Pharmaceuticals

20 pages, 6350 KB

Open AccessArticle

Identification of Metabolites and Antioxidant Constituents from Pyrus ussuriensis

by Ducdat Le, Thientam Dinh, Soojung Yu, Yun-Jin Lim, Hae-In Lee, Jin Woo Park, Deuk-Sil Oh and Mina Lee

Pharmaceuticals 2026, 19(1), 192; https://doi.org/10.3390/ph19010192 - 22 Jan 2026

Viewed by 555

Abstract

Background/Objectives: Pyrus ussuriensis Maxim. has been cultivated in many regions worldwide. This plant is also regarded as a profitable fruit crop for the development of many food and functional products. There is limited research on the application of the LC-MS associated reaction [...] Read more.

Background/Objectives: Pyrus ussuriensis Maxim. has been cultivated in many regions worldwide. This plant is also regarded as a profitable fruit crop for the development of many food and functional products. There is limited research on the application of the LC-MS associated reaction method for screening active compounds. In this study, we developed an analytical technique employing an ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) system. Methods: The metabolite annotation procedure was used to interpret and validate data analysis via spectral matching against public databases. Results: As a result, metabolites from P. ussuriensis water and EtOH extracts were identified, and their quantities were further evaluated. The established method was employed to determine antioxidant capacity using a pre-incubation UHPLC-2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, thereby identifying antioxidant ingredients. The antioxidative interference of active constituents was predicted by calculating the decrease in the peak areas of the chemical composition detected in chromatograms between treated and non-treated samples. Furthermore, drug-likeness was also assessed via pharmacokinetics (absorption, distribution, metabolism, and excretion: ADME) evaluation. Conclusions: The online UHPLC-MS-DPPH method would be a powerful tool for the rapid characterization of antioxidant ingredients in plant extracts. The current study highlights the value of P. ussuriensis for improved health benefits. Full article

(This article belongs to the Section Natural Products)

► Show Figures

Graphical abstract

15 pages, 1036 KB

Open AccessArticle

Fourier Transform Infrared Spectroscopic Characterization of Aortic Wall Remodeling by Stable Gastric Pentadecapeptide BPC 157 After Unilateral Adrenalectomy in Rats

by Ivan Maria Smoday, Vlasta Vukovic, Katarina Oroz, Hrvoje Vranes, Luka Kalogjera, Ozren Gamulin, Josipa Vlainic, Marija Milavic, Suncana Sikiric, Nora Nikolac Gabaj, Domagoj Marijancevic, Antun Koprivanac, Lidija Beketic Oreskovic, Ivana Oreskovic, Sanja Strbe, Ivan Barisic, Mario Kordic, Ante Tvrdeic, Sven Seiwerth, Predrag Sikiric, Alenka Boban Blagaic and Anita Skrtic Show full author list Hide full author list

Pharmaceuticals 2026, 19(1), 191; https://doi.org/10.3390/ph19010191 - 22 Jan 2026

Cited by 3 | Viewed by 1456

Abstract

Background: No Fourier transform infrared (FTIR) spectroscopy studies have directly evaluated adrenalectomy vessels, the technique’s established ability to probe collagen/elastin-associated spectral features and lipid peroxidation-related signatures, and protein structural damage. Stable gastric pentadecapeptide BPC 157 therapy was found to maintain the vascular function [...] Read more.

Background: No Fourier transform infrared (FTIR) spectroscopy studies have directly evaluated adrenalectomy vessels, the technique’s established ability to probe collagen/elastin-associated spectral features and lipid peroxidation-related signatures, and protein structural damage. Stable gastric pentadecapeptide BPC 157 therapy was found to maintain the vascular function under severe stress, as FTIR spectroscopy recently demonstrated rapid peptide-induced molecular changes in healthy rat blood vessels, particularly in lipid content and protein secondary structure. Methods: To extend these findings and highlight the BPC 157 vascular background in the special circumstances of the course following unilateral adrenalectomy, abdominal aortas were collected at 15 min, 5 h, and 24 h after unilateral adrenalectomy for the FTIR spectroscopy assessment. Results: FTIR spectra were acquired, preprocessed, and analyzed using principal component analysis (PCA), support vector machine discriminant analysis (SVMDA), and band-specific statistics. BPC 157 (10 ng/kg intragatrically immediately after unilateral adrenalectomy) produced a clear, reproducible separation of aortic spectra from control samples at all time points. The main discriminatory spectral signatures were observed in three regions, including amide I and amide II (protein-related bands, consistent with collagen/elastin contributions) and lipid C–H stretching bands. These spectral signatures are consistent with early extracellular matrix reinforcement and membrane preservation in the vascular wall and align with the recovering effect on the lesions in counteraction of the severe vascular and multiorgan failure, attenuation/elimination of thrombosis and blood pressure disturbances in various occlusion/occlusion-like syndromes. Conclusions: Together, after unilateral adrenalectomy, the FTIR data provide molecular-level spectral signatures consistent with rapid remodeling of the aortic wall toward a more structurally stable and functionally favorable state. Full article

(This article belongs to the Section Biopharmaceuticals)

► Show Figures

Figure 1

30 pages, 14265 KB

Open AccessArticle

Vasicine Attenuates Allergic Asthma by Suppressing Mast Cell Degranulation and Th2 Inflammation via Modulation of the FcεRI/Lyn + Syk/MAPK Pathway

by Lu Qu, Wenxia Du, Zizai Ren, Mengmeng Chen, Xiangnong Wu, Xue Cao, Gaoxiong Rao, Xiaoyun Tong, Feng Huang and Yun Sun

Pharmaceuticals 2026, 19(1), 190; https://doi.org/10.3390/ph19010190 - 22 Jan 2026

Cited by 2 | Viewed by 904

Abstract

Background: Vasicine (Vas) is a quinazoline alkaloid derived from Adhatoda vasica Nees, which has good anti-allergic asthma and anti-inflammatory effects. However, its specific functional mechanism on allergic asthma is unclear. This study aims to investigate the protective effect of Vas on allergic [...] Read more.

Background: Vasicine (Vas) is a quinazoline alkaloid derived from Adhatoda vasica Nees, which has good anti-allergic asthma and anti-inflammatory effects. However, its specific functional mechanism on allergic asthma is unclear. This study aims to investigate the protective effect of Vas on allergic asthma and its underlying mechanisms. Methods: Initially, the therapeutic effects of Vas were assessed in ovalbumin-sensitized BALB/c mice using airway hyperresponsiveness (AHR), histopathological examinations, immunohistochemistry, and enzyme-linked immunosorbent assays (ELISA). Subsequently, a non-targeted metabolomic analysis was performed to examine the influence of Vas on lung metabolites, while molecular docking was utilized to clarify the mechanisms by which Vas intervenes in allergic asthma. Lastly, RBL-2H3 cells were employed in vitro to validate the metabolomic findings by measuring intracellular Ca²⁺ concentrations, in addition to conducting ELISA and Western blot analyses. Results: In vivo, Vas alleviates AHR in mice with allergic asthma, enhances histopathological conditions, and reduces inflammatory factors. Non-targeted metabolomics analyses indicate that the primary pathway implicated in its intervention in allergic asthma may be the FcεRI pathway. Furthermore, molecular docking techniques were utilized to evaluate the binding affinity between Vas and proteins associated with this pathway. In vitro, Vas effectively inhibits degranulation in RBL-2H3 cells and diminishes the release of inflammatory factors by modulating the FcεRI/Lyn + Syk/MAPK pathway. Conclusions: These findings indicate that Vas may effectively alleviate allergic asthma by reducing inflammatory responses, decreasing AHR, and improving histopathological features. Furthermore, Vas seems to inhibit mast cell degranulation and modulate the FcεRI/Lyn + Syk/MAPK pathway. Full article

(This article belongs to the Section Pharmacology)

► Show Figures

Figure 1

14 pages, 682 KB

Open AccessArticle

Efficacy and Safety of SA001 in Patients with Primary Sjögren’s Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

by Jaewon Park, Kyoung Yul Seo, Hyunmin Ahn, Yearim Shin, Ikhyun Jun, Tae-im Kim, Bum Kyu Shin, Da-Young Yoon and Soo-Min Lee

Pharmaceuticals 2026, 19(1), 189; https://doi.org/10.3390/ph19010189 - 22 Jan 2026

Viewed by 703

Abstract

Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren’s syndrome (pSS), this trial aimed to [...] Read more.

Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren’s syndrome (pSS), this trial aimed to assess whether the improved bioavailability of SA001 could translate into clinical benefits. Methods: This multicenter, randomized, double-blind, placebo-controlled Phase 2a study enrolled adults who met the 2016 ACR–EULAR criteria for pSS. The participants were randomly assigned to one of four groups: SA001 at 360, 720, or 1080 mg/day (administered twice daily for 8 weeks) or placebo. Exploratory ocular assessments included tear break-up time, ocular surface staining, the Schirmer test, and the Standard Patient Evaluation of Eye Dryness. Oral endpoints included unstimulated whole salivary flow and the Xerostomia Inventory. Anti-SSA(Ro) antibodies were assessed both quantitatively and qualitatively. Safety evaluations comprised adverse events (AEs), ophthalmic examinations, laboratory tests, and vital signs. The efficacy outcomes were exploratory, and this study was not powered to formally test efficacy hypotheses. Results: Twenty-eight women (mean age 58.54 ± 9.29 years; range 41–75 years) were enrolled in this study and randomly assigned to one of the study groups. SA001 showed no statistically significant improvements versus placebo in ocular or oral endpoints, and no consistent dose–response relationship was observed. The anti-SSA(Ro) findings did not differ meaningfully across the groups. SA001 was generally well-tolerated, with infrequent, mostly mild-to-moderate AEs; however, one serious AE occurred in the placebo group. No clinically relevant ophthalmic or laboratory safety signals were detected. Conclusions: Despite the fact that markedly increased systemic exposure has been demonstrated previously, SA001 did not improve the dryness outcomes in pSS. These findings suggest that systemic exposure alone may be insufficient in established glandular disease and highlight the need for tissue-exposure-driven strategies and biomarker-informed patient selection in future studies. Predefined primary efficacy endpoints and objective, gland-proximal measures of target engagement (e.g., standardized salivary gland ultrasonography and salivary or tear fluid biomarker assessments) may help to better interpret local pharmacodynamic activity and the likelihood of a clinically meaningful benefit. Full article

(This article belongs to the Section Pharmacology)

► Show Figures

Graphical abstract

27 pages, 1350 KB

Open AccessSystematic Review

Anti-Inflammatory Potential of Ganoderma lucidum Triterpenes: A Systematic Review and Meta-Analysis of Preclinical Evidence

by Rafaela Guedes Pozzobon, Renata Rutckeviski, Luíza Siqueira de Lima, Cláudia Sirlene Oliveira and Fhernanda Ribeiro Smiderle

Pharmaceuticals 2026, 19(1), 188; https://doi.org/10.3390/ph19010188 - 21 Jan 2026

Viewed by 2735

Abstract

Background: Ganoderma lucidum triterpenes are bioactive compounds with recognized anti-inflammatory, antitumor, and immunomodulatory properties. This systematic review synthesizes evidence regarding the anti-inflammatory activity of these triterpenes based on studies from the last two decades. Methods: A systematic search was performed in [...] Read more.

Background: Ganoderma lucidum triterpenes are bioactive compounds with recognized anti-inflammatory, antitumor, and immunomodulatory properties. This systematic review synthesizes evidence regarding the anti-inflammatory activity of these triterpenes based on studies from the last two decades. Methods: A systematic search was performed in PubMed, Medline, and Embase (2003–2025) for original in vitro and in vivo (non-clinical) studies evaluating G. lucidum triterpene extracts or isolated compounds. Clinical trials, reviews, and multi-species extracts were excluded. The review is registered on PROSPERO (CRD42024510982), and animal study quality was assessed using the SYRCLE Risk of Bias tool. Findings: From over 3000 records, 23 articles were included. Studies utilized diverse models, including macrophages, human PBMCs, and various animal strains (mice, rats, chickens). All studies reported significant anti-inflammatory effects via reduction in pro-inflammatory markers (TNF-α, IL-1β, IL-6), primarily through downregulation of MAPK and TLR-4/NF-κB signaling pathways. Meta-analysis of in vitro data confirmed significant reductions in NO levels (−3.29 [95% CI: −5.21, −1.37]; p = 0.0008), IL-6 (−3.51 [−4.73, −2.29]; p < 0.00001), and TNF-α (−2.20 [−2.93, −1.48]; p < 0.00001). Similar anti-inflammatory profiles were observed in vivo across hepatic and splenic tissues. Interpretation: Evidence consistently demonstrates the potent anti-inflammatory activity of G. lucidum triterpenes, highlighting their potential as therapeutic candidates for inflammatory diseases. However, the structural complexity and isomer diversity of these compounds remain significant barriers to pharmacological standardization. Future research must prioritize clinical translation by investigating compound synergism, bioavailability, and long-term toxicity profiles, which were notably absent in current non-clinical literature. Full article

(This article belongs to the Section Natural Products)

► Show Figures

Figure 1

16 pages, 2123 KB

Open AccessArticle

Effects of Modified Gamchogeongang-Tang on Lung Injury in a Chronic Obstructive Pulmonary Disease Mice Model: An Experimental Study

by Won-Kyung Yang, Jin Hoo Kim, Seung-Hyung Kim, Su Won Lee, In Chul Jung, Seong-Cheon Woo and Yang Chun Park

Pharmaceuticals 2026, 19(1), 187; https://doi.org/10.3390/ph19010187 - 21 Jan 2026

Viewed by 632

Abstract

Objectives: This study evaluated the effects of modified Gamchogeongang-tang (GGS01) on lung injury using a COPD mouse model. Methods: C57BL/6 mice were exposed to cigarette smoke extract and lipopolysaccharide and treated with GGS01 (100, 200, or 400 mg/kg). Bronchoalveolar lavage fluid (BALF) and [...] Read more.

Objectives: This study evaluated the effects of modified Gamchogeongang-tang (GGS01) on lung injury using a COPD mouse model. Methods: C57BL/6 mice were exposed to cigarette smoke extract and lipopolysaccharide and treated with GGS01 (100, 200, or 400 mg/kg). Bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed using cytospin, enzyme-linked immunosorbent assay, real-time polymerase chain reaction (PCR), flow cytometry analysis, hematoxylin and eosin (H&E) and Masson’s trichrome staining, and immune histology fluorescent staining. Results: GGS01 significantly inhibited the increase in neutrophils in BALF, decreased immune cell activity in BALF and lung tissue, and inhibited the increase in the levels of IL-1α, TNF-α, IL-17A, MIP2, and CXCL-1 in BALF. Conclusions: Real-time PCR analysis showed that MUC5AC mRNA expression in lung tissue significantly decreased compared with the control group. The score of histological analysis of lung tissue damage was significantly reduced, and a decrease in IRAK1 and TNF-α expression in lung tissue was observed. Full article

(This article belongs to the Section Pharmacology)

► Show Figures

Graphical abstract

26 pages, 2283 KB

Open AccessSystematic Review

Emerging Breakthroughs in Nano-Ginseng Innovations and Their Therapeutic Implications in Type 2 Diabetes

by Pragya Tiwari, Kyeung-Il Park and Sayanti Mandal

Pharmaceuticals 2026, 19(1), 186; https://doi.org/10.3390/ph19010186 - 21 Jan 2026

Viewed by 1006

Abstract

Background/Objectives: Diabetes is characterized by multiple metabolic disorders, defined by high blood sugar levels over a prolonged duration. Type 2 diabetes (T2D) comprises defective insulin secretion, its ineffective utilization, or both, resulting in hyperglycemia. The disease is one of the leading causes of [...] Read more.

Background/Objectives: Diabetes is characterized by multiple metabolic disorders, defined by high blood sugar levels over a prolonged duration. Type 2 diabetes (T2D) comprises defective insulin secretion, its ineffective utilization, or both, resulting in hyperglycemia. The disease is one of the leading causes of mortality, according to the WHO, and necessitates the development of advanced therapeutics. Methods: This systematic review was conducted in accordance with the PRISMA guidelines. The study and execution of the literature review followed a timeframe of 3–6 months, during which the conceptualization, execution, analysis, writing, and editing were conducted. Ginsenosides, triterpenoids from the Panax genus, are widely recognized for their promising antidiabetic effects, mediated through mechanisms that include glucose uptake, insulin secretion, antioxidant activity, and anti-inflammatory pathways. Ongoing clinical trials in patients with IGT or Type 2 diabetes have shown an improvement in insulin sensitivity and glucose control, and consolidate the therapeutic potential of ginseng pharmacotherapy. Results: This viewpoint summarizes the most recent discoveries on the hypoglycemic mechanisms of ginsenosides for Type 2 diabetes and its associated complications, with a major focus on ginseng-based drug development. An emphasis is placed on how ginsenosides control blood glucose levels and regulate signaling pathways, investigating their antidiabetic mechanisms and potential. Conclusions: Preclinical studies suggest that nano-innovations in ginseng have the potential to address therapeutic challenges, improve systemic circulation, lower the toxicity of biomolecules, and improve bioavailability, defining exciting outcomes. Furthermore, well-designed human clinical trials are necessary to understand the antidiabetic mechanisms and pharmacological potential of ginseng and/or ginsenosides in drug development. Full article

(This article belongs to the Special Issue Cutting-Edge Biotechnologies and Applications of Natural Products in Drug R&D and Disease Treatment)

► Show Figures

Figure 1

14 pages, 3287 KB

Open AccessArticle

Econazole Exhibits In Vitro and In Vivo Efficacy Against Leishmania amazonensis

by Juliana Tonini Mesquita, Ingrid de Oliveira Dias, Andre Gustavo Tempone and Juliana Quero Reimão

Pharmaceuticals 2026, 19(1), 185; https://doi.org/10.3390/ph19010185 - 21 Jan 2026

Cited by 1 | Viewed by 763

Abstract

Background/Objectives: Cutaneous leishmaniasis (CL) remains a major neglected tropical disease, and current chemotherapeutic options are limited by toxicity and emerging resistance. Repurposing azole antifungals is a promising approach, as they target ergosterol biosynthesis, a pathway also essential in Leishmania spp. This study investigated [...] Read more.

