Optimized Automated Cassette-Based Synthesis of [⁶⁸Ga]Ga-DOTATOC
Development of Orally Disintegrating Tablets of Standardized Rhodiola rosea Extract
Ivermectin as an Alternative Anticancer Agent: A Review of Its Chemical Properties and Therapeutic Potential
A Comprehensive Review of Azelaic Acid Pharmacological Properties, Clinical Applications, and Innovative Topical Formulations
Artificial Intelligence in Small-Molecule Drug Discovery: A Critical Review of Methods, Applications, and Real-World Outcomes

Journal Description

Pharmaceuticals

Pharmaceuticals is a peer-reviewed, open access journal of medicinal chemistry and related drug sciences, published monthly online by MDPI. The Academy of Pharmaceutical Sciences (APS) is affiliated with Pharmaceuticals and its members receive discounts on the article processing charges.

Open Access free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
Journal Rank: JCR - Q1 (Pharmacology and Pharmacy) / CiteScore - Q1 (Pharmaceutical Science)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 14 days after submission; acceptance to publication is undertaken in 2.9 days (median values for papers published in this journal in the first half of 2025).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Testimonials: See what our editors and authors say about Pharmaceuticals.
International Electronic Conference on Medicinal Chemistry (https://sciforum.net/series/ecmc/latest)
Companion journals for Pharmaceuticals include: Pharmacoepidemiology, Psychoactives and Drugs and Drug Candidates.
Journal Clusters-Pharmaceutical Science: Scientia Pharmaceutica, Marine Drugs, Pharmaceuticals, Pharmaceutics, Pharmacy, Future Pharmacology, Pharmacoepidemiology, Drugs and Drug Candidates and Journal of Pharmaceutical and BioTech Industry.

Impact Factor: 4.8 (2024); 5-Year Impact Factor: 4.9 (2024)

Imprint Information Journal Flyer Open Access ISSN: 1424-8247

Latest Articles

19 pages, 2138 KB

Open AccessArticle

The GLP-1 Analog Liraglutide Reduces Fever Through Sex-Dependent Neuroinflammatory Modulation

by Gabriela L. Soares de Sousa, Ester K. Martins da Cruz, Sara C. Rojas de Aguiar, Ana P. Lima do Nascimento, Bruna R. Bezerra Gomes, Anna B. Rodrigues Londe, Luana J. Faria Gonçalves, Carine Royer, Regina Azevedo Costa, Aleksander Roberto Zampronio, Paulo Eduardo Narcizo de Souza and Fabiane H. Veiga-Souza

Pharmaceuticals 2025, 18(11), 1738; https://doi.org/10.3390/ph18111738 (registering DOI) - 15 Nov 2025

Abstract

Background/Objectives: Thermoregulation is essential for survival, with the hypothalamic preoptic area integrating peripheral signals to maintain core body temperature. While fever enhances immune responses, excessive hyperthermia causes cellular damage. Previous work has shown that central glucagon-like peptide-1 (GLP-1) receptor antagonism intensifies lipopolysaccharide (LPS)-induced fever, suggesting a role for GLP-1 signaling in temperature regulation. However, the direct effects of GLP-1 receptor agonists on fever remained unexplored. This study investigated the effects of liraglutide (LIRA), a GLP-1 analog used to treat diabetes and obesity, on temperature regulation and fever in rats, with a focus on sex-dependent mechanisms. Methods: Male and female Wistar rats received lipopolysaccharide (LPS, i.p.) to induce fever, followed by LIRA treatment (0.3 mg/kg, i.p.) one hour later. Body temperature was monitored for up to six hours post-LPS injection. Results: LIRA reduced body temperature in both euthermic and febrile rats of both sexes. LPS increased PGE₂ concentration in both sexes, with males showing a twofold increase compared to females. LIRA treatment reduced PGE₂ levels in LPS-challenged males (62%, p < 0.01) but not in female rats. LPS elevated interleukin (IL)-6 levels in both sexes, while LIRA treatment decreased IL-6 only in females (45%, p < 0.05). In males, LPS reduced hypothalamic serotonin (5-HT) levels, and LIRA further decreased 5-HT in saline-treated animals. In females, LIRA increased 5-HT levels (84%, p < 0.01) in LPS-challenged animals. Additionally, LIRA exhibited sex-specific effects on hypothalamic JNK phosphorylation, increasing activation in LPS-treated males and reducing it in LPS-treated females. Conclusions: LIRA demonstrates antipyretic properties through distinct, sex-specific mechanisms. In males, temperature reduction correlates with decreased hypothalamic PGE₂, whereas in females, antipyretic effects are associated with reduced IL-6, decreased JNK phosphorylation, and increased 5-HT. These findings reveal sexually dimorphic GLP-1R-mediated thermoregulatory pathways during inflammation. However, the causal relationships between these molecular changes and temperature regulation require further investigation, particularly regarding whether observed biochemical alterations represent primary mechanisms or secondary consequences of temperature modulation. Future studies should investigate the functional significance of the apparent contradiction in serotonergic responses between sexes. Full article

(This article belongs to the Section Pharmacology)

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21 pages, 9128 KB

Open AccessArticle

Discovery and Mechanistic Elucidation of Glycyrrhizic Acid Composite Gel in Promoting Wound Healing: A Modernized Study Based on Shengji Yuhong Ointment

by Hai-Xin Liu, Min-Yu Wang, Ying-Wei Li, Bin Xu, Zi-Xuan Wang, Xiang-Long Meng, Hui-Fang Li and Shi-Yuan Wen

