Pharmaceutical Biology最新文献

{"title":"Delivery of small interfering RNA through lyophilized natural lipid nanoparticles: effects of natural lipid selection.","authors":"Hangjie Wang, Wei Li, Junyan Chen, Rong Chen, Yuwei Qi, Linshuang Shen, Kaidi Chen, Lewei Dai, Yuxin Sheng, An Wang, Hong Wang, Chujian Chen, Xiao Cheng, Mancang Gu","doi":"10.1080/13880209.2025.2498169","DOIUrl":"https://doi.org/10.1080/13880209.2025.2498169","url":null,"abstract":"<p><strong>Context: </strong>Lipid nanoparticles (LNPs) are the primary non-viral vectors for siRNA delivery. However, synthetic lipids face issues, such as low lysosomal escape efficiency and high cost.</p><p><strong>Objective: </strong>This study aimed to use three natural lipids to construct LNPs, optimize their preparation and freeze-drying processes, and evaluate their siRNA delivery efficiency <i>in vitro</i>.</p><p><strong>Materials and methods: </strong><i>Coix</i> seed lipid [<i>Coix lacryma-jobi</i> L. var. <i>mayuen</i> (Roman.) Stapf (Poaceae), CSL], <i>Brucea javanica</i> seed lipid [<i>Brucea javanica</i> (L.) Merr. (Simaroubaceae), BJL], and Soybean oil [<i>Glycine max</i> (L.) Merr. (Fabaceae), SO] were used to construct LNPs. The Z-average size, zeta potential, Polymer Dispersity Index, and N/P ratio of the LNPs were characterized. Transmission electron microscope was used for morphology observation and the MTS assay for cytotoxicity. Confocal laser scanning microscope assessed cell uptake, lysosomal escape, and co-localization of lipid droplets. The efficiency of siRNA knockdown was evaluated in three cells using qPCR and Western blot. The freeze-drying processes were optimized.</p><p><strong>Results: </strong>The optimal LNPs exhibited a size of 160-180 nm, zeta of 44-50 mV, and PDI of <0.2. At 200 μg/mL, the LNPs did not affect cell viability. CSL-LNPs, BJL-LNPs, and SO-LNPs reduced KRAS^G12D mRNA levels in AsPC-1 cells by 67.87 ± 3.89, 47.18 ± 7.65, and 42.52 ± 8.90%, respectively. Freeze-dried LNPs retained their basic physical properties and the three LNPs reducing KRAS^G12D mRNA levels by 58.47 ± 4.00, 51.83 ± 4.57, and 38.00 ± 4.89%, respectively.</p><p><strong>Discussion and conclusion: </strong>Natural lipids are promising components for LNPs construction, offering new avenues for siRNA delivery in gene therapy.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"343-356"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007342","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":"Involvement of ionomic metabolism of both the cerebrospinal fluid and the spinal cord in the analgesic efficacy of matrine in rats.","authors":"Jin-Lu Huang, Chen-Yue Tang, Yao Fu, Li-Li Wan, Jie Li, Xi-Peng Sun, Jia-Lu Hu, Yue-Yi Zhang, Li-Ying Qu, Miao-Jia Fu, Yuan-Yuan Zhang, Le Ma, Cheng Guo, Jiu-Geng Chen","doi":"10.1080/13880209.2025.2492872","DOIUrl":"https://doi.org/10.1080/13880209.2025.2492872","url":null,"abstract":"<p><strong>Context: </strong>Matrine has antinociceptive properties, and spinal cord ionomic changes are involved in bone cancer pain.</p><p><strong>Objective: </strong>To investigate the relationship between ionomic metabolism in cerebrospinal fluid (CSF) and spinal cord and matrine's analgesic efficacy.</p><p><strong>Materials and methods: </strong>The antinociceptive effects of matrine were identified in rats <i>via</i> intraperitoneal (i.p.) injection using the tail-immersion and formalin tests. Pharmacodynamic parameters for matrine against formalin-induced pain were calculated with nonlinear regression analysis. Inductively coupled plasma mass spectrometry (ICP-MS) technology was utilized to detect contents of the ionome in CSF and spinal cord. Variations in ionomic metabolism in different treated groups were examined using Pearson's correlation coefficients and principal component analysis (PCA).