Yuanye Jiang , Jiaqi Zhang , Wangzhenzu Liu , Xiaojing Qian , Xiaoyu Zhuang , Cheng Hu
{"title":"Scutellariae Radix and Coptidis Rhizoma improve NAFLD via regulation of SIRT6/ACSL5 pathway and SCD1","authors":"Yuanye Jiang , Jiaqi Zhang , Wangzhenzu Liu , Xiaojing Qian , Xiaoyu Zhuang , Cheng Hu","doi":"10.1016/j.jep.2025.119834","DOIUrl":"10.1016/j.jep.2025.119834","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The herbal pair <em>Scutellariae Radix</em>-<em>Coptidis Rhizoma</em> (SR-CR) has been widely used in Traditional Chinese Medicine (TCM) for treating metabolic disorders, including nonalcoholic fatty liver disease (NAFLD) -related conditions. Its traditional use highlights its potential in addressing the multifaceted pathogenesis of NAFLD, though the underlying mechanisms remain unclear.</div></div><div><h3>Aim of the study</h3><div>To evaluate the therapeutic efficacy of the SR-CR herbal pair in alleviating NAFLD and to elucidate its mechanisms of action, with a specific focus on lipid metabolism pathways.</div></div><div><h3>Materials and methods</h3><div>The therapeutic effects of SR-CR were assessed using a high-fat diet (HFD)-induced NAFLD rat model and HepG2 cell model. Multi-omics analyses were employed to identify molecular targets and pathways, while affinity ultrafiltration-mass spectrometry characterized bioactive constituents. Findings were validated in vivo and in vitro via Western blot and immunofluorescence. Protein-constituent interactions were further characterized by surface plasmon resonance and molecular docking.</div></div><div><h3>Results</h3><div>SR-CR significantly alleviated NAFLD symptoms in HFD-fed rats by reducing hepatic lipid accumulation, inflammation, and hepatocyte ballooning while normalizing biochemical indicators. Mechanistic studies revealed that SR-CR regulates the SIRT6/ACSL5 pathway and SCD1, both critical to lipid metabolism. <em>Scutellariae Radix</em> (SR) and its major constituent, baicalin, enhanced ACSL5 activity via SIRT6-mediated deacetylation, promoting fatty acid oxidation and intracellular lipid utilization. <em>Coptidis Rhizoma</em> (CR) and its primary component, berberine, inhibited SCD1, thereby reducing de novo lipogenesis. These complementary effects synergistically enhanced energy expenditure and reduced lipid synthesis.</div></div><div><h3>Conclusion</h3><div>The SR-CR herbal pair effectively alleviates HFD-induced NAFLD by synergistically modulating lipid metabolism, enhancing energy expenditure, and reducing de novo lipogenesis through the regulation of the SIRT6/ACSL5 pathway and SCD1. These findings provide molecular evidence for the traditional use of SR-CR in treating metabolic disorders and highlight its potential as a plant-based therapeutic for NAFLD.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119834"},"PeriodicalIF":4.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850197","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}
Engy Mohsen , Ahlam M. El Fishawy , Abeer Salama , Rania Elgohary , Ahmed Refaat , Abdelbaset M. Elgamal , Inas Y. Younis , Rania M. Kamal
{"title":"Unveiling the gastroprotective effect of the ethyl acetate fraction of Cordia africana Lam. roots against ethanol-induced gastric ulcer and Helicobacter pylori","authors":"Engy Mohsen , Ahlam M. El Fishawy , Abeer Salama , Rania Elgohary , Ahmed Refaat , Abdelbaset M. Elgamal , Inas Y. Younis , Rania M. Kamal","doi":"10.1016/j.jep.2025.119841","DOIUrl":"10.1016/j.jep.2025.119841","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Traditionally, <em>Cordia africana</em> Lam. roots<em>,</em> have been used in the treatment of gastro-intestinal complaints and the management of peptic ulcer diseases.</div></div><div><h3>Aim of the study</h3><div>Quantitative determination of <em>Cordia africana</em> Lam. roots constituents was performed to investigate their phytochemical composition and their anti-ulcer mechanism.</div></div><div><h3>Materials and methods</h3><div><em>Cordia africana</em> Lam. roots were subjected to extraction and fractionation. Antimicrobial activities of the extract and its factions were tested against <em>Helicobacter pylori,</em> and minimum inhibitory concentration (MIC) was measured. Then, an <em>in vivo</em> ethanol-induced model in rats was performed (at two tested doses: 200 mg/kg, 400 mg/kg, and pantoprazol 10 mg/kg against ethanol 5 mL/kg by oral gavage) with subsequent histopathological analysis. Oxidative and gastric inflammatory markers were measured. The phytochemical profile was confirmed using quantitative High-performance liquid chromatography (HPLC). Finally, molecular docking was performed to investigate the binding mode among the most abundant quantified compounds, <em>viz</em>., kaempferol, myricetin, naringenin, quercetin, and rosmarinic acid and three chosen proteins.