Pub Date : 2026-05-10Epub Date: 2026-02-06DOI: 10.1016/j.jep.2026.121329
Zhiren Yao , Can Hu , Siyang Fang , Yaping Huang , Yanhua Qin , Lei Wang , Jian Zhang , Zhiqi Yin , Ke Pan
Ethnopharmacological relevance
Cyclocarya paliurus (Batal.) Iljinsk, a millennia-old traditional Chinese herb, is prized for its ability to clear the lungs and nourish the liver. Additionally, it is employed in traditional Chinese medicine practice for heat clearance and detoxification, addressing conditions such as lung diseases.
Aim of the study
This study aimed to evaluate beneficial effects of polysaccharides (CPP) from C. paliurus on chronic obstructive pulmonary disease (COPD) and its potential mechanisms.
Materials and methods
The chemical characterization of the isolated and purified CPP was conducted using fourier-transform infrared spectroscopy, ultraviolet spectroscopy and scanning electron microscopy. COPD was induced in male BALB/c mice by intranasal infusion of LPS and exposure to cigarette smoke for 28 days. Lung tissues were then collected for subsequent histopathological and molecular analyses. The mechanism of CPP against COPD was investigated through transcriptomic data mining and Western blot analysis. Additionally, acute toxicity of CPP was assessed in mice following a single oral dose of 15 g/kg.
Results
Experimental evidence established that CPP consists of six monosaccharides: fucose, arabinose, rhamnose, galactose, glucose, and xylose. CPP treatment significantly reduced the levels of PCO2 and HCO3− in the blood of COPD mice, concurrently alleviating pulmonary inflammation. Mechanistic investigations have revealed that CPP exerts its anti-inflammatory effect by modulating the AhR/NF-κB pathway. In addition, CPP demonstrated safety at doses exceeding 100 times the effective level.
Conclusion
The results suggest that CPP holds promise as a potential therapeutic agent for the intervention of COPD. These findings provide a theoretical basis for the development of the ethnic medicinal herb Cyclocarya paliurus.
{"title":"Polysaccharide from Cyclocarya paliurus ameliorates chronic obstructive pulmonary disease through the inflammatory pathway regulated by the AhR/NF-κB pathway","authors":"Zhiren Yao , Can Hu , Siyang Fang , Yaping Huang , Yanhua Qin , Lei Wang , Jian Zhang , Zhiqi Yin , Ke Pan","doi":"10.1016/j.jep.2026.121329","DOIUrl":"10.1016/j.jep.2026.121329","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Cyclocarya paliurus (Batal.)</em> Iljinsk, a millennia-old traditional Chinese herb, is prized for its ability to clear the lungs and nourish the liver. Additionally, it is employed in traditional Chinese medicine practice for heat clearance and detoxification, addressing conditions such as lung diseases.</div></div><div><h3>Aim of the study</h3><div>This study aimed to evaluate beneficial effects of polysaccharides (CPP) from <em>C. paliurus</em> on chronic obstructive pulmonary disease (COPD) and its potential mechanisms.</div></div><div><h3>Materials and methods</h3><div>The chemical characterization of the isolated and purified CPP was conducted using fourier-transform infrared spectroscopy, ultraviolet spectroscopy and scanning electron microscopy. COPD was induced in male BALB/c mice by intranasal infusion of LPS and exposure to cigarette smoke for 28 days. Lung tissues were then collected for subsequent histopathological and molecular analyses. The mechanism of CPP against COPD was investigated through transcriptomic data mining and Western blot analysis. Additionally, acute toxicity of CPP was assessed in mice following a single oral dose of 15 g/kg.</div></div><div><h3>Results</h3><div>Experimental evidence established that CPP consists of six monosaccharides: fucose, arabinose, rhamnose, galactose, glucose, and xylose. CPP treatment significantly reduced the levels of PCO<sub>2</sub> and HCO<sub>3</sub><sup>−</sup> in the blood of COPD mice, concurrently alleviating pulmonary inflammation. Mechanistic investigations have revealed that CPP exerts its anti-inflammatory effect by modulating the AhR/NF-κB pathway. In addition, CPP demonstrated safety at doses exceeding 100 times the effective level.</div></div><div><h3>Conclusion</h3><div>The results suggest that CPP holds promise as a potential therapeutic agent for the intervention of COPD. These findings provide a theoretical basis for the development of the ethnic medicinal herb <em>Cyclocarya paliurus.</em></div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121329"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142543","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}
Pub Date : 2026-05-10Epub Date: 2026-02-05DOI: 10.1016/j.jep.2026.121276
Ye-Lim You , Ha-Jun Byun , Jin-Young Jeon , Bo-Ra Kim , Ji Eun Hwang , Jun Hee Lee , Hyeon-Son Choi
Ethnopharmacological relevance
Euglena gracilis has a history of traditional use in East Asia as a functional food with reported antioxidant and immunomodulatory benefits. This study investigates the pharmacological potential of its bioactive component, standardized alkali-treated β-glucan (AEGB), in mitigating systemic toxicity induced by environmental pollutants, providing a rationale to investigate its protective effects in the context of particulate matter (PM2.5)-induced injury.
Aim of the study
To evaluate the protective effects of standardized alkali-treated E. gracilis β-glucan (AEGB) against PM2.5-induced pulmonary and cerebral toxicity in BALB/c mice via the lung–brain axis.
Materials and methods
AEGB was prepared and standardized to contain 93% (w/w) β-glucan. BALB/c mice were intranasally exposed to PM2.5 and orally administered AEGB (200/400 mg/kg). Efficacy was evaluated via BALF analysis, histopathology, and immunoblotting, focusing on MAPK, NF-κB, NRF2–HO-1, and CREB–BDNF–TrkB pathways.
Results
AEGB exhibited higher antioxidant activity than untreated β-glucan. In PM2.5-exposed mice, AEGB (400 mg/kg) reduced inflammatory cells in BALF by 69.5% and suppressed lung pro-inflammatory cytokines (IL-1β, IL-6). Histologically, it attenuated bronchial thickening and mucin production. In the brain, AEGB downregulated NF-κB by 72.1% and restored hippocampal neuronal area (+41.1%) and tight junction marker expression associated with blood–brain barrier integrity. At the molecular level, AEGB inhibited pulmonary MAPK/NF-κB and activated NRF2–HO-1, while enhancing the cerebral CREB–BDNF–TrkB neurotrophic pathway.
Conclusions
AEGB mitigates PM2.5-induced damage in both lung and brain tissues, accompanied by anti-inflammatory and neuroprotective responses consistent with inter-organ inflammatory/oxidative pathways relevant to the lung–brain axis. These findings validate the potential of E. gracilis-derived β-glucan as a functional agent for preserving respiratory and neural health.
