Cairong Han , Zhongrui Zhang , Akida Adiham , Feifei Huang , Yulu Yan , Dapeng Li , Puyang Gong
{"title":"Santali Albi Lignum: From traditional efficacies to pharmacological properties and modern therapeutic applications","authors":"Cairong Han , Zhongrui Zhang , Akida Adiham , Feifei Huang , Yulu Yan , Dapeng Li , Puyang Gong","doi":"10.1016/j.jep.2025.120031","DOIUrl":"10.1016/j.jep.2025.120031","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Santali Albi Lignum (SA), the dry heartwood of the trunk of <em>Santalum album</em> L., was originally discovered in India. It has a long history of use in Ayurveda and traditional Chinese medicine (TCM), mainly to treat skin, cardiovascular and lung diseases. In recent years, SA has received worldwide attention because of its diverse pharmacological effects, including anti-tumour, neuroprotective and gastrointestinal regulatory effects.</div></div><div><h3>Purpose</h3><div>This paper aims to systematically review progress in the research on SA, focusing on its ethnopharmacology, phytochemical ingredients, pharmacological effects, quality control and clinical applications; directions for further research and development of this herbal medicine are also discussed.</div></div><div><h3>Methods</h3><div>Information on SA was obtained mainly from published materials, classic ancient books on TCM and electronic databases (PubMed, Google Scholar, Science Direct, Web of Science China National Knowledge Infrastructure and traditional Chinese medicine classics).</div></div><div><h3>Results</h3><div>A total of 216 molecules have been identified in SA, including terpenoids, fatty acids, organic acids, phenols, aldehydes, alkanes, esters, ketones, steroids, alcohols, phenylpropanoids and other compounds, of which sesquiterpenes have emerged as the primary bioactive ingredients. A wide spectrum of biological activities of extracts or compounds of SA, including neuroprotective, antitumour, anti-inflammatory, antioxidant and gastrointestinal effects, have been verified in <em>in vitro</em> and <em>in vivo</em> pharmacological studies. Quality is monitored by the quantification and identification of α⁃santalol, β⁃santalol and volatile oils. TCM formulations that contain SA are commonly used to treat coronary heart disease, heart failure, ischaemic stroke, skin diseases and others.</div></div><div><h3>Conclusions</h3><div>This systematic review demonstrates that modern bioactivities and clinical research reports provide scientific evidence for the efficacy of SA, especially the ability to circulate <em>qi</em> and alleviate pain. Current studies have focused mainly on the chemical composition and pharmacological effects of the volatile oil fraction of SA. Moreover, the integrated pharmacological mechanisms of the active compounds and extracts of SA still need to be comprehensively elucidated. Furthermore, research on its toxicology and pharmacokinetics should be expanded to ensure the reasonable and safe clinical use of SA.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120031"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intestinal anti-inflammatory, histopathologic and anti-oxidative regulatory effects of total alkaloids extract from Linum usitatissimum L. (flaxseed) in vivo","authors":"Mohamed Sofiane Merakeb, Noureddine Bribi, Riad Ferhat, Safia Afenai","doi":"10.1016/j.jep.2025.120001","DOIUrl":"10.1016/j.jep.2025.120001","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Linum usitatissimum</em> L., commonly known as flaxseed, is a perennial herb in the Lineaceae family that has been traditionally used to manage gastrointestinal disorders and diarrhea. The health benefits and medicinal applications of flaxseed can be attributed to the presence of some beneficial compounds, such as omega-3 fatty acids, tocopherol, cyclic peptides, alkaloids, mucilage, and phenylpropanoids.</div></div><div><h3>Aim of the study</h3><div>This investigation explored the potential anti-inflammatory and antioxidant properties of the total alkaloid extract of <em>Linum usitatissimum</em> L. seeds (ALU) in a model of Crohn's disease induced by 2,4-dinitrobenzenesulfonic acid (DNBS) in BALB/c mice.