Die Pharmazie最新文献

{"title":"Suppressing Bitterness in Orally Disintegrating Films by Coating Drug Particles With a pH-Dependent Polymer.","authors":"Yuichi Okubo, Yoshiko Takeuchi, Hirofumi Takeuchi","doi":"10.31083/Pharmazie53415","DOIUrl":"https://doi.org/10.31083/Pharmazie53415","url":null,"abstract":"<p><strong>Background: </strong>Orally disintegrating films (ODFs) disintegrate and dissolve in the mouth, which creates challenges such as bitter taste and particle roughness. One of the most useful methods for suppressing bitterness in solid dosage forms is coating drug particles with a polymer to physically prevent contact between the drug and the taste buds. Because ODFs are extremely thin, the volume available for particle incorporation is limited; therefore, it is necessary to prepare fine coated drug particles with a size smaller than 200 µm, which also helps mitigate particle roughness in the oral cavity. In this study, we designed and prepared ODFs incorporating taste-masked drug particles for easy administration and improved adherence to drug therapy.</p><p><strong>Methods: </strong>We used quinine hydrochloride (QH) as a model bitter active pharmaceutical ingredient (API), polyvinylacetal diethylaminoacetate (AEA), a pH-dependent polymer, as a coating agent, and hydroxypropyl methylcellulose (HPMC) as the film-forming agent. The ODFs containing taste-masked QH granules and the corresponding granules themselves were evaluated using a taste-sensing system. The disintegration, drug dissolution profiles, and physical properties of the ODFs were also evaluated.</p><p><strong>Results: </strong>We prepared QH granules with the targeted median diameter (d₅₀) and geometric standard deviation (σ_g), and the initial release of QH from these granules was less than 5% within 2 min. We also demonstrated, using the same system, that ODFs containing these granules delayed and suppressed the emergence of QH-induced bitterness. The disintegration time of the ODFs was less than 30 s, and their tensile strength remained above the 2 MPa threshold required for handling.</p><p><strong>Conclusion: </strong>We successfully prepared ODFs that suppressed the bitterness of QH while maintaining a short disintegration time and practical mechanical strength.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 8","pages":"53415"},"PeriodicalIF":0.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotechnology-Based Strategies for Treating Skin Hyperpigmentation: A Review of Current Advances and Challenges.","authors":"Gabriela Fátima de Lima Flores, Gabriela Fusinatto de Oliveira, Debora Cristine Chrisostomo Dias, Ana Paula Horn, Cristiana Lima Dora, Letícia Scherer Koester, Flávia Nathiely Silveira Fachel, Helder Ferreira Teixeira","doi":"10.31083/Pharmazie52238","DOIUrl":"https://doi.org/10.31083/Pharmazie52238","url":null,"abstract":"<p><p>Skin hyperpigmentation is a common dermatological condition characterized by excessive melanin accumulation in the epidermis, dermis, or both, resulting from disorders such as melasma, post-inflammatory hyperpigmentation, drug-induced hyperpigmentation, and solar lentigo. Conventional treatments are mainly based on tyrosinase inhibition; however, many depigmenting agents have limitations, including low stability, poor skin permeation, prolonged treatment durations, and adverse effects such as irritation and dermatitis. In this context, nanotechnology-based delivery systems have emerged as promising alternatives for the topical administration of depigmenting compounds. Therefore, this review discusses recent advances in nanotechnology-based strategies for treating skin hyperpigmentation, with a primary focus on lipid-based nanosystems, including liposomes, nanoemulsions, solid lipid nanoparticles, and nanostructured lipid carriers. A total of 33 studies published between 2000 and 2025 were analyzed. The reviewed studies demonstrated that nanoencapsulation may improve the physicochemical stability, enable controlled release, enhance skin permeation/retention, and increase the therapeutic performance of depigmenting agents while reducing toxicity and adverse effects. <i>In vitro</i> studies also reported enhanced tyrosinase inhibition, high cell viability, and increased accumulation of active compounds in different skin layers. Overall, nanotechnology-based delivery systems represent a promising and versatile approach for improving the efficacy and safety of topical treatments for skin hyperpigmentation.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 8","pages":"52238"},"PeriodicalIF":0.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Saxifraga umbellulata</i> Attenuates Cholestatic Liver Injury and Modulates Farnesoid X Receptor-Related Bile Acid Homeostasis.","authors":"Mozili Adu, Bowei Xia, Ying Wang, Yaodong Hu, Yingying Gao, Caiyun Sun, Wei Jiang","doi":"10.31083/Pharmazie53907","DOIUrl":"https://doi.org/10.31083/Pharmazie53907","url":null,"abstract":"<p><strong>Background: </strong>Disrupted bile acid homeostasis represents a central feature of cholestatic liver injury, for which effective therapeutic options remain limited. <i>Saxifraga umbellulata</i> Hook. f. et Thoms. (SU) has traditionally been used in Tibetan medicine to treat hepatobiliary disorders, yet the pharmacological basis of SU remains unclear. Therefore, this study aimed to evaluate the effects of SU on cholestatic liver injury and explore the regulatory mechanisms underlying these effects.</p><p><strong>Methods: </strong>A mouse model of cholestatic liver injury was established by administering α-naphthyl isothiocyanate (ANIT). The effects of SU were evaluated using serum biochemical measurements, liver histopathology, and targeted profiling of hepatic bile acids. Protein expression associated with farnesoid X receptor (FXR) signaling was assessed by Western blotting in liver and ileal tissues. Representative triterpenoids in the SU extract were further examined using molecular docking and HepG2 cell experiments.</p><p><strong>Results: </strong>SU administration reduced serum markers of hepatocellular injury and cholestasis and lessened hepatic necrosis and inflammatory cell infiltration in ANIT-treated mice. SU also shifted the altered hepatic bile acid profile toward a more balanced state, including partial correction of the disturbed proportions of primary and secondary bile acids. These metabolic changes were accompanied by reduced hepatic CYP7A1 expression and increased expression of BSEP and MRP2. In addition, SU increased ileal FXR and FGF15 expression and hepatic FGFR4 expression, a pattern consistent with coordinated regulation of the intestinal FXR-FGF15/hepatic FGFR4 axis. Meanwhile, molecular docking and HepG2 cell experiments suggested that cucurbitacin IIb and saxifragic acid may contribute to the observed FXR-related responses.</p><p><strong>Conclusions: </strong>SU mitigated ANIT-induced cholestatic liver injury and promoted partial recovery of hepatic bile acid homeostasis. The protective effects of SU were associated with coordinated changes in hepatic and intestinal FXR-related signaling and with reduced inflammatory injury. These results provide experimental evidence supporting the traditional use of SU for hepatobiliary disorders and highlight cucurbitacin IIb and saxifragic acid as potential bioactive triterpenoids.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 8","pages":"53907"},"PeriodicalIF":0.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Aminoacyl-2-Cyanopyrrolidine Compounds and Their Inhibitory Effect on the DPP-4 Enzyme.","authors":"Liyuan Guo, Man Di, Zhiyan Dong, Da Zhang, Xiaoqing Zhu, Shi Wu, Chao Liu","doi":"10.31083/Pharmazie53112","DOIUrl":"https://doi.org/10.31083/Pharmazie53112","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus is a major global health concern. DPP-4 (dipeptidyl peptidase-4) inhibitors containing a 2-cyanopyrrolidine scaffold are in clinical use; however, systematic evaluation of amides derived from amino acids adjacent to the <i>N</i>-2 position of GLP-1 (glucagon-like peptide-1) has not been reported.</p><p><strong>Methods: </strong>A total of eight 2-cyanopyrrolidine derivatives, grouped into three series, were synthesized from <i>N</i>-Boc-protected amino acids via condensation with 2-cyanopyrrolidine followed by deprotection. The compounds were characterized by nuclear magnetic resonance (NMR), elemental analysis, and mass spectrometry (MS). DPP-4 inhibitory activity was evaluated <i>in vitro</i> using a DPP-IV Glo™ assay, with sitagliptin as a control. IC₅₀ (Half Maximal Inhibitory Concentration) values were determined from three independent replicates (n = 3) and calculated by nonlinear regression.</p><p><strong>Results: </strong>Compounds <b>4d</b>, <b>4g</b>, and <b>4h</b> exhibited excellent DPP-4 inhibition, with IC₅₀ values of 1.36 ± 0.09, 5.24 ± 0.31, and 4.83 ± 0.22 nM, respectively. Compound <b>4d</b> (histidine) was more potent than sitagliptin (6.13 ± 0.42 nM). The bis-cyanopyrrolidine derivatives <b>4g</b> and <b>4h</b> also showed strong activity. The remaining compounds (<b>4a</b>-<b>4c</b>, <b>4e</b>, <b>4f</b>) displayed moderate inhibition (IC₅₀ 112-181 nM).</p><p><strong>Conclusions: </strong>Aminoacyl-2-cyanopyrrolidine derivatives bearing an imidazole or bis-cyanopyrrolidine structure are potent DPP-4 inhibitors. These findings highlight the importance of neighboring GLP-1 amino acid residues (positions 1 and 3) in inhibitor design. Further cellular and <i>in vivo</i> studies are warranted to evaluate the therapeutic potential of these compounds.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 8","pages":"53112"},"PeriodicalIF":0.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sappanchalcone Attenuates Platelet Activation and Clot Retraction Through Coordinated Modulation of Cyclic Nucleotides and PI3K/MAPK Signaling Pathways.","authors":"Ga Hee Lee, Jin Pyo Lee, Chang Eun Park, Dong-Ha Lee","doi":"10.31083/Pharmazie54071","DOIUrl":"https://doi.org/10.31083/Pharmazie54071","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Aberrant platelet activation is a major contributor to thrombotic disorders, prompting interest in naturally derived candidates that can safely regulate platelet function. Sappanchalcone, a chalcone-type flavonoid derived from &lt;i&gt;Caesalpinia sappan&lt;/i&gt; L&lt;i&gt;.&lt;/i&gt;, has diverse biological activities; however, its effects on platelet activation and clot retraction remain unclear. This study evaluated the antiplatelet potential of sappanchalcone and its underlying mechanisms in human platelets.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Washed human platelets and platelet-rich plasma were used to assess platelet activation and clot retraction, respectively. Samples were pretreated with sappanchalcone (16-128 μM, depending on the assay) and stimulated with collagen or thrombin. Platelet aggregation and cytotoxicity were assessed by light transmission aggregometry and lactate dehydrogenase (LDH) leakage assay. cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and thromboxane B&lt;sub&gt;2&lt;/sub&gt; (TXB&lt;sub&gt;2&lt;/sub&gt;) levels were quantified using enzyme-linked immunosorbent assay (ELISA) kits, and intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; mobilization was measured by Fura-2/AM-based fluorescence analysis. Protein phosphorylation was examined by Western blotting, whereas integrin αIIbβ&lt;sub&gt;3&lt;/sub&gt;-fibrinogen binding was analyzed by flow cytometry. Dense granule secretion was evaluated using adenosine triphosphate (ATP) luminescence and serotonin ELISA assays. Thrombin-induced clot retraction was quantified by ImageJ (v1.54k, U.S. National Institutes of Health, Bethesda, MD, USA)-based residual clot area analysis. Data are presented as mean ± standard deviation (SD) and analyzed by one-way analysis of variance (ANOVA) with Tukey-Kramer post hoc test (n = 4; &lt;i&gt;p&lt;/i&gt; &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Sappanchalcone concentration-dependently inhibited collagen-induced platelet aggregation, reducing aggregation from 83.0% to 10.7% at 128 μM, with a half-maximal inhibitory concentration (IC&lt;sub&gt;50&lt;/sub&gt;) of 57.16 μM, without cytotoxicity. At 128 μM, sappanchalcone increased cAMP from 7.02 ± 0.85 to 11.96 ± 0.57 pmol/10&lt;sup&gt;8&lt;/sup&gt; platelets and reduced Ca&lt;sup&gt;2+&lt;/sup&gt; mobilization from 711.97 ± 47.29 to 66.11 ± 6.83 nM. Vasodilator-stimulated phosphoprotein (VASP) Ser&lt;sup&gt;157&lt;/sup&gt; and Ser&lt;sup&gt;239&lt;/sup&gt; phosphorylation increased by 2.97- and 2.07-fold, respectively, whereas fibrinogen binding decreased from 74.43 ± 5.67% to 21.90 ± 1.25%. Phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 phosphorylation was reduced to 0.69-, 0.21-, 1.81-, 0.27-, and 0.49-fold, respectively. ATP secretion, serotonin release, TXB&lt;sub&gt;2&lt;/sub&gt; levels reflecting thromboxane A&lt;sub&gt;2&lt;/sub&gt; (TXA&lt;sub&gt;2&lt;/sub&gt;) generation, cytosolic phospholipase A&lt;sub&gt;2&lt;/sub&gt; (cPLA&lt;sub&gt;2&lt;/sub&gt;) phosphorylation, and thrombin-induced clot retraction were also suppressed.&lt;/p&gt;&lt;p&gt;&lt;stro","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 8","pages":"54071"},"PeriodicalIF":0.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Entinostat and Tucidinostat Potentiate Temozolomide Response in Glioblastoma Models.","authors":"Ruijie Chen, Junhui Su, Xinjue Dong, Xinyi Tang, Yuqi Yang, Qingquan Li","doi":"10.31083/Pharmazie51570","DOIUrl":"https://doi.org/10.31083/Pharmazie51570","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) frequently develops resistance to temozolomide (TMZ), limiting the effectiveness of standard therapy. Histone deacetylase (HDAC) inhibitors have emerged as potential chemosensitizers; however, the comparative performance of these inhibitors and the associated mechanistic impact remain incompletely characterized.</p><p><strong>Methods: </strong><i>In vitro</i>, this study systematically evaluated the effects of the Class I-selective HDAC inhibitors Entinostat and Tucidinostat, and the pan-HDAC inhibitor Vorinostat on TMZ sensitivity in multiple GBM cell lines (U87, U251, LN229). Additionally, this study assessed cell viability, morphology, and the expression of selected markers glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), class III β-tubulin (TUBB3), and synapsin I (SYN1). <i>In vivo</i>, the therapeutic efficacy of Entinostat combined with TMZ was evaluated in a U87 xenograft mouse model by measuring tumor growth, and the expression of GFAP and TUBB3 was examined in tumor tissues. Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9 (CRISPR-Cas9)-mediated knockout of HDAC1/2/3 was used to test the dependence of these effects on canonical Class I HDACs.</p><p><strong>Results: </strong>Entinostat and Tucidinostat significantly enhanced TMZ-induced cytotoxicity across all cell lines, demonstrating greater TMZ-sensitizing activity than Vorinostat under the conditions tested. Treatment was associated with altered cell morphology and changes in marker expression, including reduced GFAP and increased MAP2 and TUBB3. In the U87 xenograft model, Entinostat combined with TMZ significantly suppressed tumor growth and was associated with decreased GFAP and increased TUBB3 expression. Importantly, both TMZ sensitization and the associated morphological and marker changes persisted in HDAC1/2/3-knockout cells, suggesting that the effects are not fully explained by HDAC1/2/3 depletion. These effects were consistent across multiple cell lines and in xenograft tumors.</p><p><strong>Conclusions: </strong>Entinostat and Tucidinostat enhance TMZ sensitivity in GBM models and are associated with specific markers and morphological changes that persist despite HDAC1/2/3 knockout. These findings support further evaluation of Entinostat and Tucidinostat as TMZ-sensitizing agents in GBM models and highlight associated phenotypic and molecular changes that warrant further mechanistic validation.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 7","pages":"51570"},"PeriodicalIF":0.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical Interventions During Inpatient Care in a French Geriatric Hospital.","authors":"Diana Lopez-Leret, Joël Schlatter","doi":"10.31083/Pharmazie53161","DOIUrl":"https://doi.org/10.31083/Pharmazie53161","url":null,"abstract":"<p><strong>Background: </strong>Since aging is associated with pharmacokinetic and pharmacodynamic changes, polypharmacy is particularly harmful in older adults. Meanwhile, clinical pharmacists contribute to safer prescribing by applying their clinical expertise during medication review. Therefore, this study aimed to characterize potential drug-related problems through the analysis of routine pharmaceutical interventions.</p><p><strong>Methods: </strong>Data were collected from the electronic health record between 2019 and 2025; potentially inappropriate medications and high-risk medications were identified. Drug-related problems were categorized according to the Pharmaceutical Care Network Europe classification.</p><p><strong>Results: </strong>Pharmacists performed 12,856 pharmaceutical interventions, of which prescribers accepted 65%. The mean patient age was 87.5 years (range, 65-113 years), and 60.2% of patients were female. Among all pharmaceutical interventions, 1779 involved a potentially inappropriate medication. The most frequent causes of drug-related problems were related to dose selection (39.8%), drug selection (14.3%), treatment duration (10.1%), and treatment safety (9.3%). The most commonly targeted drug categories were the nervous system (24.7%), the digestive tract and metabolism (21.5%), blood and hematopoietic organs (19.8%), and the cardiovascular system (13.6%).</p><p><strong>Conclusions: </strong>Pharmaceutical interventions that prevent prescribing errors in older adults are essential in clinical practice. Understanding potential drug-related problems and the nature of pharmaceutical interventions can help ensure safe pharmacotherapy by alerting prescribers and caregivers to major medication-related risks.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 7","pages":"53161"},"PeriodicalIF":0.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Therapeutic Mechanism of <i>Ginkgo Biloba</i> Extract in Alzheimer's Disease via Integrated Network Pharmacology and Molecular Docking.","authors":"Yipei Li, Juan Gong, Liu Yang, Li Jin, Ruirui Peng, Fang Wang, Li Wang","doi":"10.31083/Pharmazie51748","DOIUrl":"https://doi.org/10.31083/Pharmazie51748","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the mechanisms through which ginkgolides in <i>Ginkgo biloba</i> extract (GBE) may protect against Alzheimer's disease (AD).</p><p><strong>Methods: </strong>Candidate ginkgolide constituents and their putative targets were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction. AD-associated genes were retrieved from OMIM and GeneCards. Overlapping targets were used to construct component-target-disease and protein-protein interaction (PPI) networks for hub target screening. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using DAVID. AutoDock Vina was used for molecular docking, and molecular dynamics simulations were conducted to evaluate ligand-target stability. The predicted mechanisms were further examined in APP/PS1 mice and Aβ1-42-treated HT22 cells.</p><p><strong>Results: </strong>A total of 27 active ginkgolide-related constituents and 336 intersecting targets were identified. Ginkgolides B and M were identified as the major active compounds, whereas MAPK3, HIF-1α, and AKT1 emerged as important targets. Enrichment analysis indicated a close association with the PI3K-Akt pathway. Docking analysis showed that ginkgolides B and M bound strongly to MAPK3 and HIF-1α with binding energies ranging from -9.34 to -8.41 kcal/mol. Molecular dynamics simulations supported the stable formation of these complexes. <i>In vivo</i> and <i>in vitro</i> experiments showed that ginkgolides B and M alleviated synaptic protein damage, decreased HIF-1α expression, and improved cognitive deficits.</p><p><strong>Conclusions: </strong>Ginkgolides B and M may contribute to anti-AD effects in experimental models, partly through modulation of HIF-1α-related stress responses and PI3K-Akt-associated survival pathways.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 7","pages":"51748"},"PeriodicalIF":0.0,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Simple Quantitative Method for the Prediction of Exposure of Drugs in Subjects With Varying Degrees of Hepatic Impairment.","authors":"Iftekhar Mahmood","doi":"10.31083/Pharmazie52625","DOIUrl":"https://doi.org/10.31083/Pharmazie52625","url":null,"abstract":"<p><strong>Background: </strong>Hepatic impairment can alter the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs due to the liver's reduced ability to metabolize drugs. The objective of this study was to develop a simple quantitative method using the Child-Pugh classification scoring system to predict the area under the curve (AUC) of drugs in subjects with mild, moderate, and severe hepatic impairment.</p><p><strong>Methods: </strong>In this study, from healthy subjects, the AUC of 64, 76, and 51 drugs in subjects with mild, moderate, and severe hepatic impairment, respectively, were predicted. The drugs used in this analysis are those that are extensively metabolized in the liver by the cytochrome P-450 system (phase I metabolism). Child-Pugh scores were used to classify varying degrees of hepatic impairment. The scores <5 (no hepatic impairment), and 5, 7, and 10 are the scores from where the Child-Pugh score begins for mild, moderate, and severe hepatic impairment, respectively. In this analysis, a Child-Pugh score of 4 was assigned to healthy subjects. The AUC of a drug in subjects with mild hepatic impairment was predicted as follows: AUC in healthy subjects × (5/4)^0.75, where 5 is the Child-Pugh score in subjects with mild hepatic impairment, and the exponent 0.75 is the exponent of basal metabolic rate or clearance. A similar approach for the prediction of the AUC of drugs was taken in subjects with moderate and severe hepatic impairment. The predicted AUC values in subjects with mild, moderate, and severe hepatic impairment were compared with the observed values obtained from dedicated clinical trials.</p><p><strong>Results: </strong>In subjects with mild, moderate, and severe hepatic impairment 96.9%, 97.4%, and 82.4% drugs were within 0.5-2-fold prediction error, respectively. No drug was predicted with >2-fold prediction error.</p><p><strong>Conclusions: </strong>Overall, the results of the study indicated that the proposed method, in its predictive performance, was fairly accurate for the prediction of the AUC of a drug in subjects with varying degrees of hepatic impairment. The proposed method will be helpful in the selection of appropriate dose(s) of drugs in subjects with varying degrees of hepatic impairment for clinical trials or, in some cases, in clinical settings (especially, in mild or moderate hepatic impairment).</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 7","pages":"52625"},"PeriodicalIF":0.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SCM198 Alleviates Pulmonary Fibrosis Through Downregulation of the TGF-β1/Smad Signalling Pathway and Activation of Nrf2-Mediated Antioxidant Defenses During EMT.","authors":"Jie Liang, Hanxuan Wang, Ruixiang Wang, Keyuan Chen, Yizhun Zhu","doi":"10.31083/Pharmazie52723","DOIUrl":"https://doi.org/10.31083/Pharmazie52723","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary fibrosis (PF) is a chronic and progressive respiratory disorder marked by aberrant activation of pulmonary fibroblasts and the occurrence of epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AECs). This disease process is primarily driven by inflammation and oxidative stress (OS), leading to excessive deposition of the extracellular matrix (ECM). Current treatments provide limited efficacy and are associated with significant side effects. Leonurine and its sulfate derivative SCM198, derived from Herba Leonuri, exhibit anti-inflammatory and antioxidant properties. However, their therapeutic effects and mechanisms of action in PF remain poorly understood.</p><p><strong>Methods: </strong>Bleomycin (BLM) was delivered intratracheally to mice to establish a model of PF. Human Fetal Lung fibroblast-1 (HFL-1) fibroblasts and A549 AECs were subjected to transforming growth factor-beta 1 (TGF-β1) exposure for <i>in vitro</i> assays. This study comprehensively evaluated the effects of SCM198 on PF and explored its underlying molecular mechanisms through metabolomics analysis, western blotting, and additional biological techniques.</p><p><strong>Results: </strong>SCM198 significantly ameliorated lung pathology and micro-Computed Tomography (CT) findings and reduced collagen deposition in BLM-treated mice. Furthermore, the levels of inflammatory markers and cytokines were decreased in lung tissue and Bronchoalveolar Lavage Fluid (BALF). <i>In vitro</i>, SCM198 inhibited fibroblast activation, EMT, and OS. It also down-regulated the TGF-β1/Smad2/3 pathway and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway.</p><p><strong>Conclusions: </strong>The ameliorative action of SCM198 on BLM-induced pulmonary fibrosis is associated with suppression of the TGF-β1/Smad2/3 signaling axis and activation of Nrf2-mediated antioxidant defenses during the EMT process. However, further studies are needed to confirm the direct involvement of these pathways.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 7","pages":"52723"},"PeriodicalIF":0.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}