</div></div><div><h3>Results</h3><div>Among the tested fractions, <em>Cordia africana</em> ethyl acetate fraction (CAEt) gave the least MIC (7.82 μg/mL). Besides, at its high dose (400 mg/kg; orally), CAEt significantly reduced the ulcer number and severity by 26 % each, lowered malondialdehyde by 39 %, and increased glutathione and prostaglandin E2 levels by 92 % and 27 %, respectively, compared to pantoprazol. It exhibited similar potency to pantoprazol in decreasing tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant-1, while it significantly decreased nuclear factor-kappa B more than pantoprazol by 7 %. Nineteen compounds were quantified using HPLC, showing that phenolic compounds and flavonoids were the most abundant phytoconstituents. <em>In-silico</em> molecular docking screening revealed the interaction between the five most quantified compounds and nuclear factor kappa B, prostaglandin E2, and tumor necrosis factor alpha proteins.</div></div><div><h3>Conclusion</h3><div>CAEt possesses potent gastroprotective properties <em>via</em> the reduction of gastric ulcer severity, decreasing oxidative stress, and inflammatory markers in ethanol-induced stomach damage. CAEt could be a promising candidate for gastric ulcer treatment and further studies on gastric-related diseases.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119841"},"PeriodicalIF":4.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855715","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}
Can Liu , Peng He , Ru Qiao , Xiaoyan Yang , Changsong Ding , Fuyuan He
{"title":"Mechanistic study of Lonicerae Japonicae Flos (Caprifoliaceae) in non-small cell lung cancer prevention and treatment through integrative pharmacology, multi-machine learning, artificial intelligence, and in vitro experiments","authors":"Can Liu , Peng He , Ru Qiao , Xiaoyan Yang , Changsong Ding , Fuyuan He","doi":"10.1016/j.jep.2025.119832","DOIUrl":"10.1016/j.jep.2025.119832","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Lonicerae Japonicae</em> Flos (Caprifoliaceae) (LJF), an herb with the homology of medicine and food, is traditionally utilized for its heat-clearing, detoxifying, and anticancer properties. Yet, the mechanism by which LJF may assist in the treatment of non-small cell lung cancer (NSCLC) remains unclear.</div></div><div><h3>Aim of the study</h3><div>To elucidate the potential mechanisms of LJF in the treatment of NSCLC through phytochemical analysis, network pharmacology, machine learning, and <em>in vitro</em> experimental validation.</div></div><div><h3>Materials and methods</h3><div>LJF was analyzed for its components using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The active compounds and targets of LJF were identified from TCMSP, and NSCLC-related targets were retrieved from GeneCards, DisGeNET and OMIM. Network pharmacology and multi-machine learning algorithms predicted key features, and GSEA/GSVA assessed pathway enrichment. Immune infiltration analysis evaluated immune cell composition in the NSCLC microenvironment, and molecular docking was performed with AlphaFold. <em>In vitro</em> experiments assessed LJF's effects on A549 cells, and Western blot analyzed protein expression.</div></div><div><h3>Results</h3><div>Network pharmacology and multi-machine learning indicated that PECAM1 and SPP1 are potential targets for LJF in the treatment of NSCLC. GSEA and immune infiltration analysis suggested PECAM1 and SPP1 influence NSCLC progression and immune evasion. <em>In vitro</em> experiments showed that LJF significantly inhibited A549 cells proliferation, migration, and invasion. Western blot results indicated upregulation of PECAM1 and SPP1 expression under LJF treatment.</div></div><div><h3>Conclusion</h3><div>LJF has an adjunctive therapeutic effect on NSCLC by regulating PECAM1 and SPP1 targets and their associated signaling pathways.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119832"},"PeriodicalIF":4.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855674","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}
Shuo Cheng , Wei Luo , Zhonghua Zhang , Jia Li , Xiang Li , Yidan Wang , Xinyu Weng , Zheng Dong
