Journal of ethnopharmacology最新文献

{"title":"Chinese medicine preparation Pudilan anti-inflammatory oral liquid: Chemical constituents and developmental toxicity","authors":"Jingjing Chen ,&nbsp;Zhen Lu ,&nbsp;Zhi Yan ,&nbsp;Yaxi Li ,&nbsp;Zhihao Hou ,&nbsp;Derui Wang ,&nbsp;Yanqiu Jiang ,&nbsp;Ranran Zhang ,&nbsp;Xiaodong Li ,&nbsp;Baozhen Jiang ,&nbsp;Huan Wang ,&nbsp;Ke Li","doi":"10.1016/j.jep.2025.120173","DOIUrl":"10.1016/j.jep.2025.120173","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Pudilan anti-inflammatory oral liquid (PDL) is a classical Chinese herbal formulation. Traditionally used to treat respiratory infections, sore throat, and mumps, it is widely administered in children and pregnant women due to its perceived safety. However, recent guidelines advise caution in these populations, raising concern about its developmental toxicity. This study investigates the chemical profile and embryotoxic effects of PDL to bridge traditional use with modern toxicological evaluation.</div></div><div><h3>Aims of the study</h3><div>To identify the chemical constituents of PDL and evaluate its developmental toxicity, as well as elucidate potential toxicological mechanisms using a zebrafish embryo model.</div></div><div><h3>Materials and methods</h3><div>The chemical composition of PDL was characterized using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Zebrafish (<em>Danio rerio</em>) embryos were exposed to various PDL concentrations. Developmental toxicity was assessed through mortality, malformation, hatching, heart rate, body length, spontaneous movement, and locomotor activity. Histological analysis, transcriptomic profiling, and qRT-PCR validation were conducted to explore underlying mechanisms.</div></div><div><h3>Results</h3><div>Baicalin was identified as the dominant flavonoid, followed by baicalein and wogonin. PDL exposure induced dose-dependent developmental toxicity, including increased mortality, malformations, and impaired cardiac and behavioral functions. Transcriptomic analysis revealed dysregulation in cell cycle, DNA replication, and steroid biosynthesis pathways.</div></div><div><h3>Conclusion</h3><div>PDL exhibits significant embryotoxicity in zebrafish, potentially mediated by flavonoid-induced disruption of developmental pathways. These findings highlight the need for safety assessments of traditional formulations, particularly in vulnerable populations.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"351 ","pages":"Article 120173"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336639","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":"Sub-chronic realgar exposure causes liver inflammatory injury in mice by inducing bile acid-mediated NLRP3 inflammasome activation through down-regulation of ileal FXR","authors":"Guangyan Li ,&nbsp;Tongshu Wang ,&nbsp;Yixuan Xie ,&nbsp;Lu He ,&nbsp;Huan Liu ,&nbsp;Hongying Chen ,&nbsp;Hong Jiang ,&nbsp;Taoguang Huo","doi":"10.1016/j.jep.2025.120174","DOIUrl":"10.1016/j.jep.2025.120174","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Realgar is extensively utilized in both modern medicine and traditional Chinese medicine. Although it has therapeutic uses, realgar exhibits hepatotoxicity, and improper use can result in liver inflammation and injury. The disruption of bile acid (BA) homeostasis, identified as an initiating event in liver injury, has been observed in the livers of realgar-exposed mice. However, the relationship between realgar-induced BA homeostasis imbalance and liver inflammation remains to be elucidated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;&lt;em&gt;Aim of the study&lt;/em&gt;&lt;/h3&gt;&lt;div&gt;To investigate the relationship between hepatic BA homeostasis disorder and liver inflammation caused by realgar exposure in mice, as well as the role and potential mechanism of intestinal farnesoid X receptor (FXR) in realgar-induced liver inflammation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A sub-chronic realgar exposure mouse model was established and subjected to interventions with an intestinal-restricted FXR agonist or inhibitor. Plasma hepatic enzyme activities and total bile acid (TBA) levels were quantified using spectrophotometry. Hepatic inflammatory cytokine levels were analyzed by ELISA or RT-qPCR. Histopathological evaluation of liver injury was performed using HE staining. F4/80 expression was assessed via immunohistochemistry (IHC). Western blot (WB) and IHC were employed to examine the expression of proteins involved in the FXR-FGF15 axis, and plasma FGF15 concentrations were determined by ELISA. The expression of proteins related to enterohepatic circulation and the NLRP3 inflammasome pathway were evaluated using WB. Ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-TOF-MS) was utilized to analyze BA profiles in both ileal and hepatic tissues.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Our findings demonstrate that realgar exposure induces changes in ileal BA composition and subsequent suppression of the FXR-FGF15 signaling axis in mice. This axis suppression promotes hepatic BA overproduction and disrupts BA homeostasis in the livers of realgar-exposed mice, particularly elevates the levels of taurochenodeoxycholic acid (TCDCA) and taurolithocholic acid (TLCA). In &lt;em&gt;vitro&lt;/em&gt; studies revealed that both TCDCA and TLCA can directly activate the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in AML-12 cells, triggering pro-inflammatory cascades. Pharmacological activation of intestinal FXR effectively ameliorated realgar-induced hepatic inflammatory damage via restoring BA homeostasis and suppressing NLRP3 inflammasome activation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Realgar exposure causes liver inflammatory injury by inducing BA-mediated NLRP3 inflammasome activation through down-regulating ileal FXR. Pharmacological activation of intestinal FXR alleviates realgar-induced liver inflammatory injury by restoring BA homeostasis and inhibitin","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"351 ","pages":"Article 120174"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321867","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":"The protective effect of Schisandra lignans on the hepatotoxicity induced by the metabolic activation of dictamnine","authors":"Dongju Lin,&nbsp;Guangyao Li,&nbsp;Haoran Deng,&nbsp;Shuo Wang","doi":"10.1016/j.jep.2025.120170","DOIUrl":"10.1016/j.jep.2025.120170","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Dictamnine (DIC) is the predominant pharmacological and hepatotoxic component of Cortex Dictamni (CD). CYP3A-mediated metabolic activation plays an important role in DIC-induced hepatotoxicity. Schisandra lignans (SCLs) are the major hepatoprotective ingredients of Schisandra chinensis (SC). CD and SC are frequently used as herb pairs in traditional Chinese medical formulas particularly for the treatment of eczema and urticarial. Our preliminary studies have shown that SC can protect against CD-induced liver injury. However, the underlying protective mechanism of SC against CD-induced liver injury has remained unknown.&lt;/div&gt;&lt;div&gt;&lt;em&gt;Aim of the study&lt;/em&gt;: This study aims to investigate the effects of SCLs on the hepatotoxicity and metabolic activation of DIC and elucidate the underlying hepatoprotective mechanism from the perspective of the inhibition of CYP3A-mediated metabolic activation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Material and methods&lt;/h3&gt;&lt;div&gt;The protective effect of SCLs against DIC-induced hepatotoxicity was evaluated by biochemical analysis and liver histological observation. The effect of SCLs on the &lt;em&gt;in vitro&lt;/em&gt; metabolic activation of DIC was assessed by detecting the level of DIC-N-acetylcysteine (NAC) conjugates in mouse liver microsomal incubations. The effect of SCLs on the metabolic activation &lt;em&gt;in vivo&lt;/em&gt; of DIC was examined by monitoring the toxicokinetic behaviors of DIC, DIC-induced hepatic GSH depletion, the cumulative urine excretion of DIC, the levels of DIC-NAC conjugates in urine and liver of mice, and the formation of DIC-derived cysteine-protein adducts.