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Aqueous extract of erigeron annuus ameliorates OVA-induced atopic dermatitis-like skin lesions through modulation of Th2-mediated immune responses and MAPK signaling. 金盏花水提物通过调节th2介导的免疫反应和MAPK信号通路改善ova诱导的特应性皮炎样皮肤病变。
IF 6 3区 医学
Pharmaceutical Biology Pub Date : 2026-12-01 Epub Date: 2026-10-16 DOI: 10.1080/13880209.2026.2748088
Yejin Ahn, Min Ji Gu, Ho-Young Park, Seol Ji Baek, Seong Un Jeong, Sang Keun Ha, Donghwan Kim
{"title":"Aqueous extract of <i>erigeron annuus</i> ameliorates OVA-induced atopic dermatitis-like skin lesions through modulation of Th2-mediated immune responses and MAPK signaling.","authors":"Yejin Ahn, Min Ji Gu, Ho-Young Park, Seol Ji Baek, Seong Un Jeong, Sang Keun Ha, Donghwan Kim","doi":"10.1080/13880209.2026.2748088","DOIUrl":"10.1080/13880209.2026.2748088","url":null,"abstract":"<p><strong>Context: </strong>Atopic dermatitis is a chronic inflammatory skin disorder characterized by epidermal barrier dysfunction and dysregulated type 2 helper T cell (Th2)-mediated immune responses. <i>Erigeron annuus</i> (L.) Desf. is traditionally used for inflammatory conditions, but its effects on atopic dermatitis remain unclear.</p><p><strong>Objective: </strong>This study evaluated the protective effects of <i>E. annuus</i> aqueous extract (EA) and associated mechanisms.</p><p><strong>Materials and methods: </strong>Atopic dermatitis-like lesions were induced in 5-week-old female BALB/c mice by repeated epicutaneous ovalbumin (OVA) sensitization, and EA was orally administered for six weeks. Epidermal barrier function, histopathology, immunoglobulins, cytokines, and mitogen-activated protein kinase (MAPK) signaling were evaluated. Pyromeconic acid (PA), a representative constituent of EA, was examined in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.</p><p><strong>Results: </strong>EA attenuated dermatitis-like lesions and reduced dermatitis scores in OVA-sensitized mice. EA decreased transepidermal water loss, increased skin hydration, restored filaggrin expression, and reduced epidermal and dermal thickening, mast cell infiltration, CD4<sup>+</sup>/CD8<sup>+</sup> T-cell accumulation, splenomegaly, serum total and OVA-specific IgE, and skin interleukin-4 and interleukin-13 levels. EA also reduced extracellular signal-regulated kinase and p38 phosphorylation and interleukin-1β expression in dorsal skin. PA suppressed MAPK activation and inflammatory mediator expression in LPS-stimulated macrophages.</p><p><strong>Discussion and conclusion: </strong>EA attenuated OVA-induced atopic dermatitis-like inflammation in association with improved epidermal barrier function, reduced Th2-associated immune responses, and attenuated MAPK signaling. PA showed anti-inflammatory activity <i>in vitro</i>, although its contribution to the <i>in vivo</i> effects of EA remains to be established. EA warrants further investigation as a plant-derived candidate for complementary intervention in atopic dermatitis.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"1125-1142"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195885","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}
引用次数: 0
Ginkgolic acid targets HSPA8 to trigger ferroptosis in hepatocellular carcinoma via chaperone-mediated autophagy-dependent GPX4 degradation. 银杏酸靶向HSPA8,通过伴侣蛋白介导的自噬依赖性GPX4降解引发肝癌铁下垂。
IF 6 3区 医学
Pharmaceutical Biology Pub Date : 2026-12-01 Epub Date: 2026-03-25 DOI: 10.1080/13880209.2026.2646350
Ruohong Liu, Yufan Zhang, Huizhen Zou, Min Zhang, Zhiyuan Yang, Kexi Liao, Guoping Wang, Beiyu Liu, Lijun Tang, Xia Kang, Shuguo Zheng