</p><p><strong>Results: </strong>In the tail-immersion test, matrine significantly prolonged tail-flick latency in rats. Matrine also dose-dependently yielded analgesia against formalin-induced biphasic pain, with an onset at around 10 min post-injection and a duration of 100 min. The ED₅₀ and E_max values were 19.01 mg/kg and 71.86% for phase I and 40.30 mg/kg and 81.51% for phase II, respectively. Pearson's correlation coefficient study and PCA revealed significant reprogramming of ionomic metabolism in the CSF and the spinal cord in the NM (normal saline + matrine), NF (normal saline + formalin), and FM (formalin + matrine) groups, compared to the NN (normal saline + normal saline) group.</p><p><strong>Discussion and conclusions: </strong>These findings broaden the known analgesic spectrum of matrine and provide novel insights into the involvement of ionomic metabolism in its analgesic efficacy.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"275-287"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037418","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":"Naringenin inhibits ferroptosis to reduce radiation-induced lung injury: insights from network Pharmacology and molecular docking.","authors":"Junlin Jiang, Xianhui Deng, Chengkai Xu, Yaxian Wu, Jianfeng Huang","doi":"10.1080/13880209.2025.2465312","DOIUrl":"10.1080/13880209.2025.2465312","url":null,"abstract":"<p><strong>Context: </strong>Naringenin is a natural flavanone with potent pharmacological properties. It has demonstrated therapeutic potential in treating various diseases and organ injuries, including radiation-induced lung injury (RILI). Ferroptosis is a newly type of cell death, and naringenin has been shown to attenuates ferroptosis.</p><p><strong>Objective: </strong>To evaluate the inhibitory effect and molecular mechanism of naringenin on ferroptosis during RILI process.</p><p><strong>Materials & methods: </strong>Firstly, BEAS-2B and HUVECs cells were pre-incubated with naringenin for 1 h prior to 8 Gy of X-ray irradiation to evaluate oxidative stress, inflammation, and the mRNA levels of ferroptosis-related genes. Next, target genes of naringenin, RILI, and ferroptosis were identified using the TCMSP, SwissTargetPrediction, and GeneCards databases. The target network was constructed with Cytoscape and STRING. Finally, the core target genes were identified through <i>in vitro</i> experiments by qRT-PCR, western blot and immunofluorescence staining.</p><p><strong>Results: </strong>Naringenin effectively reduced radiation-induced increasement of oxidative stress, inflammation, and ferroptosis markers in both cell lines. Network pharmacology identified 14 target genes, with prostaglandin endoperoxide synthase (PTGS2) and Valosin-containing protein (VCP) mRNA levels being prominent, which were crucial for ferroptosis regulation. Molecular docking revealed strong binding interactions between naringenin and the two target proteins. Subsequently, experimental validation confirmed that naringenin reduced the elevated levels of PTGS2 and VCP induced by radiation.</p><p><strong>Discussion & conclusion: </strong>Naringenin alleviates radiation-induced lung damage by inhibiting ferroptosis, with PTGS2 and VCP emerging as potential therapeutic targets.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"1-10"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449905","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":"Mechanism of action of genistein on breast cancer and differential effects of different age stages.","authors":"Zhebin Xiang, Bo Ma, Xiujun Pei, Wenjie Wang, Weilun Gong","doi":"10.1080/13880209.2025.2469607","DOIUrl":"10.1080/13880209.2025.2469607","url":null,"abstract":"<p><strong>Context: </strong>Genistein, a soy-derived isoflavone, exhibits structural similarities with 17β-estradiol and demonstrates antioxidant, anti-inflammatory, and estrogenic properties. Despite its low bioavailability limiting its clinical application, it shows potential for breast cancer prevention and treatment.</p><p><strong>Objective: </strong>This review aims to summarize the pharmacological effects and molecular mechanisms of genistein in breast cancer, focusing on its therapeutic potential, strategies to overcome bioavailability limitations, and its role in personalized medicine. Differential impacts among population subgroups are also discussed.