Background/Objectives: Cutaneous leishmaniasis (CL) remains a major neglected tropical disease, and current chemotherapeutic options are limited by toxicity and emerging resistance. Repurposing azole antifungals is a promising approach, as they target ergosterol biosynthesis, a pathway also essential in Leishmania spp. This study investigated the antileishmanial potential of econazole through in vitro and in vivo assays. Methods: Econazole activity was evaluated against Leishmania amazonensis promastigotes and intracellular amastigotes using MTT and luminescence-based methods. Cytotoxicity in NCTC cells was determined to calculate the selectivity index (SI). Drug interactions with miltefosine were assessed by fixed-ratio isobologram analysis. In vivo efficacy was examined in BALB/c mice infected with L. amazonensis and orally treated with econazole (2.5, 5, or 10 mg/kg/day) for 28 days. Lesion development and parasite burden were monitored. Molecular docking simulations were performed using SwissDock. Results: Econazole showed potent in vitro activity, with EC₅₀ values of 8.9 µM for promastigotes and 11 µM for intracellular amastigotes, and a CC₅₀ of 31 µM. Isobologram analysis revealed additive interactions with miltefosine (ΣFIC 0.5–1.2; mean 0.95). In vivo, econazole reduced lesion size and parasite load, achieving up to 75% reduction at 10 mg/kg/day. Docking results suggested that econazole may inhibit sterol biosynthesis, potentially through interaction with 14α-demethylase. Conclusions: These findings provide the first evidence of econazole activity against L. amazonensis in vitro and in vivo. Its exploratory efficacy and compatibility with miltefosine support further investigation of econazole as a repurposed candidate for CL, including optimization of dosing strategies and combination regimens. Full article

(This article belongs to the Special Issue Novel Drug Targets and Drug Candidates for Neglected Tropical Diseases)

► Show Figures

Graphical abstract

11 pages, 879 KB

Open AccessCommunication

Extraction of pH-Dependent DNA-Binding Anti-Tumoral Peptides from Saccharomyces cerevisiae

by Francesco Ragonese and Loretta Mancinelli

Pharmaceuticals 2026, 19(1), 184; https://doi.org/10.3390/ph19010184 - 21 Jan 2026

Viewed by 552

Abstract

Cancer remains a significant challenge in the field of medicine, primarily due to its inherent plasticity and the development of resistance to conventional therapeutic interventions. Genomic mutations and the activation of oncogenes enable cancer cells to resist senescence and apoptosis, leading to uncontrolled [...] Read more.

Cancer remains a significant challenge in the field of medicine, primarily due to its inherent plasticity and the development of resistance to conventional therapeutic interventions. Genomic mutations and the activation of oncogenes enable cancer cells to resist senescence and apoptosis, leading to uncontrolled growth with harmful consequences. Small peptides are molecules with interesting anti-tumour properties and represent a valid alternative to conventional treatments. Our group has previously identified a class of small peptides bound to the DNA that can be extracted from the chromatin of various tissues, including wheat germ and trout. These peptide pools have been shown to possess interesting antiproliferative and apoptotic properties, and they are associated with cell cycle regulation. However, given the complexity of the extraction process, it is necessary to identify a substrate that will enable a more efficient extraction of these peptides, while also ensuring a composition that is simple to investigate. The present study developed a method for the extraction of this group of peptides from yeast, and the extract was then tested on cancer cells in order to confirm its anti-tumoral properties. The peptides were obtained from chromatin extracted from Saccharomyces cerevisiae cells through alkalisation and purification by gel filtration chromatography. The extract was tested on HeLa cells to verify its effects on vitality and the cell cycle. The data demonstrate that the chromatographic profile of this peptide extract indicates a more basic composition than the pool extracted from other tissues and exhibits comparable antiproliferative properties. The ability to rapidly obtain a biologically active, analytically accessible, and adequately purified fraction from the widely available substrate Saccharomyces cerevisiae represents a significant advance in the study of these DNA-binding peptides. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

► Show Figures

Graphical abstract

26 pages, 5310 KB

Open AccessReview

Neutrophil Extracellular Traps: Potential Therapeutic Targets of Traditional Chinese Medicine and Natural Products for Cardiovascular Diseases

by Yichen Liu, Yunhe Guo, Xinru Wu, Peiyu Yan and Yan Wei

Pharmaceuticals 2026, 19(1), 183; https://doi.org/10.3390/ph19010183 - 20 Jan 2026

Cited by 2 | Viewed by 1863

Abstract

Cardiovascular disease (CVD) remains a leading cause of global morbidity and mortality, and its initiation and progression are closely associated with multiple molecular mechanisms. Neutrophil extracellular traps (NETs) are mesh-like structures composed of DNA, histones, and antimicrobial proteins that are released by neutrophils [...] Read more.

Cardiovascular disease (CVD) remains a leading cause of global morbidity and mortality, and its initiation and progression are closely associated with multiple molecular mechanisms. Neutrophil extracellular traps (NETs) are mesh-like structures composed of DNA, histones, and antimicrobial proteins that are released by neutrophils during inflammation or infection. They play a crucial role in innate immune defense. However, when the dynamic balance of NETs is disrupted by excessive formation, persistent accumulation, or impaired clearance, NETs are no longer merely bystanders. Instead, they actively drive pathological processes in multiple CVDs and serve as a critical link between inflammation and cardiovascular injury. Given the central role of NETs in CVD pathogenesis, including atherosclerosis, myocardial ischemia–reperfusion injury, pulmonary arterial hypertension, atrial fibrillation, and heart failure, therapeutic strategies targeting NETs, such as inhibiting aberrant formation, enhancing clearance, or neutralizing toxic components, have emerged as promising approaches. In recent years, traditional Chinese medicine (TCM) and natural products have shown potential therapeutic value by modulating NET formation and promoting NET degradation, owing to their multitarget, multipathway regulatory effects. This article reviews the mechanisms by which NETs operate in CVDs and explores potential pathways through which TCM and natural active ingredients prevent and treat CVDs by regulating NETs. This review provides theoretical support for further research and clinical application. Full article

(This article belongs to the Section Natural Products)

► Show Figures

Figure 1

32 pages, 2940 KB

Open AccessArticle

Integrated In Vitro and In Silico Profiling of Piperazinyl Thiosemicarbazone Derivatives Against Trypanosoma cruzi: Stage-Specific Activity and Enzyme Inhibition

by Héctor A. Baldoni, María L. Sbaraglini, Darío E. Balcazar, Diego G. Arias, Sergio A. Guerrero, Catalina D. Alba Soto, Wioleta Cieslik, Marta Rogalska, Jaroslaw Polański, Ricardo D. Enriz, Josef Jampilek and Robert Musiol

Pharmaceuticals 2026, 19(1), 182; https://doi.org/10.3390/ph19010182 - 20 Jan 2026

Viewed by 1097

Abstract

Background: Trypanosoma cruzi, the causative agent of Chagas disease, remains a major public health concern, and there is a continued need for new antitrypanosomal agents. Thiosemicarbazone (TSC) derivatives have emerged as a promising class of compounds with potential antiparasitic activity. Objectives: [...] Read more.

Background: Trypanosoma cruzi, the causative agent of Chagas disease, remains a major public health concern, and there is a continued need for new antitrypanosomal agents. Thiosemicarbazone (TSC) derivatives have emerged as a promising class of compounds with potential antiparasitic activity. Objectives: This study aimed to report the synthesis, characterization, and biological profiling of a novel series of thiosemicarbazone derivatives as antitrypanosomal agents against Trypanosoma cruzi. Methods: Fourteen new compounds and six previously described analogues were prepared and characterized by ¹H/¹³C nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). As a preliminary in vitro screen, activity was assessed by direct parasite counting in epimastigote and bloodstream trypomastigote forms, as tractable models of replicative and infective stages sharing core metabolic targets with intracellular amastigotes. Epimastigote potency was quantified as half-maximal effective concentrations (EC₅₀) derived from dose–response curves, whereas trypomastigote response was evaluated as percent viability after treatment at a fixed concentration of 20 µM. Mechanistic profiling included inhibition assays against the cysteine protease cruzipain (CZP) and selected redox defense enzymes, complemented by in silico similarity clustering and binding-pose affinity scoring. Results: A nitro-methoxy-substituted TSC showed potent CZP inhibition but limited trypomastigote efficacy, whereas brominated analogues displayed dual-stage activity independent of CZP inhibition. Tanimoto similarity analysis identified distinct structure–activity clusters, linking nitro-methoxy substitution to epimastigote selectivity and brominated scaffolds to broader antiparasitic profiles, with hydrophobicity and steric complementarity as key determinants. Enzymatic assays revealed no significant inhibition of cytosolic tryparedoxin peroxidase (cTXNPx) or glutathione peroxidase type I (TcGPx-I), suggesting redox disruption is not a primary mode of action. In vitro and in silico analyses showed low or no non-specific cytotoxicity under the tested conditions, supporting further optimization of these derivatives as antitrypanosomal preliminary hits. Key hits included derivative 3e (epimastigote EC₅₀ = 0.36 ± 0.02 µM) and brominated analogues 2c and 2e (epimastigote EC₅₀ = 3.92 ± 0.13 and 4.36 ± 0.10 µM, respectively), while docking supported favorable binding-pose affinity (e.g., ΔG_S_-pose = −20.78 ± 2.47 kcal/mol for 3e). Conclusions: These results support further optimization of the identified thiosemicarbazone derivatives as preliminary antitrypanosomal hits and provide insight into structure–activity relationships and potential mechanisms of action. Full article

(This article belongs to the Special Issue Novel Drug Targets and Drug Candidates for Neglected Tropical Diseases)

► Show Figures

Graphical abstract

16 pages, 969 KB

Open AccessSystematic Review

Effectiveness of Eicosapentaenoic and Docosahexaenoic Acid Supplementation for Reducing Uremic Pruritus: A Meta-Analysis of Randomized Controlled Trials

by Chia-An Chou, Lung-Chih Li, Wen-Chin Lee and Chiang-Chi Huang

Pharmaceuticals 2026, 19(1), 181; https://doi.org/10.3390/ph19010181 - 20 Jan 2026

Viewed by 1085

Abstract

Background: Uremic pruritus is a distressing and common symptom in patients with end-stage renal disease. The development of uremic pruritus involves a multifactorial pathogenesis, including systemic inflammation, dysregulated immune responses, and altered opioid receptor activity. Omega-3 polyunsaturated fatty acids have been reported to [...] Read more.

