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Mechanisms of action and therapeutic potential of PCSK9-regulating drugs. pcsk9调控药物的作用机制及治疗潜力。
IF 3.9 3区 医学
Pharmaceutical Biology Pub Date : 2025-12-01 Epub Date: 2025-06-23 DOI: 10.1080/13880209.2025.2514021
Chenrui Qi, Daming Fan, Lei Wang, Lubo Guo, Huihui Jiang, Lu Wang
{"title":"Mechanisms of action and therapeutic potential of PCSK9-regulating drugs.","authors":"Chenrui Qi, Daming Fan, Lei Wang, Lubo Guo, Huihui Jiang, Lu Wang","doi":"10.1080/13880209.2025.2514021","DOIUrl":"https://doi.org/10.1080/13880209.2025.2514021","url":null,"abstract":"<p><strong>Context: </strong>Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma low-density lipoprotein cholesterol (LDL-C) metabolism and is a key target for cardiovascular therapies. It also plays roles in inflammation, cancer, and metabolic disorders, prompting interest in repurposing PCSK9-targeting drugs for non-lipid conditions.</p><p><strong>Objective: </strong>This review comprehensively summarizes PCSK9-regulating medications, delves into their mechanisms of action, and explores their increasingly expanding therapeutic potential across multiple organ systems, such as the liver, immune system, small intestine, heart, brain, and pancreas.</p><p><strong>Methods: </strong>A comprehensive literature search was carried out in databases such as PubMed, with keywords like 'PCSK9 inhibitors', 'lipid metabolism', 'liver', 'immune system', 'neoplasms' and 'PCSK9-related diseases'. The search was meticulously designed to cover relevant research extensively. Only those studies that delved into the molecular mechanisms underlying PCSK9 regulation and the practical clinical applications of PCSK9-targeting therapies were selected for inclusion.</p><p><strong>Results: </strong>PCSK9-regulating drugs, encompassing monoclonal antibodies, small peptides, antisense oligonucleotides, small interfering RNAs, and vaccines, modulate PCSK9 expression or activity at different levels. These drugs are effective in lowering LDL-C levels and demonstrate potential benefits in the treatment of inflammation, non-alcoholic fatty liver disease, renal lipotoxicity, and various metabolic disorders. They mainly exert their effects by controlling PCSK9 gene transcription, influencing mRNA translation, and blocking the interaction between PCSK9 and LDL-R.</p><p><strong>Conclusions: </strong>PCSK9-regulating drugs hold great promise for treating a diverse array of diseases. Future research should focus on optimizing their application in personalized therapies that target multiple pathways.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"428-446"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476283","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
Correction. 修正。
IF 3.9 3区 医学
Pharmaceutical Biology Pub Date : 2025-12-01 Epub Date: 2024-12-22 DOI: 10.1080/13880209.2025.2444094
{"title":"Correction.","authors":"","doi":"10.1080/13880209.2025.2444094","DOIUrl":"10.1080/13880209.2025.2444094","url":null,"abstract":"","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"14"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876902","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
Tanshinone IIA reduces tubulointerstitial fibrosis by suppressing GSDMD-mediated pyroptosis. 丹参酮IIA通过抑制gsdmd介导的焦亡来减少小管间质纤维化。
IF 3.9 3区 医学
Pharmaceutical Biology Pub Date : 2025-12-01 Epub Date: 2025-05-07 DOI: 10.1080/13880209.2025.2498166
Xueling Yang, Qinglin Luo, Zhifen Wu, Chunxuan Wang, Yuanjing Yang, Luquan Zheng, Ke Li, Lei Zhao, Yang Jurong
{"title":"Tanshinone IIA reduces tubulointerstitial fibrosis by suppressing GSDMD-mediated pyroptosis.","authors":"Xueling Yang, Qinglin Luo, Zhifen Wu, Chunxuan Wang, Yuanjing Yang, Luquan Zheng, Ke Li, Lei Zhao, Yang Jurong","doi":"10.1080/13880209.2025.2498166","DOIUrl":"https://doi.org/10.1080/13880209.2025.2498166","url":null,"abstract":"<p><strong>Context: </strong>Tanshinone IIA (Tan IIA), a bioactive compound derived from the traditional Chinese herb <i>Salvia miltiorrhiza (Family Lamiaceae, Authority Bunge)</i>, is well-known for its protective effects in various kidney diseases. However, its role in obstructive nephropathy has not been thoroughly investigated.