{"title":"Standardized alkali-treated Euglena gracilis β-glucan mitigates PM2.5-induced pulmonary and cerebral injury through NF-κB, NRF2, and CREB–BDNF–TrkB pathways","authors":"Ye-Lim You , Ha-Jun Byun , Jin-Young Jeon , Bo-Ra Kim , Ji Eun Hwang , Jun Hee Lee , Hyeon-Son Choi","doi":"10.1016/j.jep.2026.121276","DOIUrl":"10.1016/j.jep.2026.121276","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Euglena gracilis</em> has a history of traditional use in East Asia as a functional food with reported antioxidant and immunomodulatory benefits. This study investigates the pharmacological potential of its bioactive component, standardized alkali-treated β-glucan (AEGB), in mitigating systemic toxicity induced by environmental pollutants, providing a rationale to investigate its protective effects in the context of particulate matter (PM2.5)-induced injury.</div></div><div><h3>Aim of the study</h3><div>To evaluate the protective effects of standardized alkali-treated <em>E. gracilis</em> β-glucan (AEGB) against PM2.5-induced pulmonary and cerebral toxicity in BALB/c mice via the lung–brain axis.</div></div><div><h3>Materials and methods</h3><div>AEGB was prepared and standardized to contain 93% (w/w) β-glucan. BALB/c mice were intranasally exposed to PM2.5 and orally administered AEGB (200/400 mg/kg). Efficacy was evaluated via BALF analysis, histopathology, and immunoblotting, focusing on MAPK, NF-κB, NRF2–HO-1, and CREB–BDNF–TrkB pathways.</div></div><div><h3>Results</h3><div>AEGB exhibited higher antioxidant activity than untreated β-glucan. In PM2.5-exposed mice, AEGB (400 mg/kg) reduced inflammatory cells in BALF by 69.5% and suppressed lung pro-inflammatory cytokines (IL-1β, IL-6). Histologically, it attenuated bronchial thickening and mucin production. In the brain, AEGB downregulated NF-κB by 72.1% and restored hippocampal neuronal area (+41.1%) and tight junction marker expression associated with blood–brain barrier integrity. At the molecular level, AEGB inhibited pulmonary MAPK/NF-κB and activated NRF2–HO-1, while enhancing the cerebral CREB–BDNF–TrkB neurotrophic pathway.</div></div><div><h3>Conclusions</h3><div>AEGB mitigates PM2.5-induced damage in both lung and brain tissues, accompanied by anti-inflammatory and neuroprotective responses consistent with inter-organ inflammatory/oxidative pathways relevant to the lung–brain axis. These findings validate the potential of <em>E. gracilis</em>-derived β-glucan as a functional agent for preserving respiratory and neural health.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121276"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137590","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}
Pub Date : 2026-05-10Epub Date: 2026-02-04DOI: 10.1016/j.jep.2026.121318
Aolei Guo , Ruixin Shi , Sipei Liu , Yang Zhang , Yan Mao , Guijun Yan , Guangyi Cao
Ethnopharmacological relevance
Lycium barbarum L. (goji berry), a traditional medicinal and edible herb, has long been employed for its anti-aging, vision-enhancing, and anti-inflammatory properties. Lycium barbarum glycopeptide (LbGP), a major bioactive glycoconjugate isolated from this plant, possesses documented antioxidant and immunomodulatory activities. However, its specific therapeutic efficacy in counteracting reproductive aging and the precise mechanisms underlying its protective effects on oocyte quality remain to be fully elucidated.
Aim of the study
To investigate the restorative effects of LbGP on ovarian function and oocyte quality in aged mice and to decipher the underlying mechanisms involving both oocyte-intrinsic metabolic regulation and extrinsic ovarian microenvironment remodeling.
Materials and methods
A reproductive aging model was established using naturally aged female mice supplemented with LbGP. Follicular development and oocyte quality were assessed via histological analysis, in vitro fertilization (IVF), and early embryonic culture. Mitochondrial function and oxidative stress levels were monitored using live-cell imaging. Mechanistic insights were generated through integrated proteomic analysis of oocytes and single-cell RNA sequencing (scRNA-seq) of ovarian tissues to identify key metabolic pathways and cellular composition changes.
Results
LbGP supplementation significantly promoted follicular development, enhanced oocyte maturation competence, and improved subsequent early embryonic potential compared to untreated aged mice. Mechanistically, proteomic analysis revealed that LbGP restored mitochondrial function in aged oocytes by activating PPAR signaling pathways, leading to reduced intracellular reactive oxygen species (ROS) accumulation and DNA damage. Furthermore, ovarian single-cell transcriptomics demonstrated that LbGP systemically remodeled the aged ovarian microenvironment by increasing functional granulosa cell populations, reducing pro-inflammatory immune cells, and repairing intercellular communication networks.
Conclusions
LbGP delays reproductive aging by concurrently restoring mitochondrial function in aged oocytes and remodeling the ovarian microenvironment. These findings provide modern pharmacological evidence supporting LbGP as a promising natural therapeutic candidate capable of improving oocyte quality and enhancing fertility outcomes in women of advanced maternal age.