</div></div><div><h3>Materials and methods</h3><div>ALU fraction was chemically characterized by liquid chromatography combined with electrospray ionization mass spectrometry (LC-ESI-MS/MS). Six groups of mice (n = 6) were divided as follow: healthy group, colitic control, Dexamethasone treated-group (2.4 mg/kg) and three group for ALU treatment (50, 100 and 200 mg/kg). Intrarectal instillation of DNBS (250 mg/kg) induced colonic inflammation accompanied by body weight loss, colonic architecture modification, inflammatory cells infiltration and excessive inflammatory markers production. Tissues sample were used to assess the histological damages and eventual goblet cells loss (H & E and PAS staining) and to evaluate inflammatory and oxidative statute (MPO, NO, H<sub>2</sub>O<sub>2</sub>, MDA, CAT and GSH).</div></div><div><h3>Results</h3><div>The phytochemical analysis of total alkaloid fraction of LU revealed the presence of 10 compounds. Oral administration of ALU (50, 100, and 200 mg/kg) significantly ameliorated DNBS-induced colitis in mice in a dose-dependent manner. ALU treatment mitigated body weight loss, reduced the weight/length (W/L) ratio, and improved clinical outcomes, including diarrhea and food intake. Histological analyses revealed that ALU treatment, preserved colonic architecture, enhanced goblet cell numbers, reduced neutrophil infiltration, and minimised mucosal damage, with a comparable effect to dexamethasone treatment. ALU also promoted mucosal healing and neutral mucin retention. Furthermore, ALU exerted potent anti-inflammatory and antioxidant effects by modulating key markers such as MPO, NO, H<sub>2</sub>O<sub>2</sub>, MDA, CAT, and GSH, supporting its protective role against colonic inflammation.</div></div><div><h3>Conclusion</h3><div>These findings indicate that alkaloid fraction extracted from <em>Linum usitatissimum</em> L. have strong anti-inflammatory and antioxidant properties in a DNBS-induced colitis model in BALB/c mice.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120001"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meng-Yuan Wang , Heng-Li Zhao , Yu-Nuo Fan , Ye Zhang , Yong-Xiang Wang , Bin Li , Hua Yang , Ping Li
{"title":"Network pharmacology-guided identification of bioactive equivalent combinatorial components in Lanqin Oral Liquid for acute pharyngitis treatment","authors":"Meng-Yuan Wang , Heng-Li Zhao , Yu-Nuo Fan , Ye Zhang , Yong-Xiang Wang , Bin Li , Hua Yang , Ping Li","doi":"10.1016/j.jep.2025.120038","DOIUrl":"10.1016/j.jep.2025.120038","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Lanqin Oral Liquid (LQL) is a pure herbal preparation with a good therapeutic effect on acute pharyngitis in clinic. However, its active ingredients and action mechanisms need further research.</div></div><div><h3>Aims of the study</h3><div>This work employed network pharmacology to uncover the bioactive equivalent combinatorial components (BECCs) of LQL and investigate their mechanisms in treating acute pharyngitis.</div></div><div><h3>Materials and methods</h3><div>In this study, a component-disease-target (C-D-T) network related to LQL and pharyngitis was constructed through network pharmacology and candidate BECCs were found based on the degree values of each node in the C-D-T network. The anti-acute pharyngitis effects between BECCs and LQL were evaluated by animal and cell experiments, and the vital signaling pathways predicted by network pharmacology were verified. Additionally, the synergistic effect of berberine (BBR) and geniposide (GE), the core active ingredients of BECCs, was further explored by the combination index (CI) method.</div></div><div><h3>Results</h3><div>Network pharmacology indicated that 25 potential active ingredients in LQL and 35 targets were involved in the treatment of acute pharyngitis, covering 20 signaling pathways. Based on network pharmacology degree values, 13 compounds were identified as BECCs. <em>In vitro</em> and <em>in vivo</em> studies revealed that BECCs exhibit comparable therapeutic efficacy to LQL in treating acute pharyngitis. BECCs could treat acute pharyngitis by reducing the release of NO, secretion of inflammatory factors (IL-6, IL-1β, and TNF-α), and expression of related proteins (TLR4 and p-p65). Notably, BBR and GE emerged as BECCs' most effective components, demonstrating significant anti-inflammatory synergy.</div></div><div><h3>Conclusion</h3><div>BECCs of LQL demonstrate comparable efficacy against acute pharyngitis to the original formula, which may exert anti-inflammatory effects by regulating the TLR4/NF-κB signaling pathway. The diverse components in BECCs potentially exhibit synergistic pharmacological effects. These findings provide a solid scientific foundation for the clinical application of LQL.