{"title":"Ginkgolic acid targets HSPA8 to trigger ferroptosis in hepatocellular carcinoma <i>via</i> chaperone-mediated autophagy-dependent GPX4 degradation.","authors":"Ruohong Liu, Yufan Zhang, Huizhen Zou, Min Zhang, Zhiyuan Yang, Kexi Liao, Guoping Wang, Beiyu Liu, Lijun Tang, Xia Kang, Shuguo Zheng","doi":"10.1080/13880209.2026.2646350","DOIUrl":"10.1080/13880209.2026.2646350","url":null,"abstract":"<p><strong>Context: </strong>Ginkgolic acid (GAC), one of the major active constituents of <i>Ginkgo biloba L. (Ginkgoaceae)</i> extract, has been reported as a potential anticancer agent.</p><p><strong>Objective: </strong>To investigate the effect of GAC on the viability of human hepatocellular carcinoma (HCC) cells and to identify its primary target and underlying mechanism.</p><p><strong>Materials and methods: </strong>Human HCC cell lines and an orthotopic HCC mouse model were employed. The mechanism of GAC was elucidated through integrated analyses of cell viability, RNA sequencing, and biomarkers. The primary target of GAC was identified by drug affinity responsive target stability (DARTS) coupled with LC-MS/MS and further validated using molecular docking (MD), cellular thermal shift assay (CETSA), and microscale thermophoresis (MST) assay. Mechanistic roles were confirmed using genetic approaches, including gene knockdown and the construction of mutant plasmids. A KFERQ reporter system was used to detect the activity of chaperone-mediated autophagy (CMA).</p><p><strong>Results: </strong>GAC effectively inhibits the viability of HCC by triggering ferroptosis. HSPA8 was identified as the direct target of GAC. The binding of GAC with HSPA8 enhances its interaction with glutathione peroxidase 4 (GPX4), which leads to the degradation of GPX4 <i>via</i> CMA. This process depleted glutathione (GSH) and caused lipid peroxidation, finally inducing ferroptosis in HCC cells. Furthermore, GAC suppressed tumor growth in an orthotopic HCC model, increased lipid peroxidation, and GPX4 degradation in tumor tissues.</p><p><strong>Discussion and conclusions: </strong>Our results revealed a novel mechanism by which GAC induces ferroptosis in HCC cells through direct targeting of HSPA8 and promoting CMA-dependent GPX4 degradation. These findings suggest GAC-mediated ferroptosis as a potential therapeutic strategy against HCC and expand the pharmacological application of CMA-targeted cancer therapies.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"514-535"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13021020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513868","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}
引用次数: 0
Simultaneous quantification of seventeen kratom alkaloids and metabolites in human plasma and its application to clinical pharmacokinetic sample analysis. 人血浆中17种苦参生物碱及其代谢物的同时定量测定及其在临床药动学分析中的应用。
IF 6 3区 医学
Pharmaceutical Biology Pub Date : 2026-12-01 Epub Date: 2026-08-17 DOI: 10.1080/13880209.2026.2715806
Siva Rama Raju Kanumuri, Manoj Gundeti, Sushobhan Mukhopadhyay, Naftali Z Zeilinger, C Austin Zamarripa, Kirsten E Smith, Christopher R McCurdy, Abhisheak Sharma
{"title":"Simultaneous quantification of seventeen kratom alkaloids and metabolites in human plasma and its application to clinical pharmacokinetic sample analysis.","authors":"Siva Rama Raju Kanumuri, Manoj Gundeti, Sushobhan Mukhopadhyay, Naftali Z Zeilinger, C Austin Zamarripa, Kirsten E Smith, Christopher R McCurdy, Abhisheak Sharma","doi":"10.1080/13880209.2026.2715806","DOIUrl":"10.1080/13880209.2026.2715806","url":null,"abstract":"<p><strong>Context: </strong><i>Mitragyna speciosa</i> Korth, commonly known as kratom, has been used traditionally in Southeast Asia by chewing fresh leaves and brewing decoctions (tea) for its stimulant and sedative-like properties. Despite its widespread use, controlled clinical trials are limited and have monitored mitragynine only or a few other major alkaloids and metabolites.</p><p><strong>Objective: </strong>The objective of the study was to develop and validate an ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of 12 kratom alkaloids along with 5 metabolites of mitragynine in human plasma.