</p><p><strong>Objective: </strong>This study aimed to explore the protective effects of Tan IIA in a mouse model of unilateral ureteral obstruction (UUO) and to elucidate the cellular and molecular mechanisms underlying these effects.</p><p><strong>Materials and methods: </strong>Gasdermin D (GSDMD) knockout mice and their wild-type (WT) littermates underwent UUO surgery, with Tan IIA treatment administered 24 h prior. Human proximal tubular cells (HK-2 cells) were treated with TGF-β1 to induce fibrosis (50 ng/mL for 24 h), followed by Tan IIA treatment (5 μM) for an additional 3 h.</p><p><strong>Results: </strong>Tan IIA significantly reduced the expression of extracellular matrix (ECM) components, including collagen I, α-smooth muscle actin (α-SMA), vimentin and fibronectin, in UUO mice. Tan IIA attenuated GSDMD-mediated pyroptosis. However, in GSDMD knockout mice subjected to UUO, the protective effects of Tan IIA on ECM gene expression and collagen deposition in the tubular interstitium were reduced. <i>In vitro</i> studies showed that Tan IIA reduced GSDMD activation and fibronectin protein expression in HK-2 cells.</p><p><strong>Discussion and conclusions: </strong>Tan IIA may mitigate GSDMD-mediated pyroptosis in renal tubular epithelial cells (RTECs) and reduce kidney fibrosis, highlighting its potential as a therapeutic strategy to prevent the progression of kidney disease after ureteral obstruction.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"364-373"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987255","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
Apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy/lipophagy and promoting RCT process. 芹菜素通过增强选择性自噬/脂噬和促进RCT过程来减轻动脉粥样硬化病变。
IF 3.9 3区 医学
Pharmaceutical Biology Pub Date : 2025-12-01 Epub Date: 2025-05-23 DOI: 10.1080/13880209.2025.2509020
Zixuan Hu, Yuting Li, Nan Yao, Haining Gan, Qiaohuang Zeng, Xuejun Huang, Dane Huang, Dake Cai, Yuxing Chen
{"title":"Apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy/lipophagy and promoting RCT process.","authors":"Zixuan Hu, Yuting Li, Nan Yao, Haining Gan, Qiaohuang Zeng, Xuejun Huang, Dane Huang, Dake Cai, Yuxing Chen","doi":"10.1080/13880209.2025.2509020","DOIUrl":"10.1080/13880209.2025.2509020","url":null,"abstract":"<p><strong>Context: </strong>Apigenin, a naturally flavonoid, is reported to have protective effects in chronic and metabolic diseases. But the therapeutic or ameliorative effects of apigenin on atherosclerosis are not known.</p><p><strong>Objective: </strong>Our study aimed to elucidate the underlying mechanism of apigenin on preventing atherosclerosis by enhancing selective autophagy/lipophagy and promoting RCT process.</p><p><strong>Materials and methods: </strong>ApoE<sup>-/-</sup> mice fed with a high-fat diet (HFD) for 18 weeks were used to establish atherosclerosis model. Oil-Red-O staining of the plaques in the aorta and the heart was used to determine the severity of atherosclerosis. The autophagy flux was evaluated by western blot and reverse transcription quantitative PCR (RT-qPCR). Then triton WR-1339 (TWR) was injected into muscles of C57BL/6 mice, and the role of autophagy was assessed by autophagy inhibitor LY294002 intervention. The transmission electron microscopy (TEM) and immunofluorescence microscopy analysis (IFM) were used to elucidate the lipid-lowering mechanism of apigenin.</p><p><strong>Results: </strong>In HFD-induced mice, apigenin inhibited the dangerous progression of atherosclerosis through decreasing lipid deposition in plaques, lowering serum and liver lipid contents, activating autophagy and promoting reverse cholesterol transport (RCT). In TWR-induced mice, apigenin reduced the serum and liver lipid levels, enhanced the autophagy flux and increased RCT, but the above effects of apigenin were weakened by LY294002. The TEM and IFM images revealed that apigenin promoted the formation of autophagosomes and the co-localization between autophagy proteins with lipid protein.</p><p><strong>Discussion and conclusions: </strong>The lipid-lowering effects of apigenin were mediated through promoting RCT and enhancing selective lipophagy, meanwhile it provided a potential therapeutic option for atherosclerosis.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"387-401"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128201","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