{"title":"Shexiang Baoxin Pill alleviates atherosclerosis by inhibiting macrophage-mediated inflammation via suppressing KMT5A mediated Irf7 transcription","authors":"Shuo Cheng , Wei Luo , Zhonghua Zhang , Jia Li , Xiang Li , Yidan Wang , Xinyu Weng , Zheng Dong","doi":"10.1016/j.jep.2025.119833","DOIUrl":"10.1016/j.jep.2025.119833","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Shexiang Baoxin Pill (SBP) is a traditional compound formulation composed of seven Chinese medicinal ingredients. Although SBP has shown promising clinical outcomes in the treatment of cardiovascular diseases, its role and underlying mechanisms in alleviating atherosclerosis remain insufficiently studied.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the effects and mechanisms of SBP in epigenetic modulating macrophage inflammatory responses to mitigate atherosclerosis.</div></div><div><h3>Materials and methods</h3><div><em>ApoE</em><sup><em>−/−</em></sup> mice were treated with high fat diet (HFD) following varying concentrations of SBP. Oil Red O staining, hematoxylin-eosin (HE) staining, and ELISA were used to assess the anti-atherosclerotic and anti-inflammatory efficiency of SBP. Subsequently, RNA sequencing (RNA-seq), RT-PCR, Western blot (WB), immunofluorescence (IF) and chromatin immunoprecipitation (ChIP) were employed in bone marrow derived macrophages (BMDMs) to elucidate the epigenetic mechanisms of SBP in alleviating macrophage inflammatory responses. Lysine methyltransferase 5A (KMT5A) was overexpressed <em>in vivo</em> and <em>in vitro</em> for further validation.</div></div><div><h3>Results</h3><div>SBP significantly attenuated atherosclerosis in HFD treated <em>ApoE</em><sup>−/−</sup> mice by decreasing plaque areas, serum inflammation levels and macrophages infiltration in the aortic root and plaques. SBP treatment reduced BMDMs inflammatory responses following oxidized low-density lipoprotein (oxLDL) treatment. Mechanistically, SBP inhibited interferon regulatory factor 7 (IRF7) expression by reducing KMT5A-mediated mono-methylation of histone H4 lysine 20 (H<sub>4</sub>K<sub>20</sub>), thus decreasing the secretion of multiple pro-inflammatory cytokines, including interferon (IFN)-α, IFN-β, TNF-α. Overexpression of KMT5A abolished the anti-atherosclerotic and anti-inflammatory effects of SBP, further confirming that KMT5A/H<sub>4</sub>K<sub>20</sub>me/IRF7 axis is a key target for SBP exerting therapeutic effect.</div></div><div><h3>Conclusion</h3><div>SBP exerts anti-atherosclerotic effects by inhibiting macrophage inflammatory responses through downregulation of the H<sub>4</sub>K<sub>20</sub> methylase KMT5A, thereby suppressing the transcription of <em>Irf7</em>. Our findings provide a novel epigenetic mechanism by which SBP alleviates atherosclerosis.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119833"},"PeriodicalIF":4.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850196","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}
Dongsheng Du , Hongjiao Zhong , Ziyi Huang , Mingzhu Gao , Ruirui Su , Mengqiu Xu , Lei Shi , Jie Hu , Huihui Cao
{"title":"Polysaccharides isolated from shufeng jiedu capsules by cross-flow ultrafiltration show anti-inflammatory effects on LPS-stimulated RAW264.7 cells and zebrafish inflammatory models","authors":"Dongsheng Du , Hongjiao Zhong , Ziyi Huang , Mingzhu Gao , Ruirui Su , Mengqiu Xu , Lei Shi , Jie Hu , Huihui Cao","doi":"10.1016/j.jep.2025.119817","DOIUrl":"10.1016/j.jep.2025.119817","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Shufeng Jiedu Capsules (SFJDC) is a traditional Chinese patent medicine comprising eight traditional Chinese medicines (TCM). SFJDC is known for its anti-inflammatory and antipyretic effects and is mainly used in clinics to treat upper respiratory tract infections. Currently, studies on the active ingredients of the SFJDC all focus on small-molecule compounds. In contrast, bio-macromolecules, such as the anti-inflammatory activities of polysaccharides in SFJDC, have not been studied, and the composition of the polysaccharides in SFJDC is also unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to isolate active polysaccharides from Shufeng Jiedu capsules and determine their structural properties and anti-inflammatory activities.</div></div><div><h3>Materials and methods</h3><div>The polysaccharides with different molecular weights were prepared by organic solvent extraction, alcohol precipitation, dialysis, and cross-flow ultrafiltration. The structural characterization of polysaccharides was clarified by high-performance size exclusion chromatography (HPGPC), ion chromatography (IC), and Fourier transform infrared spectroscopy (FT-IR). Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR) assay were used to investigate the anti-inflammatory effects of polysaccharides on Lipopolysaccharides (LPS)-stimulated RAW264.7 cells. The <em>in vivo</em> study was employed on the CuSO<sub>4</sub>-induced and LPS-stimulated zebrafish inflammatory models, and the survival analysis, observation of neutrophil migration, hematoxylin-eosin (H&E) staining, and qRT-PCR assays were used to investigate the <em>in vivo</em> anti-inflammatory effect of polysaccharides.</div></div><div><h3>Results</h3><div>The crude polysaccharides SFJDC-CP were obtained from the mixed aqueous extract of SFJDC with a yield of 38.72 %. Both SFJDC and SFJDC-CP dose-dependently inhibited the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β in LPS-stimulated RAW264.7 cells, and SFJDC-CP was more effective at a lower dosage. SFJDC-CP was further separated into three fractions, SFJDC-CP1—CP3, by cross-flow ultrafiltration apparatus with nominal molecular weight cut-offs of 100 kDa, 50 kDa, and 10 kDa membrane cassettes, and the yields were approximately 58.19 %, 10.88 %, and 30.94 %, respectively. The MWs of the SFJDC-CP and its SFJDC-CP1—CP3 were 35.7 kDa, 149.1 kDa, 34.5 kDa, and 15.1 kDa, respectively. The four polysaccharides were composed of rhamnose, arabinose, galactose, glucose, and galacturonic acid in different molar ratios. Non-toxic concentrations of the four polysaccharides ranged from 12.5 to 200 μg/mL. The four polysaccharides significantly reduced the mRNA expression levels and release of IL-1β, IL-6, and TNF-α (<em>P</em> < 0.0001) in LPS-stimulated RAW264.7 cells. Polysaccharides also decreased inflammatory cell infiltration and neutrophil mig","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119817"},"PeriodicalIF":4.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854744","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}
Yuzhen Liu , ZhuXia Wu , Chen Gu , Jing Fang , Yusi Peng , Lei Peng , Weidong Chen , Liang Yao , Ling He
{"title":"ShenJiaoLingCao decoction ameliorates cyclophosphamide-induced splenic injury and immunosuppression via the inhibition of MEK/ERK signaling pathway activity and modulation of amino acid metabolism","authors":"Yuzhen Liu , ZhuXia Wu , Chen Gu , Jing Fang , Yusi Peng , Lei Peng , Weidong Chen , Liang Yao , Ling He","doi":"10.1016/j.jep.2025.119830","DOIUrl":"10.1016/j.jep.2025.119830","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>ShenJiaoLingCao Decoction (SJLCD) is derived from the classic Chinese medicine prescription, which consists of ten kinds of herbs. In China, SJLCD has been used as an immunomodulator in clinical practice for more than ten years. However, no relevant studies have been done to clarify the pharmacodynamic underpinnings of its regulation of the body's immune system and its related processes.</div></div><div><h3>Aim of the study</h3><div>This study aims to assess the immunomodulatory effects of SJLCD.</div></div><div><h3>Materials and methods</h3><div>Ultra performance liquid chromatography-quadrupole-orbitrap mass spectrometry (UPLC-Q-Orbitrap MS) was utilized to characterize the chemical constituents in SJLCD and establish its fingerprint profile. Predicting potential bioactive compounds in SJLCD for immunomodulatory effects and elucidating their mechanisms of action using artificial intelligence technology. Experiments at the animal level were carried out to verify the accuracy of the predictions. Firstly, an immunocompromised model was constructed by intraperitoneal injection of 80 mg/kg of cyclophosphamide (CTX) into rats for 3 consecutive days, and SJLCD was administered by oral administration for 14 days. The immunomodulatory effect of SJLCD on immune organs was verified by evaluating the immune organ index and histopathological examinations using hematoxylin and eosin (H&E) staining. The effect of SJLCD on relevant immune cells was examined by measuring erythrocytes, leukocytes and lymphocytes. The effect of SJLCD on relevant immune molecules was assessed by detecting the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), matrix metalloproteinase-9 (MMP9), cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8). Western blot was used to verify and analyze the possible immunomodulatory mechanisms of SJLCD. Finally, serum untargeted metabolomics was used to detect the differential metabolites of SJLCD in immunocompromised rats.