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Our findings indicated that SCLs protected against DIC-induced hepatotoxicity in a dose-dependent manner. SCLs exhibited dose-dependent inhibitory effect on the formation of DIC-NAC conjugates in liver microsomal incubations, indicating SCLs inhibited the metabolic activation of DIC &lt;em&gt;in vitro&lt;/em&gt;. SCLs increased C&lt;sub&gt;max&lt;/sub&gt; and AUC&lt;sub&gt;s&lt;/sub&gt; of DIC in the blood and liver of mice, leading to the enhancive accumulation of DIC in the circulation. Pretreatment with SCLs relieved hepatic GSH depletion induced by DIC, promoted the urinary excretion of DIC, inhibited the formation of reactive metabolite of DIC in urine and liver of mice, and reduced the production of DIC-derived cysteine-protein adducts, suggesting that SCLs influenced absorption, distribution, metabolism, and excretion (ADME) of DIC by suppressing the metabolic activation of DIC &lt;em&gt;in vivo&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The study demonstrated the protective effect of SCLs against hepatotoxicity induced by DIC was related to the inhibition of CYP3A-mediated metabolic activation of DIC. Therefore, the study demonstrated that SCLs may serve as the candidate drugs for the intoxication of DIC. Moreover, our findings may interpret the protective mechanism of SC against CD-induced liver injury.&lt;/div&gt;&lt;/di","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120170"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336642","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":"Matricaria chamomilla L. leaf and flower extracts improved scopolamine-induced amnesia via regulation of cholinergic dysfunction and brain antioxidant status: An in-vivo and in-silico study","authors":"Gufran Ullah Khan ,&nbsp;Saira Saeed Khan ,&nbsp;Sadaf Naeem ,&nbsp;Asia Naz Awan ,&nbsp;Faheema Siddiqui ,&nbsp;Humera Siddiqui ,&nbsp;Ali Asgher Shuja ,&nbsp;Anosh Tahir","doi":"10.1016/j.jep.2025.120141","DOIUrl":"10.1016/j.jep.2025.120141","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Chamomile (<em>M. Chamomilla</em> L. flowers, Family: Asteraceae) is a notable folk medicine in western Asia and Europe. It has traditionally been used to calm the nerves, induce sleep, and relieve digestive issues like stomach cramps and diarrhea. Nonetheless, studies suggest that its leaf extract also possesses memory-enhancing and antioxidant characteristics.</div></div><div><h3>Aim of the study</h3><div>The present study aimed to provide evidence showing that the hydroalcoholic extracts of <em>M. Chamomilla</em> L. leaf and flower may regulate memory in a scopolamine-induced amnestic rat model via exerting neuroprotective effects.</div></div><div><h3>Materials and methods</h3><div>For 21 days, rats were given hydroalcoholic extracts of the leaf and flower extracts (200 and 300 mg/kg per day) orally, while scopolamine hydrobromide (1 mg/kg) was administered intraperitoneally, 30 min before the treatment to cause memory impairment. Initially, the extract's total flavonoid, polyphenolic content, and GC-MS analysis were carried out. The antioxidant and MTT assay testing were also quantified. Passive avoidance, open field, stationary rod, rotarod, and water maze tests were employed for memory and locomotor assessment. In the rat's brain, ACh and AChE activity were assessed along with histopathological changes. The total amount of anti-inflammatory biomarkers in the rat brain and the levels of glutathione peroxidase, C-reactive protein, and superoxide dismutase were measured. And at last, predict the binding affinity of some identified compounds with the AChE receptor by In-silico molecular docking.</div></div><div><h3>Results</h3><div>Our results showed that <em>M. Chamomilla</em> L. leaf and flower extracts have 60 compounds in the flower extract and 70 compounds in the leaf extract, which significantly restored memory impairment and locomotor activities as compared to the scopolamine group. Treatment with both extracts significantly reversed not only scopolamine-induced changes in the oxidative-antioxidative balance, acetylcholine and acetylcholinesterase activity in the rat's brain (P&lt;0.05). Moreover, we have found that the flower and leaf extract significantly reduced IL-1β and TNF-α expression in the rat's brain and restored scopolamine-induced histopathological distortion. The molecular docking analysis revealed a high probability of AChE inhibition by the identified compounds in the extracts.</div></div><div><h3>Conclusion</h3><div>Thus, <em>In-silico</em> and <em>In-vivo</em> results suggest that <em>M. Chamomilla</em> L. leaf and flower extracts may be an effective neuropharmacological treatment for memory loss by enhancing the cholinergic system and antioxidant activities.