HD does not suppress the synthetic pathways of LOX, COX, or cytochrome P450 (CYP450). The level of adipose tissue has a greater impact on the inflammatory processes in HD than a gluten-free diet. This study does not confirm the suppressive effect of a gluten-free diet on the pro-inflammatory arachidonic acid cascade in any of the three analyzed mediator synthesis LOX, COX, CYP450 pathways. Full article
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24 pages, 4677 KiB  
Article
Dysregulation of Arachidonic Acid Metabolism Drives Inflammatory Lipid Production in Localized Provoked Vulvodynia
by Sarah A. Fischer, Oluwademilade Oladele, Zahra Mahamed, Emanuelle Chrysilla, Anna Baumer, Tamari Bekauri, Krishna Rao Maddipati, Tanzy Love, Mitchell Linder and Megan Falsetta
Nutrients 2025, 17(13), 2233; https://doi.org/10.3390/nu17132233 - 5 Jul 2025
Cited by 1 | Viewed by 461
Abstract
Background/Objectives: Localized provoked vulvodynia (LPV) is characterized by chronic vulvar pain upon light touch to the vestibule, a specialized ring of tissue immediately surrounding the vaginal opening. LPV affects about 14 million people in the US, yet the etiopathology of the disease [...] Read more.
Background/Objectives: Localized provoked vulvodynia (LPV) is characterized by chronic vulvar pain upon light touch to the vestibule, a specialized ring of tissue immediately surrounding the vaginal opening. LPV affects about 14 million people in the US, yet the etiopathology of the disease is unknown. In LPV, the vestibule expresses elevated levels of the pro-nociceptive pro-inflammatory mediators prostaglandin E2 (PGE2) and interleukin-6 (IL-6), which corresponds to lower pain thresholds. Previous studies have shown reduced amounts of arachidonic acid (AA)-derived pro-resolving lipid mediators in tissue biopsies from LPV patients that might impede the resolution of inflammation. AA is obtained from dietary linoleic acid, pointing to a defect in the metabolism of dietary polyunsaturated fatty acids in LPV. We aimed to further explore the involvement of AA metabolism in LPV, which appears dysregulated in the vestibule of LPV patients and culminates in chronic inflammation and chronic pain. Methods: Vestibular and vulvar tissue biopsies obtained from LPV and non-LPV patients were used to generate fibroblast strains and assessed for COX/LOX expression using qRT-PCR. Fibroblast strains were treated with inflammatory stimuli, and then COX-1 and COX-2 expression was assessed using Western blot analysis. Pro-inflammatory mediator production was assessed using enzyme-linked immunosorbent assays (ELISAs). ALOX5 and ALOX12 expression was assessed using qRT-PCR. Finally, lipidomic analysis was carried out to screen for 143 lipid metabolites following inflammatory challenge. Results: Tissue and fibroblasts from LPV patients exhibited altered expression of COX/LOX enzymes and production of AA-derived lipid mediators compared to non-LPV patients. Conclusions: Lipid profiles of tissue and vestibular fibroblasts from LPV patients differed from non-LPV patients, and this difference was attributed to differential COX/LOX expression and activity, which metabolizes AA derived from dietary linoleic acid. This dysregulation fosters chronic inflammation and reduced resolution capacity in LPV patients, causing chronic pain. While further work is needed, these findings suggest that dietary modifications could impact the LPV mechanism. Full article
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25 pages, 3312 KiB  
Article
In Silico Evaluation of Terpene Interactions with Inflammatory Enzymes: A Blind Docking Study Targeting Arachidonic Acid Metabolism
by Djeni Cherneva, Kaloyan Mihalev, Ivelin Iliev, Nadya Agova, Galina Yaneva, Tsonka Dimitrova and Svetlana Georgieva
Appl. Sci. 2025, 15(13), 7536; https://doi.org/10.3390/app15137536 - 4 Jul 2025
Viewed by 297
Abstract
Terpenes represent a structurally diverse class of natural compounds with increasing scientific interest due to their potential anti-inflammatory properties. This study investigates the in silico binding behavior of six plant-derived terpenes—α-pinene, β-pinene, menthol, camphor, limonene, and linalool—against four key enzymes in the arachidonic [...] Read more.