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120038"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ethnomedicine, phytochemistry, pharmacology, pharmacokinetics, and clinical application of Salvia miltiorrhiza Bunge (Lamiaceae): A comprehensive review","authors":"Tingting Lan , Daixin Yu , Qingrong Zhao , Cheng Qu , Qinan Wu","doi":"10.1016/j.jep.2025.120032","DOIUrl":"10.1016/j.jep.2025.120032","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Salvia miltiorrhiza</em> Bunge (Lamiaceae), known as Danshen in China, is a widely utilized traditional Chinese medicine (TCM). Danshen is classified within the heart and liver meridians and renowned for its ability to activate collaterals and blood vessels, facilitate the removal of blood stasis without compromising vital Qi. It plays a pivotal role in promoting blood circulation and alleviating blood stasis. Clinically, it is commonly used to treat uterine bleeding, irregular menstruation, blood stasis, and abdominal pain, among other symptoms.</div></div><div><h3>Aim of the study</h3><div>This paper reviews the traditional use, botany, phytochemistry, pharmacology, toxicity, pharmacokinetics and clinical application of Danshen from 1981 to 2024. The goal is to offer valuable reference materials that can inform and guide future research related to Danshen.</div></div><div><h3>Materials and methods</h3><div>A literature search was performed on Danshen based on classic books about Chinese herbal medicine and different electronic databases including Web of Science, PubMed, Elsevier, ScienceDirect, Google Scholar, SciFinder, TPL, and CNKI.</div></div><div><h3>Results</h3><div>Traditional uses of Danshen have been documented in China for centuries. A large number of studies have shown that Danshen is rich in chemical components. To date, more than 318 chemical compounds have been isolated and identified, including diterpenoid quinones, phenolic acids, triterpenes, essential oils, neolignans, alkaloids, flavonoids, saccharides, and others. Crude extracts and pure compounds isolated from Danshen exhibit a wide range of pharmacological effects, including anti-atherosclerotic, anti-arrhythmic, anti-thrombotic, anti-hypertensive, anti-myocardial ischemia-reperfusion injury, endothelial dysfunction protection, sedative and analgesic, neuroprotective, anti-depressive, anti-hepatic fibrosis, anti-pulmonary fibrosis, anti-renal fibrosis, anti-inflammatory, anti-oxidative, anti-tumor, anti-diabetic effects. The results of pharmacokinetic studies showed that the presence of various compounds within the extract of Danshen can significantly influence the pharmacokinetic characteristics of individual constituents through several mechanisms. These mechanisms may include enhanced bioavailability, reduced potential for toxicity, and alterations in the distribution of metabolites.</div></div><div><h3>Conclusions</h3><div>Danshen has been demonstrated to be a valuable medicinal resource in TCM. This paper provides a comprehensive review of the ethnopharmacology, chemical composition, pharmacological effects, toxicology, pharmacokinetics and clinical applications of Danshen, aiming to serve as a thorough reference for its further development and utilization. Additionally, further research in pharmacokinetics and toxicology is essential to enhance our understanding of its clinical applications and quality control.</di","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120032"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriel Carvalho de Souza Santana , Maria Vitória Abreu Cardoso de Jesus , Anna Beatriz Oliveira Cruz , Alyne Almeida de Lima , Pedro Santana Sales Lauria , Thalisson Amorim de Souza , Marcelo Sobral da Silva , Max Denisson Maurício Viana , Cristiane Flora Villarreal