Phenolic compounds from Origanum majorana with biofilm-inhibitory activity against methicillin-resistant Staphylococcus aureus and Escherichia coli strains. 牛头草酚类化合物对耐甲氧西林金黄色葡萄球菌和大肠杆菌具有生物膜抑制活性。
IF 3.9 3区 医学
Pharmaceutical Biology Pub Date : 2025-12-01 Epub Date: 2025-06-02 DOI: 10.1080/13880209.2025.2511805
Annamária Kincses, Tasneem Sultan Abu Ghazal, Katalin Veres, Gabriella Spengler, Judit Hohmann
{"title":"Phenolic compounds from <i>Origanum majorana</i> with biofilm-inhibitory activity against methicillin-resistant <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> strains.","authors":"Annamária Kincses, Tasneem Sultan Abu Ghazal, Katalin Veres, Gabriella Spengler, Judit Hohmann","doi":"10.1080/13880209.2025.2511805","DOIUrl":"10.1080/13880209.2025.2511805","url":null,"abstract":"<p><strong>Context: </strong>Antibiotic resistance in bacteria is a growing global problem, with biofilm formation and efflux pumps playing crucial roles in this issue.</p><p><strong>Objective: </strong>This study explores the effects of phenolic compounds of <i>Origanum majorana</i> against <i>Escherichia coli</i> and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) strains by inhibiting biofilm formation and efflux pumps.</p><p><strong>Materials and methods: </strong>The methanolic extract of <i>O. majorana</i> was fractionated guided by an antibiofilm assay, and the active fractions were analyzed by multistep chromatographic separation to yield five pure compounds. Their structures were then determined using 1D and 2D nuclear magnetic resonance spectroscopy. The minimum inhibitory concentrations of the extracts, fractions, and isolated compounds were determined <i>via</i> the microdilution method in a 96-well plate. Antibiofilm activity was assessed using the crystal violet method, and the effect on efflux pumps was tested by a real-time ethidium bromide accumulation assay.</p><p><strong>Results: </strong>Arbutin (<b>1</b>), apigenin 7-<i>O</i>-glucoside (<b>2</b>), 6'-caffeoylarbutin (<b>3</b>), rosmarinic acid (<b>4</b>), and 2-deoxy-d-1,4-ribonolactone (<b>5</b>) were isolated from the aqueous methanolic extract. Compounds <b>1</b>, <b>2</b>, and <b>4</b> reduced <i>E. coli</i> biofilm formation by 24.82%-42.98% at 100 µM, whereas only arbutin (<b>1</b>) moderately suppressed biofilm formation of MRSA (23.15 ± 1.56% at 50 µM). Arbutin also demonstrated efflux pump inhibitory activity against MRSA (relative fluorescence index of 0.49 at 100 µM).</p><p><strong>Discussion and conclusions: </strong>The newly discovered natural antibiofilm agents show promise as candidates for treating biofilm-associated infections and combating antibiotic-resistant bacteria.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"402-410"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209116","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
Modified Xiao-Qing-Long-decoction prevents inflammation and promotes Nur77 expression in mice with acute respiratory distress syndrome by inhibiting HDAC7 expression. 加味小清龙汤对急性呼吸窘迫综合征小鼠炎症的抑制作用及通过抑制HDAC7的表达促进Nur77的表达。
IF 3.9 3区 医学
Pharmaceutical Biology Pub Date : 2025-12-01 Epub Date: 2025-02-04 DOI: 10.1080/13880209.2025.2459247
Qing Zhang, Yafen Liu, Lu Jiang, Dongdong Yang
{"title":"Modified Xiao-Qing-Long-decoction prevents inflammation and promotes Nur77 expression in mice with acute respiratory distress syndrome by inhibiting HDAC7 expression.","authors":"Qing Zhang, Yafen Liu, Lu Jiang, Dongdong Yang","doi":"10.1080/13880209.2025.2459247","DOIUrl":"10.1080/13880209.2025.2459247","url":null,"abstract":"<p><strong>Context: </strong>Modified Xiao-Qing-Long-decoction (MXQLD) is believed to have the potential to alleviate lung diseases.</p><p><strong>Objective: </strong>We explored the effects and mechanisms of MXQLD in acute respiratory distress syndrome (ARDS).