Pharmaceuticals 2025, 18(11), 1737; https://doi.org/10.3390/ph18111737 - 14 Nov 2025

Abstract

Objectives: Shengji Yuhong Ointment (SJYHO) is a classic Traditional Chinese Medicine prescription used for refractory wounds, yet its systemic pharmacological mechanisms remain unclear. This study aimed to identify its key active compounds and develop a simplified, effective topical formulation. Methods: We employed an integrated approach, combining network pharmacology and machine learning to screen the key constituents and core targets of SJYHO. The lead compound, glycyrrhizic acid, was formulated into a hydrogel (GA-Gel). Its therapeutic efficacy was evaluated in a full-thickness excisional wound model in Sprague-Dawley rats over 21 days, assessing healing kinetics, histology, and pain behavior. The interaction between glycyrrhizic acid and the identified target PPIA, along with its immunomodulatory effects, was validated through molecular docking, molecular dynamics simulation, and RT-qPCR. Results: Our integrated analysis identified PPIA as the core target and glycyrrhizic acid as a key bioactive component of SJYHO. Animal experiments demonstrated that GA-Gel significantly accelerated wound closure, which was driven by its multi-faceted actions: reducing inflammation, promoting collagen deposition, alleviating pain, and modulating late-stage angiogenesis. Mechanistically, we confirmed that glycyrrhizic acid stably binds to PPIA. Furthermore, GA-Gel treatment mediated wound immune infiltration by specifically regulating CD8⁺ T cells, neutrophils, and memory B cells, an effect that was dependent on PPIA targeting. Conclusions: This study demonstrates that glycyrrhizic acid, formulated as GA-Gel, recapitulates the wound-healing benefits of SJYHO by specifically targeting PPIA and modulating the immune microenvironment. Our findings not only elucidate a key mechanistic pathway but also present GA-Gel as a rationally designed, clinically translatable therapy for acute and chronic wounds. Full article

(This article belongs to the Section Pharmaceutical Technology)

18 pages, 10717 KB

Open AccessArticle

Evodiamine Inhibits Colorectal Cancer by Downregulating ASS1 via Wnt/β-Catenin/c-MYC Pathway to Block Arginine Synthesis

by Huimin Wang, Hao Deng, Jiaming He, Jing Ma, Yunying Li, Haoyue Lv, Jianhua Ran, Dilong Chen and Jing Li

Pharmaceuticals 2025, 18(11), 1736; https://doi.org/10.3390/ph18111736 - 14 Nov 2025

Abstract

Background: Argininosuccinate synthase 1 (ASS1), a key enzyme in arginine biosynthesis, is highly expressed in colorectal cancer (CRC) and promotes cancer progression, making it a potential therapeutic target. Evodiamine (EVO), a natural alkaloid from Evodia rutaecarpa acts as a novel Wnt signaling pathway inhibitor with strong anticancer activity against various cancers. However, its exact therapeutic mechanism in CRC remains unclear. Methods: To address this gap, experiments included enzyme-linked immunosorbent assay (ELISA) to test EVO’s effect on CRC arginine production; CCK-8, EdU, colony formation, and wound-healing assays to assess CRC cell proliferation and migration; RT-qPCR, Western blot, immunofluorescence (IF), and ShASS1 for mechanism exploration and target validation; and a syngeneic tumor allograft model to study EVO’s metabolic regulation and anticancer efficacy in CRC. Results: In vitro, EVO significantly inhibited arginine synthesis metabolism and reduced CRC cell proliferation/migration. In vivo, it suppressed tumor tissue arginine metabolism, slowed allograft tumor growth, and decreased ASS1 expression. Mechanistically, EVO concentration-dependently reduced ASS1 via the Wnt/β-catenin/c-MYC pathway; ShASS1 replicated EVO’s anticancer effects, confirming ASS1’s mediating role. Conclusions: EVO downregulates ASS1 via the Wnt/β-catenin/c-MYC pathway disrupts CRC arginine synthesis metabolism and inhibits CRC cell proliferation/migration. These results support the interaction between metabolic regulation and signaling pathways, highlighting EVO as a promising CRC therapeutic candidate. Full article

(This article belongs to the Section Medicinal Chemistry)

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25 pages, 3515 KB

Open AccessSystematic Review

Is Crocin Effective in Modulating Blood Lipid Levels? An Updated Systematic Review and Meta-Analysis with Dose– and Time–Response Assessments

by Lucas Fornari Laurindo, Eduardo Federighi Baisi Chagas, Victória Dogani Rodrigues, Ricardo de Argollo Haber, Flávia Cristina Castilho Caracio, Maria Clara Capobianco Marangão, Manuela dos Santos Bueno, Eliana de Souza Bastos Mazuqueli Pereira, Cláudia Rucco Penteado Detregiachi, Vitor Engrácia Valenti, Mayara Longui Cabrini and Sandra Maria Barbalho

Pharmaceuticals 2025, 18(11), 1735; https://doi.org/10.3390/ph18111735 - 14 Nov 2025