{"title":"Schinus terebinthifolius essential oil and its major component delta-3-carene induce antinociception mediated by serotonergic receptors","authors":"Gabriel Carvalho de Souza Santana , Maria Vitória Abreu Cardoso de Jesus , Anna Beatriz Oliveira Cruz , Alyne Almeida de Lima , Pedro Santana Sales Lauria , Thalisson Amorim de Souza , Marcelo Sobral da Silva , Max Denisson Maurício Viana , Cristiane Flora Villarreal","doi":"10.1016/j.jep.2025.120021","DOIUrl":"10.1016/j.jep.2025.120021","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Schinus terebinthifolius</em> Raddi. (Anacardiaceae) is a South American species that widely occurs in Brazil, where it is popularly known as “pimenta rosa”. <em>S. terebinthifolius</em> essential oil (STEO) is traditionally used for pain management.</div></div><div><h3>Aim of the study</h3><div>To investigate the antinociceptive effects of inhaled STEO and its mechanisms of action.</div></div><div><h3>Materials and methods</h3><div>Male <em>Swiss</em> mice were exposed to STEO (150–600 μL) via inhalation and assessed for thermal nociception (tail flick test) and motor integrity (rota-rod test). Functional antagonism assays were performed to investigate mechanisms of action. STEO was chemically characterized by GC/MS, and its major component, delta-3-carene (D3C), was tested for antinociceptive activity. SwissADME was used to predict D3C druggability.</div></div><div><h3>Results</h3><div>Inhalation of STEO (300–600 μL) significantly elevated thermal nociceptive thresholds without impairing motor performance. Methysergide, but not naloxone or yohimbine, reversed STEO-induced antinociception, implying serotonergic receptor involvement. D3C was identified as the major constituent of STEO and, when administered orally (1.5–25 mg/kg), also promoted antinociceptive effects reversed by methysergide. <em>In silico</em> pharmacokinetics predicted favorable drug-like properties for D3C, supporting its role in STEO's antinociceptive effects.</div></div><div><h3>Conclusions</h3><div>STEO inhalation promoted antinociception mediated by serotonergic receptors, corroborating its traditional use. D3C was likely a significant contributor to STEO's antinociceptive properties.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120021"},"PeriodicalIF":4.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yunhua Liu , Yanmo Cai , Xiaoyu Wei , Kun Gao , Ge Jin , Xin Zhou , Zongjiang Zhao
{"title":"Molecular mechanisms of Potentilla Discolor Bunge in regulating ferroptosis to alleviate DKD via the Nrf2 signaling pathway","authors":"Yunhua Liu , Yanmo Cai , Xiaoyu Wei , Kun Gao , Ge Jin , Xin Zhou , Zongjiang Zhao","doi":"10.1016/j.jep.2025.120035","DOIUrl":"10.1016/j.jep.2025.120035","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Potentilla Discolor Bunge</em> (PDB), a plant belonging to the Rosaceae family, is often used in traditional folk medicine to treat diabetes and prevent related complications. Additionally, fresh and tender PDB stems could be consumed as a vegetable or used to make tea.</div></div><div><h3>Aim of the study</h3><div>To explore the potential targets and mechanisms of PDB in treating Diabetic Kidney Disease (DKD) through network pharmacology, and to investigate its role in modulating the Nrf2 signaling pathway to inhibit ferroptosis using <em>in vivo</em> and <em>in vitro</em> experiments, thereby presenting a potential therapeutic avenue for DKD.</div></div><div><h3>Materials and methods</h3><div>Targets of PDB compounds were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, while PDB action targets were screened using the DrugBank, OMIM, GeneCards, DisGeNET, and TTD databases. The intersecting targets were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Meanwhile, the binding modes of PDB core monomers to key targets were analyzed using Molecular Docking (MD) and Surface Plasmon Resonance (SPR) experiments. Experimental validation was conducted using a High-Fat/Sucrose Diet (HFD) combined with Streptozotocin (STZ)-induced DKD rat model and an Advanced Glycation End Products (AGEs)-damaged human renal proximal tubular cell (HK-2) model.</div></div><div><h3>Results</h3><div>As predicted through network pharmacology, PDB exerted therapeutic effects against DKD through multiple pathways, including AGE/RAGE, Nrf2 signaling, Oxidative Stress, and apoptosis. Furthermore, PDB's primary active constituents were Quercetin, Kaempferol, and β-sitosterol, with MD analyses suggesting strong binding affinities to the Nrf2 and Ho-1 proteins. <em>In vivo</em> experiments further revealed that PDB treatment reduced the 24 h urinary protein, Serum Creatinine (SCr), and urea levels. It also downregulated Malondialdehyde (MDA), Fe<sup>2+</sup>, and Reactive Oxygen Species (ROS) accumulation in renal tissues. Additionally, PDB alleviated the histopathological damage in DKD-afflicted rats and significantly upregulated Nrf2, Ho-1, Gpx4, and Slc7a11 in renal tissues. Moreover, Quercetin, Kaempferol, and β-sitosterol significantly upregulated Nrf2, Ho-1, and Gpx4, increased intracellular Glutathione (GSH) levels, reduced ROS and MDA content, and mitigated mitochondrial damage in the AGEs-exposed HK-2 cell injury model.