</p><p><strong>Methods: </strong>A systematic review was conducted using PubMed, ScienceDirect, and Google Scholar databases. Studies were selected based on their focus on genistein's mechanisms of action, strategies to enhance its bioavailability, and interactions with other therapies.</p><p><strong>Results: </strong>Genistein exerted anticancer effects by modulating estrogen receptor β (ERβ), inhibiting angiogenesis, arresting the cell cycle, and inducing apoptosis. Its antioxidant properties help mitigate tumor-associated oxidative stress. Bioavailability enhancement strategies, such as nanoparticle and lipid-based formulations, show promise. Age-dependent effects were evident, with distinct responses observed in prepubertal, menopausal, and postmenopausal populations, underscoring its potential for personalized therapies. Furthermore, genistein influences epigenetic modifications, including DNA methylation and miRNA expression, bolstering its anticancer efficacy.</p><p><strong>Conclusion: </strong>Genistein is a promising candidate for breast cancer therapy, particularly for personalized treatment. Strategies to enhance bioavailability and further clinical research are essential to optimize its therapeutic potential and evaluate its efficacy in combination therapies.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"141-155"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493093","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":"Harmine derivative H-2-168 induces the death of <i>Echinococcus granulosus</i> by regulating mitochondrial fusion and fission.","authors":"Yuehong Gong, Meiling Zhao, Meichi Pan, Yicong Zhao, Junpeng Liu, Hao Wen, Jianhua Wang","doi":"10.1080/13880209.2025.2485898","DOIUrl":"10.1080/13880209.2025.2485898","url":null,"abstract":"<p><strong>Context: </strong>H-2-168 has pharmacological effects similar to those of harmine, with less toxicity. The health of cells and organisms depends on a delicate balance between mitochondrial fusion and fission.</p><p><strong>Objective: </strong>This study investigated the roles of H-2-168 and mitochondrial fusion and fission in <i>Echinococcus granulosus</i>.</p><p><strong>Materials and methods: </strong>Notably, <i>E. granulosus</i> were isolated from fresh sheep livers, and then treated with H-2-168 (25 μg/mL), mitochondrial division inhibitor 1 (Mdivi-1, 25 μg/mL) or the combination of H-2-168:Mdivi-1 (25 μg/mL:12.5 μg/mL). After 24 h of culture, the indices related to <i>E. granulosus</i> were measured. Additionally, Drp1 was knocked down to explore its effects on <i>E. granulosus</i> growth.</p><p><strong>Results: </strong>The EC₅₀ values of H-2-168, Mdivi-1 and H-2-168:Mdivi-1 against <i>E. granulosus</i> were 44.171, 117.882 and 32.924 μg/mL, respectively. Compared with H-2-168 or Mdivi-1, the combination of H-2-168 and Mdivi-1 showed better inhibitory effects on <i>E. granulosus</i> viability, as well as increased levels of ROS and LDH, decreased ATP levels, inhibited mitochondrial activity and reduced mitochondrial membrane potential (<i>p</i> < 0.05), with the upregulation of Caspase-3, Cyt-c, Drp1, Fis1 and downregulation of Bcl-2, Mfn2 and OPA1. Additionally, <i>Drp1</i> knockdown was successfully performed in <i>E. granulosus</i>, which significantly inhibited <i>E. granulosus</i> viability (<i>p</i> < 0.05) and further downregulated Mfn2 expression induced by H-2-168.</p><p><strong>Discussion and conclusion: </strong><i>Drp1</i> is closely associated with mitochondrial fusion and fission, and H-2-168 may promote <i>E. granulosus</i> death through disrupting the balance between mitochondrial fusion and fission.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"188-200"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795892","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":"Qing-Xin-Jie-Yu Granule attenuates myocardial infarction-induced inflammatory response by regulating the MK2/TTP pathway.","authors":"Jianghan Qi, Xiaoyao Gao, Ying Han, Meiling Yang, Chenyi Wei, Ling Zhang, Jianfeng Chu","doi":"10.1080/13880209.2025.2467377","DOIUrl":"10.1080/13880209.2025.2467377","url":null,"abstract":"<p><strong>Context: </strong>Qing-Xin-Jie-Yu Granule (QXJYG) has shown promise in the treatment of myocardial infarction. However, the mechanism of action of QXJYG underlying its anti-inflammation remain unknown.