Terpenes represent a structurally diverse class of natural compounds with increasing scientific interest due to their potential anti-inflammatory properties. This study investigates the in silico binding behavior of six plant-derived terpenes—α-pinene, β-pinene, menthol, camphor, limonene, and linalool—against four key enzymes in the arachidonic acid (AA) metabolic pathway: cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and phospholipase A2 (PLA2). AA serves as a reference for binding energy comparison. Blind rigid-body molecular docking is performed using AutoDock 4.2 and the Lamarckian Genetic Algorithm, with 100 runs per ligand–enzyme pair and the energy-based selection of optimal poses. The analysis includes binding energy (ΔG), inhibition constants (Ki), root-mean-square deviation (RMSD), and residue-level interactions. Several terpenes exhibit favorable binding energies and inhibition constants across the evaluated enzymes. For COX-1 and COX-2, menthol and camphor show low Ki values, indicating stable binding. Menthol and limonene also show the strongest affinities for PLA2, exceeding AA. The focus is on compounds with potential to modulate arachidonic acid metabolism. In this context, β-pinene engages the catalytic site of PLA2, linalool forms multiple contacts within key regions of 5-LOX, and menthol, α-pinene, and β-pinene align with functionally important regions in both COX isoforms. These targeted interactions suggest that the highlighted compounds may selectively interfere with enzymatic activity in inflammation-related pathways. By modulating key steps in AA metabolism, these terpenes may influence the biosynthesis of pro-inflammatory mediators, offering a promising avenue for the development of safer, plant-derived anti-inflammatory agents. The findings lay the groundwork for further experimental validation and the structure-based optimization of terpene-derived modulators. Full article
(This article belongs to the Section Biomedical Engineering)
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17 pages, 861 KiB  
Article
Investigating COX-2 and 5-LOX Enzyme-Related Anti-Inflammatory and Antioxidant Activities and Phytochemical Features of Scutellaria salviifolia Benth
by Gülsüm Metkin, İpek Süntar, Fatma Sezer Şenol Deniz, Osman Tugay, Mustafa Demiralp and Valeria Pittalà
Int. J. Mol. Sci. 2025, 26(12), 5608; https://doi.org/10.3390/ijms26125608 - 11 Jun 2025
Viewed by 1032
Abstract
Scutellaria species are widely utilized and have demonstrated diverse biological effects for various diseases, both globally and in traditional Chinese medicine, due to the presence of bioactive compounds with unique structures. This study was conducted to reveal the in vitro effects and phytochemical [...] Read more.
Scutellaria species are widely utilized and have demonstrated diverse biological effects for various diseases, both globally and in traditional Chinese medicine, due to the presence of bioactive compounds with unique structures. This study was conducted to reveal the in vitro effects and phytochemical properties of Scutellaria salviifolia Benth., an endemic species of Türkiye. The inhibitory effects of methanol extracts prepared separately from the aerial and root parts of S. salviifolia on the COX-2 and 5-LOX enzymes and their DPPH and ABTS radical scavenging activities were evaluated using in vitro methods. Additionally, the phenolic compounds of the extracts were compared based on Q-TOF LC/MS analysis. The extracts of S. salviifolia exhibited a high inhibitory effect on COX-2 enzyme activity, comparable to that of celecoxib. Still, they showed no significant effects in the 5-LOX enzyme inhibition assay. In the antioxidant activity assays, the percentage of inhibitory effects of both extracts against DPPH and ABTS were similar. A total of 29 and 27 compounds were detected in the aerial part and root extracts, respectively. Among the identified compounds, 18 were common to both the aerial part and root extracts. S. salviifolia may serve as a valuable alternative to the most well-known Scutellaria species, including S. baicalensis and S. barbata. Full article
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24 pages, 5739 KiB  
Article
Multifaceted Biological Activities of Culinary Herb and Spice Extracts: In Vitro and In Silico Simulation Insights into Inflammation-Related Targets
by Nance Hontman, Jéssica Gonçalves, José S. Câmara and Rosa Perestrelo
Foods 2025, 14(9), 1456; https://doi.org/10.3390/foods14091456 - 23 Apr 2025
Viewed by 668
Abstract
Culinary herbs and spices are valued worldwide for their flavor, aroma, and medicinal benefits. They encompass diverse bioactive metabolites, such as polyphenols and terpenoids, which contribute to plant defense and offer anticarcinogenic, anti-inflammatory, antioxidant, and cognitive-enhancing effects. This study aimed to establish the [...] Read more.