</p><p><strong>Materials and methods: </strong>A sensitive UPLC-MS/MS based bioanalytical method for the simultaneous quantification of kratom alkaloids, including mitragynine, speciogynine, speciociliatine, mitraciliatine, paynantheine, isopaynantheine, corynantheidine, corynoxine-A, corynoxine-B, mitraphylline, speciofoline, and ajmalicine, along with five metabolites of mitragynine, 7-hydroxymitragynine, 9-hydroxycorynantheidine, mitragynine 16-carboxylic acid, mitragynine pseudoindoxyl, and 3-dehydromitragynine in human plasma was developed and validated following FDA guidelines. Chemically unstable metabolites, 7-hydroxymitragynine and 9-hydroxycorynantheidine, were stabilized in human plasma. The bioanalytical method was further used for the analysis of plasma samples collected during a clinical trial involving four regular kratom users.</p><p><strong>Results: </strong>The method was linear over the concentration range of 1-250 ng/mL. A simple protein precipitation method was used to extract analytes. Upon oral administration of kratom products, most of the alkaloids were absorbed quickly and showed peak plasma concentrations within 1-2 h post-dose.</p><p><strong>Discussion and conclusions: </strong>Mitragynine, speciociliatine, mitraciliatine, isopaynantheine, and paynantheine are major circulating alkaloids, with mitragynine 16-carboxylic acid and 9-hydroxycorynantheidine being the major circulating metabolites of mitragynine in plasma upon kratom oral administration.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"902-920"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13482927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761196","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}
引用次数: 0
A design of experiments approach to production of medicinal bioactives in Mitragyna speciosa (Korth.) Havil. 北米特拉吉那药用生物活性物质生产的实验方法设计Havil。
IF 6 3区 医学
Pharmaceutical Biology Pub Date : 2026-12-01 Epub Date: 2026-09-12 DOI: 10.1080/13880209.2026.2727756
Ryland T Giebelhaus, Paula N Brown, Mariam Ali, Amy M Dodds, Lauren A E Erland
{"title":"A design of experiments approach to production of medicinal bioactives in <i>Mitragyna speciosa</i> (Korth.) Havil.","authors":"Ryland T Giebelhaus, Paula N Brown, Mariam Ali, Amy M Dodds, Lauren A E Erland","doi":"10.1080/13880209.2026.2727756","DOIUrl":"10.1080/13880209.2026.2727756","url":null,"abstract":"<p><strong>Context: </strong><i>Mitragyna speciosa</i> (Korth.) commonly known as 'kratom' is a tropical tree native to southeast Asia, that produces psychoactive monoterpenoid indole alkaloids including mitragynine. Kratom products are growing in popularity for increasing energy, improving mood and alleviating minor pain, but availability of commercial plant material is limited in North America. Propagation relies primarily on shoot cuttings rooted in soils with high levels of humus and is relatively inefficient.</p><p><strong>Objective: </strong>This study aimed to optimize <i>in vitro</i> shoot induction system for kratom using a Design of Experiments (DOE) approach and compare the metabolite profiles of <i>in vitro</i> and greenhouse-grown plants using metabolomics.</p><p><strong>Materials and methods: </strong>A DOE approach was used to minimize the number of treatments necessary to optimize <i>in vitro</i> culture media to induce shoot and root morphogenesis in kratom explants. A clean mother stock of <i>in vitro</i> cultures was established and evaluated for medicinal bioactives <i>via</i> targeted and untargeted analyses by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).</p><p><strong>Results: </strong>We found no significant difference in the quantified levels of mitragynine, melatonin, and some related metabolites, between <i>in vitro-</i>grown and greenhouse-grown plants within the experimental conditions of this study.</p><p><strong>Discussion and conclusions: </strong>The presence of similar specialized metabolite profiles in greenhouse and <i>in vitro</i>-grown kratom plants paves the way for further studies on biotechnological engineering and production of these valuable compounds. <i>In vitro</i> propagation is a viable approach to produce bioactive compounds in kratom plants.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"1017-1033"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956335","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}
引用次数: 0
Kaempferol activity on Cryptosporidium parvum infection in an experimentally infected immunocompromised mouse model: In silico and in vivo investigations. 山奈酚对实验性感染免疫功能低下小鼠模型中细小隐孢子虫感染的活性:计算机和体内研究。