</div></div><div><h3>Results</h3><div>In this study, a total of 91 compounds were identified in the SJLCD, and the results showed a high degree of similarity (S1-S11 > 0.935) among the 11 samples in positive ion mode. Artificial intelligence computer techniques predicted that quercetin, kaempferol, and fumarine in SJLCD bound better to core targets, especially MAPK1. On animal-level validation, it was found that from an immune organ perspective, SJLCD ameliorated CTX-induced thymus and spleen damage. From an immune cell perspective, SJLCD significantly increased peripheral erythrocyte, leukocyte and lymphocyte counts in immunocompromised rats. From the immune molecular level, SJLCD down-regulated the levels of TNF-α, IL-6, IL-1β, MMP9, CD8 and up-regulated the level of CD3 and CD4 which normalize its secretion. Mechanistically, SJLCD regulates immunity possibly through the MEK/","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119830"},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850319","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}
Liqiang Shi , Yutong Wang , Yunhui Guan , Lihui Men , Jinghui Sun , Guangxin Yuan
{"title":"To establish a new quality assessment method based on the regulation of intestinal microbiota in type 2 diabetes by lignans of Schisandra chinensis (Turcz.) Baill","authors":"Liqiang Shi , Yutong Wang , Yunhui Guan , Lihui Men , Jinghui Sun , Guangxin Yuan","doi":"10.1016/j.jep.2025.119822","DOIUrl":"10.1016/j.jep.2025.119822","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The mature fruit of <em>Schisandra chinensis</em>, a traditional Chinese medicinal herb, is primarily utilized for the management of diabetes. Its principal bioactive constituents include lignans, polysaccharides, and organic acids. Nonetheless, a standardized quality control methodology grounded in the therapeutic efficacy of <em>Schisandra chinensis</em> (Turcz.) Baill. for diabetes treatment has yet to be developed.</div></div><div><h3>Aim of the study</h3><div>Due to the diverse origins, intricate composition, and multiple therapeutic targets of <em>Schisandra chinensis</em> Fructus, relying on a single index component for quality control is challenging. Consequently, this study proposes a novel quality evaluation approach, integrating pharmacological activity and intestinal microbiota analysis, to assess the efficacy of <em>Schisandra chinensis</em> Fructus in diabetes management.</div></div><div><h3>Materials and methods</h3><div>Twelve batches of <em>Schisandra chinensis</em> Fructus from diverse origins were selected for lignan content analysis, and 3 representative batches were subsequently chosen for pharmacological experiments pertaining to diabetes. The relationship between lignan content in <em>Schisandra chinensis</em> Fructus and its pharmacological efficacy was assessed by evaluating the recovery rates of eleven serum biochemical markers affected by Schisandra lignans. Furthermore, 16S rRNA gene sequencing was utilized to explore the association between the gut microbiota in diabetic rats and the lignan content in <em>Schisandra chinensis</em> Fructus.</div></div><div><h3>Results</h3><div>The results of serum biochemistry analyses demonstrate that Schisandra lignans significantly decrease bone gamma-carboxyglutamate protein (BGP), blood lipid levels, and oxidative stress in diabetic rats, thereby conferring hepatoprotective effects. Correlation analysis between the constituents and pharmacological effects revealed a positive relationship between the anti-diabetic efficacy of <em>Schisandra chinensis</em> Fructus and its total lignan content. Furthermore, Schisandra lignans were observed to enhance gut microbiota diversity in diabetic rats, mitigate the dysbiosis induced by Type 2 Diabetes Mellitus (T2DM), and increase the abundance of beneficial bacterial species.</div></div><div><h3>Conclusions</h3><div>The observed variations in the efficacy of <em>Schisandra chinensis</em> Fructus from different sources may be attributed to differences in total lignan content. The higher the total lignan content in <em>Schisandra chinensis</em> Fructus, the stronger its protective effect. Based on the analysis of component-efficacy-microbiota correlation this study has identified a chisandrin content of ≥3.5 mg/g and a total lignan content of≥17 mg/g as quality evaluation indicators for the improvement of T2DM by <em>Schisandra chinensis</em> Fructus.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119822"},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848374","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}