{"title":"Supplementation with Lycium barbarum glycopeptide (LbGP) rescues the quality of aged oocytes","authors":"Aolei Guo , Ruixin Shi , Sipei Liu , Yang Zhang , Yan Mao , Guijun Yan , Guangyi Cao","doi":"10.1016/j.jep.2026.121318","DOIUrl":"10.1016/j.jep.2026.121318","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Lycium barbarum</em> L. (goji berry), a traditional medicinal and edible herb, has long been employed for its anti-aging, vision-enhancing, and anti-inflammatory properties. <em>Lycium barbarum</em> glycopeptide (LbGP), a major bioactive glycoconjugate isolated from this plant, possesses documented antioxidant and immunomodulatory activities. However, its specific therapeutic efficacy in counteracting reproductive aging and the precise mechanisms underlying its protective effects on oocyte quality remain to be fully elucidated.</div></div><div><h3>Aim of the study</h3><div>To investigate the restorative effects of LbGP on ovarian function and oocyte quality in aged mice and to decipher the underlying mechanisms involving both oocyte-intrinsic metabolic regulation and extrinsic ovarian microenvironment remodeling.</div></div><div><h3>Materials and methods</h3><div>A reproductive aging model was established using naturally aged female mice supplemented with LbGP. Follicular development and oocyte quality were assessed via histological analysis, in vitro fertilization (IVF), and early embryonic culture. Mitochondrial function and oxidative stress levels were monitored using live-cell imaging. Mechanistic insights were generated through integrated proteomic analysis of oocytes and single-cell RNA sequencing (scRNA-seq) of ovarian tissues to identify key metabolic pathways and cellular composition changes.</div></div><div><h3>Results</h3><div>LbGP supplementation significantly promoted follicular development, enhanced oocyte maturation competence, and improved subsequent early embryonic potential compared to untreated aged mice. Mechanistically, proteomic analysis revealed that LbGP restored mitochondrial function in aged oocytes by activating PPAR signaling pathways, leading to reduced intracellular reactive oxygen species (ROS) accumulation and DNA damage. Furthermore, ovarian single-cell transcriptomics demonstrated that LbGP systemically remodeled the aged ovarian microenvironment by increasing functional granulosa cell populations, reducing pro-inflammatory immune cells, and repairing intercellular communication networks.</div></div><div><h3>Conclusions</h3><div>LbGP delays reproductive aging by concurrently restoring mitochondrial function in aged oocytes and remodeling the ovarian microenvironment. These findings provide modern pharmacological evidence supporting LbGP as a promising natural therapeutic candidate capable of improving oocyte quality and enhancing fertility outcomes in women of advanced maternal age.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121318"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131913","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}
Pub Date : 2026-05-10Epub Date: 2026-02-04DOI: 10.1016/j.jep.2026.121326
Jue Chen , MengKe Wu , RongRong Zhang , Yun Cao , Xiangyan Chen , Xinyu Liu , Yanqing Liu , Wei Jiang , Qiang Wang
<div><h3>Ethnopharmacological relevance</h3><div><em>Celastrus orbiculatus</em> Thunb. is a traditional herb with the effects of eliminating wind and dampness, activating blood circulation and detoxifying.It is commonly used in the treatment of malignant tumors and rheumatoid arthritis in China. Previous basic research has confirmed its significant anti-tumor activity. However, the underlying mechanism of its treatment in cervical cancer has not been reported.</div></div><div><h3>Aim of the study</h3><div>Building on findings from a retrospective clinical analysis, this study applied bioinformatics and experimental validation to elucidate the mechanism by which luteolin, a major constituent of <em>Celastrus orbiculatus</em> stem, and its target protein Carbonic Anhydrase II (CA2) exert inhibitory effects on cervical cancer.</div></div><div><h3>Methods</h3><div>A retrospective clinical analysis was first conducted to assess the impact of <em>Celastrus orbiculatus</em> stem (30 g/day) combined with postoperative concurrent chemoradiotherapy (weekly cisplatin) on recurrence in cervical cancer patients. Liquid chromatography–mass spectrometry (LC–MS) was then used to identify the principal active components of <em>Celastrus orbiculatus</em> stem. Public databases were employed to determine the core targets of these active components against cervical cancer. Prognostic analysis was performed using data from The Cancer Genome Atlas (TCGA). Expression of core target proteins was validated in clinical surgical specimens of cervical cancer. Finally, the inhibitory effects of the identified active compound (luteolin) acting through the target protein (CA2) were confirmed using lactate dehydrogenase (LDH) release assays, gene expression modulation, and a murine xenograft tumor model.</div></div><div><h3>Results</h3><div>Retrospective clinical analysis demonstrated that <em>Celastrus orbiculatus</em> stem (30 g/day) combined with weekly cisplatin concurrent radiotherapy significantly prolonged postoperative disease-free survival in cervical cancer patients. In vitro, the extract of <em>Celastrus orbiculatus</em> stem suppressed cervical cancer cell proliferation. Luteolin was identified as a major constituent of the extract. Further analysis revealed that CA2 was characteristically overexpressed in epithelial tumor cells of cervical cancer tissues, but not in stromal cells, and served as a core target of luteolin. Modulation of CA2 expression or luteolin-mediated intervention effectively inhibited cervical cancer cell proliferation and invasion, promoted apoptosis in vitro, and suppressed the growth of xenograft tumors in vivo.</div></div><div><h3>Conclusion</h3><div>Luteolin is the primary bioactive constituent of <em>Celastrus orbiculatus</em> stem responsible for its inhibitory effects on cervical cancer. CA2, characteristically overexpressed in epithelial-derived cervical cancer cells, plays a pivotal role in promoting cancer cell proliferation and invas
{"title":"Luteolin, a bioactive compound from Celastrus orbiculatus stem, inhibits cervical cancer via CA2 suppression: A translational study bridging basic research and clinical application","authors":"Jue Chen , MengKe Wu , RongRong Zhang , Yun Cao , Xiangyan Chen , Xinyu Liu , Yanqing Liu , Wei Jiang , Qiang Wang","doi":"10.1016/j.jep.2026.121326","DOIUrl":"10.1016/j.jep.2026.121326","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Celastrus orbiculatus</em> Thunb. is a traditional herb with the effects of eliminating wind and dampness, activating blood circulation and detoxifying.It is commonly used in the treatment of malignant tumors and rheumatoid arthritis in China. Previous basic research has confirmed its significant anti-tumor activity. However, the underlying mechanism of its treatment in cervical cancer has not been reported.</div></div><div><h3>Aim of the study</h3><div>Building on findings from a retrospective clinical analysis, this study applied bioinformatics and experimental validation to elucidate the mechanism by which luteolin, a major constituent of <em>Celastrus orbiculatus</em> stem, and its target protein Carbonic Anhydrase II (CA2) exert inhibitory effects on cervical cancer.</div></div><div><h3>Methods</h3><div>A retrospective clinical analysis was first conducted to assess the impact of <em>Celastrus orbiculatus</em> stem (30 g/day) combined with postoperative concurrent chemoradiotherapy (weekly cisplatin) on recurrence in cervical cancer patients. Liquid chromatography–mass spectrometry (LC–MS) was then used to identify the principal active components of <em>Celastrus orbiculatus</em> stem. Public databases were employed to determine the core targets of these active components against cervical cancer. Prognostic analysis was performed using data from The Cancer Genome Atlas (TCGA). Expression of core target proteins was validated in clinical surgical specimens of cervical cancer. Finally, the inhibitory effects of the identified active compound (luteolin) acting through the target protein (CA2) were confirmed using lactate dehydrogenase (LDH) release assays, gene expression modulation, and a murine xenograft tumor model.