IF 4.8 3区 医学
Pharmaceutical Biology Pub Date : 2026-12-01 Epub Date: 2025-12-19 DOI: 10.1080/13880209.2025.2603384
Majed H Wakid, Eman S El-Wakil, Muslimah N Alsulami, Haytham Azab
{"title":"Kaempferol activity on <i>Cryptosporidium parvum</i> infection in an experimentally infected immunocompromised mouse model: <i>In silico</i> and <i>in vivo</i> investigations.","authors":"Majed H Wakid, Eman S El-Wakil, Muslimah N Alsulami, Haytham Azab","doi":"10.1080/13880209.2025.2603384","DOIUrl":"10.1080/13880209.2025.2603384","url":null,"abstract":"<p><strong>Context: </strong>No vaccine or effective therapy for cryptosporidiosis currently exists, except for nitazoxanide (NTZ), which has limited effectiveness in immunocompromised hosts. Kaempferol (KPF), a naturally occurring flavonoid, has various pharmacological effects and promising antiparasitic properties.</p><p><strong>Objective: </strong>The current work aimed to examine the impact of KPF compared with NTZ on <i>Cryptosporidium parvum</i> (<i>C. parvum</i>) using both <i>in silico</i> molecular docking and <i>in vivo</i> studies with an experimentally infected immunocompromised mouse model.</p><p><strong>Materials and methods: </strong>The present study utilized KPF and NTZ as multi-target ligands to predict, determine, and evaluate their <i>in silico</i> target-interacted forms, thereby demonstrating their therapeutic properties against <i>C. parvum</i>. Mice were immunosuppressed and divided into six groups: DEXA, Model, KPF as prophylaxis, treatment with KPF, NTZ, and a combination of KPF and NTZ. Treatment efficacy was assessed through parasitological, histopathological examination, and immunohistochemical analysis of intestinal tissues using NLRP3 protein.</p><p><strong>Results: </strong>The <i>in silico</i> findings supported the use of KPF and NTZ as inhibitors of <i>C. parvum</i> growth by blocking the action of <i>C. parvum</i> choline and pyruvate kinases. The <i>in vivo</i> study demonstrated that KPF exhibits anti-cryptosporidial efficacy, particularly when combined with NTZ. The KPF+NTZ had the best results, as evidenced by a significant decrease (<i>p</i> < 0.001) in oocyst shedding of 83%, improved intestinal histological damage, and inhibition of the NLRP3 inflammasome pathway.</p><p><strong>Discussion and conclusion: </strong>KPF demonstrated the potential to mitigate the consequences of cryptosporidiosis and serve as an adjuvant agent to NTZ by reducing the oocyst burden, alleviating intestinal inflammation, and facilitating mucosal repair.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"27-45"},"PeriodicalIF":4.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12720632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782374","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}
引用次数: 0
Mechanistic insight into the anti-inflammatory and lung-protective effects of Agrimonia pilosa extract via NF-κB/MAPK inhibition in ovalbumin- and lipopolysaccharide-induced respiratory inflammation models. 通过抑制NF-κ b /MAPK对卵清蛋白和脂多糖诱导的呼吸道炎症模型的抗炎和肺保护作用的机制研究
IF 6 3区 医学
Pharmaceutical Biology Pub Date : 2026-12-01 Epub Date: 2026-03-01 DOI: 10.1080/13880209.2026.2627661
Yeong-Geun Lee, Jeong Eun Kwon, Dae Won Park, Hae Rim Lee, Jinhyuk Lee, Yong-Min Choi, Eun-Ji Cho, Se Chan Kang
{"title":"Mechanistic insight into the anti-inflammatory and lung-protective effects of <i>Agrimonia pilosa</i> extract via NF-κB/MAPK inhibition in ovalbumin- and lipopolysaccharide-induced respiratory inflammation models.","authors":"Yeong-Geun Lee, Jeong Eun Kwon, Dae Won Park, Hae Rim Lee, Jinhyuk Lee, Yong-Min Choi, Eun-Ji Cho, Se Chan Kang","doi":"10.1080/13880209.2026.2627661","DOIUrl":"10.1080/13880209.2026.2627661","url":null,"abstract":"<p><strong>Context: </strong>Asthma and COPD involve airway inflammation, oxidative stress, and epithelial cell apoptosis. While corticosteroids are common, long-term use can cause adverse effects, prompting interest in plant-based anti-inflammatory alternatives. <i>Agrimonia pilosa</i> (AP) shows promise, but its effectiveness in airway inflammation requires further study.