Abstract

Background/Objectives: Dyslipidemia is a global health concern. It refers to increased blood levels of LDL-C, triglycerides, and total cholesterol, accompanied by decreased blood HDL-C levels. Many pharmacological and non-pharmacological approaches have been designed to improve dyslipidemia management. However, nutritional therapies have gained more attention due to their antioxidant and anti-inflammatory properties. In this scenario, the carotenoid crocin stands out as a prominent anti-dyslipidemia phytochemical. Its unique structure permits lipid-lowering effects via various mechanisms, including the enhancement of lipid breakdown, reduction in lipid formation, bolstering of antioxidant defenses to diminish lipid toxicity, and decreased absorption of dietary fats. However, no recent systematic review or meta-analysis has addressed its anti-dyslipidemia effects with statistical power. Therefore, we aim to fill this gap with our current meta-analysis, as well as dose and time–response assessments. Methods: PubMed, SpringerLink, ScienceDirect, Cochrane, and Google Scholar databases were searched, and PRISMA guidelines were followed. Ten studies comprising eleven results were included. Results: Crocin did not improve LDL-C (0.2120, 95% CI: −0.0799 to 0.5040), HDL-C (−0.1937, 95% CI: −0.4896 to 0.1022), triglyceride (−0.2063, 95% CI: −0.5764 to 0.1638), or total cholesterol (0.1528, 95% CI: −0.1074 to 0.4129). The dose–response or time–response was also not statistically significant. Conclusions: More clinical studies with robust designs must be conducted to thoroughly assess crocin’s effectiveness in modulating lipid levels with the utmost care. Full article

(This article belongs to the Section Natural Products)

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21 pages, 7354 KB

Open AccessArticle

Catharanthus roseus Phytochemicals as Multi-Target Modulators of Disability-Linked Neurodegeneration: Bio-Computational Insights

by Qazi Mohammad Sajid Jamal, Ali H. Alharbi, Varish Ahmad and Khurshid Ahmad

Pharmaceuticals 2025, 18(11), 1734; https://doi.org/10.3390/ph18111734 - 14 Nov 2025

Abstract

Background: Disability-linked neurodegeneration involves cholinergic dysfunction, amyloidogenesis, glutamatergic excitotoxicity, and dopaminergic imbalance, highlighting the need for multi-target modulation. Catharanthus roseus contains a diverse array of metabolites with potential polypharmacological properties. Methods: We curated 318 Catharanthus roseus metabolites and performed structure-based virtual screening against five CNS targets, namely BACE1, AChE, MAO-B, NMDAR, and D1, using target-specific positive controls. Cross-target intersection ranking nominated three hits. We assessed dynamic stability by 200 ns all-atom molecular dynamics simulations (MDS) and MM/PBSA; ADMET-AI profiled CNS-relevant properties. Results: The three metabolites (PubChem CIDs 485711, 56964592, and 162963996) repeatedly ranked among top binders across targets. All five protein–ligand complexes reached stable MD plateaus (RMSD < ~0.30 nm) with sustained key interactions; BACE1 and AChE showed the highest contact persistence and most favorable ΔG_total/ligand-efficiency. Conclusions: Convergent docking, MDS, and MM/PBSA support these metabolites as tractable multi-target leads, with BACE1/AChE prioritized for enzyme-level validation and the remaining targets for follow-up studies. Full article

(This article belongs to the Special Issue Natural Product-Derived Treatments of Neurological and Neuropsychiatric Disorders)

20 pages, 1080 KB

Open AccessArticle

Quinazoline-Derivatives of Imino-1,2,3-Dithiazoles Promote Biofilm Dispersion of Pseudomonas aeruginosa

by Mathieu Gonzalez, Anne-Sophie Tareau, Daphnée de Crozals, Corentin Layec, Nathan Broudic, Magalie Barreau, Adrien Forge, Olivier Lesouhaitier, Corinne Fruit, Sylvie Chevalier, Thierry Besson and Ali Tahrioui

Pharmaceuticals 2025, 18(11), 1733; https://doi.org/10.3390/ph18111733 - 14 Nov 2025

Abstract

Background/Objectives: Biofilm-associated infections pose a major clinical challenge since bacteria within biofilms exhibit highly antibiotic tolerance. Pseudomonas aeruginosa forms persistent biofilms that cause chronic infections in vulnerable patients, including those with cystic fibrosis, burns, or medical implants. Such biofilm-associated chronic infections require prolonged treatments that promote antimicrobial resistance. To address this, recent strategies focus on enhancing biofilm dispersion. Methods: Thirty-six N-arylimino-1,2,3-dithiazoles were screened for their biofilm dispersal activity using a crystal violet assay. Their cytotoxicity was assessed on A549 and HaCat eukaryotic cells. Moreover, their influence on bacterial growth and virulence was investigated. Lastly, fluorescence anisotropy was used to measure membrane fluidity to obtain the first insights on the mechanism of action of these chemicals. Results: Our results showed that quinazoline-derivatives of imino-1,2,3-dithiazoles display biofilm dispersion activity. These compounds do not increase virulence through pyocyanin production, do not modify the growth kinetics of P. aeruginosa, and do not show cytotoxicity towards eucaryotic cells. Conclusions: These findings highlight the potential use of N-arylimino-1,2,3-dithiazole-derived compounds as safe and effective dispersal agents of P. aeruginosa biofilms. Full article

(This article belongs to the Special Issue Challenges in Discovering Innovations Related to Biofilms: Virulence, Spread, Control Strategies and Treatment)

4 pages, 169 KB

Open AccessEditorial

Bioactive Compounds Derived from Plants and Their Medicinal Potential

by Sónia M. R. Oliveira, Ana Paula Girol, Veeranoot Nissapatorn and Maria de Lourdes Pereira