</p><p><strong>Objective: </strong>The study aimed to evaluate the effectiveness and mechanism of QXJYG in a mouse model of myocardial infarction and hypoxia-induced H9C2 cells.</p><p><strong>Materials and methods: </strong>Myocardial infarction was induced in mice <i>via</i> left anterior descending coronary artery ligation, and hypoxia-induced H9C2 cells was served as the <i>in vitro</i> model. The cardiac function was evaluated by echocardiography, while myocardial tissue pathology was examined using HE and Masson's trichrome staining. Changes in serum markers of cardiac injury were measured using ELISA kits. The levels of inflammatory cytokines in both the serum and cardiac tissue were quantified using the Bio-Plex Pro Mouse Chemokine assay, and hypoxia-induced inflammatory factors in H9C2 cells were assessed by RT-qPCR. Additionally, western blot analysis was conducted to evaluate the expression of proteins related to the MK2/TTP signaling pathway both <i>in vivo</i> and <i>in vitro</i> experiments.</p><p><strong>Results: </strong>QXJYG significantly enhanced cardiac function in mice with myocardial infarction, as evidenced by improved myocardial tissue structure, reduced collagen fiber deposition, and lowered serum levels of creatine kinase isoenzyme MB (CK-MB), cardiac Troponin T (cTnT), and brain Natriuretic Peptide (BNP). QXJYG may reduce the expression of inflammatory factors in both the heart and serum of myocardial infarction-induced mice and attenuate hypoxia-induced levels of inflammatory factors in cardiomyocytes by decreasing the ratio of p-MK2/MK2 and increasing the protein expression of TTP.</p><p><strong>Discussion and conclusions: </strong>QXJYG improved cardiac function and reduced injury, fibrosis, and inflammation after myocardial infarction, likely through modulation of the MK2/TTP signaling pathway.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"128-140"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468813","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":"Characterization of global research trends and prospects on celastrol, a principal bioactive ingredient of <i>Tripterygium wilfordii</i> Hook F: bibliometric analysis.","authors":"Huizi Ye, Yufang Wang, Xue Zhang, Lin Yang, Banglan Cai, Denghai Zhang, Bin Peng","doi":"10.1080/13880209.2024.2443424","DOIUrl":"10.1080/13880209.2024.2443424","url":null,"abstract":"<p><strong>Context: </strong>Celastrol, acknowledged as a prominent exemplar of the potential for transforming traditional medicinal compounds into contemporary pharmaceuticals, has garnered considerable attention owing to its extensive pharmacological activities. The increasing volume of publications concerning celastrol highlights its importance in current scientific inquiry. Despite the growing interest in this compound, a bibliometric analysis focused on this subject remains to be undertaken.</p><p><strong>Objective: </strong>Our study explored a bibliometric approach to identify and characterize global research trends and frontiers related to celastrol, including mapping research outputs, influential contributors, and thematic areas, as well as highlighting gaps and opportunities for future investigations.</p><p><strong>Materials and methods: </strong>In this study, we utilized the Web of Science Core Collection (WoSCC) to source and review articles related to celastrol published from 1997 to 2023. The bibliometric analysis was conducted using the R package 'Bibliometrix,' supplemented by visualization tools including CiteSpace, VOSviewer, and GraphPad Prism 10.</p><p><strong>Results: </strong>Celastrol related research papers have exhibited an upward trend annually and can be categorized into three distinct phases, each highlighting different areas of focus. China, the United States, and South Korea rank as the top three nations for publication volume, with varied research interests across these countries. Several prolific research teams have emerged, each with distinct areas of interest. Examining the primary research domains of celastrol (anti-inflammatory, anticancer, and toxicity) reveals a notable intersection between the first two domains.