</p><p><strong>Objective: </strong>To assess anti-inflammatory and lung-protective effects in LPS-stimulated A549 cells and an OVA+LPS mouse model, focusing on NF-κB/MAPK pathways and apoptosis-related markers.</p><p><strong>Materials and methods: </strong>A549 cells were pretreated with AP and stimulated with LPS. Pro-inflammatory cytokine mRNA levels and phosphorylation of NF-κB p65, p38, ERK, JNK were measured. <i>In vivo</i>, AP was given orally during OVA+LPS challenges. Cytokines and chemokines in bronchoalveolar lavage fluid (BALF), lung matrix metalloproteinases (MMP-1/9/12), Bax/Bcl-2 ratio, histopathological analysis, and systemic toxicity markers (AST, ALT, ALP, and BUN), body and organ weights, and gross examination were evaluated.</p><p><strong>Results: </strong>In A549 cells, AP reduced LPS-induced pro-inflammatory mRNA and inhibited NF-κB p65 and MAPK phosphorylation. In the OVA+LPS model, oral AP lowered BALF levels of CXCL-1, CXCL-2, IL-1β, IL-6, and TNF-α, and downregulated lung MMP-1/9/12, reducing Bax/Bcl-2 ratio with histological improvements. At 100 mg/kg, CXCL-1 and CXCL-2 decreased to about 73.2% and 89.2%, respectively. IL-1β and IL-6 levels decreased by 72.5% and 37.4%, respectively, with IL-6 significant only at the high dose. No systemic toxicity was observed, with stable serum toxicity markers and no abnormal findings.</p><p><strong>Discussion and conclusions: </strong>AP exhibits anti-inflammatory and lung-protective effects by inhibiting NF-κB/MAPK signaling and regulating proteolysis and apoptosis, indicating it as a safe, effective treatment for airway inflammation.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"363-378"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326666","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}
引用次数: 0
Total flavonoids of Abelmoschus manihot (L.) medic attenuate early renal injury in diabetic kidney disease by modulating the LINC00665/miR-379-5p axis. 麻豆总黄酮通过调节LINC00665/miR-379-5p轴减轻糖尿病肾病早期肾损伤。
IF 6 3区 医学
Pharmaceutical Biology Pub Date : 2026-12-01 Epub Date: 2026-02-23 DOI: 10.1080/13880209.2026.2630430
Nan Li, Yuhe Zeng, Yaohui Fang, Jie Wu, Harvest F Gu, Ying Wang
{"title":"Total flavonoids of <i>Abelmoschus manihot</i> (L.) medic attenuate early renal injury in diabetic kidney disease by modulating the LINC00665/miR-379-5p axis.","authors":"Nan Li, Yuhe Zeng, Yaohui Fang, Jie Wu, Harvest F Gu, Ying Wang","doi":"10.1080/13880209.2026.2630430","DOIUrl":"10.1080/13880209.2026.2630430","url":null,"abstract":"<p><p>‌<b>Context:</b>‌ Huangkui capsule (HKC), derived from <i>Abelmoschus manihot</i> (L.) Medic, is clinically utilized for diabetic kidney disease (DKD) treatment. Its primary bioactive components are the total flavonoids of <i>A. manihot</i> (L.) (TFA). Evidence has implicated the negative interaction between long non-coding RNA LINC00665 and miR-379-5p in DKD pathogenesis.</p><p><p>‌<b>Objective:</b>‌ To investigate the therapeutic effects of TFA on early DKD renal injury and its mechanism involving LINC00665/miR-379-5p axis modulation.</p><p><p>‌<b>Materials and Methods:</b>‌ Db/db mice and non-diabetic controls received TFA or vehicle. Urinary albumin/creatinine ratio (UACR) was measured with ELISA; renal histopathology was assessed with H&E staining. SV40-MES-13 and HK-2 cells were treated with TFA-intestinal absorption fluid (TFA-IAF). LINC00665 and miR-379-5p expression analyzed with RT-qPCR and Western blot. LINC00665/miR-379-5p interaction validated with dual-luciferase reporter assays. Functional effects assessed using LINC00665 siRNA silencing and miR-379-5p mimics.