</div></div><div><h3>Results</h3><div>Retrospective clinical analysis demonstrated that <em>Celastrus orbiculatus</em> stem (30 g/day) combined with weekly cisplatin concurrent radiotherapy significantly prolonged postoperative disease-free survival in cervical cancer patients. In vitro, the extract of <em>Celastrus orbiculatus</em> stem suppressed cervical cancer cell proliferation. Luteolin was identified as a major constituent of the extract. Further analysis revealed that CA2 was characteristically overexpressed in epithelial tumor cells of cervical cancer tissues, but not in stromal cells, and served as a core target of luteolin. Modulation of CA2 expression or luteolin-mediated intervention effectively inhibited cervical cancer cell proliferation and invasion, promoted apoptosis in vitro, and suppressed the growth of xenograft tumors in vivo.</div></div><div><h3>Conclusion</h3><div>Luteolin is the primary bioactive constituent of <em>Celastrus orbiculatus</em> stem responsible for its inhibitory effects on cervical cancer. CA2, characteristically overexpressed in epithelial-derived cervical cancer cells, plays a pivotal role in promoting cancer cell proliferation and invas","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121326"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131901","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}
Pub Date : 2026-05-10Epub Date: 2026-02-08DOI: 10.1016/j.jep.2026.121347
Mengqi Zhou , Min Xiang , Yuan Li , Zizhong Wang , Jiangtao Lin
<div><h3>Ethnopharmacological relevance</h3><div>Danlong Oral Liquid (DLOL) is a proprietary Traditional Chinese Medicine (TCM) with documented clinical efficacy against asthma, yet its underlying mechanism of action remains incompletely understood. The bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) and its receptor S1PR2 signaling axis are critically implicated in asthma pathogenesis, particularly in driving airway smooth muscle cell (ASMC) remodeling, a key pathological feature of asthma. Despite this, the mechanistic involvement of DLOL in this specific pathway has not been explored.</div></div><div><h3>Aim of the study</h3><div>This study aimed to validate the effect of DLOL against asthma-associated airway remodeling and to elucidate whether its mechanism of action involves the modulation of the S1PR2/ROCK1/YAP signaling pathway in ASMCs.</div></div><div><h3>Materials and methods</h3><div>The therapeutic effects and mechanisms of DLOL were investigated using a combination of <em>in vivo</em> and <em>in vitro</em> approaches. An <em>in vivo</em> rat model of allergic asthma was induced by ovalbumin (OVA) sensitization and challenge. We assessed airway hyperresponsiveness (AHR) and performed inflammatory cell counts in bronchoalveolar lavage fluid (BALF) using Wright-Giemsa staining. Lung histopathology was evaluated by Hematoxylin and Eosin (H&E) staining, Periodic Acid-Schiff (PAS) staining, and Masson's trichrome staining to assess inflammation, goblet cell hyperplasia, and collagen deposition. Levels of S1P and cytokines (IL-4, IL-5, IL-13) in BALF and serum, along with OVA-IgE in serum, were measured by enzyme-linked immunosorbent assay (ELISA). The protein and gene expression of key molecules in the S1PR2/ROCK1/YAP signaling pathway were analyzed by Western blotting (WB), immunohistochemistry (IHC), and Real-time quantitative polymerase chain reaction (RT-qPCR). For <em>in vitro</em> studies, primary rat ASMCs were stimulated with S1P. The impact of DLOL-containing serum (DL-CS) on proliferation was assessed using the Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2′-deoxyuridine (EdU) incorporation assays. Cell migration and contraction were evaluated by scratch assay and collagen gel contraction assay, respectively. Underlying mechanisms were further examined by WB, RT-qPCR, and immunofluorescence (IF).</div></div><div><h3>Results</h3><div>DLOL administration significantly alleviated AHR, airway inflammation, and remodeling in a rat model of asthma. Mechanistically, DLOL downregulated the S1PR2/ROCK1/YAP signaling axis in lung tissues, inhibiting the expression of S1PR2, RhoA, and ROCK1, promoting YAP inactivation, and suppressing the downstream targets FOXM1 and CyclinD1. Consistently, DL-CS potently inhibited S1P-induced proliferation, migration, and contraction of ASMCs <em>in vitro</em>, further confirming its robust anti-remodeling activity.</div></div><div><h3>Conclusions</h3><div>Our integrated findings demonstrate
{"title":"Danlong oral liquid alleviates airway remodeling in asthma by targeting the S1PR2/ROCK1/YAP signaling pathway in airway smooth muscle cells","authors":"Mengqi Zhou , Min Xiang , Yuan Li , Zizhong Wang , Jiangtao Lin","doi":"10.1016/j.jep.2026.121347","DOIUrl":"10.1016/j.jep.2026.121347","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Danlong Oral Liquid (DLOL) is a proprietary Traditional Chinese Medicine (TCM) with documented clinical efficacy against asthma, yet its underlying mechanism of action remains incompletely understood. The bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) and its receptor S1PR2 signaling axis are critically implicated in asthma pathogenesis, particularly in driving airway smooth muscle cell (ASMC) remodeling, a key pathological feature of asthma. Despite this, the mechanistic involvement of DLOL in this specific pathway has not been explored.</div></div><div><h3>Aim of the study</h3><div>This study aimed to validate the effect of DLOL against asthma-associated airway remodeling and to elucidate whether its mechanism of action involves the modulation of the S1PR2/ROCK1/YAP signaling pathway in ASMCs.</div></div><div><h3>Materials and methods</h3><div>The therapeutic effects and mechanisms of DLOL were investigated using a combination of <em>in vivo</em> and <em>in vitro</em> approaches. An <em>in vivo</em> rat model of allergic asthma was induced by ovalbumin (OVA) sensitization and challenge. We assessed airway hyperresponsiveness (AHR) and performed inflammatory cell counts in bronchoalveolar lavage fluid (BALF) using Wright-Giemsa staining. Lung histopathology was evaluated by Hematoxylin and Eosin (H&E) staining, Periodic Acid-Schiff (PAS) staining, and Masson's trichrome staining to assess inflammation, goblet cell hyperplasia, and collagen deposition. Levels of S1P and cytokines (IL-4, IL-5, IL-13) in BALF and serum, along with OVA-IgE in serum, were measured by enzyme-linked immunosorbent assay (ELISA). The protein and gene expression of key molecules in the S1PR2/ROCK1/YAP signaling pathway were analyzed by Western blotting (WB), immunohistochemistry (IHC), and Real-time quantitative polymerase chain reaction (RT-qPCR). For <em>in vitro</em> studies, primary rat ASMCs were stimulated with S1P. The impact of DLOL-containing serum (DL-CS) on proliferation was assessed using the Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2′-deoxyuridine (EdU) incorporation assays. Cell migration and contraction were evaluated by scratch assay and collagen gel contraction assay, respectively. Underlying mechanisms were further examined by WB, RT-qPCR, and immunofluorescence (IF).</div></div><div><h3>Results</h3><div>DLOL administration significantly alleviated AHR, airway inflammation, and remodeling in a rat model of asthma. Mechanistically, DLOL downregulated the S1PR2/ROCK1/YAP signaling axis in lung tissues, inhibiting the expression of S1PR2, RhoA, and ROCK1, promoting YAP inactivation, and suppressing the downstream targets FOXM1 and CyclinD1. Consistently, DL-CS potently inhibited S1P-induced proliferation, migration, and contraction of ASMCs <em>in vitro</em>, further confirming its robust anti-remodeling activity.</div></div><div><h3>Conclusions</h3><div>Our integrated findings demonstrate","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121347"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157248","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}
Pub Date : 2026-05-10Epub Date: 2026-02-10DOI: 10.1016/j.jep.2026.121352
Weijue Nie , Minghao Lu , Xin Sun , Hong Zhu , Baoping Jiang , Lingling Zhou , Xueping Zhou
Ethnopharmacological relevance
Tripterygium wilfordii Hook. f. (TW) is widely used to treat autoimmune and inflammatory diseases, but its clinical utility is limited by hepatotoxicity. Qingluo Tongbi Formula (QTF), a classic multi-herb prescription for rheumatoid arthritis containing TW, has shown good efficacy with fewer liver adverse effects in clinical practice.