Lin-Xia Chen , Yao Wang , Run-Wen Zhu , Jing Zhou , Ji-Chen Shen , Cheng-Ying Wu , Hong Shen , Xiang-Ling Qin , Fang Long , Song-Lin Li
{"title":"Ethanol precipitation process affects the pharmacokinetic characteristics of major active glycosides of Qiong-Yu-Gao: evidences in normal and cisplatin-induced acute kidney injury rats","authors":"Lin-Xia Chen , Yao Wang , Run-Wen Zhu , Jing Zhou , Ji-Chen Shen , Cheng-Ying Wu , Hong Shen , Xiang-Ling Qin , Fang Long , Song-Lin Li","doi":"10.1016/j.jep.2025.119809","DOIUrl":"10.1016/j.jep.2025.119809","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Qiong-Yu-Gao (QYG) is a classical formula that shows protective effects against cisplatin-induced acute kidney injury (AKI). Recent evidence indicates that iridoid glycosides and ginsenosides are the main active substances of QYG. In the production of modern Chinese medicine preparations, ethanol precipitation is a commonly applied but not fully verified refining process.</div></div><div><h3>Aim of study</h3><div>Pharmacokinetic profiling approaches were used for evaluating the rationality of ethanol precipitation process in the production of modern QYG preparations.</div></div><div><h3>Materials and methods</h3><div>Ethanol precipitation was used to prepare the glycoside-rich fraction (QYG-GS). UPLC-TQ-MS/MS methods were established for quantification of iridoid glycosides and ginsenosides of QYG in plasma and fecal samples. The pharmacokinetic profiles of major glycosides were characterized and compared after oral administration of QYG and QYG-GS in both normal and cisplatin-induced AKI rats.</div></div><div><h3>Results</h3><div>Using the validated quantitative methods, 6 glycosides were determined in plasma samples, and 14 glycosides were determined in fecal samples. More significant pharmacokinetic differences were observed in AKI rats than in normal rats. The ethanol precipitation process significantly increased the C<sub>max</sub> and AUC<sub>0-t</sub> of catalpol, rehmannioside D, melittoside, leonuride and ginsenoside Rb1, and decreased the T<sub>1/2</sub> and MRT<sub>0-t</sub> values, indicating the increased absorption and accelerated elimination. Additionally, ethanol precipitation significantly decreased the fecal contents of above compounds, but increased the fecal contents of compound K.</div></div><div><h3>Conclusions</h3><div>UPLC-TQ-MS methods were developed and validated for quantification and comparison of QYG glycosides in biological samples. The ethanol precipitation process significantly altered the pharmacokinetic profiles of major active glycosides in QYG, especially in AKI rats. The findings could provide a helpful reference for selection of ethanol precipitation process in the production of modern QYG preparations.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119809"},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850321","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}
Wenxuan Dong , Xinrui Wang , Wenqian Wang , Lifei Luo , Kai Li , Guotong Li , Dailin Liu , Jingze Zhang
{"title":"Study on the compatibility of japonica rice in Xie-Bai-San decoction based on characterization, multi components quantification, and pharmacokinetics","authors":"Wenxuan Dong , Xinrui Wang , Wenqian Wang , Lifei Luo , Kai Li , Guotong Li , Dailin Liu , Jingze Zhang","doi":"10.1016/j.jep.2025.119791","DOIUrl":"10.1016/j.jep.2025.119791","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Xie-Bai-San decoction (XBS), which is effective in treating coughs associated with lung heat, is composed of four Chinese medicines: Morus alba L. (known as Sangbaipi), Lycii Cortex (known as Digupi), licorice (Glycyrrhiza uralensis Fisch.), and japonica rice. The original prescription of XBS and its modified prescriptions have been greatly expanded in clinical application. However, japonica rice as a guiding drug is often ignored, which effects on composition and metabolism <em>in vivo</em> have not been fully studied.</div></div><div><h3>Aim of the study</h3><div>The purpose of this study was to explain the compatibility of japonica rice in the XBS. By comparing the physical state of the XBS without japonica rice decoction (XBS-JM) and measuring the content of 26 indicative components in both XBS and XBS-JM decoctions, this study illustrated how japonica rice affected the overall physical state and the dissolution of components during the decoction process.