Background: Uremic pruritus is a distressing and common symptom in patients with end-stage renal disease. The development of uremic pruritus involves a multifactorial pathogenesis, including systemic inflammation, dysregulated immune responses, and altered opioid receptor activity. Omega-3 polyunsaturated fatty acids have been reported to mitigate uremic pruritus symptoms. Among omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported as potential candidates for alleviating uremic pruritus due to their anti-inflammatory properties. Methods: A meta-analysis of seven randomized controlled trials was conducted to evaluate the efficacy of omega-3 supplementation in alleviating uremic pruritus among patients affected with end-stage renal disease. Effect sizes were calculated using Hedges’ g with a random-effects model. Heterogeneity, sensitivity, and meta-regression analyses were performed to explore influencing factors. Results: A total of 266 participants were included for analysis. Omega-3 supplementation significantly reduced pruritus severity compared with placebo. Sensitivity analyses were conducted to exclude a single large trial contributing to the results. Meta-regression indicated that higher EPA, DHA, and total omega-3 dosages, and longer treatment duration, were associated with reduced severity of the uremic pruritus than the placebo. No serious adverse events were reported. Conclusions: Omega-3 fatty acid supplementation significantly alleviates uremic pruritus in patients with ESRD. These findings support the use of omega-3 fatty acids as a safe and effective adjunct therapy. Further large-scale, long-term trials are warranted to verify these results and assess the long-term effects and safety of omega-3 fatty acids in attenuating uremic pruritus. Full article

(This article belongs to the Special Issue New Development in Pharmacotherapy of Kidney Diseases)

► Show Figures

Figure 1

32 pages, 4721 KB

Open AccessReview

Benzimidazole-Quinoline Hybrids: Synthesis and Antimicrobial Properties

by Maria Marinescu

Pharmaceuticals 2026, 19(1), 180; https://doi.org/10.3390/ph19010180 - 20 Jan 2026

Cited by 1 | Viewed by 3923

Abstract

Background: Heterocyclic compounds are particularly important in medicinal chemistry. With a range of therapeutic uses, benzimidazoles and quinolines are both key heterocycles in medicinal chemistry. A number of hybrid heterocyclic compounds have been reported in recent years because they typically have better [...] Read more.

Background: Heterocyclic compounds are particularly important in medicinal chemistry. With a range of therapeutic uses, benzimidazoles and quinolines are both key heterocycles in medicinal chemistry. A number of hybrid heterocyclic compounds have been reported in recent years because they typically have better therapeutic properties than single heterocyclic rings. Methods: A literature search was conducted across relevant scientific literature from peer-reviewed sources, using keywords, including “benzimidazole”, “quinoline”, “benzimidazole-quinoline hybrids”, “antibacterial”, “antifungal”, “antimalarial” and “hybrid complexes”. Results: This review summarizes the synthetic methodologies for benzimidazole–quinoline hybrids, benzimidazole– quinolinones, and benzimidazole–quinoline metal complexes, along with their antimicrobial and antimalarial activities and the reported structure–activity relationship (SAR) studies. The importance of halogen substitution, particularly with chlorine and fluorine atoms, as well as the structure of the linker between the benzimidazole and quinoline rings—specifically chain length, the presence of oxygen, sulfur, or nitrogen atoms, and heterocyclic moieties—is highlighted. A series of benzimidazole–quinoline hybrids exhibit antimalarial and antitrypanosomal activities or show enhanced antimicrobial properties due to the incorporation of a five-membered heterocycle in addition to the two existing heterocyclic rings. Notably, several hybrids from different compound series exhibit very low minimum inhibitory concentrations (MICs) in the range of 1–8 µg/mL, along with low cytotoxicity, supporting their potential for further investigation as antimicrobial agents. Conclusions: This review summarizes the synthetic methods, medicinal properties, and structure–activity relationship (SAR) studies of benzimidazole–quinoline hybrids reported between 2002 and 2026. Full article

(This article belongs to the Special Issue Advances in the Synthesis and Application of Heterocyclic Compounds)

► Show Figures

Graphical abstract

18 pages, 7843 KB

Open AccessArticle

Mechanistic Evaluation of Roxadustat for Pulmonary Fibrosis: Integrating Network Pharmacology, Transcriptomics, and Experimental Validation

by Congcong Zhang, Xinyue Huang, Huina Ye, Haidong Tang, Minwei Huang, Shu Jia, Jingping Shao, Jingyi Wu and Xiaomin Yao

Pharmaceuticals 2026, 19(1), 179; https://doi.org/10.3390/ph19010179 - 20 Jan 2026

Viewed by 802

Abstract

Background: Pulmonary fibrosis (PF) currently lacks effective therapeutic interventions. Roxadustat, an oral small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase, has been shown in several studies to attenuate the progression of fibrotic diseases. However, its therapeutic efficacy in PF remains to be fully [...] Read more.

Background: Pulmonary fibrosis (PF) currently lacks effective therapeutic interventions. Roxadustat, an oral small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase, has been shown in several studies to attenuate the progression of fibrotic diseases. However, its therapeutic efficacy in PF remains to be fully elucidated. The aim of this study was to evaluate roxadustat’s therapeutic benefits on PF as well as the underlying mechanisms of action. Methods: Bleomycin was administered intraperitoneally to establish a PF mouse model. H&E staining, Masson staining, and immunohistochemistry (IHC) were used to assess histopathological and fibrotic changes. Changes in the expression levels of inflammatory mediators, including IL-1β, TGF-β1, and TNF-α, were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Network pharmacology combined with transcriptomic analysis was employed to identify potential target genes and associated signaling pathways. Subsequently, RT-qPCR and Western blot analyses were carried out to experimentally validate the predicted targets and pathways and to verify the protective effects of roxadustat in PF mice. Results: Roxadustat markedly ameliorated bleomycin-induced pulmonary fibrosis in mice. The therapeutic effect was evidenced by a reduction in alveolar damage, thinner alveolar septa, diminished infiltration of inflammatory cells, and decreased collagen deposition. Concomitantly, the expression levels of inflammatory mediators, including IL-1β, TGF-β1, and TNF-α, were significantly lowered. Integrated network pharmacology and transcriptomic analyses revealed the involvement of critical signaling pathways, specifically nuclear factor-kappa B (NF-κB) and peroxisome proliferator-activated receptor (PPAR). Experimental validation further demonstrated that roxadustat downregulated the expression of key genes (S100A8, S100A9, and Fos) in murine lung tissues. It also suppressed the protein ratios of phosphorylated p65 to total p65 and phosphorylated IκBα to total IκBα. Moreover, roxadustat treatment upregulated PPARγ protein expression. Conclusions: These data indicate that roxadustat ameliorates bleomycin-induced PF in mice, an effect associated with modulation of the NF-κB and PPAR signaling pathways. The findings provide a preclinical rationale for further investigation of roxadustat as a potential treatment for PF. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

29 pages, 6922 KB

Open AccessArticle

Protection by Vitis vinifera L. Against Cisplatin-Induced Testicular Injury: Oxidative Stress, Inflammation, and Ferroptosis

by Salman A. A. Mohammed, Hebatallah M. Saad, Kariman A. Esmail, Duaa Eliwa, Aya H. Rohiem, Amal A. Awad, Samar A. El-Adawy, Shimaa S. Amer and Ehab Y. Abdelhiee

Pharmaceuticals 2026, 19(1), 178; https://doi.org/10.3390/ph19010178 - 20 Jan 2026

Cited by 2 | Viewed by 970

Abstract

Background/Objectives: Testicular toxicity is one of the most important chemotherapeutic adverse effects of Cisplatin (Cisp), which restricts its use and effectiveness. This study investigated the preventive effects of Vitis vinifera L. extract on Cisp-induced testicular injury in rats. Methods: Forty adult [...] Read more.

Background/Objectives: Testicular toxicity is one of the most important chemotherapeutic adverse effects of Cisplatin (Cisp), which restricts its use and effectiveness. This study investigated the preventive effects of Vitis vinifera L. extract on Cisp-induced testicular injury in rats. Methods: Forty adult albino male rats were allocated into four groups: control, Vitis vinifera L. extract, Cisp, and co-treated (Vitis vinifera L. extract + Cisp). Sperm motility and count, serum reproductive hormones, oxidative/antioxidant biomarkers, pro-inflammatory cytokines, ferroptosis biomarkers, and gene expression profiles were evaluated. Results: Cisp administration markedly impaired reproductive performance, as evidenced by significant declines in serum FSH, LH, testosterone, and sperm motility and count. Cisp also induced oxidative stress by elevating MDA, GSSG, GPx, and 8-OHdG, while reducing SOD, Catalase, NRF2, and Ho-1 along with total and reduced GSH levels. Moreover, it triggered strong inflammatory responses and ferroptosis activation, with notable up-regulation of NFκB, TNF-α, IL-1β, ferritin, and cathepsin. Gene expression analysis revealed down-regulation of ARNTL, PI3K, and miR-125b and up-regulation of ASCL4, GSK3B, and COX2 following Cisp exposure. Conversely, co-treatment with Vitis vinifera L. extract significantly ameliorated these alterations, restoring sperm quality, hormone balance, antioxidant defenses, and modulating inflammatory, ferroptosis, and genetic responses toward normalcy in addition to restoring testicular and epididymal histoarchitecture without any significant effect in NRF2 and ARNTL expression. Additionally, co-treated groups with Vitis vinifera L. extract showed a significant decline in NF-kB p65 and increased PCNA testicular immunoreactivity with a substantial down-regulation in NF-kB p65 and PCNA epididymal immunoreactivity. Vitis vinifera L. extract alone did not affect any studied parameters as compared to the control group. Conclusions: These findings suggested that Vitis vinifera L. extract has a significant protective effect against Cisp-related testicular injury through antioxidative, anti-inflammatory, and anti-ferroptotic mechanisms. Full article

(This article belongs to the Section Natural Products)

► Show Figures

Figure 1

25 pages, 377 KB

Open AccessArticle

The Impact of H1–H4 Receptor Antagonists on the Levels of Selected Oxidative Stress Markers in Liver and Muscle Tissue in an Animal Model of Colitis

by Bartosz Bogielski, Katarzyna Michalczyk, Wojciech Gębski, Katarzyna Rozpędek, Elżbieta Szulińska, Bartosz Tempka, Aleksandra Zorychta, Elżbieta Chełmecka, Ewa Kaczmar, Piotr Głodek, Jakub John, Kamil Nikiel, Bronisława Skrzep-Poloczek, Jerzy Jochem, Katarzyna Kieć-Kononowicz, Dorota Łażewska and Dominika Stygar

Pharmaceuticals 2026, 19(1), 177; https://doi.org/10.3390/ph19010177 - 20 Jan 2026

Viewed by 1034

Abstract

Background/Objectives: The global prevalence and incidence of inflammatory bowel diseases have risen in the past two decades. Among them, Crohn’s disease and ulcerative colitis are still challenging to treat due to vascular and proliferative alterations. Studies in rats suggest that blocking histamine receptors [...] Read more.