</div></div><div><h3>Conclusion</h3><div>We predicted the mechanism of action of natural botanical PDB against DKD through network pharmacology, revealing that it significantly upregulated the Nrf2 signaling pathway and inhibited ferroptosis initiation, thus decelerating DKD progression. These findings were further validated through <em>in vivo</em> and <em>in vitro</em> experiments.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120035"},"PeriodicalIF":4.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abudureyimu Alimujiang , Hongzhi Wang , Liangmian Chen , Yutong Kang , Jingcheng Zhao , Wenjing Wei , Shixia Huo , Dengqiu Xu , Zhijian Li
{"title":"Euphorbia humifusa Willd. extract alleviates imiquimod-induced psoriasis-like skin lesions in mice by modulating the IL-17 signaling pathway","authors":"Abudureyimu Alimujiang , Hongzhi Wang , Liangmian Chen , Yutong Kang , Jingcheng Zhao , Wenjing Wei , Shixia Huo , Dengqiu Xu , Zhijian Li","doi":"10.1016/j.jep.2025.120030","DOIUrl":"10.1016/j.jep.2025.120030","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Psoriasis is a chronic immune-mediated skin disease characterized by the infiltration of multiple inflammatory cells and abnormal differentiation of keratinocytes in the skin. The treatment of psoriasis is primarily based on immunosuppressive drugs; however, their long-term use can lead to various adverse effects. <em>Euphorbia humifusa</em> Willd. (EuH) is used in traditional Chinese medicine for its anti-inflammatory properties and effects on skin diseases such as psoriasis.</div></div><div><h3>Aim of the study</h3><div>This study aimed to evaluate the anti-psoriasis effects of EuH extract, and explore its underlying mechanisms.</div></div><div><h3>Methods and materials</h3><div>The main components of EuH extract were analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) technology. Then, we administered EuH extract to imiquimod-induced psoriasis mice for 6 consecutive days, and evaluated the effects according to the psoriasis area and severity index (PASI), spleen index, histological analysis, immunohistochemical and immunofluorescence staining, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and flow cytometry analysis. The potential mechanism was revealed using RNA sequencing (RNA-seq) and validated by target prediction, ELISA, qRT-PCR and Western blot (WB) analysis.</div></div><div><h3>Results</h3><div>The UPLC-QTOF-MS/MS analysis showed that phenolics were the essential components in the water extracts of EuH, including flavonoids, phenolic acids, and gallotannins. Treatment with EuH alleviated psoriatic symptoms including skin condition, high PASI scores (erythema, scaling, and thickness), and spleen index values in imiquimod-induced mice. EuH treatment also inhibited keratinocyte hyperproliferation, reduced epidermal thickness, reduced inflammatory cell infiltration into skin lesions, decreased the mRNA levels of inflammatory factors, and restored T and Treg cellular balance in the spleen. RNA-seq, ELISA, qRT-PCR and WB analyses indicated that EuH extract reduced the inflammatory response and keratinocyte hyperproliferation by inhibiting the IL-17 signaling pathway.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that EuH extract suppresses keratinocyte hyperproliferation and inflammation in psoriasis by inhibiting the IL-17 signaling pathway, supporting EuH as a potential treatment for psoriasis.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120030"},"PeriodicalIF":4.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shaoting Chen , Yanpei Zhu , Jingxiao Wang , Xin Zhao , Xingran Zhai , Linlan Hu , Xian He , Zhihan Li , Yafei Guo , Sihao Wang , Dong Ji , Zhengsheng Zou , Guangde Zhou , Yongping Yang , Jiabo Wang , Yan Chen , Yawen Lu