Culinary herbs and spices are valued worldwide for their flavor, aroma, and medicinal benefits. They encompass diverse bioactive metabolites, such as polyphenols and terpenoids, which contribute to plant defense and offer anticarcinogenic, anti-inflammatory, antioxidant, and cognitive-enhancing effects. This study aimed to establish the volatile fingerprint of culinary herbs (lemon verbena, chives, basil, sage, coriander, and parsley) and spices (curcuma, nutmeg, cumin, black pepper, Jamaica pepper, and juniper berry) using headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME/GC-MS). The predominant volatile organic metabolites (VOMs) identified were subjected to in silico molecular docking simulations of anti-Alzheimer’s (e.g., acetylcholinesterase (AChE), butyrylcholinesterase (BChE)), antioxidants (e.g., monoamine oxidase B (MAO-B), inducible nitric oxide synthase (iNOS)), and anti-inflammatory receptors (e.g., 5-lipoxygenase (5-LOX), cyclooxygenase-2 (COX-2)). The culinary herb and spice extracts were also subjected to in vitro assays to evaluate their potential as antioxidant (DPPH, ABTS, and ORAC) and anti-inflammatory (% protein denaturation) agents. A total of 121 VOMs were identified in the culinary herbs and spices, with the predominant chemical families being monoterpenoids (48.3%), sesquiterpenoids (14.0%), esters (11.9%), and carbonyl compounds (8.8%). In silico molecular docking simulations revealed that cuminaldehyde, β-caryophyllene, γ-curcumene, germacrene D, and τ-cadinol exhibited the strongest inhibitory activities against the selected receptors. Among the extracts, Jamaica pepper showed the highest antioxidant and anti-inflammatory activities, while lemon verbena exhibited the lowest ones. These findings highlight the promising potential of the studied culinary herbs and spices in the modulation of inflammatory processes related to Alzheimer’s disease. However, further investigations, particularly clinical studies, are recommended to validate these results and explore their therapeutic applications. Full article
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29 pages, 405 KiB  
Review
Insects as Source of Nutraceuticals with Antioxidant, Antihypertensive, and Antidiabetic Properties: Focus on the Species Approved in Europe up to 2024
by Annalaura Brai, Claudia Pasqualini, Federica Poggialini, Chiara Vagaggini and Elena Dreassi
Foods 2025, 14(8), 1383; https://doi.org/10.3390/foods14081383 - 17 Apr 2025
Viewed by 1139
Abstract
Insects represent a traditional food in different parts of the world, where eating insects is not only related to nutrition, but also results from a variety of sociocultural customs. Insects’ nutritional profiles typically vary by species. Nevertheless, in terms of nutrition, edible insects [...] Read more.