Background/Objectives: The global prevalence and incidence of inflammatory bowel diseases have risen in the past two decades. Among them, Crohn’s disease and ulcerative colitis are still challenging to treat due to vascular and proliferative alterations. Studies in rats suggest that blocking histamine receptors (H1–H4) can improve colitis progression. However, the specific histamine receptor responsible for this effect remains debated. The experiment aimed to assess the role of specific histamine receptor subtypes in colitis development, focusing on oxidative stress markers in the liver and skeletal muscle. Methods: The study involved 60 adult male Wistar rats, divided into control and colitis experimental groups. Colitis was induced through intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid. Animals in both experimental groups received intramuscular injections of NaCl (non-treated, NT) or H1, H2, H3, and H4 receptor antagonists (10 study subgroups in total). On day eight, the animals were re-anesthetized and euthanized via exsanguination. Then, liver and skeletal muscle (m. soleus) samples were collected for analysis of oxidative stress markers. Results: The analyses of skeletal muscle samples showed that using the H1 and H2 receptor antagonists increased superoxide dismutase (SOD) and catalase (CAT) activities, as well as parameters related to glutathione metabolism (reduced glutathione (GSH), glutathione S-transferase (GST)) in rats from the control groups, indicating enhanced antioxidant defense. In rats with chemically induced colitis, we observed that H1 receptor antagonists elevated CAT activity, whereas β-esterase (β-EST) activity remained elevated across all colitis subgroups. In the liver, histamine receptor antagonists produced receptor-specific redox effects: the H2 receptor antagonist reduced oxidative damage (malondialdehyde (MDA)); the H1 receptor antagonist attenuated SOD hyperactivity, but depleted GSH; and the H4 receptor antagonist increased GSH while elevating MDA. Chemically induced colitis increased α- and β-EST activities, whereas administration of the H1 or H3 antagonist reduced β-EST levels. Conclusions: Histamine receptor antagonists modulated oxidative stress responses in both liver and skeletal muscle tissues in a receptor-dependent manner. Among them, the H2 receptor antagonist most effectively mitigated hepatic oxidative injury, highlighting its potential as a therapeutic target in colitis-associated systemic oxidative stress. Full article

(This article belongs to the Special Issue Recent Advances in the Discovery and Development of Drugs for Civilization Diseases, 2nd Edition)

27 pages, 741 KB

Open AccessReview

Advances in the Management of Pediatric Inflammatory Bowel Disease: From Biologics to Small Molecules

by Benedetta Mucci, Elisabetta Palazzolo, Flaminia Ruberti, Lorenzo Ientile, Marco Natale and Susanna Esposito

Pharmaceuticals 2026, 19(1), 176; https://doi.org/10.3390/ph19010176 - 20 Jan 2026

Viewed by 2054

Abstract

Background: The management of pediatric inflammatory bowel disease (PIBD) has evolved significantly over the past two decades, transitioning from corticosteroids and immunomodulators to biologic and small-molecule therapies. These advances have aimed not only to control inflammation but also to promote mucosal healing, improve [...] Read more.

Background: The management of pediatric inflammatory bowel disease (PIBD) has evolved significantly over the past two decades, transitioning from corticosteroids and immunomodulators to biologic and small-molecule therapies. These advances have aimed not only to control inflammation but also to promote mucosal healing, improve growth, and enhance long-term quality of life. Objectives: This narrative review summarizes current evidence on the efficacy, safety, and clinical applications of biologic and novel small-molecule therapies in PIBD, highlighting emerging trends in personalized and precision-based management. Methods: A literature search was performed across PubMed, Embase, and the Cochrane Library, focusing on studies published within the last five years. Additional data were retrieved from key guidelines and position papers issued by ECCO–ESPGHAN, SIGENP, the FDA, and the EMA. Results: Anti–tumor necrosis factor (TNF) agents such as infliximab and adalimumab remain first-line biologics with proven efficacy in remission induction and maintenance. Newer biologics—vedolizumab, ustekinumab, risankizumab, and mirikizumab—offer alternatives for anti-TNF-refractory cases, showing encouraging short-term results and favorable safety profiles. Although many are approved only for adults with limited pediatric evidence, emerging small molecules—including Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib) and sphingosine-1-phosphate (S1P) modulators (etrasimod)—provide oral, rapidly acting, and non-immunogenic treatment options for refractory disease. Furthermore, the gut microbiome is increasingly recognized as an emerging therapeutic target in PIBD, with growing evidence that host–microbiome interactions can influence both the efficacy and safety of biologics and small-molecule therapies. Conclusions: While biologics and small molecules have transformed PIBD management, challenges remain, including high treatment costs, limited pediatric trial data, and variable access worldwide. Future directions include multicenter pediatric studies, integration of pharmacogenomics, and biomarker-guided precision medicine to optimize early, individualized treatment and improve long-term outcomes. Full article

(This article belongs to the Special Issue Advances in Drug Treatment for Pediatric Gastroenterology)

► Show Figures

Figure 1

29 pages, 668 KB

Open AccessReview

Bovine Mastitis Therapy at a Crossroads: Pharmacokinetic Barriers, Biofilms, Antimicrobial Resistance, and Emerging Solutions

by Alexandra Ban-Cucerzan, Adriana Morar, Emil Tîrziu, Iulia-Maria Bucur, Sebastian-Alexandru Popa and Kálmán Imre

Pharmaceuticals 2026, 19(1), 175; https://doi.org/10.3390/ph19010175 - 19 Jan 2026

Cited by 6 | Viewed by 1628 | Correction

Abstract

Bovine mastitis remains a major challenge in dairy production despite extensive antimicrobial use, with therapeutic failure increasingly attributed to factors beyond classical antimicrobial resistance (AMR). Growing evidence indicates that treatment inefficacy arises from the combined effects of pharmacokinetic/pharmacodynamic (PK/PD) constraints, biofilm-mediated tolerance, intracellular [...] Read more.

Bovine mastitis remains a major challenge in dairy production despite extensive antimicrobial use, with therapeutic failure increasingly attributed to factors beyond classical antimicrobial resistance (AMR). Growing evidence indicates that treatment inefficacy arises from the combined effects of pharmacokinetic/pharmacodynamic (PK/PD) constraints, biofilm-mediated tolerance, intracellular persistence, and the adaptive capacity of mastitis pathogens. Intramammary therapy is particularly limited by poor tissue penetration, episodic drug elimination via milk flow, and inactivation by milk components, frequently resulting in subtherapeutic exposure at the site of infection. These limitations are amplified in chronic and subclinical mastitis, where biofilms and intracellular reservoirs reduce antimicrobial susceptibility and promote relapse and resistance selection. This narrative review integrates current knowledge on pharmacokinetic and pharmacodynamic (PK/PD) barriers, microbial survival strategies, and antimicrobial resistance (AMR) mechanisms that underlie treatment failure in bovine mastitis. It critically evaluates conventional antimicrobial therapies alongside emerging approaches, including antimicrobial peptides, bacteriophages and endolysins, nanoparticle-based delivery systems, immunomodulators, CRISPR-guided antimicrobials, and drug repurposing strategies. Overall, available evidence highlights the potential of these approaches to enhance therapeutic durability, particularly in settings where biofilm formation, intracellular persistence, and resistance limit conventional treatment efficacy. By mapping research coverage across mastitis phenotypes and therapeutic outcomes, this review identifies key gaps in long-term efficacy and resistance mitigation and underscores the need for PK/PD-guided, biofilm-aware, and resistance-conscious strategies to support durable next-generation mastitis management. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Misuse)

► Show Figures

Figure 1

17 pages, 1892 KB

Open AccessArticle

A New Trichlorinated Xanthone and Compounds Isolated from Cladonia skottsbergii with Antimicrobial Properties

by Marvin J. Rositzki, Achara Raksat, Charles J. Simmons, Clifford Smith, Reverend Danette V. Choi, Supakit Wongwiwatthananukit and Leng Chee Chang

Pharmaceuticals 2026, 19(1), 174; https://doi.org/10.3390/ph19010174 - 19 Jan 2026

Viewed by 855

Abstract

Background/Objectives: The global rise in multidrug-resistant (MDR) bacteria, particularly methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA and MSSA), continues to pose a major public health challenge, including in Hawaii. This underscores the need to discover new antimicrobial agents from natural sources. Guided by [...] Read more.