</p><p><strong>Materials and methods: </strong>Thirty male C57BL/6 mice were randomized into sham (distilled water), model (distilled water), MXQLD (1 g/kg MXQLD), DEX (distilled water + 0.7 mg/kg dexamethasone), MXQLD + oe-HDAC7 (HDAC7 over-expression + 1 g/kg MXQLD) groups. Except for HDAC7 over-expression on day 0 and dexamethasone injection on day 12, all treatments were administered every two days from day 0 to day 10. On day 12, except for the sham group, all mice underwent cecal ligation and puncture surgery to establish ARDS models. After surgery, pulmonary functions, protein concentration of bronchoalveolar lavage fluid (BALF) and lung tissue morphology in mice were detected. Furthermore, pro-inflammatory cytokine concentrations (IL-6, IL-1β, and TNF-α) in BALF supernatant and serum were quantified. Additionally, HDAC7, Nur77, ZO-1, occludin, and claudin protein expressions were detected.</p><p><strong>Results: </strong>MXQLD treatment improved pulmonary functions and alleviated lung injury for ARDS mice. Furthermore, MXQLD treatment decreased protein concentration in BALF, and inhibited pro-inflammatory cytokine release in BALF supernatant and serum for ARDS mice. Additionally, MXQLD treatment down-regulated HDAC7 expression, but up-regulated Nur77, ZO-1, occludin, and claudin expressions for ARDS mice. Importantly, the preventive effects of MXQLD in ARDS mice were reversed by HDAC7 over-expression.</p><p><strong>Discussion and conclusion: </strong>MXQLD may prevent inflammation and promote Nur77 expression in ARDS by inhibiting HDAC7 expression, indicating that MXQLD may be a promising drug for preventing ARDS.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"110-117"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189931","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
Bioactive constituents from the edible seaweed Halymenia hawaiiana (Rhodophyta). 食用海带夏威夷红海带的生物活性成分。
IF 3.9 3区 医学
Pharmaceutical Biology Pub Date : 2025-12-01 Epub Date: 2025-06-26 DOI: 10.1080/13880209.2025.2521285
Achara Raksat, Md Samiul Huq Atanu, Karla J McDermid, Marisa M Wall, Boon Loong Chang, Supakit Wongwiwatthananukit, Leng Chee Chang
{"title":"Bioactive constituents from the edible seaweed <i>Halymenia hawaiiana</i> (Rhodophyta).","authors":"Achara Raksat, Md Samiul Huq Atanu, Karla J McDermid, Marisa M Wall, Boon Loong Chang, Supakit Wongwiwatthananukit, Leng Chee Chang","doi":"10.1080/13880209.2025.2521285","DOIUrl":"10.1080/13880209.2025.2521285","url":null,"abstract":"<p><strong>Context: </strong>The marine macroalga, <i>Halymenia hawaiiana</i>, holds significant commercial potential due to its culinary uses among various ethnic groups in Hawai'i and its success in aquaculture.</p><p><strong>Objective: </strong>To investigate the chemical components and potential medicinal properties of <i>H. hawaiiana</i>.</p><p><strong>Materials and methods: </strong>Dried, ground <i>H. hawaiiana</i> was sequentially extracted with three solvents: ethyl acetate, methanol, and <i>n</i>-butanol. Chromatographic procedures were sequentially applied, leading to the isolation of several compounds. Structure determination of these compounds was performed using spectroscopic methods. The isolated compounds were then assessed through several <i>in vitro</i> assays.</p><p><strong>Results: </strong>A total of 11 compounds were isolated and identified: two nucleosides (<b>1</b> and <b>2</b>), a cytosine analog (<b>3</b>), five saturated long-chain fatty acids (<b>4</b>-<b>8</b>), cholesterol (<b>9</b>), and two of its derivatives (<b>10</b>-<b>11</b>) were isolated. Compounds <b>10</b> and <b>11</b> displayed promising antimicrobial activity against <i>Staphylococcus aureus</i>, both exhibiting MIC values of 8 μg/mL, and methicillin-susceptible <i>S. aureus</i>, with MIC values of 32 and 64 μg/mL, respectively. Furthermore, using a cell culture model, compounds <b>9</b>, <b>10</b>, and <b>11</b> exhibited significant anti-inflammatory effects as indicated by their inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production, with IC<sub>50</sub> values ranging from 50.2 to 60.8 µM. These compounds also effectively inhibited the generation of reactive oxygen species (ROS)/reactive nitrogen species (RNS) in RAW 264.7 mouse macrophage cells with IC<sub>50</sub> values of 55-73.7 µM without inducing cytotoxicity. Compounds <b>9-11</b> also exhibited mild cytotoxicity against the non-small cell lung cancer cell line A549, with compound <b>10</b> eliciting the strongest response (IC<sub>50</sub> 86.1 µM).</p><p><strong>Conclusions: </strong>This study uncovered a diverse array of constituents from <i>H. hawaiiana</i>. Notably, compounds <b>10</b> and <b>11</b>, which feature peroxide side chains, show significant promise as lead compounds for the development of novel anti-inflammatory and antimicrobial agents.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"447-459"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497648","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