Insects represent a traditional food in different parts of the world, where eating insects is not only related to nutrition, but also results from a variety of sociocultural customs. Insects’ nutritional profiles typically vary by species. Nevertheless, in terms of nutrition, edible insects can be a rich source of protein, dietary fiber, healthy fatty acids, and micronutrients, including minerals and vitamins. Insects have a low carbon footprint and require fewer resources in terms of land, water, and food with respect to animal livestock. Interestingly, insects are a source of bioactive compounds with different pharmacological activities, including antioxidant, antimicrobial, antidiabetic, antiobesity, antihypertensive, and antilipidemic. Among the bioactive compounds, polyphenols, chitosan, and protein hydrolysates are the most important ones, with direct activity on ROS quenching and enzymatic inhibition. Glucosidase, DPP-IV, ACE, and lipases are directly inhibited by insects’ bioactive peptides. Lipids and tocopherols reduce inflammation and lipid peroxidation by acting on LOX and COX-2 enzymes and on ROS quenching. The insects’ nutrient composition, coupled with their easy and economical breeding, is the cause of the growing interest in edible insects. During the last 20 years, the study and development of novel insect-based products increased, with relevant effects on the market. This review focuses on the edible insects currently approved in Europe, namely, Acheta domesticus, Alphitobus diaperinus, Locusta migratoria, and Tenebrio molitor. The nutrient profile and the functional compounds are examined, with an eye on market trends and on the patent applications filed in the last decades. Full article
(This article belongs to the Section Food Security and Sustainability)
22 pages, 1497 KiB  
Article
Investigations of In Vitro Anti-Acetylcholinesterase, Anti-Diabetic, Anti-Inflammatory, and Anti-Cancer Efficacy of Garden Cress (Lepidium sativum Linn.) Seed Extracts, as Well as In Vivo Biochemical and Hematological Assays
by Ahmed M. Naglah, Abdulrahman A. Almehizia, Mohamed A. Al-Omar, Asma S. Al-Wasidi, Mayada H. Mohamed, Sanad M. Alsobeai, Ashraf S. Hassan and Wael M. Aboulthana
Pharmaceutics 2025, 17(4), 446; https://doi.org/10.3390/pharmaceutics17040446 - 31 Mar 2025
Cited by 1 | Viewed by 806
Abstract
Background/Objectives: The current research was designed to quantify the active phyto-constituents and investigate the in vitro biological efficiency of different garden cress (Lepidium sativum Linn.) seed extracts against chronic diseases as well as the in vivo toxicities that may be induced in [...] Read more.
Background/Objectives: The current research was designed to quantify the active phyto-constituents and investigate the in vitro biological efficiency of different garden cress (Lepidium sativum Linn.) seed extracts against chronic diseases as well as the in vivo toxicities that may be induced in mice upon the administration of each extract at both studied therapeutic doses. Methods: The in vitro biological efficiency of different L. sativum extracts, such as methanolic, aqueous, acetone, and ethyl acetate extracts, was assessed. The inhibition percentage (%) and the median inhibitory concentration (IC50) values of different L. sativum extracts were estimated against acetylcholinesterase enzyme, diabetes mellitus (α-amylase and α-glucosidase enzymes), and inflammation (cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) enzymes). Additionally, the median inhibitory concentration (IC50) values of different L. sativum extracts against HepG-2, Caco-2, and A549 cells were assessed using 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Moreover, the toxicities that might be induced in mice at hematological (using an automatic blood analyzer) and biochemical levels were evaluated. Results: It was found that the methanolic L. sativum extract possessed the highest in vitro biological activities