Background/Objectives: The global rise in multidrug-resistant (MDR) bacteria, particularly methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA and MSSA), continues to pose a major public health challenge, including in Hawaii. This underscores the need to discover new antimicrobial agents from natural sources. Guided by teachings from a Buddhist master regarding the medicinal value of lichens, we investigated the endemic Hawaiian lichen Cladonia skottsbergii. Methods: Specimens of C. skottsbergii were collected from the Lotus Buddhist Monastery in Mountain View, Hawaii. A methanolic extract was prepared and purified using chromatographic techniques, and compound structures were elucidated through spectroscopic analyses and single-crystal X-ray diffraction. The antibacterial activity of the compounds was assessed against Gram-positive strains (MRSA, MSSA) and Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa). Cytotoxicity was assessed using A549 (non-small cell lung cancer) and Vero E6 (non-tumorigenic) cell lines. Results: Three compounds were isolated: clarosione (1), a newly identified trichlorinated xanthone, and two known metabolites, (S)-usnic acid (2) and perlatolic acid (3). Compounds 2 and 3 demonstrated strong inhibitory effects against MRSA and MSSA. Their minimum inhibitory concentrations (MICs) ranged from 2 to 4 µg/mL, compared with vancomycin (0.5–1 µg/mL). Cytotoxicity testing showed higher sensitivity in A549 cells than in Vero E6 cells, resulting in favorable selectivity indices for the active compounds. Conclusions: In the current study, a new compound, clarosione (1) was discovered. This enhances our understanding of the constituents of C. skottsbergii and its potential antibacterial properties. Lichen-derived compounds may serve as lead candidates for further development, and further study is warranted. Full article

(This article belongs to the Special Issue Natural Products for Anticancer, Anti-Inflammatory and Antimicrobial Therapies)

► Show Figures

Graphical abstract

16 pages, 742 KB

Open AccessArticle

Preclinical Studies on Plant Based-Antacid Formulations as New Therapies for Gastro-Oesophageal Reflux Disease

by Paola De Cicco, Nunzio Antonio Cacciola, Rebecca Amico, Barbara Romano, Umberto Di Maio, Natasa Milic, Antonino Bagnulo, Maria Francesca Nanì, Laura Viscovo, Marcello Scivicco, Raffaele Capasso, Ester Pagano and Francesca Borrelli

Pharmaceuticals 2026, 19(1), 173; https://doi.org/10.3390/ph19010173 - 19 Jan 2026

Viewed by 1403

Abstract

Background/Objectives: Gastro-oesophageal reflux disease (GERD) refers to a disease in which stomach acid rises into the oesophagus. Currently, proton pump inhibitors (PPIs) are the most commonly used medications to treat GERD. However, long-term use of PPIs is not free from side effects, and [...] Read more.

Background/Objectives: Gastro-oesophageal reflux disease (GERD) refers to a disease in which stomach acid rises into the oesophagus. Currently, proton pump inhibitors (PPIs) are the most commonly used medications to treat GERD. However, long-term use of PPIs is not free from side effects, and new treatment strategies are needed. The present study was conducted to evaluate the gastroprotective potential of four different formulations containing both antiacids and medicinal plants considered useful for the treatment of GERD. Methods: The protective effects of the formulations on gastric ulcers in pyloric ligation-induced gastric mucosal lesions in mice were evaluated by measuring gastric emptying, the ulcer index, gastric content, total acidity, and the pH of the gastric fluid. Gastric damage was also assessed by measuring myeloperoxidase (MPO) activity. Results: Formulations containing Glycyrrhiza glabra L. or Glycyrrhiza glabra L. plus Opuntia ficus-indica Mill. and Olea europaea L. (formulations 3 and 4, respectively) increased gastric emptying. All formulations decreased gastro-oesophageal damage (ulceration and MPO activity) and gastric contents and had no effects on total acidity or gastric fluid pH in the pyloric ligation ulcer model. Conclusions: Our results show that all formulations are able to exert cytoprotective and anti-ulcerative effects. However, among the formulations, formulation 4 seems to be the most promising because of its better effects on gastric injury and gastric emptying. These results support the hypothesis of the possible use of medicinal plants in combination with antacid agents in the treatment of GERD. Full article

(This article belongs to the Special Issue New and Emerging Treatment Strategies for Gastrointestinal Diseases)

► Show Figures

Graphical abstract

12 pages, 1419 KB

Open AccessArticle

Alpha Therapy Beyond TOC and TATE—Production, Quality Control, and In-Human Results for the SSTR2 Antagonist DOTA-LM3

by Lukas Greifenstein, Marcel Martin, Sarah Stephan, Aleksandr Eismant, Carsten S. Kramer, Christian Landvogt, Corinna Mueller, Frank Rösch and Richard P. Baum

Pharmaceuticals 2026, 19(1), 172; https://doi.org/10.3390/ph19010172 - 19 Jan 2026

Viewed by 1077

Abstract

Objectives: Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs) commonly relies on somatostatin receptor subtype 2 (SSTR2) agonists such as DOTA-TOC/TATE, which may show limited efficacy due to high hepatic uptake and therapy resistance in some patients. SSTR2 antagonists have demonstrated [...] Read more.

Objectives: Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs) commonly relies on somatostatin receptor subtype 2 (SSTR2) agonists such as DOTA-TOC/TATE, which may show limited efficacy due to high hepatic uptake and therapy resistance in some patients. SSTR2 antagonists have demonstrated superior tumor targeting. This study aimed to establish the production and quality control of the Actinium-225-labeled SSTR2 antagonist [²²⁵Ac]Ac-DOTA-LM3 and to report in-human clinical experience with targeted alpha therapy (TAT). Methods: [²²⁵Ac]Ac-DOTA-LM3 was produced by radiolabeling DOTA-LM3 with Actinium-225 under validated conditions. Radiochemical conversion, purity, yield, and stability were assessed using radio-TLC, fractionated radio-HPLC combined with gamma spectroscopy, and in vitro serum stability testing. Clinical feasibility and therapeutic response were evaluated in a patient with metastatic neuroendocrine pancreatic neoplasm refractory to prior ¹⁷⁷Lu-based PRRT. Results: Radiolabeling achieved reproducibly high radiochemical purity (>97%) and decay-corrected yields exceeding 80%. The radiopharmaceutical showed high in vitro stability with minimal release of free Actinium-225 over five days. Fractionated radio-HPLC enabled indirect purity assessment. In the reported patient, [²²⁵Ac]Ac-DOTA-LM3 therapy resulted in partial remission without clinically relevant hematologic, renal, or hepatic toxicity and was associated with marked clinical improvement. Conclusions: [²²⁵Ac]Ac-DOTA-LM3 can be produced with high purity and stability using clinically applicable procedures. In-human results suggest promising efficacy and safety, supporting further clinical investigation of Actinium-225-labeled SSTR2 antagonists for advanced NETs. Full article

(This article belongs to the Special Issue Advancements in Radiopharmaceutical Theranostics)

► Show Figures

Figure 1

20 pages, 15922 KB

Open AccessArticle

Investigation of the Efficacy and Mechanism of Monoacylglycerol Lipase Inhibitors in Diabetic Foot Ulcers

by Zixia Liang, Ying Wang, Meijia Li, Honghua Li, Yanzhong Han, Yun Zhao, Jian Yang, Yujun Tan, Guoxin Dai, Na Guo, Jingchun Yao, Xiaoyan Lu and Guimin Zhang

Pharmaceuticals 2026, 19(1), 171; https://doi.org/10.3390/ph19010171 - 19 Jan 2026

Viewed by 825

Abstract

Background/Objectives: Wound healing proceeds in a timely and sequential manner through four well-defined phases: hemostasis, inflammation, proliferation, and remodeling. To explore the therapeutic efficacy and underlying mechanism of a novel monoacylglycerol lipase (MAGL) inhibitor (designated as MAGL11), a diabetic mouse model of [...] Read more.

Background/Objectives: Wound healing proceeds in a timely and sequential manner through four well-defined phases: hemostasis, inflammation, proliferation, and remodeling. To explore the therapeutic efficacy and underlying mechanism of a novel monoacylglycerol lipase (MAGL) inhibitor (designated as MAGL11), a diabetic mouse model of skin wounds was established. Methods: Wound healing progression was assessed via gross observation, while histological analyses (including HE staining and Masson staining) were conducted to evaluate tissue repair. Additionally, proteomic analysis and in vitro experiments were employed to validate the therapeutic effects and clarify the molecular mechanism of MAGL11. Results: In vivo studies revealed that treatment with MAGL11 significantly accelerated wound closure in diabetic mice. Compared with the control group, MAGL11-treated wounds exhibited notably increased granulation tissue formation and collagen deposition, which was accompanied by a distinct anti-inflammatory effect. Results from proteomic profiling and in vitro experiments further demonstrated that MAGL11 exerted its pro-healing effects by promoting the activation of the Rap1/PI3K/Akt signaling pathway. Specifically, MAGL11 enhanced the migration and chemotaxis of fibroblasts (NIH3T3), human umbilical vein endothelial cells (HUVECs), and keratinocytes (HaCaT) while simultaneously inhibiting cellular apoptosis—all of which collectively contributed to improved wound healing. Conclusions: These findings suggest that MAGL11 holds promise as a potential candidate for diabetic wound therapy, primarily through its ability to promote angiogenesis, fibroblast activation, and epithelial regeneration. Full article

(This article belongs to the Special Issue Emerging Therapies for Diabetes and Obesity)

► Show Figures

Graphical abstract

17 pages, 2761 KB

Open AccessArticle

Plasma miRNA-Metabolite Dysregulation in People with HIV with Cirrhosis Despite Successful HCV Cure

by Ana Virseda-Berdices, Raquel Behar-Lagares, Juan Berenguer, Juan González-García, Belen Requena, Oscar Brochado-Kith, Cristina Díez, Victor Hontañon, Sergio Grande-García, Carolina González-Riano, Coral Barbas, Salvador Resino, Amanda Fernández-Rodríguez, María Ángeles Jiménez-Sousa and the Marathon Study Group

Pharmaceuticals 2026, 19(1), 170; https://doi.org/10.3390/ph19010170 - 19 Jan 2026

Viewed by 696

Abstract

Background: Persistent liver pathology despite a sustained virologic response (SVR) to hepatitis C virus (HCV) therapy is a major clinical concern. This is particularly relevant for people with HIV (PWH) with HCV coinfection, a population prone to accelerated liver disease progression. This [...] Read more.