Pharmaceuticals 2025, 18(11), 1732; https://doi.org/10.3390/ph18111732 - 14 Nov 2025

Abstract

The inaugural edition of the Special Issue “Bioactive compounds derived from plants and their medicinal potential” offers a comprehensive exploration of the therapeutic promise inherent in plant-based compounds [...] Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)

21 pages, 1087 KB

Open AccessReview

Targeting Amyloid-β Proteins as Potential Alzheimer’s Disease Therapeutics: Anti-Amyloid Drug Discovery, Emerging Therapeutics, Clinical Trials and Implications for Public Health

by Asaad Abdulrahman Abduljawad, Khadijah B. Alkinani, Aysha Zaakan, Abeer S. AlGhamdi, Alashary Adam Eisa Hamdoon, Batool H. Alshanbari, Ahmed Abdullah Alshehri, Badria Bakheet Alluhaybi, Shahad Othman Ibrahim Alqashi and Ryan Abdulrahman Abduljawad

Pharmaceuticals 2025, 18(11), 1731; https://doi.org/10.3390/ph18111731 - 14 Nov 2025

Abstract

Alzheimer’s disease (AD), a neurodegenerative disorder of the aging brain, is associated with behavioral and cognitive issues and poses a huge burden on the global health care system. One of the key features of AD is the deposition of abnormal proteins called amyloid-beta (Aβ) in the brain, causing inflammatory changes, oxidative stress, and neuronal loss. Recent advancements in the anti-Aβ therapies have considerably improved the management of AD, resulting in better clinical outcomes for patients and caregivers. This review offers an inclusive update on current drug discovery efforts, innovative approaches, and ongoing clinical trials targeting Aβ, a key player in AD pathogenesis. We have evaluated the most recent developments in monoclonal antibodies, including aducanumab (discontinued November 2024), lecanemab, and donanemab, emerging therapeutic options, as well as emerging strategies such as tau-targeting therapies, gene therapy, and small molecule inhibitors. Moreover, we highlighted the challenges and opportunities in AD research, including the need for early diagnosis, personalized medicine, and combination therapies. Our review will offer a concise and informative overview of the current landscape and future directions in anti-Aβ therapeutics for AD, shedding light on potential treatments and prospects for improving patient outcomes. Full article

(This article belongs to the Special Issue Pharmacotherapy for Alzheimer’s Disease)

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13 pages, 2023 KB

Open AccessArticle

by Roberto De Masi, Stefania Orlando, Assunta Greco and Maria Carmela Costa

Pharmaceuticals 2025, 18(11), 1730; https://doi.org/10.3390/ph18111730 - 14 Nov 2025

Abstract

Background: The role of age and time-dependent variables in determining the response to disease-modifying therapies (DMTs) has aroused growing interest in the Multiple Sclerosis (MS) field. Although it is a very hot topic, related literature on the subject is considerably lacking. Objectives: The aim of this study is to deepen the understanding of how time-dependent variables influence disability accumulation and drug response in an MS population, assuming DMF as the first-line treatment, and to expand our knowledge of the risk–benefit evaluation of DMF. Methods: We investigated, in a real-world setting, the efficacy of Dimethyl Fumarate (DMF) in naive versus switcher MS patients, correlated with age, in preventing disability accumulation. Starting from an initial population of 234 DMF-treated patients, we selected 169 of them based on their similar time in therapy (TinT) with DMF of 5.9 ± 2.3 year and sex ratio. Of these, 74 were naive and 95 were lateral switchers at the start of treatment. The mean Expanded Disability Status Scale (EDSS), Disease Duration (DD), age and age at onset were compared between groups. Results: The switcher group showed higher EDSS and age compared to the naive group (2.7 vs. 1.8, p < 0.001; 40.2 vs. 35.5, p = 0.005, respectively). Age correlated with DD, EDSS and age at onset in both naive (r = 0.39, p = 0.007; r = 0.53, p = 0.000; r = 0.63, p = 0.000, respectively) and switcher (r = 0.46, p = 0.002; r = 0.49, p = 0.000; r = 0.61, p = 0.000, respectively) groups. Kaplan–Meier curves, adjusted for age, also indicated that the naive group retained an EDSS score status of 0.5–3.5 more frequently (p < 0.001) and reached elevated disability less frequently (p = 0.002) than switchers. The mean EDSS percentage ratio between paired naive and switcher patients, representing the differential neurological impairment (DNI), was 69%, inversely correlating with age in both naive (r = −0.52, p < 0.001) and switcher patients (r = −0.47, p < 0.001). Finally, logistic regression analysis indicated age as an independent and predictive variable with respect to EDSS. Conclusions: We conclude that age is the main contributor to disability progression and the primary predictive factor for treatment effectiveness for DMF in both naive and switcher MS patients. Full article

(This article belongs to the Section Pharmacology)

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13 pages, 508 KB

Open AccessArticle

PDE-4 Inhibition in Sarcoidosis Patients: A Retrospective Single-Center Analysis of 51 Patients

by Martin Elias Feineis, Charlott Terschluse, Louis Jouanjan, Daniel Soriano, Prerana Agarwal, Jonas Schupp, Joachim Müller-Quernheim, Daiana Stolz and Björn Christian Frye

Pharmaceuticals 2025, 18(11), 1729; https://doi.org/10.3390/ph18111729 - 14 Nov 2025