Aim of the study
To evaluate whether QTF alleviates TW-induced hepatotoxicity and to elucidate the underlying metabolic and molecular mechanisms.
Materials and methods
A TW-induced hepatotoxicity model was established in C57BL/6J mice treated with TW alone, QTF, or TW combined with individual constituent herbs. Liver injury, oxidative stress, and lipid peroxidation were evaluated by serum biochemistry and histopathology. Untargeted metabolomics was performed to profile hepatic energy metabolism. In vitro, triptolide-injured AML12 hepatocytes were used to evaluate the protective effects of catalpol (CAT) and Panax notoginseng saponins (PNS) on cellular bioenergetics and the sirtuin 1 (SIRT1)/hypoxia-inducible factor-1α (HIF-1α) axis.
Results
In vivo, QTF significantly attenuated TW-induced hepatotoxicity, hypoglycaemia, oxidative stress, and lipid peroxidation, and partially normalized amino acid and glucose metabolism. In vitro, combined CAT and PNS restored mitochondrial respiration, rebalanced glycolysis and oxidative phosphorylation, improved glycogen utilization, and upregulated SIRT1 while suppressing HIF-1α in AML12 hepatocytes.
Conclusions
QTF protects against TW-induced hepatotoxicity, at least in part by modulating the SIRT1/HIF-1α axis, thereby alleviating oxidative stress and restoring hepatic energy and glucose metabolism. These findings provide a mechanistic basis for the detoxifying compatibility of QTF and support safer clinical application of TW-containing formulations.
{"title":"Qingluo Tongbi Formula attenuates Tripterygium wilfordii Hook. f.-induced hepatic metabolic dysfunction and oxidative stress via the SIRT1/HIF-1α pathway","authors":"Weijue Nie , Minghao Lu , Xin Sun , Hong Zhu , Baoping Jiang , Lingling Zhou , Xueping Zhou","doi":"10.1016/j.jep.2026.121352","DOIUrl":"10.1016/j.jep.2026.121352","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Tripterygium wilfordii</em> Hook. f. (TW) is widely used to treat autoimmune and inflammatory diseases, but its clinical utility is limited by hepatotoxicity. Qingluo Tongbi Formula (QTF), a classic multi-herb prescription for rheumatoid arthritis containing TW, has shown good efficacy with fewer liver adverse effects in clinical practice.</div></div><div><h3>Aim of the study</h3><div>To evaluate whether QTF alleviates TW-induced hepatotoxicity and to elucidate the underlying metabolic and molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>A TW-induced hepatotoxicity model was established in C57BL/6J mice treated with TW alone, QTF, or TW combined with individual constituent herbs. Liver injury, oxidative stress, and lipid peroxidation were evaluated by serum biochemistry and histopathology. Untargeted metabolomics was performed to profile hepatic energy metabolism. <em>In vitro</em>, triptolide-injured AML12 hepatocytes were used to evaluate the protective effects of catalpol (CAT) and <em>Panax notoginseng</em> saponins (PNS) on cellular bioenergetics and the sirtuin 1 (SIRT1)/hypoxia-inducible factor-1α (HIF-1α) axis.</div></div><div><h3>Results</h3><div><em>In vivo</em>, QTF significantly attenuated TW-induced hepatotoxicity, hypoglycaemia, oxidative stress, and lipid peroxidation, and partially normalized amino acid and glucose metabolism. <em>In vitro</em>, combined CAT and PNS restored mitochondrial respiration, rebalanced glycolysis and oxidative phosphorylation, improved glycogen utilization, and upregulated SIRT1 while suppressing HIF-1α in AML12 hepatocytes.</div></div><div><h3>Conclusions</h3><div>QTF protects against TW-induced hepatotoxicity, at least in part by modulating the SIRT1/HIF-1α axis, thereby alleviating oxidative stress and restoring hepatic energy and glucose metabolism. These findings provide a mechanistic basis for the detoxifying compatibility of QTF and support safer clinical application of TW-containing formulations.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121352"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180476","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}
Pub Date : 2026-05-10Epub Date: 2026-02-10DOI: 10.1016/j.jep.2026.121348
Chengcheng Zhang , Guofeng Yu , Miaomiao Liu , Ruikun Du , Jing Ma , Xuran Gu , Lijun Rong , Xuxiao Lv , Qinghua Cui
Ethnopharmacological relevance
Viral pneumonia remains a major global health concern. Sangbaipi Decoction (SBPD), a traditional Chinese medicine formula, which is used clinically to treat pneumonia, exhibits antiviral and anti-inflammatory effects. However, its pharmacological basis and mechanism of action (MOA) in vivo remain unclear.
Aim of the study
This study aimed to evaluate the therapeutic efficacy of SBPD on viral pneumonia and to elucidate its underlying MOA.
Materials and methods
The protective effects of SBPD were assessed in H1N1 (A/Puerto Rico/8/1934)-infected mice using histopathology, Western blot, and RT-qPCR. RNA sequencing was performed to identify key pathways modulated by SBPD. PANoptosis-related markers were examined both in vivo and in vitro, and Z-DNA-binding protein 1 (ZBP1) overexpression assays were conducted to verify its role in SBPD-mediated regulation of PANoptosis. A Poly(I:C)-induced acute lung injury model was used for further validation. Blood-absorbed constituents of SBPD were screened to identify bioactive components.