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120141"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336640","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":"Reducing neuroinflammation through PKCγ/p38/NF-κB signaling pathway: the mechanism of Danzhi Xiaoyaosan in improving post-stroke depression","authors":"Jiuseng Zeng ,&nbsp;Zhiqiang Xie ,&nbsp;Hongxiao Xie ,&nbsp;Xiumeng Zhang ,&nbsp;Xi Peng ,&nbsp;Jingwen Hu ,&nbsp;Li Chen ,&nbsp;Hu Qi ,&nbsp;Nan Zeng","doi":"10.1016/j.jep.2025.120151","DOIUrl":"10.1016/j.jep.2025.120151","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Post-stroke depression (PSD) is a common sequela of stroke, causing tremendous mental burden to patients. Danzhi Xiaoyao San (DZX) is a widely used traditional Chinese medicine formula for the clinical treatment of PSD and has favorable therapeutic effects. However, its mechanism of action in treating PSD is still unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of study&lt;/h3&gt;&lt;div&gt;This study aimed to assess the therapeutic effects of DZX on rats with PSD and further investigate its underlying mechanism.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;The active ingredients of DZX aqueous extract were quantified by the high-performance liquid chromatography (HPLC). Neurological function and depression-like behavioral tests were performed to evaluate the therapeutic effects of DZX on PSD after establishing a rat model of PSD by the MCAO + CUMS protocol. Laser speckle is used to evaluate brain tissue blood flow, TTC staining is used to evaluate cerebral infarction volume, and transmission electron microscopy (TEM) is used to observe the ultrastructure of the hippocampus. ELISA was conducted to detect the levels of inflammatory factors in serum and cortical tissues, combined with HE staining to assess the neuroinflammatory response in the cortex of PSD rats. Then, network pharmacology combined with untargeted metabolomics of hippocampus tissue predicted the possible targets and pathways of DZX. In addition, flow cytometry was performed to detect Ca&lt;sup&gt;2+&lt;/sup&gt; content in cortical tissues, Western blot was used to detect the expression levels of key proteins of the PKCγ/p38/NF-κB signaling pathway, and immunofluorescence staining was performed to assess the M1/M2 polarization of hippocampal microglia. Moreover, specific inhibitors of PKCγ were used to validate the critical role of the PKCγ/p38/NF-κB signaling pathway in the treatment of PSD with DZX.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;DZX was found to increase cerebral blood flow, reduce infarct volume, and enhance the sucrose preference rate in the sucrose preference test (SPT), grooming time in the splash test (ST), and time spent in the central zone in the open field test (OFT) in PSD rats. Additionally, it significantly decreased immobility time in the forced swim test (FST). Furthermore, DZX ameliorated neuronal damage and ultrastructural abnormalities in the hippocampal region of PSD rats. In addition, DZX treatment effectively reduced Ca&lt;sup&gt;2+&lt;/sup&gt; and inflammatory factor levels, inhibited the phosphorylation of PLCγ, and activated PKCγ to suppress the p38/NF-κB pathway, thereby balancing the M1/M2 polarization phenotype of hippocampal microglia. More importantly, the specific PKCγ inhibitor reversed the neuroprotective effects of DZX and its inhibition of hippocampal neuroinflammation in PSD rats.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The findings demonstrated that DZX exhibits the ability to ameliorate PSD symptoms by activating PKCγ-mediated suppress","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120151"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336641","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":"Solidago decurrens Lour. controls LPS-induced acute lung injury by reducing inflammatory responses and modulating the TLR4/NF-κB/NLRP3 signaling pathway","authors":"Dan-Yang Ma ,&nbsp;Ling-Feng Peng ,&nbsp;Xue-Yan Gao ,&nbsp;Tian-Jiao Xing ,&nbsp;Zhi-Hui Hao","doi":"10.1016/j.jep.2025.120172","DOIUrl":"10.1016/j.jep.2025.120172","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Acute lung injury (ALI) is a lethal respiratory disease associated with severe inflammatory responses. &lt;em&gt;Solidago decurrens&lt;/em&gt; Lour. (SdL) has been shown to exhibit anti-inflammatory and antibacterial activities. However, the pharmacological effects of SdL on ALI and the underlying mechanisms remain unexplored.