Abstract

Background: Several sarcoidosis patients require treatment with corticosteroids to prevent organ damage and control symptoms. However, corticosteroids are associated with numerous side effects and can be detrimental to patients if used long-term. Roflumilast is approved for the treatment of chronic obstructive pulmonary disease (COPD) and has been studied with positive results in patients with fibrosing sarcoidosis. Due to its mode of action, it targets proinflammatory and profibrotic pathways involved in sarcoidosis and could be a suitable medication for sarcoidosis. Methods: We retrospectively analyzed a cohort of 51 sarcoidosis patients treated with Roflumilast off-label between 2010 and 2020 at the Department of Pneumology, University Hospital Freiburg. Medical records, lung function, and laboratory results were reviewed. Results: Of the 51 patients, 33 patients received Roflumilast for at least 6 months, whereas 18 discontinued treatment, mostly due to mild to moderate gastrointestinal side effects (n = 7). No severe adverse events were observed. Patients on Roflumilast were less likely to have a decrease in FEV1 of more than 10% of their mean FEV1 compared to patients without Roflumilast (OR = 0.2; 95% CI 0.08–0.5). Escalation of therapy was documented in 49/97 (51%) of ambulatory visits for patients taking Roflumilast compared to 100/144 (69%) for patients without Roflumilast (OR = 0.45; 95% CI 0.26–0.76). Conclusions: Sarcoidosis patients receiving Roflumilast had less lung function loss and were less likely to require therapy escalation. Roflumilast could be a therapeutic option in sarcoidosis. Full article

(This article belongs to the Special Issue Pharmacotherapeutics of Sarcoidosis)

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45 pages, 10162 KB

Open AccessReview

Review of the Most Important Research Trends in Potential Chemotherapeutics Based on Coordination Compounds of Ruthenium, Rhodium and Iridium

by Agnieszka Gilewska, Barbara Barszcz and Joanna Masternak

Pharmaceuticals 2025, 18(11), 1728; https://doi.org/10.3390/ph18111728 - 13 Nov 2025

Abstract

This review paper presents a comprehensive literature analysis that elucidates the global engagement of research teams in addressing the important problem of finding effective oncology drugs based on the following platinum group metal ions: ruthenium, rhodium and iridium. The necessity to search for new drugs can be attributed, in part, to the predominance of platinum-based chemotherapeutics in clinical practice. However, these drugs face limitations in their clinical application due to their inherent toxicity and the development of resistance by cancer cells. A distinctive attribute of these metal compounds is the formation of diamagnetic stable complexes on +II (Ru) and +III (Rh, Ir) oxidation degrees with a d⁶ electron configuration, a coordination number of six and an octahedral or pseudo-octahedral structure. In this paper we have systematised the findings presented in the literature by classifying the most significant categories of ruthenium, rhodium and iridium compounds, namely piano-stool-type arenes, polypyridine and cyclometalated complexes, dimers and multinuclear complexes. Additionally, the most crucial research challenges connected with metal complexes that have been addressed by scientists have been presented: (i) the application of prodrugs in cancer therapy; (ii) the deployment of complexes as sensitizers in PDT and PACT; (iii) the exploration of complexes as inhibitors of enzymes and biocatalysts; and (iv) the investigation of multiple-target complexes. Furthermore, the objective was to emphasise the accomplishments in this domain in recent years by identifying compounds that have entered the clinical trial phase. Full article

(This article belongs to the Special Issue Metal Complexes in Medicinal Chemistry: From Coordination Chemistry to Pharmaceutical Applications)

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17 pages, 263 KB

Open AccessArticle

Vitamin D Supplementation and Its Interaction with Common Medications: Impact on Serum Levels and Quality of Life in Adults with Comorbidities

by Fernando Lopez-Carmona, Antonio Toro-Ruiz, Celia Piquer-Martinez, Manuel Gomez-Guzman, Francisco Javier Ferreira-Alfaya, Maria Isabel Valverde-Merino, Francisco Rivas-Garcia and Maria Jose Zarzuelo

Pharmaceuticals 2025, 18(11), 1727; https://doi.org/10.3390/ph18111727 - 13 Nov 2025

Abstract

Background/Objectives: Vitamin D deficiency is highly prevalent worldwide and is associated with multiple comorbidities and pharmacological treatments that may interfere with its metabolism. Evidence on the effect of supplementation across different drug user groups remains limited. Methods: A prospective study was conducted across community pharmacies over twelve months. Baseline socio-demographic, serum 25(OH)D concentration, quality of life (QoL), lifestyle habits, and medication use were collected. Participants received vitamin D supplementation for 12 months. Changes in vitamin D status and QoL were analyzed according to medication use. Logistic regression identified predictors of achieving adequate serum vitamin D levels (>30 ng/mL). Statistical significance was set at p < 0.05. Results: At baseline, 87.2% of 210 participants had insufficient or deficient vitamin D levels. After supplementation, mean serum vitamin D increased significantly from 21.3 ± 8.2 to 32.1 ± 12.6 ng/mL (p < 0.001), and QoL scores improved from 68.6 ± 18.7 to 77.8 ± 18.5 (p < 0.001). Dietary intake of vitamin D–rich foods and outdoor activity also increased. Supplementation improved vitamin D status among users of benzodiazepines, proton pump inhibitors, beta-blockers, statins, levothyroxine, metformin, and angiotensin-converting enzyme inhibitors, but not among corticosteroid, nonsteroidal anti-inflammatory drugs, or vitamin K antagonist. Multivariate analysis confirmed adherence as a strongest predictor of vitamin D adequacy (OR = 15.31, 95% CI = 2.90–80.75), while corticosteroid therapy, diabetes, and hypercholesterolemia were negatively associated. Conclusions: Vitamin D supplementation effectively corrected deficiency and improved QoL, but its efficacy varied according to comorbidities and medication use. Personalized supplementation strategies, emphasizing adherence and considering pharmacological profiles, may optimize outcomes. Further studies should explore mechanistic drug–nutrient interactions and long-term clinical implications. Full article