Beneficial effects of Elaeagnus rhamnoides (L.) A. Nelson and its most abundant flavonoids on the main mechanisms related to diabetic bone disease. 沙棘的有益作用Nelson及其最丰富的黄酮类化合物对糖尿病骨病的主要机制相关。
IF 3.9 3区 医学
Pharmaceutical Biology Pub Date : 2025-12-01 Epub Date: 2025-07-03 DOI: 10.1080/13880209.2025.2523392
Roman Biro, Radoslav Omelka, Anna Sarocka, Noemi Penzes, Veronika Kovacova, Vladimira Mondockova, Monika Martiniakova
{"title":"Beneficial effects of <i>Elaeagnus rhamnoides</i> (L.) A. Nelson and its most abundant flavonoids on the main mechanisms related to diabetic bone disease.","authors":"Roman Biro, Radoslav Omelka, Anna Sarocka, Noemi Penzes, Veronika Kovacova, Vladimira Mondockova, Monika Martiniakova","doi":"10.1080/13880209.2025.2523392","DOIUrl":"10.1080/13880209.2025.2523392","url":null,"abstract":"<p><strong>Context: </strong>Diabetes mellitus represents a group of metabolic disorders that can adversely affect numerous organ systems, including the skeletal system. It elevates bone fragility and causes secondary osteoporosis, known as diabetic bone disease (DBD). The treatment of DBD depends on the control of hyperglycemia supplemented with anti-osteoporotic agents, but this has unsatisfactory efficiency.</p><p><strong>Objective: </strong>This article provides a comprehensive review on the effects of <i>Elaeagnus rhamnoides</i> (L.) A. Nelson (sea buckthorn; family <i>Elaeagnaceae</i>), a prospective anti-diabetic and osteoprotective supplement, and its most abundant flavonoids (quercetin, isorhamnetin, kaempferol) on major mechanisms related to DBD.</p><p><strong>Methods: </strong>'Sea buckthorn' (SB), 'quercetin', 'isorhamnetin', 'kaempferol', 'DBD', 'hyperglycemia', 'inflammatory state', 'insulin resistance' (IR), 'advanced glycation end products' (AGEs) were used as keywords, and relevant literature was obtained from online databases (PubMed, Web of Science, Scopus).</p><p><strong>Results and conclusions: </strong>SB and flavonoids mentioned above exert hypoglycemic and anti-inflammatory properties, attenuate IR, inhibit AGEs formation, thereby positively affecting the main DBD-related mechanisms. The direct effect of SB on DBD has not been investigated yet, but the beneficial impact of quercetin on DBD has been revealed. Therefore, it can be assumed that SB could favorably influence DBD, as its great potential to treat other bone-related diseases (osteoporosis, rheumatoid arthritis) has been reported. Further research, including high-quality <i>in vitro</i> and animal model studies, as well as large-scale clinical trials, is needed to confirm such a putative positive effect and to identify more efficient therapies against various diabetic complications, including DBD.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"460-489"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12231332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554101","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
Non-linear oral bioavailability and clinical pharmacokinetics of high-dose Andrographis paniculata ethanolic extract: relevant dosage implications for COVID-19 treatment. 大剂量穿心莲乙醇提取物的非线性口服生物利用度和临床药代动力学:对COVID-19治疗的相关剂量影响
IF 3.9 3区 医学
Pharmaceutical Biology Pub Date : 2025-12-01 Epub Date: 2025-01-06 DOI: 10.1080/13880209.2024.2444446
Phanit Songvut, Jaratluck Akanimanee, Tawit Suriyo, Nanthanit Pholphana, Nuchanart Rangkadilok, Duangchit Panomvana, Porranee Puranajoti, Jutamaad Satayavivad