</p><p><strong>Discussion and conclusions: </strong>The scope and depth of celastrol research have been steadily expanding, with regional and team-specific variations. Key research areas include anti-inflammatory, anticancer, and toxicity studies. Future research is expected to focus on enhancing the effectiveness and reducing the toxicity of celastrol. Meanwhile, given the multi-target characteristics of celastrol's effects, integrating methods such as network biology and molecular simulation will provide a novel perspective for celastrol research.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"15-26"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biologically active withanolides from <i>Physalis peruviana</i>.","authors":"Mayuramas Sang-Ngern, Ashley Fukuchi, Tamara P Kondratyuk, Eun-Jung Park, Charles J Simmons, Marisa M Wall, Sam E Lorch, John M Pezzuto, Leng Chee Chang","doi":"10.1080/13880209.2025.2488136","DOIUrl":"https://doi.org/10.1080/13880209.2025.2488136","url":null,"abstract":"<p><strong>Context: </strong><i>Physalis peruviana</i> L. (Solanaceae), also known as Poha, has been used in traditional medicine since pre-Columbian times, particularly in treating cancer.</p><p><strong>Objective: </strong>To study the chemical composition and potential medicinal properties of Poha.</p><p><strong>Materials and methods: </strong>The fresh fruits and aerial parts of Poha were extracted. The isolation of extract yields a novel withanolide (physaperuvin K; <b>1</b>) from the edible fruit, and seven withanolides (<b>2</b>-<b>8</b>), including a rare chlorinated withanolide (physalolactone; <b>2</b>) from the aerial parts. Structure elucidation/determination was performed, some acetate derivatives were prepared (<b>2a</b>-<b>6a</b>), and the compounds were evaluated with <i>in vitro</i> assays indicative of anti-inflammatory activity.</p><p><strong>Results: </strong>The structure of <b>1</b> was elucidated through NMR spectroscopic analyses. The absolute configuration of compound <b>2</b> was determined using single-crystal X-ray diffraction. Compounds <b>1</b>, <b>2</b>, and <b>3</b> exhibited inhibition of tumor necrosis factor-α-induced nuclear factor-kappa B (NF-κB) activity with IC₅₀ values of 10, 60, and 40 nM, respectively, without causing cytotoxicity at a concentration of 50 μM. Furthermore, compounds <b>1</b>-<b>3</b> reduced nitric oxide (NO) production in lipopolysaccharide-activated RAW 264.7 mouse macrophage cells with IC₅₀ values ranging from 0.32 to 13.3 μM without overt cytotoxicity. Overall, acetylation did not significantly impact activity, except for compound <b>4</b>, wherein the IC₅₀ values in the NF-κB and NO assays were reduced from 11.0 to 0.33 μM, and 1.8 to 0.24 μM, respectively.</p><p><strong>Conclusions: </strong>These findings enhance our understanding of Poha's constituents and potential medicinal properties. One of the most bioactive compounds identified in this study, physaperuvin K, is found in edible fruit.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"334-343"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039236","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":"A novel strategy for the protective effect of ginsenoside Rg1 against ovarian reserve decline by the PINK1 pathway.","authors":"Pengdi Yang, Meiling Fan, Ying Chen, Dan Yang, Lu Zhai, Baoyu Fu, Lili Zhang, Yanping Wang, Rui Ma, Liwei Sun","doi":"10.1080/13880209.2025.2453699","DOIUrl":"10.1080/13880209.2025.2453699","url":null,"abstract":"<p><strong>Context: </strong>The decline in ovarian reserve is a major concern in female reproductive health, often associated with oxidative stress and mitochondrial dysfunction. Although ginsenoside Rg1 is known to modulate mitophagy, its effectiveness in mitigating ovarian reserve decline remains unclear.