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;In this study, we investigated the ability of SdL to control lipopolysaccharide (LPS)-induced inflammation &lt;em&gt;in vitro&lt;/em&gt; and &lt;em&gt;in vivo&lt;/em&gt;. We took an integrated approach of using network pharmacology with molecular and cellular techniques to understand the molecular mechanisms for SdL's anti-inflammatory activity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;UHPLC-QE-Orbitrap-MS was employed to identify bioactive compounds in SdL. Using network pharmacology approaches, we investigated SdL's potential targets and pathways against ALI. The active components and potential targets of SdL were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and target genes of ALI were obtained from Online Mendelian Inheritance in Man (OMIM), GeneCards, Therapeutic Target Database (TTD), DisGeNET database. The common target genes were collected using Venny. The SdL-compounds-common targets-ALI network was constructed using Cytoscape 3.9.1. The protein-protein interaction (PPI) network of SdL-ALI targets was established, with core targets identified and visualized through Cytoscape 3.9.1. The DAVID database was used for GO and KEGG enrichment analysis. Subsequently, we used the MTT assay, qPCR technique, ELISA, and immunoblotting to determine cell viability, gene expression, cytokines, and specific protein modulators, respectively. We used H&amp;E staining to detect pathological changes in the lung tissues.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 19 compounds in SdL were screened through the UHPLC-QE-Orbitrap-MS and TCMSP databases, and a total of 209 potential gene targets were obtained from these 19 compounds. ALI obtained a total of 1,932 gene targets from OMIM, GeneCards, TTD, DisGeNET database. A total of 140 common gene targets of SdL and ALI were obtained through Venn diagrams. The results of the SdL-compounds-common targets-ALI network indicate that quercetin and kaempferol may be the main compounds for SdL in the treatment of ALI. The PPI results indicated that TNF, IL6 and IL1B played important roles in the regulation of ALI by SdL. The results of GO and KEGG enrichment analysis indicated TNF, Toll-like receptors and NF-kappa B pathways, suggesting the mechanism by which SdL controls ALI through its anti-inflammatory function. Subsequently, our results indicated that SdL treatments reduced COX-2 and iNOS, as well as suppressed the LPS-induced inflammatory cytokines (IL-1β and IL-6) in RAW 264.7 macrophage and lung tissues of mice. SdL treatment was able to suppress the LPS-induced NLRP3 inflammasome activation","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120172"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484616","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":"Therapeutic effects of self-assembled berberine-glycyrrhizic acid and matrine-glycyrrhizic acid complexes from Qingchang Wenzhong decoction on DSS-induced ulcerative colitis: Mechanisms of anti-inflammatory action","authors":"Zhi Qiao,&nbsp;Yi-nuo Zhang,&nbsp;Rui-ying Xu,&nbsp;Po Hu,&nbsp;Xia-chang Wang,&nbsp;Jing Cao,&nbsp;Yang Pan","doi":"10.1016/j.jep.2025.120169","DOIUrl":"10.1016/j.jep.2025.120169","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Qingchang Wenzhong Decoction (QCWZD), a traditional Chinese medicine (TCM) formula, has been clinically utilized for ulcerative colitis (UC) treatment due to its anti-inflammatory and intestinal barrier-protective effects. However, the mechanisms by which its naturally self-assembled supramolecular complexes, formed during aqueous decoction, contribute to therapeutic outcomes remain underexplored, representing a critical gap in understanding TCM's holistic pharmacology.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;This study sought to elucidate the self-assembly mechanisms underlying QCWZD's therapeutic effects, with a focus on characterizing the anti-inflammatory properties of its naturally self-assembled complexes formed during decoction and their role in UC intervention.