</div><div>Combined with the analysis of the pharmacokinetic characteristics of 18 active components absorbed into the blood, the effect of japonica rice and the scientific basis of prescription compatibility were comprehensively discussed.</div></div><div><h3>Methods</h3><div>A sensitive and reliable UPLC-Q-TOF-MS qualitative analysis method was developed to analyze the chemical constituents of XBS. Taking the change of the remaining volume of the decoction as the index, the decoction time of 30, 50 and 90 min was selected. A Malvern particle size apparatus and transmission electron microscopy (TEM) were utilized to investigate the influence of japonica rice on phase states. Additionally, a highly selective and sensitive UPLC-MS/MS quantitative analysis method was established to detect changes in the content of 26 chemical components in the decoctions at three different decoction time. The pharmacokinetic parameters of 18 components were also studied following the oral administration of XBS and XBS-JM in both control and model animals.</div></div><div><h3>Results</h3><div>The results showed that the particle size of the XBS and XBS-JM decoction, following dialysis-ultracentrifugation, was predominantly in the nano-scale range. The addition of japonica rice (JM) enhanced the stability of the nanoparticles, and the concentrations of guanosine, chlorogenic acid, kukoaMine B, astragalin, and naringenin in the XBS decoction were significantly higher than those in the XBS without japonica rice (XBS-JM) decoction. The results of pharmacokinetics showed that compared with the administration of XBS-JM, XBS significantly enhanced the absorption of eight components in the control group, such as kukoaMine B, kuwanon G, wogonoside, and liquiritin. In the model group, following the administration of XBS, the absorption rates of six components, such as kukoaMine B, kuwanon G, and 18β-glycyrrhetinic acid were significantly increased (p < 0.05), with the pe","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119791"},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868503","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}
Yixin Zhang , Yan Yu , Jianbo Xue , Wenyi Yu , Xianqiang Zhou , Mengtong Jin , Peng Liu , Tongxing Wang , Zhancheng Gao , Cuiling Feng
{"title":"Lianhua qingke alleviates cigarette smoke induced cellular senescence in COPD mice by regulating the Sp1/SIRT1/HIF-1α pathway","authors":"Yixin Zhang , Yan Yu , Jianbo Xue , Wenyi Yu , Xianqiang Zhou , Mengtong Jin , Peng Liu , Tongxing Wang , Zhancheng Gao , Cuiling Feng","doi":"10.1016/j.jep.2025.119831","DOIUrl":"10.1016/j.jep.2025.119831","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Lianhua Qingke (LHQK) has been utilized as a complementary therapy for respiratory diseases like tracheobronchitis and acute exacerbations of COPD in China. However, its therapeutic efficacy and underlying mechanisms for COPD remain elusive.</div></div><div><h3>Aim of the study</h3><div>This study aimed to elucidate the mechanisms underlying the effects of LHQK on COPD, focusing on its anti-senescence properties.</div></div><div><h3>Materials and methods</h3><div>The therapeutic effects of LHQK were assessed by chronic cigarette smoke exposure induced COPD mice model. Lung function, histopathology investigation, cytokines detection and bio-molecular analysis were conducted to assess the impact of LHQK on pulmonary inflammation, mucin secretion, and cellular senescence of cigarette smoke (CS)-induced COPD mice.</div></div><div><h3>Results</h3><div>A comprehensive analysis identified a total of 41 compounds as the key compounds of LHQK. Oral administration of LHQK markedly reversed the decline in pulmonary function, suppressed inflammation and mucus secretion, mitigated emphysema, and histopathology damage in lungs of COPD mice. In addition, LHQK attenuated secretory phenotype associated with cellular senescence in pulmonary and circulatory, and reduced the senescence-associated markers levels, such as SA-β-gal, miR-125a-5p, p21, p27 and p53. Network pharmacology and molecular assays indicated that LHQK enhanced Sp1 and SIRT1 expression, resulting to repression of HIF-1α, finally alleviating cellular senescence in COPD mice.</div></div><div><h3>Conclusions</h3><div>LHQK demonstrates potential as a complementary therapy for COPD, attenuating CS-triggered emphysema and pulmonary inflammation by targeting cellular senescence processes and modulation of Sp1/SIRT1/HIF-1α pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119831"},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851543","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}