(This article belongs to the Section Pharmacology)

19 pages, 1231 KB

Open AccessReview

Potential Implications of Body Mass Composition Changes in Heart Failure Patients in the Era of SGLT2i, GLP-1 RA, and GIP/GLP-1 RA

by Katarzyna Gryglewska-Wawrzak, Agnieszka Kapłon-Cieślicka, Agnieszka Pawlak, Anna Tomaszuk-Kazberuk, Paweł Rubiś, Jacek Niedziela and Agata Bielecka-Dąbrowa

Pharmaceuticals 2025, 18(11), 1726; https://doi.org/10.3390/ph18111726 - 13 Nov 2025

Abstract

Obesity is a complex, multifactorial disease wherein the excessive accumulation of adipose tissue leads to adverse health outcomes, such as diabetes, cardiovascular disease and musculoskeletal disorders. Obesity also impacts both the risk and the clinical prognosis of heart failure (HF). The accumulation of adipose tissue results in metabolic dysregulation, including increased levels of pro-inflammatory cytokines and adipokines. These alterations are strongly associated with the development and progression of HF. Another significant comorbidity in patients with HF is sarcopenia, characterized by progressive loss of muscle mass and strength, affecting the quality of life. The study aims to critically synthesize the mechanisms by which modern pharmacological treatments—sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dual GIPR/GLP-1R agonists—modulate body mass composition, and to analyze the specific implications of these changes (e.g., visceral fat reduction versus lean mass loss) for heart failure (HF) prognosis and management. Full article

(This article belongs to the Special Issue Advancements in Cardiovascular and Antidiabetic Drug Therapy, 2nd Edition)

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26 pages, 5834 KB

Open AccessArticle

New Anti-Cancer Impact of Cerium Oxide, Lithium, and Sn-38 Synergy via DNA Methylation-Mediated Reduction of MMP-2 and Modulation of the PI3K/Akt/mTOR Pathway

by Sidika Genc, Hayrunnisa Nadaroglu, Ramazan Cinar, Esmanur Nigde, Kubra Karabulut and Ali Taghizadehghalehjoughi

Pharmaceuticals 2025, 18(11), 1725; https://doi.org/10.3390/ph18111725 - 13 Nov 2025

Abstract

Background/Objectives: Glioblastoma, the most common primary tumor of the central nervous system, is characterized by high malignancy and poor prognosis. One of the main challenges in neurological disorders is to develop an effective treatment modality that can cross the blood–brain barrier. Nanoparticles are revolutionary for neurodegenerative diseases due to their targeted delivery and ability to overcome biological barriers. Cerium oxide (Ce₂O₃) nanoparticles are suitable for use as drug delivery systems. Methods: In our study, we investigated the anticancer mechanism using SN-38, lithium, and Ce₂O₃, a powerful agent used in GBM treatment. We evaluated their anticancer activities separately and in combination with U373 cell lines. GBM cell line U373 cells were cultured. Then, all groups except the control group were treated with different doses of SN-38 and lithium combination therapy with SN-38, lithium, and Ce₂O₃ combination therapy. The results were evaluated using MTT and ELISA tests. Results: When the results were examined, anticancer activity was detected at PTEN, AKT, mTOR, and BAX/Bcl-2 levels in the SN-38 + NPs 25 µg/mL + Lithium 50 µg/mL and SN-38 + NPs 50 µg/mL + Lithium 50 µg/mL dose groups. In addition, findings that inflammation markers were correlated with the apoptosis mechanism were obtained. Conclusion: This study is the first to report that combining lithium with SN-38 and NPs increased oxidative stress more than lithium with SN-38, leading glioblastoma cells to apoptosis and its potential anticancer activity. These results provide a basis for further investigation of its clinical application in cancer treatment. Full article

(This article belongs to the Section Pharmacology)

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24 pages, 1326 KB

Open AccessArticle

Protective Effects of Bauhinia forficata on Bone Biomechanics in a Type 2 Diabetes Model

by Isadora Castaldi Sousa, Letícia Pitol-Palin, Fábio Roberto de Souza Batista, Odir Nunes de Oliveira Filho, Sabrina Cruz Tfaile Frasnelli, Victor Eduardo de Souza Batista, Dóris Hissako Matsushita and Roberta Okamoto

Pharmaceuticals 2025, 18(11), 1724; https://doi.org/10.3390/ph18111724 - 13 Nov 2025