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The submicron precipitate of QCWZD was isolated via gradient centrifugation and characterized for size and morphology using dynamic light scattering (DLS) and scanning electron microscopy (SEM). A DSS-induced murine UC model was used to evaluate the efficacy of QCWZD and its fractions (supernatant and submicron precipitate). Meanwhile, UPLC-ZenoTOF-MS/MS and triple quadrupole LC-MS/MS were employed to identify and quantify the bioactive components. Representative self-assembled complexes were synthesized under conditions mimicking decoction and characterized using DLS and SEM. Thermodynamic binding behavior was probed using isothermal titration calorimetry (ITC). Non-covalent interaction mechanisms of complex formation were characterized by UV, FT-IR, and &lt;sup&gt;1&lt;/sup&gt;H NMR spectroscopy. Anti-inflammatory activity of the self-assembled complexes was validated in LPS-stimulated RAW264.7 macrophages.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;QCWZD's submicron precipitate accelerated UC remission in mice, reducing the disease activity index (DAI), restoring colon length, and suppressing NF-κB p65 phosphorylation compared to the model group. Mass spectrometry identified berberine-glycyrrhizic acid (BER-GL) and matrine-glycyrrhizic acid (MAT-GL) as dominant self-assembled complexes. ITC revealed binding affinity between glycyrrhizic acid (GL) and alkaloids (BER: &lt;em&gt;K&lt;/em&gt;&lt;sub&gt;d&lt;/sub&gt; = 2.55 × 10&lt;sup&gt;−4&lt;/sup&gt; M, 1:1 binding ratio; MAT: &lt;em&gt;K&lt;/em&gt;&lt;sub&gt;d&lt;/sub&gt; = 6.77 × 10&lt;sup&gt;−4&lt;/sup&gt; M, 1:2 binding ratio), driven by enthalpy. Charge-transfer and hydrogen-bonding interactions between glycyrrhizic acid (GL) and the alkaloids berberine (BER) and matrine (MAT) lead to stable self-assemblies. BER-GL and MAT-GL complexes significantly suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while upregulating IL-10 in RAW264.7 cells, outperforming free alkaloids.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Building on QCWZD's established efficacy in treating ulcerative colitis (UC) via the NF-κB pathway, this work demonstrates that the aqueous self-assembly of BER-GL and MAT-GL, derived from QCWZD's submicron p","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120169"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336643","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":"Investigating therapeutic effects and the underlying mechanisms of jia-wei-yin-chen-hao-tang in non-alcoholic fatty liver disease based on network pharmacology analysis and experimental validation","authors":"Rong-Yu Zhou ,&nbsp;Qin Song ,&nbsp;Hu Hu ,&nbsp;Shang-Yu Zeng ,&nbsp;Xiao-Yan Tan ,&nbsp;Zang-Jia Geng ,&nbsp;Zi-Ge Feng","doi":"10.1016/j.jep.2025.120158","DOIUrl":"10.1016/j.jep.2025.120158","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Yin–Chen–Hao–Tang (YCHT) was initially recorded in the Chinese medicine classic <em>Shang Han Lun</em>, which was written by Zhang Zhongjing, and it has long been used orally as a classic formula. Jia–Wei–Yin–Chen–Hao–Tang (JWYCHT) comprises YCHT added with the widely used Chinese Yi medicine Liangtoumao (<em>Incarvillea arguta</em> (Royle) Royle). JWYCHT has become a promising therapeutic option for several liver and gallbladder disorders, including nonalcoholic fatty liver disease (NAFLD), among the Chinese Yi population. However, its specific mechanism of action remains poorly understood.</div></div><div><h3>Aim of the study</h3><div>This study aimed to explore the therapeutic effects and underlying mechanism of action of JWYCHT through network pharmacological analysis and experimental validation.</div></div><div><h3>Methods</h3><div>NAFLD-related transcriptome data and target genes associated with JWYCHT were retrieved from public databases. Initially, candidate genes were obtained by overlapping differentially expressed genes (DEGs) from NAFLD and control samples in GSE63067 with the drug target genes. Subsequently, candidate biomarkers were further obtained using the algorithm in cytoHubba plug-in. Biomarkers were further identified via receiver operating characteristic (ROC) analysis and expression validation, and enrichment analysis was executed to explore the potential mechanisms of NAFLD biomarkers. HPLC and UPLC/QE-HFX were used to determine the chemical components of JWYCHT. Finally, the findings were validated through molecular biology experiments involving a mouse model of NAFLD induced by high-fat diet.