</p><p><p>‌<b>Results:</b>‌ TFA administration reduced UACR in db/db mice compared to vehicle-treated controls and ameliorated renal histological damage. Renal miR-379-5p expression was decreased in db/db mice versus non-diabetic controls, while TFA treatment <i>in vivo</i> upregulated miR-379-5p expression. TFA-IAF treatment <i>in vitro</i> modulated the expression of genes implicated in DKD progression, specifically affecting cell proliferation and ECM accumulation pathways in SV40-MES-13 and HK-2 cells. TFA-IAF downregulated LINC00665 expression in the cultured cells. Furthermore, dual-luciferase assays confirmed miR-379-5p binding to LINC00665, as miR-379-5p mimics suppressed wild-type LINC00665 reporter activity. Silencing LINC00665 increased miR-379-5p expression, potentiating by co-treatment with TFA.</p><p><p>‌<b>Conclusions:</b>‌ The LINC00665/miR-379-5p axis contributes to DKD pathogenesis. TFA exerts therapeutic effects against early renal injury in DKD by suppressing LINC00665 and consequently upregulating miR-379-5p activity.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"351-362"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271925","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}
引用次数: 0
A proposed evaluation of new approach methodologies for dermal toxicity assessment of botanicals. 植物性皮肤毒性评价新方法的评价建议。
IF 6 3区 医学
Pharmaceutical Biology Pub Date : 2026-12-01 Epub Date: 2026-08-18 DOI: 10.1080/13880209.2026.2717803
Julie Krzykwa, Allison Hilberer, Karin Ames, Cécile Bascoul, WanYun Cheng, Rachel Doerer, Stefan Gafner, Dori Germolec, Hilva Gjoni, Shomit Nazare, Argel Islas-Robles, Çiğdem Kahraman, Isabelle Lee, Hans Raabe, Phillip Wages, Donna Webster, Hong Xie, Constance A Mitchell, Gertrude-Emilia Costin
{"title":"A proposed evaluation of new approach methodologies for dermal toxicity assessment of botanicals.","authors":"Julie Krzykwa, Allison Hilberer, Karin Ames, Cécile Bascoul, WanYun Cheng, Rachel Doerer, Stefan Gafner, Dori Germolec, Hilva Gjoni, Shomit Nazare, Argel Islas-Robles, Çiğdem Kahraman, Isabelle Lee, Hans Raabe, Phillip Wages, Donna Webster, Hong Xie, Constance A Mitchell, Gertrude-Emilia Costin","doi":"10.1080/13880209.2026.2717803","DOIUrl":"https://doi.org/10.1080/13880209.2026.2717803","url":null,"abstract":"<p><strong>Background: </strong>Botanicals are widely used in topical formulations for cosmetics, hair care, and personal care products, reflecting consumer interest in plant-derived materials. Their complex and variable composition, presents challenges for traditional toxicological approaches developed for single chemicals. Although many botanicals are well tolerated, reports of skin irritation, sensitization, and phototoxicity highlight the need for reliable approaches to identify dermal hazards and evaluate risk. Established in silico, in chemico, and <i>in vitro</i> test methods, often referred to as New Approach Methodologies (NAMs), may offer efficient and mechanistically informed tools.</p><p><strong>Objective: </strong>The Dermal Working Group within the Botanical Safety Consortium (BSC) developed a strategy for evaluating existing NAMs for assessing dermal toxicity endpoints in botanicals, using literature evidence and data-rich botanicals to inform assay selection and anticipated performance. This narrative review describes the literature-based considerations used to select candidate assays and characterized reference botanicals for subsequent experimental evaluation.</p><p><strong>Methods: </strong>This narrative review describes considerations in the selection and application of <i>in vitro</i> and <i>in chemico</i> assays addressing skin irritation (OECD TG 439), phototoxicity (OECD TG 432), and skin sensitization (OECD TG 442 C, 442D, and 442E), together with <i>in silico</i> approaches.</p><p><strong>Results & discussion: </strong>A set of reference botanicals spanning a range of expected outcomes, from botanicals not expected to have effects to known irritants, sensitizers, and phototoxicants, was chosen to provide a foundation for evaluating assay performance and identifying technical considerations.</p><p><strong>Conclusion: </strong>This manuscript describes the botanicals and assays being evaluated as part of the BSC's planned dermal toxicity work. The goal of this work is to investigate the utility of NAMs for dermal safety evaluations of botanicals.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"922-948"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796607","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}