Background: Persistent liver pathology despite a sustained virologic response (SVR) to hepatitis C virus (HCV) therapy is a major clinical concern. This is particularly relevant for people with HIV (PWH) with HCV coinfection, a population prone to accelerated liver disease progression. This study aimed to characterize the plasma miRNA profile in PWH with cirrhosis one year after successful completion of HCV therapy, and to explore their relationship with metabolite alterations. Methods: This cross-sectional study enrolled 47 PWH who achieved HCV clearance with antiviral therapy. Using plasma samples collected approximately one year after completion of HCV therapy, participants were stratified into two groups based on liver stiffness measurement (LSM): compensated cirrhosis (n = 32, LSM ≥ 12.5 kPa) and non-cirrhosis (n = 15, LSM < 12.5 kPa). Plasma miRNAs and metabolites were determined using small RNA sequencing and untargeted capillary electrophoresis-mass spectrometry (CE-MS), respectively. Significantly differentially expressed (SDE) miRNAs were identified using generalized linear models (GLM) with a negative binomial distribution, and their correlation with metabolite levels was quantified using Spearman’s correlation. Results: In the cirrhosis group (n = 32), we identified a distinct signature of 15 SDE miRNAs (9 upregulated, 6 downregulated) compared to the non-cirrhotic group (n = 15), showing hsa-miR-10401-3p, hsa-miR-548ak, hsa-miR-141-3p, and hsa-miR-3940-3p the largest expression changes. miRNA-gene interaction and pathway enrichment analysis suggested that these 15 SDE miRNAs potentially regulate multiple genes involved in immune response and amino acid metabolism. In addition, correlation analyses with our metabolomic data revealed significant associations between specific SDE miRNAs and amino acids and their derivatives. Specifically, the expression of upregulated miRNAs (e.g., hsa-miR-10401-3p and hsa-miR-16-5p) was positively correlated with plasma levels of L-methionine and its derivatives, while downregulated miRNAs (e.g., hsa-miR-625-5p) were inversely correlated with L-tryptophan. Conclusions: In cirrhotic PWH with history of HCV coinfection, a distinct plasma miRNA signature linked to dysregulated amino acid metabolism is found one year after completion of HCV therapy. This underscores that the HCV cure does not equate to complete hepatic recovery, highlighting the critical need for long-term monitoring in this high-risk population. Full article

(This article belongs to the Special Issue HIV and Viral Hepatitis Prevention, Treatment and Coinfection, 2nd Edition)

► Show Figures

Figure 1

52 pages, 16801 KB

Open AccessReview

Delving into the Inception of BODIPY Dyes: Paradigms of In Vivo Bioimaging, Chemosensing, and Photodynamic/Photothermal Therapy

by Olivia Basant, Edgardo Lobo, Gyliann Peña and Maged Henary

Pharmaceuticals 2026, 19(1), 169; https://doi.org/10.3390/ph19010169 - 18 Jan 2026

Cited by 3 | Viewed by 1784

Abstract

Boron-dipyrromethene (BODIPY) dyes belong to a class of organoboron compounds that have become ubiquitous for researchers in areas of fluorescence imaging, photodynamic therapy, and optoelectronics. The intrinsic qualities of BODIPY dyes and their meso-modified structural analogs, Aza-BODIPY dyes, have propelled their recent increase [...] Read more.

Boron-dipyrromethene (BODIPY) dyes belong to a class of organoboron compounds that have become ubiquitous for researchers in areas of fluorescence imaging, photodynamic therapy, and optoelectronics. The intrinsic qualities of BODIPY dyes and their meso-modified structural analogs, Aza-BODIPY dyes, have propelled their recent increase in use in biomedical applications. The two scaffolds have high quantum yields, narrow absorption, and emission bandwidths with large Stokes’ shifts, and high photostability and thermal stability. Because their properties are independent of solvent polarity and dye functionality, they can be tuned to promote novel analytical methods, resulting in the adaptation of the physicochemical and spectral properties of the dyes. In this review of BODIPY and Aza-BODIPY scaffolds, we will summarize their spectral properties, synthetic methods of preparation, and applications reported between 2014 and 2025. This review aims to summarize the advances in chemosensing, especially pH sensor development, and the advances in NIR-II window bioimaging probes. We hope that this succinct overview of Aza-BODIPY scaffolds will highlight their untapped potential, elucidating insights that may catalyze novel ideas in the physical organic realm of BODIPY. Full article

(This article belongs to the Special Issue Photodynamic Therapy: 3rd Edition)

► Show Figures

Graphical abstract

39 pages, 1895 KB

Open AccessReview

Therapeutic Potential of Bovine Colostrum- and Milk-Derived Exosomes in Cancer Prevention and Treatment: Mechanisms, Evidence, and Future Perspectives

by Yusuf Serhat Karakülah, Yalçın Mert Yalçıntaş, Mikhael Bechelany and Sercan Karav

Pharmaceuticals 2026, 19(1), 168; https://doi.org/10.3390/ph19010168 - 17 Jan 2026

Viewed by 2100

Abstract

Due to their therapeutic potential and effects on cells, exosomes derived from bovine colostrum (BCE) and milk (BME) are molecules that have been at the center of recent studies. Their properties include the ability to cross biological barriers, their natural biocompatibility, and their [...] Read more.

Due to their therapeutic potential and effects on cells, exosomes derived from bovine colostrum (BCE) and milk (BME) are molecules that have been at the center of recent studies. Their properties include the ability to cross biological barriers, their natural biocompatibility, and their structure, which enable them to act as stable nanocarriers. Exosomes derived from milk and colostrum stand out in cancer prevention and treatment due to these properties. BMEs can be enriched with bioactive peptides, lipids, and nucleic acids. The targeted drug delivery capacity of BMEs can be made more efficient through these enrichment processes. For example, BME enriched with an iRGD peptide and developed using hypoxia-sensitive lipids selectively transported drugs and reduced the survival rate of triple-negative breast cancer (TNBC) cells. ARV-825-CME formulations increased antitumor activity in some cancer types. The anticancer effects of exosomes are supported by these examples. In addition to their anticancer activities, exosomes also exhibit effects that maintain immune balance. BME and BCE can regulate inflammatory responses with their miRNA and protein loads. These effects of BMEs have been demonstrated in studies on colon, breast, liver, and lung cancers. The findings support the safety and scalability of these effects. However, significant challenges remain in terms of their large-scale isolation, load heterogeneity, and regulatory standardization. Consequently, BMEs represent a new generation of biogenic nanoplatforms at the intersection of nutrition, immunology, and oncology, paving the way for innovative therapeutic approaches. Full article

(This article belongs to the Special Issue Natural Products for Anticancer, Anti-Inflammatory and Antimicrobial Therapies)

► Show Figures

Graphical abstract

22 pages, 3586 KB

Open AccessArticle

Targeting Infected Host Cell Heme Metabolism to Kill Malaria Parasites

by Faiza A. Siddiqui, Swamy R. Adapa, Xiaolian Li, Jun Miao, Liwang Cui and Rays H. Y. Jiang

Pharmaceuticals 2026, 19(1), 167; https://doi.org/10.3390/ph19010167 - 17 Jan 2026

Cited by 3 | Viewed by 1196

Abstract

Background/Objectives: Malaria remains a major global health burden, increasingly complicated by resistance to artemisinin-based therapies. Because artemisinin activation depends on heme and porphyrin chemistry, we sought to exploit host red blood cell (RBC) heme metabolism as a therapeutic vulnerability. This study aims [...] Read more.

Background/Objectives: Malaria remains a major global health burden, increasingly complicated by resistance to artemisinin-based therapies. Because artemisinin activation depends on heme and porphyrin chemistry, we sought to exploit host red blood cell (RBC) heme metabolism as a therapeutic vulnerability. This study aims to develop and evaluate a host-directed “bait-and-kill” strategy that selectively sensitizes malaria-infected RBCs to artemisinin. Methods: We integrated quantitative proteomics, erythropoiesis transcriptomic analyses, flow cytometry, and in vitro malaria culture assays to characterize heme metabolism in mature RBCs and Plasmodium falciparum-infected RBCs (iRBCs). The heme precursor 5-aminolevulinic acid (ALA) was used to induce porphyrin accumulation, and dihydroartemisinin (DHA) was applied as the killing agent. Drug synergy, porphyrin accumulation, reactive oxygen species (ROS) induction, and parasite survival were assessed, including ring-stage survival assays using artemisinin-resistant clinical isolates. Results: Mature RBCs retain a truncated heme biosynthesis pathway capable of accumulating porphyrin intermediates, while uninfected RBCs are impermeable to ALA. In contrast, iRBCs exhibit increased membrane permeability, allowing selective ALA uptake and porphyrin accumulation. ALA alone did not induce cytotoxicity or ROS, whereas DHA induced ROS and parasite killing. The ALA + DHA combination resulted in synergistic parasite elimination, including complete clearance of artemisinin-resistant P. falciparum isolates from the Greater Mekong Subregion, with no recrudescence observed over three weeks of culture. Evidence supports a predominant role for host-derived heme metabolites in mediating this synergy. Conclusions: The bait-and-kill strategy selectively exploits host RBC heme metabolism to restore and enhance artemisinin efficacy while sparing uninfected cells. Using clinically safe compounds, this host-directed approach provides a promising, resistance-bypassing framework for malaria treatment and combination drug development. Full article

(This article belongs to the Special Issue Natural Products for Anticancer, Anti-Inflammatory and Antimicrobial Therapies)

► Show Figures

Graphical abstract

18 pages, 1521 KB

Open AccessSystematic Review

Neuroprotective Potential of SGLT2 Inhibitors in Animal Models of Alzheimer’s Disease and Type 2 Diabetes Mellitus: A Systematic Review

by Azim Haikal Md Roslan, Tengku Marsya Hadaina Tengku Muhazan Shah, Shamin Mohd Saffian, Lisha Jenny John, Muhammad Danial Che Ramli, Che Mohd Nasril Che Mohd Nassir, Mohd Kaisan Mahadi and Zaw Myo Hein

Pharmaceuticals 2026, 19(1), 166; https://doi.org/10.3390/ph19010166 - 16 Jan 2026

Viewed by 1305

Abstract

Background: Alzheimer’s disease (AD) features progressive cognitive decline and amyloid-beta (Aβ) accumulation. Insulin resistance in type 2 diabetes mellitus (T2DM) is increasingly recognised as a mechanistic link between metabolic dysfunction and neurodegeneration. Although sodium–glucose cotransporter-2 inhibitors (SGLT2is) have established glycaemic and cardioprotective benefits, [...] Read more.