compared to the other studied extracts. The inhibition percentage values of the methanolic extract were 51.34, 54.35, 44.10, 43.48, and 40.78% against acetylcholinesterase, α-amylase, α-glucosidase, protein denaturation, and proteinase enzymes, respectively. The methanolic extract also exhibited an inhibitory effect against the COX-1 (55.05%), COX-2 (57.30%), and 5-LOX (50.15%) enzymes. Additionally, the methanolic extract possesses the highest cytotoxic activity against HepG-2, Caco-2, and A549 cells, with IC50 values of 52.27, 40.73, and 37.95 μg/mL, respectively. The median lethal doses (LD50) showed that the methanolic extract was safer when administered orally, followed by aqueous and acetone, then ethyl acetate extract. It was found that methanolic, aqueous, and acetone extracts showed no alterations when administered orally at two studied doses (1/10 and 1/20 of LD50) compared to the control. Conclusions: This study concluded that the methanolic extract possessed the highest in vitro biological activities and was safer than the other studied extracts, followed by aqueous, acetone, and then ethyl acetate extract. In the future, the in vivo biological efficacy of the methanolic L. sativum extract will be evaluated, as well as an elucidation of its mechanism against chronic diseases. Full article
(This article belongs to the Section Drug Targeting and Design)
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19 pages, 6713 KiB  
Article
In Vitro Enzymatic and Computational Assessments of Pyrazole–Isatin and Pyrazole–Indole Conjugates as Anti-Diabetic, Anti-Arthritic, and Anti-Inflammatory Agents
by Ahmed M. Naglah, Abdulrahman A. Almehizia, Mohammed Ghazwani, Asma S. Al-Wasidi, Abdelrahman A. Naglah, Wael M. Aboulthana and Ashraf S. Hassan
Pharmaceutics 2025, 17(3), 293; https://doi.org/10.3390/pharmaceutics17030293 - 23 Feb 2025
Cited by 2 | Viewed by 1175
Abstract
Background/Objectives: Recently, the prevalence of diseases such as diabetes, arthritis, and inflammatory diseases, along with their complications, has become a significant health problem. This is in addition to the various biomedical applications of pyrazole, isatin, and indole derivatives. Accordingly, cooperation will continue [...] Read more.
Background/Objectives: Recently, the prevalence of diseases such as diabetes, arthritis, and inflammatory diseases, along with their complications, has become a significant health problem. This is in addition to the various biomedical applications of pyrazole, isatin, and indole derivatives. Accordingly, cooperation will continue between chemistry scientists, pharmaceutical scientists, and human doctors to produce hybrid compounds from pyrazole with isatin or indole possessing biological activities as anti-diabetic, anti-arthritic, and anti-inflammatory agents. Methods: The two series of pyrazole–isatin conjugates 12ah and pyrazole–indole conjugates 14ad were prepared from our previous works via the direct reaction of 5-amino-pyrazoles 10ad with N-alkyl isatin 11a,b, and 1H-indole-3-carbaldehyde (13), respectively, using the previously reported procedure. The potential biological activities of 12ah and 14ad as anti-diabetic, anti-arthritic, and anti-inflammatory agents were assessed through estimated inhibition percentage (%) and the median inhibitory concentrations (IC50) using methods described in the literature. Further, the computational assessments of 12ah and 14ad such as toxic doses (the median lethal dose, LD50), toxicity classes, drug-likeness model scores (DLMS), molecular lipophilicity potential (MLP) maps, polar surface area (PSA) maps, and topological polar surface area (TPSA) values were predicted using available free websites. Results: The in vitro enzymatic assessment results showed that pyrazole–indole conjugate 14b possesses powerful activities against (i) α-amylase (% = 65.74 ± 0.23, IC50 = 4.21 ± 0.03 µg/mL) and α-glucosidase (% = 55.49 ± 0.23, IC50 = 2.76 ± 0.01 µg/mL); (ii) the