Abstract

The use of herbal medicines has gained popularity, both in science and among the public, as a natural alternative for the treatment of numerous diseases, including type 2 diabetes. Objective: The objective of this study was to evaluate peri-implant and long bone biomechanics in type 2 diabetic animals, treated or not with Bauhinia forficata. Methods: Thirty-two rats were allocated into four groups: normoglycemic (NG), normoglycemic + Bauhinia forficata (NGBf), type 2 diabetes (T2D), and T2D + Bauhinia forficata (T2DBf). Diabetes was induced using a cafeteria diet and streptozotocin (35 mg/kg). Bauhinia forficata tea (50 g/L) was administered to the NGBf and T2DBf groups. After 14 days, titanium implants were installed in the tibial metaphysis of all animals. Biomechanical analysis (removal torque), computerized microtomography, three-point bending test, confocal microscopy, and real-time PCR were performed. The results were tabulated, and a statistical test was conducted with a significance level of 5%. Results: Bauhinia forficata significantly improved the weight and blood glucose levels of the animals. In terms of biomechanics and the microarchitecture of long bones, T2D did not impair bone metabolism, and the use of the therapy did not cause significant changes in the parameters evaluated. However, T2D promoted significant impairment in the structural, biomechanical, and molecular characteristics of the peri-implant repair process, and the use of Bauhinia forficata increased the parameters evaluated in T2DBf. Conclusions: Type 2 diabetes mellitus significantly compromises peri-implant bone repair, with no influence on the metabolism of long bones, and Bauhinia forficata acts positively on both the etiopathogenesis of the disease and the tissue response to bone repair. Full article

(This article belongs to the Special Issue Natural Products and Bioactive Compounds for the Prevention and Treatment of Non-Communicable Chronic Diseases)

39 pages, 2446 KB

Open AccessReview

Sirtuins as Therapeutic Targets for Treating Cancer, Metabolic Diseases, and Neurodegenerative Diseases

by Maxwell Akantibila and Valerie J. Carabetta

Pharmaceuticals 2025, 18(11), 1723; https://doi.org/10.3390/ph18111723 - 13 Nov 2025

Abstract

Sirtuins are NAD⁺-dependent enzymes that are conserved in all domains of life, including mammals, metazoans, plasmodia, yeast, bacteria, and archaea. In humans, there are seven isoforms (SIRT1 to 7), and they function in cellular homeostasis, aging, DNA repair, survival, metabolism, and stress responses. Recent advances highlight the diverse functions of sirtuins in the pathogenesis and progression of cancer, metabolic diseases, and neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). To date, there is evidence that all seven isoforms contribute to cancer development, while SIRT1-3 and 6 contribute to metabolic and neurodegenerative diseases. Modulators of sirtuin activity are being actively explored to understand their biological and molecular mechanisms and potential for the treatment of various diseases. In this review, we begin with a broad discussion of post-translational modifications, protein deacetylation, and the mechanism of action of sirtuins. Next, we discuss the role of sirtuins in cancer, including inhibitors and activators of sirtuin activity as cancer therapies. In addition, we discuss the relationship of sirtuins to metabolic diseases and as possible treatment targets. Finally, we discuss the role of sirtuins in AD, PD, and HD, and sirtuin modulators for treating neurodegenerative diseases. Full article

(This article belongs to the Special Issue Sirtuins as Novel Biological Targets for Pharmacological Intervention in Physiology and Pathology—2nd Edition)

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21 pages, 738 KB

Open AccessReview

Biological Activities of Novel Kombuchas Based on Alternative Ingredients to Replace Tea Leaves

by Noemi Hontana-Moreno and Diego Morales

Pharmaceuticals 2025, 18(11), 1722; https://doi.org/10.3390/ph18111722 - 13 Nov 2025

Abstract

Background/Objectives: Traditional kombucha is produced by fermenting a sweetened infusion of Camellia sinensis leaves with a symbiotic consortium of bacteria and yeasts (SCOBY). The growing interest in this beverage has driven the exploration of alternative substrates, including a wide range of plant-based raw materials, such as leaves, fruits, flowers, and seeds. Consequently, numerous products are being investigated for their differential properties, not only organoleptic but also nutritional and bioactive. This review aims to summarize recent advances in alternative kombucha research, focusing on the substrates used, their physicochemical and biochemical characteristics, and the biological activities studied. Methods: A comprehensive literature search was conducted to select articles related to alternative kombuchas. A critical analysis of their current state was carried out through the Strengths, Weaknesses, Opportunities, and Threats (SWOT) methodology. Results: The SWOT analysis led to the identification of strengths, including promising in vitro results and growing consumer interest; weaknesses, including a lack of animal studies, clinical trials, and approved health claims, and an excessive focus on antioxidant activity and phenolic compounds; opportunities, including substrate diversity, innovation, and consumer education; and threats, including elaboration risks, misinformation, competitors, and potential consumer rejection. Conclusions: Despite the promising results achieved to date, it is essential that the scientific community and the food industry continue efforts to generate robust evidence, particularly through clinical validation, in order to draw reliable conclusions regarding the benefits of alternative kombuchas for human health. Full article

(This article belongs to the Special Issue Plant-Derived Natural Compounds as Bioactive Molecules with Beneficial Effects on Human Health, 2nd Edition)

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23 pages, 2128 KB

Open AccessReview

Point of Care Testing, Rapid Next Generation Sequencing and Artificial Intelligence in Pediatric and Neonatal Healthcare: A Narrative Review

by Alessandra Cianflone, Luigi Coppola, Pasquale Primo, Giovanna Maisto, Fiorenza Mastrodonato, Maria Antonia Di Palma, Rosanna Parasole, Daniela Omodei and Peppino Mirabelli