{"title":"Biejia ruangan tablet alleviated liver fibrosis in murine models by hindering the crosstalk between hepatic stellate cells and M2-like macrophages through PDGF-AA/PI3K/AKT pathway","authors":"Shaoting Chen , Yanpei Zhu , Jingxiao Wang , Xin Zhao , Xingran Zhai , Linlan Hu , Xian He , Zhihan Li , Yafei Guo , Sihao Wang , Dong Ji , Zhengsheng Zou , Guangde Zhou , Yongping Yang , Jiabo Wang , Yan Chen , Yawen Lu","doi":"10.1016/j.jep.2025.120029","DOIUrl":"10.1016/j.jep.2025.120029","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Biejia Ruangan Tablet (BJRG) is a patented traditional Chinese medicine formula with demonstrated efficacy against liver fibrosis. However, its underlying molecular mechanisms remain unclear.</div></div><div><h3>Aim</h3><div>This study aimed to investigate the anti-fibrotic effects of BJRG and elucidate its molecular mechanisms.</div></div><div><h3>Methods</h3><div>Liver fibrosis was induced in murine models using carbon tetrachloride (CCl4) or bile duct ligation (BDL) to evaluate the efficacy of BJRG. Network pharmacology was employed to predict the mechanisms of BJRG. The expression of PDGF-AA was assessed in both murine and human samples. The interaction between BJRG and PDGF-AA was investigated in vitro using primary mouse bone marrow-derived macrophages (BMDMs) and LX-2 cells. Ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) was used to identify liver-entry active components of BJRG. Molecular docking was performed to predict their binding affinity with PDGF-AA.</div></div><div><h3>Results</h3><div>BJRG significantly alleviated liver fibrosis in both CCl4-and BDL-induced murine models. Network pharmacology suggested that BJRG targeted the PDGF/PI3K/AKT signaling pathway. Then we revealed that BJRG specifically downregulated PDGF-AA expression and PI3K/AKT signaling in M2-like macrophages, thereby attenuating hepatic stellate cell (HSC) activation. Clinical data demonstrated that PDGF-AA was associated with liver cirrhosis, and BJRG suppressed PDGF-AA levels in patients with lower Ishak inflammation scores. Molecular docking indicated that the liver-entry components of BJRG exhibited strong binding affinity with PDGF-AA.</div></div><div><h3>Conclusion</h3><div>BJRG ameliorated liver fibrosis by disrupting the crosstalk between M2-like macrophages and HSCs through downregulation of the PDGF-AA/PI3K/AKT pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120029"},"PeriodicalIF":4.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhun Xiao , Siqi Gao , Shengsheng Li , Fangming Yang , Dingqi Zhang , Zhenyi Niu , Yu Zhang , Zhongping Duan , Shenglan Qi , Suping Ma
{"title":"Taohong Siwu Decoction modulates glutathione metabolism to suppress hepatocyte ferroptosis and demonstrates anti-fibrotic effects in the liver","authors":"Zhun Xiao , Siqi Gao , Shengsheng Li , Fangming Yang , Dingqi Zhang , Zhenyi Niu , Yu Zhang , Zhongping Duan , Shenglan Qi , Suping Ma","doi":"10.1016/j.jep.2025.120025","DOIUrl":"10.1016/j.jep.2025.120025","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The ameliorative effect of traditional Chinese medicine (TCM) on hepatic fibrosis has been widely recognized and researched, but studies on the mechanism of action have been hampered by its complex composition, which requires more in-depth studies to elucidate why and how TCM works. The theory of TCM believes that the liver is closely related to blood circulation, and hepatic fibrosis is caused by blood stagnation. Taohong Siwu Decoction (THSW) is a classic formula for nourishing and invigorating blood and has been used clinically for centuries. Current evidence has demonstrated its ameliorative effect on hepatic fibrosis, but the exact mechanism of action remains unclear.</div></div><div><h3>Aim of the study</h3><div>Exploring the possible mechanism of the anti-hepatic fibrosis effect of THSW by proteomics and validating with <em>in vivo</em> and <em>in vitro</em> studies.</div></div><div><h3>Materials and methods</h3><div>The carbon tetrachloride (CCl<sub>4</sub>)-induced fibrosis model was conducted in mice and treated with THSW <em>in vivo</em> with colchicine as the positive control. Then serum biomarker alanine aminotransferase (ALT), aspartate aminotransferase (AST), and histopathological analysis were evaluated to examine the effects of THSW. And hepatic fibrosis indicators alpha-smooth muscle actin (α-SMA) and Collagen Ⅰ (Col-Ⅰ) were detected by western blotting, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Additionally, the 4D Label-free quantitative proteomic analysis of liver samples was applied. <em>In vitro</em>, erastin-induced BRL-3A cells, a rat hepatocyte line, were performed as a hepatocyte ferroptosis model and treated with or without drug-containing serum of THSW. Finally, molecular docking was used to verify the binding ability of the main components of THSW to potential targets.