protein denaturation enzyme (% = 49.30 ± 0.17) and against the proteinase enzyme (% = 46.55 ± 0.17) with an IC50 value of 6.77 ± 0.01 µg/mL; (iii) the COX-1, COX-2, and 5-LOX enzymes with an IC50 of 5.44 ± 0.03, 5.37 ± 0.04, and 7.52 ± 0.04, respectively, which is almost close to the IC50 of the indomethacin and zileuton drugs. Also, the computational assessment results showed (i) the conjugate 14b possesses lipophilic surface properties thus can cross cell membranes, and is effective for treatment; (ii) all the conjugates possess a TPSA value of more than 140 Å2 thus possess good intestinal absorption. Conclusions: The two series of pyrazole–isatin conjugates 12ah and pyrazole–indole conjugates 14ad were synthesized from our previous works. The results of these in vitro enzymatic and computational assessments concluded that the pyrazole–indole conjugate 14b possesses powerful activities against various studied enzymes and possesses good computational results. In the future, our research team will present in vitro, in vivo biological, and computational assessments to hopefully obtain effectual agents such as anti-diabetic, anti-arthritic, and anti-inflammatory. Full article
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20 pages, 1717 KiB  
Article
Antitumor Activity of Warbugia ugandensis: Methanolic Extracts and Gene Regulation in Colorectal Cancer
by John M. Macharia, John K. Maina, Afshin Zand, Betsy Rono Cheriro, Tímea Varjas, Dávid Sipos, Zsolt Káposztás, Ferenc Budán, Orsolya Liza Kövesdi and Bence L. Raposa
Nutrients 2025, 17(3), 471; https://doi.org/10.3390/nu17030471 - 28 Jan 2025
Cited by 1 | Viewed by 1149
Abstract
A promising approach to accelerating the development of innovative anti-cancer therapies involves the evaluation of natural plant compounds. In this study, we focused on examining the effects of Warbugia ugandensis (W. ugandensis) methanolic root and stem infusions on the activity of [...] Read more.
A promising approach to accelerating the development of innovative anti-cancer therapies involves the evaluation of natural plant compounds. In this study, we focused on examining the effects of Warbugia ugandensis (W. ugandensis) methanolic root and stem infusions on the activity of five target genes—COX-2, CASPS-9, Bcl-xL, Bcl2, and 5-LOX—using colorectal cancer (CRC) cell lines (Caco-2). The plant extracts were prepared for testing by dissolving them in dimethyl sulfoxide (DMSO) after undergoing a step-by-step extraction process. Caco-2 cells were then treated with different concentrations of the extracts, and RNA was extracted and purified for analysis. Our results demonstrated a dose-dependent relationship between the phytoconstituents of W. ugandensis and the overexpression of CASP9, along with the downregulation of COX-2, 5-LOX, Bcl-xL, and Bcl2 genes. This suggests that W. ugandensis acts as a potent natural inhibitor of CRC progression. Given the potential clinical benefits, we propose the use of W. ugandensis methanolic root and stem extracts as promising organic inhibitors for CRC tumorigenesis, with more in vitro studies warranted to validate and expand on our findings. Additionally, we recommend further studies to identify and characterize the specific metabolites in W. ugandensis that contribute to the modulation of pathways responsible for inhibiting CRC growth. Full article
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22 pages, 3576 KiB  
Review
Lipoxin A4 (LXA4) as a Potential Drug for Diabetic Retinopathy
by Undurti N. Das
Medicina 2025, 61(2), 177; https://doi.org/10.3390/medicina61020177 - 21 Jan 2025
Cited by 1 | Viewed by 1852
Abstract
The purpose of this review is to propose that lipoxin A4 (LXA4), derived from arachidonic acid (AA), a potent anti-inflammatory, cytoprotective, and wound healing agent, may be useful to prevent and manage diabetic retinopathy (DR). LXA4 suppresses inappropriate angiogenesis and the production of [...] Read more.