{"title":"Non-linear oral bioavailability and clinical pharmacokinetics of high-dose <i>Andrographis paniculata</i> ethanolic extract: relevant dosage implications for COVID-19 treatment.","authors":"Phanit Songvut, Jaratluck Akanimanee, Tawit Suriyo, Nanthanit Pholphana, Nuchanart Rangkadilok, Duangchit Panomvana, Porranee Puranajoti, Jutamaad Satayavivad","doi":"10.1080/13880209.2024.2444446","DOIUrl":"10.1080/13880209.2024.2444446","url":null,"abstract":"<p><strong>Aim: </strong>Insufficient quality control and limited dissolution of <i>Andrographis paniculata</i> extract capsules restricts their bioavailability and hinder the clinical use for treating mild coronavirus disease 2019 (COVID-19) patients.</p><p><strong>Objective: </strong>This study aims to investigate pharmacokinetics and safety of high-dosage <i>A. paniculata</i> ethanolic extract (equivalent to 180 or 360 mg/day of andrographolide), relevant dosages used for mild COVID-19 treatment.</p><p><strong>Methods: </strong>An open-label, single-dose, and repeated-dose conducted in healthy volunteers. Subjects received capsules containing ethanolic extract equivalent to andrographolide dosage of either 60 or 120 mg per dose, taken every eight hours daily (totaling 180 or 360 mg/day). Safety was assessed through blood chemical analysis and adverse event monitoring after 7 days of ethanolic extract administration.</p><p><strong>Results: </strong>Pharmacokinetics of ethanolic extract indicated low plasma levels of the major diterpenoids. The maximum plasma concentration (Cmax) of andrographolide did not exhibit a dose-proportional increase, reaching 6.44 and 11.62 µg/L for single and repeated doses of 60 mg/day, respectively. Doubling the dose (120 mg/day) only resulted in slightly higher Cmax (6.97 and 15.03 µg/L for single and repeated doses, respectively). Safety evaluation revealed mild, transient adverse events, but all parameters remained within normal ranges.</p><p><strong>Conclusions: </strong>This study highlights limitations in the pharmacokinetics of the ethanolic extract of <i>A. paniculata</i>. It indicated non-linear proportionality in the oral bioavailability of andrographolide. These findings suggest that current extraction process of ethanolic extract may hinder its effectiveness. Further research is warranted to explore alternative extraction methods or formulation developments that can enhance the bioavailability of andrographolide and its potential therapeutic effects for COVID-19 treatment.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"42-52"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932585","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
Research progress of Chinese medicinal monomers in the process of melanoma occurrence. 中药单体在黑色素瘤发生过程中的研究进展。
IF 3.9 3区 医学
Pharmaceutical Biology Pub Date : 2025-12-01 Epub Date: 2025-01-10 DOI: 10.1080/13880209.2024.2445695
Yan Shang, Hailong Zhao
{"title":"Research progress of Chinese medicinal monomers in the process of melanoma occurrence.","authors":"Yan Shang, Hailong Zhao","doi":"10.1080/13880209.2024.2445695","DOIUrl":"10.1080/13880209.2024.2445695","url":null,"abstract":"<p><strong>Context: </strong>Melanoma's aggressiveness and resistance to radiotherapy highlight an urgent need for innovative treatments. Traditional Chinese medicine (TCM) offers a unique approach through its 'four natures' theory-cold, cool, warm, and hot.</p><p><strong>Objective: </strong>This review aims to explore the potential of TCM's 'four natures' herbal monomers in melanoma treatment, providing an alternative to conventional therapies.</p><p><strong>Materials & methods: </strong>A systematic literature review was conducted by accessing various databases, including Baidu Scholar, PubMed, Science Citation Index Expanded (SCIE), and China National Knowledge Infrastructure (CNKI), to synthesize the most recent findings on traditional Chinese medicine monomers. Furthermore, this review elucidated the mechanisms underlying their role in melanoma retention.</p><p><strong>Results: </strong>TCM's multi-component, multi-target approach has shown promise in addressing melanoma's complexity, with specific monomers demonstrating the ability to modulate tumor behavior.</p><p><strong>Discussion and conclusions: </strong>The 'four natures' theory in TCM presents a novel perspective for melanoma treatment, warranting further investigation into its clinical applications and potential integration with modern oncology.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"53-67"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953117","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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