</div></div><div><h3>Results</h3><div>A total of 416 DEGs were acquired, with 51 candidate genes subjected to enrichment analysis. Seven candidate biomarkers, including C-X-C motif chemokine ligand 10 (CXCL10) and caspase-1 (CASP1), were identified from an algorithm in cytoHubba plug-in. ROC analysis confirmed CASP1 and CXCL10 as viable biomarkers, with the latter (odds ratio = 1.305, <em>p</em> &lt; 0.05) emerging as a risk factor for NAFLD. 41 compounds were identified by UPLC/QE-HFX in JWYCHT. The HPLC results demonstrated distinct variations in chemical profiles between JWYCHT, YCHT, and their component medicinal herbs. A series of molecular experiments revealed that JWYCHT effectively treated NAFLD in the mouse model. It can reduce the expressions of CXCL10 and CASP1, improve liver function biochemical indicators and histopathological changes, and alleviate inflammation and lipid deposition.</div></div><div><h3>Conclusion</h3><div>Bioinformatics and experimental validation revealed that JWYCHT can alleviate hepatic inflammation and lipid deposition in NAFLD by reducing the expressions of CXCL10 and CASP1. Our research results offer an experimental foundation for the therapeutic efficacy and mechanism of JWYCHT and guidance for its clinical application.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120158"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364587","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":"Fabiana imbricata Ruiz & Pav. (Solanaceae) essential oil analysis in prostate cancer cells: relevance of reactive oxygen species in proapoptotic activity","authors":"Alejandro Madrid ,&nbsp;Rosanna Avola ,&nbsp;Adriana C.E. Graziano ,&nbsp;Venera Cardile ,&nbsp;Alessandra Russo","doi":"10.1016/j.jep.2025.120162","DOIUrl":"10.1016/j.jep.2025.120162","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Fabiana imbricata</em> Ruiz &amp; Pav. (Solanaceae) is a Patagonian plant widely used in traditional medicine, in particular as a diuretic, digestive and for genito-urinary system diseases. Essential oils are considered promising candidates for prostate cancer treatments. Prostate cancer is the second leading cause of death among men. Therefore, new therapeutic strategies of prevention are needed for this tumor.</div></div><div><h3>Aim of the study</h3><div>The present research was designed to explore the chemical composition of essential oil from fresh leaves of <em>F. imbricata</em> plants collected in Valparaíso region, Chile, and its activity on human prostate cancer cell lines.</div></div><div><h3>Materials and methods</h3><div>Chemical characterization was performed by chromatographic techniques and the biological activity was evaluated in androgen-sensitive (LNCaP) and androgen-insensitive (DU-145) human prostate cancer cell lines. The cells were exposed to essential oil for 72 h and cell viability and cell membrane integrity were evaluated. Genomic DNA and caspase-3 activity was tested to confirm the cell death for apoptosis. Western blot analysis was employed to evaluate the expression of Bcl-2, Bax, cleaved caspase-3, cleaved caspase-9, SOD, Hsp70 and STAT-3 proteins. Assays to evaluate reactive oxygen species (ROS) and GSH levels were also performed.</div></div><div><h3>Results</h3><div>The results showed the capacity of essential oil, for its active components (oxygenated sesquiterpenes, 77.54 %), to reduce cell viability in prostate cancer cells. At a concentration of 200 μg/mL, the cell viability in LNCaP and DU-145 cells, was 23 % and 26 %, respectively. On the contrary, it showed no significant effect on normal cells, also at this high concentration. In addition, it induced apoptosis cell death, involving the downregulation of Hsp70 and STAT-3 proteins, correlated, at least in part, to an increase of reactive oxygen species (ROS).