</p><p><strong>Objective: </strong>To investigate the role of ginsenoside Rg1 in promoting mitophagy to preserve ovarian reserve.</p><p><strong>Materials and methods: </strong>Ovarian reserve function, reproductive capacity, oxidative stress levels, and mitochondrial function were compared between ginsenoside Rg1-treated and untreated naturally aged female <i>Drosophila</i> using behavioral, histological, and molecular biological techniques. The protective effects of ginsenoside Rg1 were analyzed in a <i>Drosophila</i> model of oxidative damage induced by tert-butyl hydroperoxide. Protein expression levels in the PINK1/Parkin pathway were assessed, and molecular docking and PINK1 mutant analyses were conducted to identify potential targets.</p><p><strong>Results: </strong>Ginsenoside Rg1 significantly mitigated ovarian reserve decline, enhancing offspring quantity and quality, increasing the levels of ecdysteroids, preventing ovarian atrophy, and elevating germline stem cell numbers in aged <i>Drosophila</i>. Ginsenoside Rg1 improved superoxide dismutase, catalase activity, and gene expression while reducing reactive oxygen species levels. Ginsenoside Rg1 activated the mitophagy pathway by upregulating PINK1, Parkin, and Atg8a and downregulating Ref(2)P. Knockdown of PINK1 in the ovary by RNAi attenuated the protective effects of ginsenoside Rg1. Molecular docking analysis revealed that the ginsenoside Rg1 could bind to the active site of the PINK1 kinase domain.</p><p><strong>Discussion and conclusions: </strong>Ginsenoside Rg1 targets PINK1 to regulate mitophagy, preserving ovarian reserve. These findings suggest the potential of ginsenoside Rg1 as a therapeutic strategy to prevent ovarian reserve decline.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"68-81"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059506","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":"<i>WDJ-S4</i>, a standardized herbal formula, promotes gastrointestinal motility via modulation of the acetylcholine pathway in a loperamide-induced functional dyspepsia mice.","authors":"Seung-Ju Hwang, Chang-Seob Seo, Dong-Cheol Baek, Tae-Wook Woo, Jing-Hua Wang, Jin-Seok Lee, Yu-Jin Choi, Ji-Yeon Gu, Dong-Seon Kim, Chang-Gue Son","doi":"10.1080/13880209.2025.2488134","DOIUrl":"https://doi.org/10.1080/13880209.2025.2488134","url":null,"abstract":"<p><strong>Context: </strong>WDJ-S4, a standardized herbal formula, has been prescribed for refractory functional dyspepsia (FD) in Korea, but the detailed mechanisms are lacking.</p><p><strong>Objective: </strong>The present study investigates the acceleration of gastrointestinal (GI) motility by WDJ-S4 and its potential mechanisms.</p><p><strong>Materials and methods: </strong>For five days, WDJ-S4 (50, 100 and 200 mg/kg) or mosapride (3 mg/kg) was orally given to BALB/c mice. After 20 h of fasting, loperamide (10 mg/kg, i.p.) was given to the mice except for normal group. To assess gastric emptying or intestinal propulsion, 500 μL of 0.05% phenol red or 200 μL of 5% charcoal diet was given once orally.</p><p><strong>Results: </strong>Loperamide delayed gastric emptying and intestinal propulsion, while WDJ-S4 ameliorated peristaltic dysfunction, evidenced by reductions of remaining phenol red in the stomach and a marked increase of charcoal propulsion in the intestine. WDJ-S4 also normalized levels of acetylcholine and acetylcholine-related enzymes, including choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), in the gastric antrum and jejunum. C-kit level and smooth muscle contraction-related genes were elevated by WDJ-S4 in both the gastric antrum and jejunum.</p><p><strong>Conclusion: </strong>Overall, WDJ-S4 can effectively promote GI motility. The efficacy is associated with modulation of acetylcholine pathway and the interstitial cells of Cajal (ICCs) activation. All the results provide scientific evidence supporting the clinical usage of WDJ-S4 for FD.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"218-228"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028097","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}