</div></div><div><h3>Results</h3><div>THSW treatment significantly ameliorated serum ALT, AST, hydroxyproline (Hyp) content, α-SMA and Col-Ⅰ mRNA expression in fibrosis mice. Further results showed that THSW decreased the malondialdehyde (MDA) and 4-Hydroxynonenal (4-HNE) content and increased the glutathione (GSH) content of liver tissue. Notably, proteomic analyses have identified 294 differentially expressed proteins in the THSW-treated group compared to the model group, with 97 proteins up-regulated and 197 down-regulated. Functional analysis of these differential proteins highlights the significant roles of inflammation and oxidative stress. Further validation <em>in vivo</em> and <em>in vitro</em>, THSW significantly improved the protein expression of glutathione S-transferase M1 (GSTM1), down-regulate the expression of transferrin receptor (TFRC), and kelch-like ECH-associated protein 1(Keap1) proteins, and promote the metabolism of GSH. Especially it reduced serum iron levels, increased total iron binding capacity, and up-regulated recombinant so","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120025"},"PeriodicalIF":4.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ludan He , Yuanyuan Ji , Linxiao Han , Wensi Zhu , Shuoyan Wei , Hui Qi , Juan Li , Xiuzhen Lv , Min Shi , Bin Hou , Tongxing Wang , Jie Shen , Yuanlin Song , Nuo Xu , Qiaoliang Zhu , Jian Zhou
{"title":"Lianhua Qingke granules alleviate cigarette smoke-induced COPD through AMPK signaling pathway","authors":"Ludan He , Yuanyuan Ji , Linxiao Han , Wensi Zhu , Shuoyan Wei , Hui Qi , Juan Li , Xiuzhen Lv , Min Shi , Bin Hou , Tongxing Wang , Jie Shen , Yuanlin Song , Nuo Xu , Qiaoliang Zhu , Jian Zhou","doi":"10.1016/j.jep.2025.120028","DOIUrl":"10.1016/j.jep.2025.120028","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by inflammation, oxidative stress, and airflow limitation, commonly associated with cigarette smoke exposure and aging. Lianhua Qingke Granules (LHQK), derived from Maxing Shigan Decoction and Qingjin Huatan Decoction, is a traditional Chinese medicine historically used to \"disperse lung Qi, clear heat, resolve phlegm, and relieve cough.\" LHQK has shown promise in alleviating respiratory disorders, including reducing inflammation and improving pulmonary function in COPD. However, its underlying mechanisms remain insufficiently explored.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the therapeutic effects and mechanisms of LHQK in cigarette smoke-induced COPD models.</div></div><div><h3>Materials and methods</h3><div>C57BL/6J mice were exposed to cigarette smoke for three months and treated with high- or low-dose LHQK for three months. Lung tissues were analyzed using histology, transcriptomics, RT-PCR, and western blotting to evaluate inflammation, cellular senescence, and pathway activation. Key cytokines (IL-6, CXCL15, TNF-α) and markers of senescence (p16, p21, p53) were measured.</div></div><div><h3>Results</h3><div>Our results demonstrated that both low- and high-dose LHQK significantly alleviated lung injury and inflammation in the COPD mouse model, with the high-dose group exhibiting more pronounced effects. Histological analysis and reduced levels of inflammatory cytokines (IL-6, CXCL15, TNF-α) in the LHQK-treated groups compared to the control and COPD groups confirmed the efficacy of LHQK in mitigating lung damage. RNA sequencing of lung tissue from the control, COPD, and LHQK-treated groups revealed that LHQK, particularly at the high dose, regulated the AMPK signaling pathway, which is implicated in aging-related processes. Furthermore, both dose groups of LHQK reduced cellular senescence and alleviated age-related exacerbations of COPD, with the high-dose treatment demonstrating stronger effects. These findings suggest that LHQK protects against smoke-induced COPD by modulating inflammation and cellular senescence through the AMPK signaling pathway.</div></div><div><h3>Conclusion</h3><div>LHQK provides protective effects against smoke-induced COPD by attenuating inflammation and cellular senescence through the AMPK pathway. These findings highlight its potential as an adjunctive therapy for COPD, particularly in aging populations.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120028"},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}