Results
SBPD treatment greatly reduced pulmonary viral load, lung index, and pro-inflammatory cytokine levels in H1N1-infected mice, alleviating lung injury. Transcriptomic analysis identified the ZBP1-mediated PANoptosis as a major regulatory target of SBPD. In vivo and in vitro studies demonstrated that SBPD downregulated the expression of ZBP1 and its downstream effectors, suppressing excessive inflammatory cell death. SBPD also attenuated Poly(I:C)-induced acute lung injury through the same pathway. Screening of blood-absorbed constituents of SBPD identified peimine, peiminine, chrysin, wogonin, and apigenin as active constituents that inhibit ZBP1-mediated PANoptosis.
Conclusion
SBPD mitigates influenza-induced pneumonia by suppressing ZBP1-mediated PANoptosis and excessive inflammation, highlighting its host-directed therapeutic potential for viral pneumonia.
{"title":"Sangbaipi Decoction mitigates influenza pneumonia in mice by inhibiting ZBP1-mediated PANoptosis","authors":"Chengcheng Zhang , Guofeng Yu , Miaomiao Liu , Ruikun Du , Jing Ma , Xuran Gu , Lijun Rong , Xuxiao Lv , Qinghua Cui","doi":"10.1016/j.jep.2026.121348","DOIUrl":"10.1016/j.jep.2026.121348","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Viral pneumonia remains a major global health concern. Sangbaipi Decoction (SBPD), a traditional Chinese medicine formula, which is used clinically to treat pneumonia, exhibits antiviral and anti-inflammatory effects. However, its pharmacological basis and mechanism of action (MOA) <em>in vivo</em> remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to evaluate the therapeutic efficacy of SBPD on viral pneumonia and to elucidate its underlying MOA.</div></div><div><h3>Materials and methods</h3><div>The protective effects of SBPD were assessed in H1N1 (A/Puerto Rico/8/1934)-infected mice using histopathology, Western blot, and RT-qPCR. RNA sequencing was performed to identify key pathways modulated by SBPD. PANoptosis-related markers were examined both <em>in vivo</em> and <em>in vitro</em>, and Z-DNA-binding protein 1 (ZBP1) overexpression assays were conducted to verify its role in SBPD-mediated regulation of PANoptosis. A Poly(I:C)-induced acute lung injury model was used for further validation. Blood-absorbed constituents of SBPD were screened to identify bioactive components.</div></div><div><h3>Results</h3><div>SBPD treatment greatly reduced pulmonary viral load, lung index, and pro-inflammatory cytokine levels in H1N1-infected mice, alleviating lung injury. Transcriptomic analysis identified the ZBP1-mediated PANoptosis as a major regulatory target of SBPD. <em>In vivo</em> and <em>in vitro</em> studies demonstrated that SBPD downregulated the expression of ZBP1 and its downstream effectors, suppressing excessive inflammatory cell death. SBPD also attenuated Poly(I:C)-induced acute lung injury through the same pathway. Screening of blood-absorbed constituents of SBPD identified peimine, peiminine, chrysin, wogonin, and apigenin as active constituents that inhibit ZBP1-mediated PANoptosis.</div></div><div><h3>Conclusion</h3><div>SBPD mitigates influenza-induced pneumonia by suppressing ZBP1-mediated PANoptosis and excessive inflammation, highlighting its host-directed therapeutic potential for viral pneumonia.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121348"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180484","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}
Pub Date : 2026-05-10Epub Date: 2026-02-07DOI: 10.1016/j.jep.2026.121323
Zihong Wu , Chong Xiao , Xueke Li , Fengming You , Li Su
Ethnopharmacological relevance
The Chinese herbal medicine Banxia Xiexin Decoction (BXD) and its modified version (mBXD) are traditional polyherbal formulations used to treat gastrointestinal diseases. Increasing evidence indicates that mBXD exhibits distinct anti-cancer properties; however, the mechanisms through which it modulates mitochondrial dynamics to inhibit colon cancer remain unclear.
Aims of the study
To investigate the mechanisms by which mBXD suppresses colon cancer by regulating mitochondrial fusion–fission dynamics.
Materials and methods
The chemical composition of mBXD was analyzed using UPLC–MS/MS. A subcutaneous CT26 colon cancer model was established and treated with mBXD. mBXD drug-containing serum was prepared and applied to HCT116 and CT26 cells. Tumor volume, small-animal live imaging, and histopathological features were evaluated. The effects of mBXD on mitochondria were examined through mitochondrial ultrastructure analysis, JC-1 detection, and assessment of ATP concentration and ROS levels. WB and qPCR were performed to determine the expression of molecules associated with the CHD6–TMEM65 axis and mitochondrial dynamics.
Results
The main components of mBXD were identified as flavonoids and alkaloids. These compounds significantly inhibited tumor growth, with higher concentrations of mBXD drug-containing serum reducing the survival, invasion, and migration of HCT116 and CT26 cells. Moreover, mBXD markedly promoted mitochondrial fission in cancer cells, reduced ATP levels, and induced ROS accumulation. It significantly upregulated DRP1 expression while inhibiting CHD6 and TMEM65, with no notable effect on OPA1.
Conclusions
The chemical constituents of mBXD mainly comprise flavonoids and alkaloids. These components markedly inhibit the growth of subcutaneous tumors in CT26 colon cancer–bearing mice and suppress the viability, invasiveness, and migratory capacity of HCT116 and CT26 cells. The underlying mechanism may involve the promotion of mitochondrial fission in cancer cells through inhibition of the CHD6–TMEM65 axis, ultimately leading to apoptosis. Nonetheless, the present study has certain limitations. The precise mechanisms by which mBXD induces mitochondrial fission and inhibits the CHD6–TMEM65 axis warrant further investigation in future research.