Pharmaceuticals 2025, 18(11), 1721; https://doi.org/10.3390/ph18111721 - 13 Nov 2025

Abstract

Laboratory tests play a crucial role in the diagnostic process for both adults and children. Indeed, they are essential for evaluating health status and formulating effective treatment strategies in the presence of disease. However, in the case of pediatrics, distinct physiological and developmental features of children should be taken into account when compared to adults. Consequently, it is necessary to consider some factors, such as reference intervals that vary significantly at different stages of development due to sexual development, cerebral maturation, and biological and environmental influences; furthermore, it must be considered that extremely small volumes of biological samples are often necessary to obtain accurate laboratory results. Finally, timely test results are critical, especially for pediatric conditions that are treatable when diagnosed early. This review article provides a comprehensive overview of advanced diagnostic technologies, including rapid next-generation sequencing and complex point-of-care testing, within the context of pediatric laboratory medicine. Special attention is given to diagnostic tools that support neonatal and pediatric intensive care units, with a focus on how innovative technologies, particularly those utilizing artificial intelligence algorithms, can accelerate diagnostic workflows. Full article

(This article belongs to the Section Pharmaceutical Technology)

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27 pages, 3031 KB

Open AccessArticle

Therapeutic Evaluation of Alginate from Brown Seaweeds: A Comparative Study of Turbinaria ornata and Hormophysa cuneiformis

by Mostafa M. El-Sheekh, Eman Bases, Shimaa M. El Shafay, Rania A. El-Shenody, Mostafa E. Elshobary, Abdel Hady A. Abdel Wahab, Wesam E. Yousuf, Dorya I. Essa and Samar Sami Alkafaas

Pharmaceuticals 2025, 18(11), 1720; https://doi.org/10.3390/ph18111720 - 12 Nov 2025

Abstract

Background: Alginate is a naturally occurring anionic polysaccharide extracted from brown marine algae and widely explored for biomedical applications due to its biocompatibility and functional versatility. This study aims to extract and compare alginates from two Red Sea brown algae, Turbinaria ornata (TA) and Hormophysa cuneiformis (HA), and to evaluate how structural differences influence their therapeutic properties. Methods: Alginate was isolated by sequential acid–alkaline extraction and characterized using FTIR, XRD, TGA, elemental analysis, and HPLC. Biological activities were assessed through antioxidant, anti-inflammatory, antidiabetic, neuroprotective, and hepatoprotective assays, supported by molecular docking and gene ontology interaction analysis. Results: Distinct physicochemical variations were observed between HA and TA. TA exhibited stronger antioxidant (IC₅₀ = 25.89 µg/mL), anti-inflammatory (COX-1 IC₅₀ = 69.61 µg/mL), antidiabetic (α-amylase IC₅₀ = 45.14 µg/mL), and hepatoprotective activities (IC₅₀ = 118.21 µg/mL), whereas HA displayed superior neuroprotective potential through butyrylcholinesterase inhibition (IC₅₀ = 39.01 µg/mL). Molecular docking supported the in vitro findings by confirming interactions with key protein targets associated with oxidative stress and metabolic pathways. Conclusions: Structural variation between species-derived alginates directly impacts their biological activities. TA represents a promising candidate for metabolic and anti-inflammatory therapies, while HA may be more suitable for neuroprotective interventions. These results emphasize the importance of source-specific alginate selection for developing targeted pharmaceutical applications. Full article

(This article belongs to the Section Natural Products)

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12 pages, 2177 KB

Open AccessCase Report

Fecal Microbiota Transplantation in Refractory Immune-Mediated Colitis: Case Series and Review of the Literature

by Marin Golčić, Laura Radoš, Iva Skočilić, Ivona Badovinac, Goran Hauser, Irena Krznarić Zrnić, Marina Šantić, Dora Fučkar Čupić, Sara Francetić, Karla Lisica, Lea Juras, Marija Škrtić, Ana Bešvir Džubur, Robert Šeparović, Vedran Tomašić, Ana Tečić Vuger and Ivana Mikolašević

Pharmaceuticals 2025, 18(11), 1719; https://doi.org/10.3390/ph18111719 - 12 Nov 2025

Abstract

Background/Objectives: Immune checkpoint inhibitors (ICI) represent a significant breakthrough in cancer management, but they can cause adverse effects such as immune-mediated colitis (IMC). The standard first-line treatment is corticosteroids, and second-line treatment is infliximab or vedolizumab. However, a proportion of immune-mediated colitis (IMC) cases are refractory to immunosuppressive treatment, which has led to the exploration of novel approaches such as fecal microbiota transplantation. Methods: We present two patients who both developed grade III IMC following application of durvalumab and pembrolizumab, respectively. Both patients were refractory to corticosteroid therapy, while the first one also showed no improvement to infliximab. We performed two separate applications of FMT on both patients, from different donors, as a rescue treatment. Results: After unsuccessful immunosuppressive treatment and following rescue FMT, both patients demonstrated a rapid and sustained improvement in inflammatory markers, clinical symptoms, quality-of-life scores, and colonoscopy findings, without additional immunosuppressive treatment. Conclusions: FMT appears to be safe and a potentially effective treatment option for patients with refractory IMC both as second- and third-line therapy options. Continued efforts toward rigorous donor screening, use of standardized biobanks, and standardizing FMT protocols will further enhance safety and reproducibility. Full article

(This article belongs to the Special Issue The Regulatory Roles of the Gut Microbiota in Multisystem Diseases)

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