引用次数: 0
Statement of Retraction: Long non-coding RNA MEG3 attends to morphine-mediated autophagy of HT22 cells through modulating ERK pathway. 撤回声明:长链非编码RNA MEG3通过调节ERK通路参与吗啡介导的HT22细胞自噬。
IF 6 3区 医学
Pharmaceutical Biology Pub Date : 2026-12-01 Epub Date: 2026-08-24 DOI: 10.1080/13880209.2026.2719337
{"title":"Statement of Retraction: Long non-coding RNA MEG3 attends to morphine-mediated autophagy of HT22 cells through modulating ERK pathway.","authors":"","doi":"10.1080/13880209.2026.2719337","DOIUrl":"10.1080/13880209.2026.2719337","url":null,"abstract":"","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"921"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809085","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}
引用次数: 0
Lavandula angustifolia as a dual pharmacological system: from essential oil to polyphenol-rich biomass. 薰衣草作为一个双重药理体系:从精油到富含多酚的生物质。
IF 6 3区 医学
Pharmaceutical Biology Pub Date : 2026-12-01 Epub Date: 2026-06-05 DOI: 10.1080/13880209.2026.2679806
Viktoriia Nechepurenko, Victoriya Georgiyants, Yuliya Prokopenko, Olha Mykhailenko
{"title":"<i>Lavandula angustifolia</i> as a dual pharmacological system: from essential oil to polyphenol-rich biomass.","authors":"Viktoriia Nechepurenko, Victoriya Georgiyants, Yuliya Prokopenko, Olha Mykhailenko","doi":"10.1080/13880209.2026.2679806","DOIUrl":"10.1080/13880209.2026.2679806","url":null,"abstract":"<p><strong>Context: </strong><i>Lavandula angustifolia</i> Mill. is a widely used medicinal and aromatic plant with well-documented pharmacological activity, primarily attributed to its essential oil. However, the contribution of nonvolatile constituents and post-distillation biomass remains insufficiently characterized despite growing evidence of their biological relevance.</p><p><strong>Objective: </strong>This study aimed to provide a structured narrative synthesis of the phytochemical composition, pharmacological properties, and translational relevance of <i>L. angustifolia</i>, with particular emphasis on polyphenol-rich aerial biomass as an underexplored bioresource.</p><p><strong>Methods: </strong>A structured narrative review was conducted using ScienceDirect, Google Scholar, Scopus, PubMed, and SpringerLink databases through an iterative literature retrieval and refinement process. Priority was given to recent peer-reviewed English-language journal articles, particularly those published after 2015, with selective inclusion of earlier foundational studies where relevant. Eligible sources included studies reporting phytochemical characterization, mechanistic, experimental, translational, or clinical pharmacological data, as well as investigations addressing post-harvest or post-distillation biomass utilization. Literature was screened and synthesized using a thematic analytical approach.</p><p><strong>Results: </strong><i>L. angustifolia</i> demonstrates a dual pharmacological profile driven by both volatile and nonvolatile fractions. Essential oil is consistently associated with antimicrobial and anxiolytic effects, including evidence from clinical and mechanistic studies. In contrast, polyphenol-rich fractions exhibit pronounced antioxidant and anti-inflammatory activity through modulation of key signaling pathways. Post-distillation biomass was identified as a relevant and underutilized source of bioactive phenolics with potential for pharmaceutical and nutraceutical applications.</p><p><strong>Conclusion: </strong>The findings establish <i>L. angustifolia</i> as a pharmacologically relevant dual-use plant system integrating essential oil production with biomass valorization. This approach supports circular bioeconomy strategies and highlights the translational potential of nonvolatile fractions in the development of value-added therapeutic products.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"821-847"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176525","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}
引用次数: 0
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