{"title":"Modified Banxia Xiexin Decoction promotes mitochondrial fission in colon cancer cells by inhibiting the CHD6–TMEM65 axis","authors":"Zihong Wu , Chong Xiao , Xueke Li , Fengming You , Li Su","doi":"10.1016/j.jep.2026.121323","DOIUrl":"10.1016/j.jep.2026.121323","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The Chinese herbal medicine Banxia Xiexin Decoction (BXD) and its modified version (mBXD) are traditional polyherbal formulations used to treat gastrointestinal diseases. Increasing evidence indicates that mBXD exhibits distinct anti-cancer properties; however, the mechanisms through which it modulates mitochondrial dynamics to inhibit colon cancer remain unclear.</div></div><div><h3>Aims of the study</h3><div>To investigate the mechanisms by which mBXD suppresses colon cancer by regulating mitochondrial fusion–fission dynamics.</div></div><div><h3>Materials and methods</h3><div>The chemical composition of mBXD was analyzed using UPLC–MS/MS. A subcutaneous CT26 colon cancer model was established and treated with mBXD. mBXD drug-containing serum was prepared and applied to HCT116 and CT26 cells. Tumor volume, small-animal live imaging, and histopathological features were evaluated. The effects of mBXD on mitochondria were examined through mitochondrial ultrastructure analysis, JC-1 detection, and assessment of ATP concentration and ROS levels. WB and qPCR were performed to determine the expression of molecules associated with the CHD6–TMEM65 axis and mitochondrial dynamics.</div></div><div><h3>Results</h3><div>The main components of mBXD were identified as flavonoids and alkaloids. These compounds significantly inhibited tumor growth, with higher concentrations of mBXD drug-containing serum reducing the survival, invasion, and migration of HCT116 and CT26 cells. Moreover, mBXD markedly promoted mitochondrial fission in cancer cells, reduced ATP levels, and induced ROS accumulation. It significantly upregulated DRP1 expression while inhibiting CHD6 and TMEM65, with no notable effect on OPA1.</div></div><div><h3>Conclusions</h3><div>The chemical constituents of mBXD mainly comprise flavonoids and alkaloids. These components markedly inhibit the growth of subcutaneous tumors in CT26 colon cancer–bearing mice and suppress the viability, invasiveness, and migratory capacity of HCT116 and CT26 cells. The underlying mechanism may involve the promotion of mitochondrial fission in cancer cells through inhibition of the CHD6–TMEM65 axis, ultimately leading to apoptosis. Nonetheless, the present study has certain limitations. The precise mechanisms by which mBXD induces mitochondrial fission and inhibits the CHD6–TMEM65 axis warrant further investigation in future research.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121323"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149704","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}
Pub Date : 2026-05-10Epub Date: 2026-02-04DOI: 10.1016/j.jep.2026.121288
Xiu Yang , Ming Gao , Junmin Zhang , Faju Chen , Lishou Yang , Liangqun Li , Qiji Li , Fulai Luo , Lei Tang , Xiaosheng Yang
Ethnopharmacological relevance
Depression is a common mental disorder and a major contributor to the global burden of mental health issues. Armillaria gallica Marxm. & Romagn (AG), an ancient Chinese herbal medicine, is traditionally used with the protective effect on the central nervous system. However, its antidepressant effect has rarely been reported.
Aim of the study
The aim of this study is to investigate the potential mechanisms of AG in treating depression based on network pharmacology, molecular docking, serum metabolomics, and experimental validation.
Material and methods
The antioxidant assay kits and PC12 and HT-22 cells were used to screen the active extract of AG fermentation. The CUMS-induced depression-like mice were applied to study the antidepressant effects of AG. Then, the integrated approach incorporating network pharmacology, molecular docking, molecular biology, and serum metabolomics was adopted to unravel the pharmacological mechanisms of AG in the treatment of depression.
Results
The ethanol part of the water layer of AG (EPWA) exhibits the highest antioxidant and cytoprotective activities which have been selected for further study. Totally, 79 non-volatile compounds were identified from EPWA, and 691 protein targets related to depression were confirmed. Topology analysis conducted on the PPI network identified 11 primary targets. Further non-targeted metabolomics experiments revealed that glycine and serine metabolism, lysine degradation, and arginine biosynthesis are the potential regulatory pathways for AG in the treatment of depression. The web-based pharmacological and serum metabolomic analysis results revealed that IL-6, PTGS2, and PIK3CA are key targets strongly associated with depression, which is consistent with the molecular docking results. Finally, molecular biology experiment results indicated that AG inhibited the protein expression of neuroinflammatory factors such as iNOS, TNF-α, IL-6, PI3KCA, PTGS2, and NLRP3, which may contribute to the protective effects of AG against depression in vivo.
Conclusions
AG exerted therapeutic effects on depression by regulating neuroinflammatory response and amino acid metabolism.
{"title":"Integrated network pharmacology, molecular docking and metabolomics studies to reveal the therapeutic effects of Armillaria gallica extract for treating depression in CUMS-induced mice","authors":"Xiu Yang , Ming Gao , Junmin Zhang , Faju Chen , Lishou Yang , Liangqun Li , Qiji Li , Fulai Luo , Lei Tang , Xiaosheng Yang","doi":"10.1016/j.jep.2026.121288","DOIUrl":"10.1016/j.jep.2026.121288","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Depression is a common mental disorder and a major contributor to the global burden of mental health issues. <em>Armillaria gallica</em> Marxm. & Romagn (AG), an ancient Chinese herbal medicine, is traditionally used with the protective effect on the central nervous system. However, its antidepressant effect has rarely been reported.</div></div><div><h3>Aim of the study</h3><div>The aim of this study is to investigate the potential mechanisms of AG in treating depression based on network pharmacology, molecular docking, serum metabolomics, and experimental validation.</div></div><div><h3>Material and methods</h3><div>The antioxidant assay kits and PC12 and HT-22 cells were used to screen the active extract of AG fermentation. The CUMS-induced depression-like mice were applied to study the antidepressant effects of AG. Then, the integrated approach incorporating network pharmacology, molecular docking, molecular biology, and serum metabolomics was adopted to unravel the pharmacological mechanisms of AG in the treatment of depression.</div></div><div><h3>Results</h3><div>The ethanol part of the water layer of AG (EPWA) exhibits the highest antioxidant and cytoprotective activities which have been selected for further study. Totally, 79 non-volatile compounds were identified from EPWA, and 691 protein targets related to depression were confirmed. Topology analysis conducted on the PPI network identified 11 primary targets. Further non-targeted metabolomics experiments revealed that glycine and serine metabolism, lysine degradation, and arginine biosynthesis are the potential regulatory pathways for AG in the treatment of depression. The web-based pharmacological and serum metabolomic analysis results revealed that IL-6, PTGS2, and PIK3CA are key targets strongly associated with depression, which is consistent with the molecular docking results. Finally, molecular biology experiment results indicated that AG inhibited the protein expression of neuroinflammatory factors such as iNOS, TNF-α, IL-6, PI3KCA, PTGS2, and NLRP3, which may contribute to the protective effects of AG against depression <em>in vivo</em>.</div></div><div><h3>Conclusions</h3><div>AG exerted therapeutic effects on depression by regulating neuroinflammatory response and amino acid metabolism.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121288"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131924","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}