</div></div><div><h3>Conclusions</h3><div>This <em>in vitro</em> experimental preclinical study, suggesting a potential application of <em>F. imbricata</em> essential oil in prostate cancer, could be considered as a start point to design further research in animal experimental models and on its active components.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120162"},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325930","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":"Investigation of the antimalarial efficacy of Ilex umbellulata (Wall.) Loes. bark against Plasmodium falciparum using in-vitro whole-cell assays, GC-MS, LC-ToF-MS, and multi-step computational studies","authors":"James H. Zothantluanga ,&nbsp;Dubom Tayeng ,&nbsp;Mohnad Abdalla ,&nbsp;Sanchaita Rajkhowa ,&nbsp;Wafa Ali Eltayb ,&nbsp;Dipak Chetia","doi":"10.1016/j.jep.2025.120150","DOIUrl":"10.1016/j.jep.2025.120150","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Ilex umbellulata&lt;/em&gt; (Wall.) Loes. (Family: Aquifoliaceae), is widely used by different tribes of Southeast Asia as a herbal remedy. The Mizo tribe in India used the stem bark to treat malaria, gland inflammation, inflammation in pregnant women, tonsillitis, dysentery, and for veterinary purposes to treat pig sickness and mange. In Meghalaya, India, the decocted bark is used for digestion. In Thailand, the raw fruit was consumed to relieve stomach aches.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;The study aims to evaluate the &lt;em&gt;in vitro&lt;/em&gt; antimalarial efficacy of &lt;em&gt;I. umbellulata&lt;/em&gt; bark by screening against chloroquine-sensitive (&lt;em&gt;Pf&lt;/em&gt;3D7) and chloroquine-resistant (&lt;em&gt;Pf&lt;/em&gt;RKL-9) strains of &lt;em&gt;Plasmodium falciparum&lt;/em&gt;. Also, the study aims to identify the phytocompounds present in the most active extract and explore the molecular mechanisms against &lt;em&gt;P. falciparum&lt;/em&gt; and malaria through &lt;em&gt;in silico&lt;/em&gt; approaches.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Material and methods&lt;/h3&gt;&lt;div&gt;&lt;em&gt;I. umbellulata&lt;/em&gt; bark, collected from Mizoram, India, was taxonomically authenticated by the Botanical Survey of India. Twelve extracts obtained using Soxhlet extraction, decoction, and cold maceration techniques were evaluated for &lt;em&gt;in vitro&lt;/em&gt; antimalarial activity against the &lt;em&gt;Pf&lt;/em&gt;3D7 and &lt;em&gt;Pf&lt;/em&gt;RKL-9. Fractions obtained from the active extract were screened for &lt;em&gt;in vitro&lt;/em&gt; antimalarial activity. The active extract and fraction were tested for their cytotoxicity using the human embryonic kidney (HEK)-293 cell line and also for their hemolytic activity. The selected extract underwent gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-time of flight (LC-ToF)-MS analyses. Molecular docking, dynamic simulations, and binding free energy calculations were also employed to identify potential targets in &lt;em&gt;P. falciparum&lt;/em&gt;. Network pharmacology revealed the malaria pathway genes affected by the phytocompounds of &lt;em&gt;I. umbellulata&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The 80 % MeOH extract (IC&lt;sub&gt;50&lt;/sub&gt; ≤ 1 μg/ml) and the polar fraction (IC&lt;sub&gt;50&lt;/sub&gt; ≤ 3 μg/ml) showed the best antimalarial activity. Cytotoxicity and hemolysis assays confirmed the safety and selectivity of the active samples. GC-MS and LC-ToF-MS analyses of the 80 % MeOH extract detected 15 and 10 phytocompounds, respectively. Molecular docking and dynamic simulations showed that the phytocompounds of &lt;em&gt;I. umbellulata&lt;/em&gt; formed stable complexes with 10 blood-stage &lt;em&gt;P. falciparum&lt;/em&gt; proteins. The network pharmacology study suggests that &lt;em&gt;I. umbellulata&lt;/em&gt; may regulate immune responses, reduce inflammation, support early immune signaling, and prevent vascular complications in malaria.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The study identifies 25 phytocompounds in the active extract of &lt;em&gt;I. umbellulata,&lt;/em&gt; elucidating their key molecular mechanisms and validating ","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"352 ","pages":"Article 120150"},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325932","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}