The purpose of this review is to propose that lipoxin A4 (LXA4), derived from arachidonic acid (AA), a potent anti-inflammatory, cytoprotective, and wound healing agent, may be useful to prevent and manage diabetic retinopathy (DR). LXA4 suppresses inappropriate angiogenesis and the production of pro-inflammatory prostaglandin E2 (PGE2), leukotrienes (LTs), 12-HETE (12-hydroxyeicosatetraenoic acid), derived from AA by the action of 12-lioxygenase (12-LOX)) interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), as well as the expression of NF-κB, inducible NO (nitric oxide) synthase (iNOS), cyclooxygenase-2 (COX-2), intracellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF)—factors that play a role in DR. Thus, the intravitreal injection of LXA4 may form a new approach to the treatment of DR and other similar conditions such as AMD (age-associated macular degeneration) and SARS-CoV-2-associated hyperinflammatory immune response in the retina. The data for this review are derived from our previous work conducted in individuals with DR and from various publications on LXA4, inflammation, and DR. Full article
(This article belongs to the Section Ophthalmology)
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15 pages, 1157 KiB  
Review
Prostaglandins: Biological Action, Therapeutic Aspects, and Pathophysiology of Autism Spectrum Disorders
by Kunio Yui, George Imataka and Mariko Ichihashi
Curr. Issues Mol. Biol. 2025, 47(2), 71; https://doi.org/10.3390/cimb47020071 - 21 Jan 2025
Cited by 4 | Viewed by 1856
Abstract
Esterified ARA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2), which is further metabolized by COXs and lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes. PGs produce detrimental effects due to their proinflammatory properties. [...] Read more.
Esterified ARA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2), which is further metabolized by COXs and lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes. PGs produce detrimental effects due to their proinflammatory properties. The generation of prostaglandin (PG)G2 and PGH2 is triggered by cyclooxygenase (COX) isozymes such as COX-1 and COX-2. Prostaglandin E2 (PGE2) is significantly elevated in ASD. Considerable data indicate that COX enzymes and their metabolites of ARA play important roles in the initiation and development of human neurodevelopmental diseases. The involvement of disrupted COX2/PGE2 signaling in ASD pathology in changing neuronal cell behavior and the expression of ASD-related genes and proteins is due to disrupted COX2/PGE2 signaling. Prostacyclin (PGI2) is synthesized from arachidonic acid by metabolic-pathway-dependent cyclooxygenase (COX) and synthesized in a primary step of ARA transformation (PGG2, PGH2), by degradation of the abovementioned prostaglandins. Full article
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22 pages, 2932 KiB  
Article
Multipotent Effect of Clozapine on Lipopolysaccharide-Induced Acetylcholinesterase, Cyclooxygenase-2,5-Lipoxygenase, and Caspase-3: In Vivo and Molecular Modeling Studies
by Minhajul Arfeen, Devendra Kumar Dhaked and Vasudevan Mani
Molecules 2025, 30(2), 266; https://doi.org/10.3390/molecules30020266 - 11 Jan 2025
Cited by 1 | Viewed by 1273
Abstract
Dual inhibition of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) is a recognized strategy for enhanced anti-inflammatory effects in small molecules, offering potential therapeutic benefits for individuals at risk of dementia, particularly those with neurodegenerative diseases, common cancers, and diabetes type. Alzheimer’s disease (AD) is [...] Read more.
Dual inhibition of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) is a recognized strategy for enhanced anti-inflammatory effects in small molecules, offering potential therapeutic benefits for individuals at risk of dementia, particularly those with neurodegenerative diseases, common cancers, and diabetes type. Alzheimer’s disease (AD) is the most common cause of dementia, and the inhibition of acetylcholinesterase (AChE) is a key approach in treating AD. Meanwhile, Caspase-3 catalyzes early events in apoptosis, contributing to neurodegeneration and subsequently AD. Structure-based virtual screening of US-FDA-approved molecules from the ZINC15 database identified clozapine (CLOZ) as the dual inhibitor of COX-2 and AChE, with significant binding affinity. Further molecular docking of CLOZ in the active site of LOX and Caspase-3 also showed significant binding potential. Further, the results from molecular docking were validated using