Pub Date : 2026-05-10Epub Date: 2026-02-04DOI: 10.1016/j.jep.2026.121265
Ángel Dzul-Beh , Haziel Eleazar Dzib-Baak , Francisco José Palacios-Can , Myrna Déciga-Campos , Avel Adolfo González-Sánchez , Andrés Humberto Uc-Cachón , Gloria María Molina-Salinas
<div><h3>Ethnopharmacological relevance</h3><div><em>Krugiodendron ferreum</em> (Vahl) Urb.<em>,</em> locally referred to as “X-chintok”, is a medicinal plant utilized in traditional Mayan medicine. It continues to be used in the treatment of urinary, skin, respiratory, and gastrointestinal infections, pain, and kidney stones. To date, research has been limited to screening the activity of their extracts on the growth and biofilm-formation of <em>Staphylococcus aureus,</em> including methicillin-resistant <em>S. aureus</em> (MRSA), which is a significant global health concern and colorimetric identification of phytoconstituents present in the anti-staphylococcal extract. Consequently, it is imperative to conduct a comprehensive investigation into its effects on bacterial resistance and virulence mechanisms as innovative strategies to combat antimicrobial resistance. Additionally, elucidating its phytochemical composition and exploring its potential targets are crucial.</div></div><div><h3>Aim of the study</h3><div>To investigate the anti-infective properties of <em>K. ferreum</em> against both methicillin-susceptible (MSSA) and MRSA strains, identify the phytoconstituents present in the bioactive extracts and perform <em>in-silico</em> analysis of relevant targets.</div></div><div><h3>Material and methods</h3><div>Organic and aqueous extracts from the bark and leaves were assessed for their effects on the resistance mechanisms and virulence factors of <em>S. aureus</em> using various <em>in-vitro</em> models. The metabolites identified by GC-MS were analyzed <em>in-silico</em> to identify the key elements contributing to the anti-infective activity of <em>K. ferreum</em>.</div></div><div><h3>Results</h3><div>Bioassays indicated that <em>n</em>-hexane bark (KFEB-1), ethyl acetate bark (KFEB-2), methanol leaves (KFEL-1), and water leaves (KFEL-4) extracts exhibited moderate to weak activity against MSSA and MRSA strains (MIC = 500-1000 μg/mL). Notably, KFEB-2 demonstrated a 64-fold reversal of ciprofloxacin-resistance in a clinical MRSA isolate (SAU- UIMY-1). Furthermore, KFEB-1 and KFEB-2 effectively inhibited biofilm-formation (IC<sub>50</sub> = 55.5 and 40.9 μg/mL, respectively) and hemolysis (IC<sub>50</sub> = 116.1 and 54.9 μg/mL, respectively) in <em>S. aureus</em> strains. GC-MS analysis identified fatty acids, phytosterols, tocopherols, and alkaloids as the major phytoconstituents in the bioactive extracts. Molecular docking studies of phytochemicals identified as having the highest percentage peak area in the GC-MS profiling of bioactive extracts demonstrated a significant binding affinity of stigmasterol (−8.8 kcal/mol) for the NorA efflux pump and stigmast-7-en-3-ol (−8.5 kcal/mol) for α-hemolysin. These findings suggest their potential roles in the observed anti-resistance and anti-virulence activities.</div></div><div><h3>Conclusions</h3><div>Our findings highlight the potential of <em>K. ferreum</em> against <em>S. aureus</em> and off
{"title":"In-vitro and in-silico anti-staphylococcal effects of the Mayan medicinal plant Krugiodendron ferreum (Vahl) Urb. (X-chintok): Disarming its resistance mechanisms and virulence factors","authors":"Ángel Dzul-Beh , Haziel Eleazar Dzib-Baak , Francisco José Palacios-Can , Myrna Déciga-Campos , Avel Adolfo González-Sánchez , Andrés Humberto Uc-Cachón , Gloria María Molina-Salinas","doi":"10.1016/j.jep.2026.121265","DOIUrl":"10.1016/j.jep.2026.121265","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Krugiodendron ferreum</em> (Vahl) Urb.<em>,</em> locally referred to as “X-chintok”, is a medicinal plant utilized in traditional Mayan medicine. It continues to be used in the treatment of urinary, skin, respiratory, and gastrointestinal infections, pain, and kidney stones. To date, research has been limited to screening the activity of their extracts on the growth and biofilm-formation of <em>Staphylococcus aureus,</em> including methicillin-resistant <em>S. aureus</em> (MRSA), which is a significant global health concern and colorimetric identification of phytoconstituents present in the anti-staphylococcal extract. Consequently, it is imperative to conduct a comprehensive investigation into its effects on bacterial resistance and virulence mechanisms as innovative strategies to combat antimicrobial resistance. Additionally, elucidating its phytochemical composition and exploring its potential targets are crucial.</div></div><div><h3>Aim of the study</h3><div>To investigate the anti-infective properties of <em>K. ferreum</em> against both methicillin-susceptible (MSSA) and MRSA strains, identify the phytoconstituents present in the bioactive extracts and perform <em>in-silico</em> analysis of relevant targets.</div></div><div><h3>Material and methods</h3><div>Organic and aqueous extracts from the bark and leaves were assessed for their effects on the resistance mechanisms and virulence factors of <em>S. aureus</em> using various <em>in-vitro</em> models. The metabolites identified by GC-MS were analyzed <em>in-silico</em> to identify the key elements contributing to the anti-infective activity of <em>K. ferreum</em>.</div></div><div><h3>Results</h3><div>Bioassays indicated that <em>n</em>-hexane bark (KFEB-1), ethyl acetate bark (KFEB-2), methanol leaves (KFEL-1), and water leaves (KFEL-4) extracts exhibited moderate to weak activity against MSSA and MRSA strains (MIC = 500-1000 μg/mL). Notably, KFEB-2 demonstrated a 64-fold reversal of ciprofloxacin-resistance in a clinical MRSA isolate (SAU- UIMY-1). Furthermore, KFEB-1 and KFEB-2 effectively inhibited biofilm-formation (IC<sub>50</sub> = 55.5 and 40.9 μg/mL, respectively) and hemolysis (IC<sub>50</sub> = 116.1 and 54.9 μg/mL, respectively) in <em>S. aureus</em> strains. GC-MS analysis identified fatty acids, phytosterols, tocopherols, and alkaloids as the major phytoconstituents in the bioactive extracts. Molecular docking studies of phytochemicals identified as having the highest percentage peak area in the GC-MS profiling of bioactive extracts demonstrated a significant binding affinity of stigmasterol (−8.8 kcal/mol) for the NorA efflux pump and stigmast-7-en-3-ol (−8.5 kcal/mol) for α-hemolysin. These findings suggest their potential roles in the observed anti-resistance and anti-virulence activities.</div></div><div><h3>Conclusions</h3><div>Our findings highlight the potential of <em>K. ferreum</em> against <em>S. aureus</em> and off","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121265"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131988","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}
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