Background: Alzheimer’s disease (AD) features progressive cognitive decline and amyloid-beta (Aβ) accumulation. Insulin resistance in type 2 diabetes mellitus (T2DM) is increasingly recognised as a mechanistic link between metabolic dysfunction and neurodegeneration. Although sodium–glucose cotransporter-2 inhibitors (SGLT2is) have established glycaemic and cardioprotective benefits, their neuroprotective role remains less well defined. Objectives: This systematic review examines animal studies on the neuroprotective effects of SGLT2i in T2DM and AD models. Methods: A literature search was conducted across the Web of Science, Scopus, and PubMed databases, covering January 2014 to November 2024. Heterogeneity was assessed with I², and data were pooled using fixed-effects models, reported as standardised mean differences with 95% confidence intervals. We focus on spatial memory performance as measured by the Morris Water Maze (MWM) test, including escape latency and time spent in the target quadrant, as the primary endpoints. The secondary endpoints of Aβ accumulation, oxidative stress, and inflammatory markers were also analysed and summarised. Results: Twelve studies met the inclusion criteria for this review. A meta-analysis showed that SGLT2i treatment significantly improved spatial memory by reducing the escape latency in both T2DM and AD models. In addition, SGLT2i yielded a significant improvement in spatial memory, as indicated by an increased target quadrant time for both T2DM and AD. Furthermore, SGLT2i reduced Aβ accumulation in the hippocampus and cortex, which met the secondary endpoint; the treatment also lessened oxidative stress and inflammatory markers in animal brains. Conclusions: Our findings indicate that SGLT2is confer consistent neuroprotective benefits in experimental T2DM and AD models. Full article

(This article belongs to the Special Issue Novel Therapeutic Strategies for Alzheimer’s Disease Treatment)

► Show Figures

Graphical abstract

31 pages, 751 KB

Open AccessReview

Artificial Intelligence and Predictive Modelling for Precision Dosing of Immunosuppressants in Kidney Transplantation

by Sholpan Altynova, Timur Saliev, Aruzhan Asanova, Zhanna Kozybayeva, Saltanat Rakhimzhanova and Aidos Bolatov

Pharmaceuticals 2026, 19(1), 165; https://doi.org/10.3390/ph19010165 - 16 Jan 2026

Cited by 2 | Viewed by 1569

Abstract

Optimizing immunosuppressant dosing presents significant challenges in kidney transplantation due to narrow therapeutic ranges and considerable inter-patient pharmacokinetic differences. Emerging strategies for precision dosing, encompassing Bayesian population pharmacokinetic models, pharmacogenomic integration, and artificial intelligence algorithms, aim to enhance drug monitoring by moving beyond [...] Read more.

Optimizing immunosuppressant dosing presents significant challenges in kidney transplantation due to narrow therapeutic ranges and considerable inter-patient pharmacokinetic differences. Emerging strategies for precision dosing, encompassing Bayesian population pharmacokinetic models, pharmacogenomic integration, and artificial intelligence algorithms, aim to enhance drug monitoring by moving beyond traditional trough-based approaches. This review critically assesses available evidence for predictive dosing models targeting immunosuppressants, including calcineurin inhibitors, antimetabolites, and mTOR inhibitors in kidney transplant patients. Available observational and simulation studies demonstrate substantial methodological diversity, with Bayesian PopPK-guided strategies showing 15–35% better target exposure achievement compared to trough-based monitoring. The absence of pooled estimates precludes a precise summary effect size, and evidence from randomized controlled trials remains limited. Machine learning models, particularly for tacrolimus, frequently reduced prediction error relative to traditional regression approaches, but substantial heterogeneity in study design, outcome definitions, and external validation limits quantitative synthesis. Hybrid Bayesian–AI frameworks and explainable AI tools show conceptual promise but are largely supported by proof-of-concept studies rather than reproducible clinical implementations. Overall, Bayesian pharmacokinetic modelling represents the most mature and clinically interpretable approach for precision dosing in transplantation, whereas AI-driven and hybrid systems remain investigational. Key gaps include the need for standardized reporting, rigorous risk-of-bias assessment, prospective validation, and clearer regulatory and implementation pathways to support safe and equitable clinical adoption. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring: Techniques and Applications in Pharmaceutical Analysis)

► Show Figures

Graphical abstract

18 pages, 994 KB

Open AccessReview

Aptamer-Based Delivery of Genes and Drugs Across the Blood–Brain Barrier

by Luona Yang, Yuan Yin, Xinli Liu and Bin Guo

Pharmaceuticals 2026, 19(1), 164; https://doi.org/10.3390/ph19010164 - 16 Jan 2026

Cited by 3 | Viewed by 1984

Abstract

The blood–brain barrier (BBB) restricts therapeutic delivery to the central nervous system (CNS), hindering the treatment of neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, brain cancers, and stroke. Aptamers, short single-stranded DNA or RNA oligonucleotides that can fold into unique 3D shapes [...] Read more.

The blood–brain barrier (BBB) restricts therapeutic delivery to the central nervous system (CNS), hindering the treatment of neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, brain cancers, and stroke. Aptamers, short single-stranded DNA or RNA oligonucleotides that can fold into unique 3D shapes and bind to specific target molecules, offer high affinity and specificity, low immunogenicity, and promising BBB penetration via receptor-mediated transcytosis targeting receptors such as the transferrin receptor (TfR) and low-density lipoprotein receptor-related protein 1 (LRP1). This review examines aptamer design through the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) and its variants, mechanisms of BBB crossing, and applications in CNS disorders. Recent advances, including in silico optimization, in vivo SELEX, BBB chip-based MPS-SELEX, and nanoparticle–aptamer hybrids, have identified brain-penetrating aptamers and enhanced the brain delivery efficiency. This review highlights the potential of aptamers to transform CNS-targeted therapies. Full article

(This article belongs to the Collection Feature Review Collection in Pharmaceutical Technology)

► Show Figures

Graphical abstract

14 pages, 2249 KB

Open AccessArticle

Food Packaging Materials for One-Dose Packaging for Enhanced Stability of Hygroscopic Medications

by Takayuki Yoshida, Kiyotaka Ushijima, Natsumi Nishimura, Makoto Toda, Miho Morikawa, Kazuhiro Iwasa and Takashi Tomita

Pharmaceuticals 2026, 19(1), 163; https://doi.org/10.3390/ph19010163 - 16 Jan 2026

Viewed by 1362

Abstract

Background/Objectives: One-dose packaging is beneficial for older adults and those on multiple medications because it ensures that no doses are missed and supports medication adherence. However, conventional one-dose packaging materials have high moisture permeability, making them unsuitable for the storage of hygroscopic medications. [...] Read more.

Background/Objectives: One-dose packaging is beneficial for older adults and those on multiple medications because it ensures that no doses are missed and supports medication adherence. However, conventional one-dose packaging materials have high moisture permeability, making them unsuitable for the storage of hygroscopic medications. We evaluated the barrier performance of food packaging materials against moisture and oxygen and investigated their potential to enhance the physical stability of the highly hygroscopic sodium valproate, under stressed storage conditions. Methods: Barrier performance was evaluated by measuring the water vapor transmission (WVTR) and oxygen transmission rates of each packaging material. Then, we evaluated the stability of sodium valproate tablets in different food packaging films by measuring weight change, breaking force, and visual appearance over 14 days under stressed storage conditions (35 °C and 75% relative humidity). Conventional cellophane-laminated polyethylene was used as the reference. Results: The WVTR of the food packaging films were below 2 g/m²/day, less than that of the conventional material. Tablets stored in Materials A and B showed weight increases of no more than 1.2% after 3 days, whereas the maximum increase among all food films was 3.7% (Material C). For Materials A and B, the breaking force remained measurable and the visual appearance unchanged throughout the 14-day period, whereas Material C became unmeasurable by day 14. Tablets packaged in cellophane-laminated polyethylene exhibited deliquescence, with visible deformation and stickiness within 3 days, rendering them unmeasurable. Conclusions: Food packaging materials with high barrier performance offer a practical, safe, and effective solution for one-dose packaging of hygroscopic medications, potentially expanding their clinical use and improving adherence. Full article

(This article belongs to the Section Pharmaceutical Technology)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Pharmaceuticals, Volume 19, Issue 1 (January 2026) – 192 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI