Pharmaceuticals最新文献

{"title":"Two Sides of the Same Coin for Health: Adaptogenic Botanicals as Nutraceuticals for Nutrition and Pharmaceuticals in Medicine.","authors":"Alexander Panossian, Terrence Lemerond","doi":"10.3390/ph18091346","DOIUrl":"10.3390/ph18091346","url":null,"abstract":"<p><p><b>Background:</b> Adaptogens, commonly used as traditional herbal medicinal products for the relief of symptoms of stress, such as fatigue and exhaustion, belong to a category of physiologically active compounds related to the physiological process of adaptability to stressors. They are used both as pharmaceuticals in medicine and as dietary supplements or nutraceuticals in nutrition, depending on the doses, indications to treat diseases, or support health functions. However, such a dual-faced nature of adaptogens can lead to inconsistencies and contradictory outcomes from Food and Drug regulatory authorities in various countries. <b>Aims:</b> This narrative literature review aimed to (i) specify five steps of pharmacological testing of adaptogens, (ii) identify the sources of inconsistencies in the assessment of evidence the safety, efficacy, and quality of multitarget adaptogenic botanicals, and (iii) propose potential solutions to address some food and drug regulatory issues, specifically adaptogenic botanicals used for prevention and treatment of complex etiology diseases including stress-induced, and aging-related disorders. <b>Overview:</b> This critically oriented narrative review is focused on (i) five steps of pharmacological testing of adaptogens are required in a sequential order, including appropriate in vivo and in vitro models in animals, in vitro model, and mechanisms of action by a proper biochemical assay and molecular biology technique in combination with network pharmacology analysis, and clinical trials in stress-induced and aging-related disorders; (ii) the differences between the requirements for the quality of pharmaceuticals and dietary supplements of botanical origin; (iii) progress, trends, pitfalls, and challenges in the adaptogens research; (iv) inadequate assignment of some plants to adaptogens, or insufficient scientific data in case of <i>Eurycoma longifolia</i>; (v) inconsistencies in botanical risk assessments in the case of <i>Withania somnifera</i>. <b>Conclusions:</b> This narrative review highlights the importance of harmonized standards, transparent methodologies, and a balanced, evidence-informed approach to ensure consumers receive effective and safe botanicals. Future perspectives and proposed solutions include (i) establish internationally harmonized guidelines for evaluating botanicals based on their intended use (e.g., pharmaceutical vs. dietary supplement), incorporating traditional use data alongside modern scientific methods; (ii) encourage peer review and transparency in national assessments by mandating public disclosure of methodologies, data sources, and expert affiliations; (iii) create a tiered evidence framework that allows differentiated standards of proof for traditional botanical supplements versus pharmaceutical candidates; (iv) promote international scientific dialogs among regulators, researchers, and industry to develop consensus positions and avoid unilateral bans that may lack ","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Hora et al. Isoorientin Improves Excisional Skin Wound Healing in Mice. <i>Pharmaceuticals</i> 2024, <i>17</i>, 1368.","authors":"Aline B Hora, Laiza S Biano, Ana Carla S Nascimento, Zaine T Camargo, Greice I Heiden, Ricardo L C Albulquerque-Júnior, Renata Grespan, Jessica M D A Aragão, Enilton A Camargo","doi":"10.3390/ph18091343","DOIUrl":"10.3390/ph18091343","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-Activity Relationship Study of 3-Alkynyl-6-aryl-isothiazolo[4,3-<i>b</i>]pyridines as Dual Inhibitors of the Lipid Kinases PIKfyve and PIP4K2C.","authors":"Demian Kalebic, Ling-Jie Gao, Belén Martinez-Gualda, Marwah Karim, Sirle Saul, Do Hoang Nhu Tran, Jef Rozenski, Leentje Persoons, Dominique Schols, Wim Dehaen, Shirit Einav, Steven De Jonghe","doi":"10.3390/ph18091341","DOIUrl":"10.3390/ph18091341","url":null,"abstract":"<p><p><b>Background/Objectives</b>: RMC-113, a 3-alkynyl-6-aryl-disubstituted isothiazolo[4,3-<i>b</i>]pyridine, is a dual inhibitor of the lipid kinases PIKfyve and PIP4K2C with broad-spectrum antiviral activity. The aim was to study the structure-activity relationship (SAR) of isothiazolo[4,3-<i>b</i>]pyridines as dual PIKfyve/PIP4K2C inhibitors. <b>Methods</b>: A series of isothiazolo[4,3-<i>b</i>]pyridines was synthesized by introducing structural variety at positions 3 and 6 of the central scaffold. The primary assay to guide the synthetic chemistry was a biochemical PIKfyve assay, with a number of analogues also tested for PIP4K2C binding affinity. Finally, isothiazolo[4,3-<i>b</i>]pyridines were also evaluated for antiviral and antitumoral activity in cell-based assays. <b>Results</b>: PIKfyve inhibition tolerated a wide variety of substituents on the aryl ring at position 6 of the isothiazolo[4,3-<i>b</i>]pyridine scaffold, with the 4-carboxamide analogue emerging as the most potent (IC₅₀ = 1 nM). The SAR at position 3 was more restricted, although the introduction of electron-donating groups (such as a methyl and methoxy) on the pyridinyl ring yielded potent PIKfyve inhibitors, with IC₅₀ values in the low nM range. The acetylenic moiety was essential for PIKfyve inhibition, and only the saturated ethyl linker displayed potent PIKfyve inhibition, albeit less active than the acetylene counterpart. The compounds were 2- to 5-fold less potent on PIP4K2C relative to PIKfyve. These dual PIKfyve/PIP4K2C inhibitors displayed antiviral activity against both the venezuelan equine encephalitis virus (VEEV) and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A screening against a panel of cancer cell lines revealed antitumoral activity, although some of the potent PIKfyve/PIP5K2C inhibitors lacked antitumoral activity. <b>Conclusions</b>: Isothiazolo[4,3-<i>b</i>]pyridines are dual PIKfyve/PIP4K2C inhibitors displaying broad-spectrum antiviral, as well as antitumoral, activity.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing Population Pharmacokinetics of Vatiquinone in Healthy Volunteers and Patients with Friedreich's Ataxia.","authors":"Yongjun Hu, Lan Gao, Lucy Lee, Jonathan J Cherry, Ronald Kong","doi":"10.3390/ph18091339","DOIUrl":"10.3390/ph18091339","url":null,"abstract":"<p><p><b>Introduction:</b> Vatiquinone is a first-in-class, small molecule designed to maintain mitochondrial function in the disorders like Friedreich's ataxia (FA). Vatiquinone inhibits 15-lipoxygenase, consequently decreasing oxidative stress and neuroinflammatory response pathways. <b>Methods</b>: Population pharmacokinetic modeling analysis was conducted to characterize vatiquinone pharmacokinetic profiles in healthy volunteers and patients and explore the effects of covariates on vatiquinone exposures. <b>Results:</b> A two-compartment model with parallel zero- and first-order absorption was developed and verified. The values of essential parameters were: absorption fraction through the first-order process, 74.4%; absorption rate constant, 0.20 h^-1; delay time, 2.79 h; zero-order absorption duration, 6.03 h; apparent volume of distribution, 180.75 L for the central and 4852.69 L for the peripheral compartment; and apparent clearance, 162.72 L/h. Strong CYP3A4 inducers could reduce exposure by 50%; strong CYP3A4 inhibitors could increase it by 252%. Vatiquinone exposure was 19% lower in patients with Friedreich's ataxia versus healthy volunteers. A medium-fat meal increased exposure up to 25-fold versus a fasted status. Body weight and body mass index had significant clinical relevance to exposures. <b>Conclusions:</b> A two-compartment model effectively described the pharmacokinetic profiles of vatiquinone after oral administration. Covariates significantly impacted exposures, including body weight, meals, disease status, comedications and body mass index.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Impact of Ultrasound-Assisted Extraction on the Phytochemical Composition and Bioactivity of <i>Tamus communis</i> L. Fruits.","authors":"Irene Gouvinhas, Maria José Saavedra, Maria José Alves, Juliana Garcia","doi":"10.3390/ph18091342","DOIUrl":"10.3390/ph18091342","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The health benefits of <i>Tamus communis</i> fruits have been associated with their high phenolic content, which comprises several flavonoids. However, the extraction methods might significantly impact these valuable compounds' bioactivity. Therefore, the current study assesses how different extraction techniques affect <i>T. communis</i> extracts' antioxidant, anti-aging, antimicrobial, cytotoxic, anti-inflammatory, and phenolic contents. <b>Methods</b>: Conventional method (TCE-CM) and ultrasound-assisted extraction (TCE-UM) were the methods employed. <b>Results</b>: The increased phenolic content of TCE-UM, particularly flavonoids and phenolic acids, was demonstrated to be a contributing factor to its higher biological activity. Key enzymes linked to dermatological conditions, such as elastase, collagenase, hyaluronidase, and tyrosinase, were significantly inhibited by both extracts at 1 mg/mL; TCE-UM showed the highest tyrosinase inhibition (65.61  ±  5.21%) compared to TCE-CM (21.78  ±  2.19%). TCE-UM also demonstrated exceptional antibacterial performance, showing notable antibiofilm and metabolic inactivation effects and potent activity against pathogens such as <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, and <i>Candida albicans</i>. Both extracts showed concentration-dependent anti-inflammatory properties; TCE-UM had a lower IC50 value (26.46 ± 2.30%) in nitric oxide inhibition tests, suggesting stronger anti-inflammatory capabilities. <b>Conclusions</b>: These findings underscore the superior bioactivity of TCE-UM and suggest that ultrasonic extraction is a more efficient method for isolating bioactive phenolic compounds from <i>T. communis</i> fruits, presenting promising applications in anti-aging and antimicrobial formulations.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-Amyloid Reactive Peptides p5+14 and p5R Exhibit Specific Charge-Dependent Binding to Glycosaminoglycans.","authors":"Trevor J Hancock, Angela D Williams, James S Foster, Jonathan S Wall, Emily B Martin","doi":"10.3390/ph18091340","DOIUrl":"10.3390/ph18091340","url":null,"abstract":"<p><p><b>Background</b>: Polybasic peptides are being developed as components of reagents for diagnosing and treating patients with systemic amyloidosis. In addition to fibrils, amyloid deposits ubiquitously contain heparan sulfate proteoglycans. We have hypothesized that pan amyloid-targeting peptides can specifically engage, in addition to fibrils, a subset of glycosaminoglycans (GAGs) with high negative charge density. In this study, we characterized the binding of peptides p5+14 (a PET imaging agent for amyloid [¹²⁴I-evuzamitide]) and p5R (a fusion protein used in the therapeutic AT-02) to GAGs. <b>Methods</b>: The peptide structure was evaluated in the presence of low molecular weight heparin using circular dichroism, and their interaction with synthetic GAGs of varying length and charge was interrogated. The binding patterns of p5+14 and p5R were compared using correlation analyses. <b>Results</b>: The peptides exist as mixed structural-fractions in solution but adopt an α-helical structure in the presence of heparin. Both peptides preferentially recognize heparin and heparan sulfate GAGs with a linear positive correlation between binding and the total charge and charge density. <b>Conclusions</b>: These peptides have previously been shown to specifically target amyloid deposits in vivo. A component of this specificity is their preferential interaction with a subset of heparan sulfate GAGs that have high charge density, potentially related to the degree of 6-O-sulfation. These data support the hypotheses that amyloid-associated GAGs have unique sulfation patterns, thereby explaining why these peptides do not bind GAGs found on the plasma membrane and extracellular matrix of healthy tissues.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Therapeutic Potential of <i>Bupleurum</i> in Medical Treatment: A Comprehensive Overview.","authors":"Yu Tian, Jiageng Guo, Xinya Jiang, Hongyu Lu, Jinling Xie, Fan Zhang, Zhengcai Du, Erwei Hao","doi":"10.3390/ph18091331","DOIUrl":"10.3390/ph18091331","url":null,"abstract":"<p><p><i>Bupleurum</i> is a Chinese medicinal material widely used in clinical practice. Its medicinal component is the dried roots of either the Umbrella plant <i>Bupleurum chinense</i> DC or <i>Bupleurum scorzonerifolium</i> Willd. This review systematically searched major scientific databases such as Web of Science, PubMed, and ScienceDirect, and found that it contains various bioactive substances including saikosaponins, polysaccharides, flavonoids, and volatile oils. These components have demonstrated significant efficacy in anti-tumor, anti-inflammatory, and neuroprotective activities. Research has confirmed that this medicinal herb can exert its pharmacological effects by promoting tumor cell apoptosis, inhibiting cell proliferation, regulating inflammatory signaling pathways, and alleviating neuroinflammation. Additionally, its antipyretic and antiviral properties have also garnered widespread attention. However, clinical data regarding its optimal dosage, administration routes, and safety are still insufficient, necessitating further trials for validation. Investigating the synergistic effects of <i>Bupleurum</i> with other drugs and the safety of its use in different populations are also key directions of current research. Given the urgent need for efficient and sustainable healthcare in modern society, a deep understanding of the mechanisms and safety of <i>Bupleurum</i> is of significant importance for its validation as a foundation for new drug development. In summary, <i>Bupleurum</i>, as a multifunctional natural product, has broad application prospects and is expected to play a greater role in future medical research and clinical practice.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenetics and Molecular Ancestry of <i>SLC22A1</i>, <i>SLC22A2</i>, <i>SLC22A3</i>, <i>ABCB1</i>, <i>CYP2C8</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> in Ecuadorian Subjects with Type 2 Diabetes Mellitus.","authors":"Adiel Ortega-Ayala, Carla González de la Cruz, Lorena Mora, Mauro Bonilla, Leandro Tana, Fernanda Rodrigues-Soares, Pedro Dorado, Adrián LLerena, Enrique Terán","doi":"10.3390/ph18091335","DOIUrl":"10.3390/ph18091335","url":null,"abstract":"<p><p><b>Background/Objectives:</b> In Ecuador, the prevalence of type 2 diabetes mellitus (T2DM) is the second leading cause of death after ischemic heart disease. Genetic variability in protein-coding genes, single nucleotide variants (SNVs), influences the response to antidiabetic drugs. The frequency of SNVs varies among different populations, so studying the ancestral proportions among SNVs is important for personalized medicine in the treatment of T2DM. This study aimed to evaluate the distribution of Native American, European, and African (NATAM, EUR, and AFR) ancestry in 23 allelic variants of the seven genes that encode the relevant enzymes that metabolize antidiabetic drugs in an Ecuadorian population. <b>Methods:</b> Twenty-three allelic variants of seven genes were analyzed in 297 patients with T2DM from Ecuador, and the molecular ancestry of the samples was analyzed considering three ancestral groups, NATAM, EUR, and AFR using 90 ancestry informative markers (AIMs). Allele and ancestry distributions were analyzed using Spearman's correlation. <b>Results</b>: The Ecuadorian population presents NATAM (61.33%), EUR (34.48%), and AFR (2.60%) ancestry components. <i>CYP2C8*1</i> and <i>CYP2C9*1</i> were positively related to NATAM ancestry, while <i>CYP2C8*4</i> and <i>CYP2C9*2</i> were positively related to EUR ancestry. <i>CYP2C19*17</i> was positively correlated to AFR ancestry. The correlation of <i>SLC22A1</i> variants such as A in rs594709 was positively correlated with NATAM, while GAT in rs72552763 was positive for EUR. The G variant of rs628031 of the <i>SLC22A1</i> gene was positively correlated with NATAM and negatively correlated with EUR. The C variant of rs2076828 of the <i>SLC22A3</i> gene was positively correlated with NATAM ancestry. <b>Conclusions:</b> In the Ecuadorian population, a predominance of Native American ancestry has been observed. Among the allelic variants related to enzymes that metabolize antidiabetic drugs, a relationship has been observed between this ancestral component and variants of the <i>CYP2C8*1</i>, <i>CYP2C9*1</i>, <i>SLC22A1</i> (rs594709 and rs628031)<i>,</i> and <i>SLC22A3</i> (rs2076828) genes. This information is fundamental for the development of strategies for the implementation of personalized medicine programs for Latin American patients.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of SGLT2 Inhibitors, GLP-1 Receptor Agonists, DPP-4 Inhibitors, and Sulfonylureas on Moderate-to-Severe COPD Exacerbations Among Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis.","authors":"Edoardo Pirera, Domenico Di Raimondo, Lucio D'Anna, Antonino Tuttolomondo","doi":"10.3390/ph18091337","DOIUrl":"10.3390/ph18091337","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) frequently coexist, contributing to worse clinical outcomes and increased risk of exacerbations. While newer glucose-lowering agents have demonstrated cardiovascular and renal benefits, their comparative efficacy on COPD exacerbations remain uncertain. <b>Methods</b>: We systematically searched PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov from inception to June 2025. We included randomised controlled trials (RCTs) and observational studies enrolling adults with COPD and T2DM that reported the risk of COPD exacerbations following initiation of SGLT2is, GLP-1RAs, DPP-4is, or sulfonylureas, with an active comparator group. The primary outcome was a composite of moderate-to-severe COPD exacerbations. Secondary outcomes included the individual components separately. A Bayesian random-effects network meta-analysis was performed to estimate risk ratio (RR) with 95% credible intervals (95% CIs). <b>Results</b>: Nine observational studies were ultimately included. No RCTs were retrieved. Compared to sulfonylureas, initiation of SGLT2is (RR 0.64, 0.59-0.69), GLP-1RAs (0.66, 0.60-0.71), and DPP-4is (0.79, 0.74-0.86) was associated with reduced risk of moderate-to-severe exacerbations. Moreover, SGLT2is (0.80, 0.75-0.86) and GLP-1RAs (0.83, 0.77-0.88) were more favourable compared to DPP4is. Consistent results were found for secondary outcomes. Sensitivity analyses confirmed the robustness of the findings for the primary outcome. Robustness was not consistently observed across all treatment comparisons for secondary outcomes. <b>Conclusions</b>: Among patients with COPD and T2DM, newer glucose-lowering agents, particularly SGLT2is and GLP-1RAs, were associated with significantly lower risk of moderate-to-severe exacerbations. These findings support the potential respiratory benefits of these agents and warrant confirmation through RCTs.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bee Venom Proteins Enhance Proton Absorption by Membranes Composed of Phospholipids of the Myelin Sheath and Endoplasmic Reticulum: Pharmacological Relevance.","authors":"Zhuoyan Zeng, Mingsi Wei, Shuhao Zhang, Hanchen Cui, Ruben K Dagda, Edward S Gasanoff","doi":"10.3390/ph18091334","DOIUrl":"10.3390/ph18091334","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Recent evidence challenges the classical chemiosmotic theory, suggesting that proton movement along membrane surfaces-not bulk-phase gradients-drives bioenergetic processes. Proton accumulation on membranes like the myelin sheath and endoplasmic reticulum (ER) may represent a universal mechanism for cellular energy storage. This study investigates whether phospholipids from these membranes, combined with anionic bee venom proteins, enhance proton absorption, potentially elucidating a novel bioenergetic pathway. <b>Methods</b>: Five phospholipids (phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, phosphatidylcholine) from rat liver were isolated to model myelin/ER membranes. Anionic proteins (p<i>I</i> 5.65-5.80) were purified from bee venom via cation exchange chromatography. Liposomes (with/without proteins) were prepared, and proton absorption was quantified by pH changes in suspensions versus pure water. Statistical significance was assessed via ANOVA and <i>t</i>-tests. <b>Results</b>: All phospholipid liposomes examined in this study absorbed protons under the tested conditions, with phosphatidylethanolamine showing the highest capacity (pH increase: 7.00 → 7.18). Liposomes enriched with anionic proteins exhibited significantly greater proton absorption (e.g., phosphatidylserine + proteins: pH 8.15 vs. 7.15 alone; <i>p</i> < 2.43 × 10^-6). Sphingomyelin-protein liposomes absorbed the most protons, suggesting that protein-phospholipid interactions modulate surface proton affinity. <b>Conclusions</b>: Anionic bee venom proteins amplify proton absorption by phospholipid membranes, supporting the hypothesis that lipid-protein complexes act as \"proton capacitors\". This mechanism may underpin extramitochondrial energy storage in myelin and ER. Pharmacologically, targeting these interactions could mitigate bioenergetic deficits in aging or disease. Further research should define the structural basis of proton capture by membrane-anchored proteins.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}