molecular dynamics simulation (MDS) studies, confirming the results from molecular docking. The results from MDS showed good binding potential and interactions with key residues. The CLOZ was further assessed using lipopolysaccharide (LPS)-challenged rats treated for thirty days at doses of 5 and 10 mg/kg, p.o. The results demonstrated modulation of COX-2, 5-LOX, AChE, Caspase-3, and MDA in LPS-induced brains. Additionally, the expression level of IL-10 was also measured. Our results showed a significant decrease in the levels of COX-2, 5-LOX, AChE, Caspase-3, and MDA. Our results also showed a significant decrement in the pro-inflammatory markers NF-κB, TNF-α, and IL-6 and an improvement in the levels of anti-inflammatory markers IL-10 and TGF-β1. Overall, the findings indicate that CLOZ has potential for neuroprotective effects against LPS-treated rats and can be explored. Full article
(This article belongs to the Special Issue Advances in Molecular Modeling in Chemistry, 2nd Edition)
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23 pages, 4831 KiB  
Article
Effects of the Maximum Recommended Levels of Fumonisins in the EU on Oxylipin Profiles in the Liver and Brain of Chickens
by Philippe Guerre, Elodie Lassallette, Amélie Guerre and Didier Tardieu
Antioxidants 2025, 14(1), 19; https://doi.org/10.3390/antiox14010019 - 27 Dec 2024
Viewed by 956
Abstract
This study aimed to assess the effects of a diet containing 20.8 mg FB1 + FB2/kg over four and nine days on oxylipin (OL) profiles in the liver and brain of chickens. A total of 96 OLs, derived from seven polyunsaturated fatty acids [...] Read more.
This study aimed to assess the effects of a diet containing 20.8 mg FB1 + FB2/kg over four and nine days on oxylipin (OL) profiles in the liver and brain of chickens. A total of 96 OLs, derived from seven polyunsaturated fatty acids (PUFAs) via the cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 (P450), and non-enzymatic pathways, were measured using HPLC-MS/MS. In the liver, a significant increase in epoxide P450-derived OLs was detected by day 4, with smaller but notable increases in COX- and LOX-derived OLs by day 9. These alterations were independent of whether the parent PUFA was ω6 or ω3. However, OLs derived from 18-carbon (C18) PUFAs, such as linoleic acid and alpha-linolenic acid, showed greater increases compared to those derived from C20 or C22 PUFAs. The diol/epoxide ratios in the liver decreased at four and nine days, suggesting that fumonisins did not induce an inflammatory response. In the brain, at four days, the most discriminative OLs were derived from ω3-PUFAs, including docosahexaenoic acid, docosapentaenoic acid, and alpha-linolenic acid, via the LOX pathway. By nine days, several OLs derived from arachidonic acid, spanning all enzymatic pathways, became discriminative. In general, the diol/epoxide ratios in the brain were decreased at 4 days and then returned to the initial levels. Taken together, these results show strong effects of fumonisins on OLs in the liver and brain that are both specific and distinct. Full article
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18 pages, 3444 KiB  
Review
Search for New Compounds with Anti-Inflammatory Activity Among 1,2,4-Triazole Derivatives
by Teresa Glomb, Julia Minta, Michalina Nowosadko, Julia Radzikowska and Piotr Świątek
Molecules 2024, 29(24), 6036; https://doi.org/10.3390/molecules29246036 - 21 Dec 2024
Cited by 2 | Viewed by 2010
Abstract
Compounds containing the 1,2,4-triazole moiety in their structure exhibit broad biological activities. Many of these compounds demonstrate anti-inflammatory activity in vitro through various mechanisms, such as inhibiting COX-1/COX-2 and LOX, modulating pro-inflammatory cytokine levels, or having effects on other specific enzymes. Some also [...] Read more.
Compounds containing the 1,2,4-triazole moiety in their structure exhibit broad biological activities. Many of these compounds demonstrate anti-inflammatory activity in vitro through various mechanisms, such as inhibiting COX-1/COX-2 and LOX, modulating pro-inflammatory cytokine levels, or having effects on other specific enzymes. Some also display activities in vivo. In many publications, the activities of new 1,2,4-triazole-based compounds exceed those of the reference drugs, suggesting their promising potential as new therapeutic agents. This review of active 1,2,4-triazole derivatives with anti-inflammatory activity is based on literature published from 2015–2024. Full article
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