Pub Date : 2025-02-23DOI: 10.1016/j.jep.2025.119551
Ruiyan Wang , Jing Jiang , Pengli Song , Qi Peng , Xuerui Jin , Bin Li , Jie Shen , Xiao Han , Jianbo Ni , Guoyong Hu
<div><h3>Ethnopharmacological relevance</h3><div>Acute pancreatitis (AP) is an inflammatory disease that can progress to systemic immune responses and multi-organ damage in its severe forms. <em>Anoectochilus roxburghii</em> (Wall.) Lindl. (AR), a traditional Chinese medicinal plant, has been reported to exhibit anti-inflammatory, hypoglycemic, hepatoprotective, and analgesic properties. Kinsenoside (KD), the primary bioactive glycoside in AR, is responsible for many of its therapeutic effects. Given its anti-inflammatory and immunomodulatory properties, KD may have the potential to mitigate pancreatic inflammation in AP. However, its protective role in AP has not yet been investigated.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the protective effects of the natural active compound KD against acute pancreatitis (AP) and its associated molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>Two AP mouse models were established: one by intraperitoneal injection of caerulein combined with lipopolysaccharide (LPS) and the other by retrograde injection of sodium taurocholate (NaT) into the biliopancreatic duct. KD (2.5, 5, 10 mg/kg) was administered as a pre-treatment 1 h before the induction of AP. The severity of AP was evaluated through histopathological analysis, while macrophage infiltration and phenotypic changes in pancreatic tissues were examined using immunofluorescence staining and flow cytometry.</div><div>Bone marrow-derived macrophages (BMDMs) were polarized into the M1 phenotype through two distinct methods: stimulation with LPS and interferon-γ (IFNγ) and indirect co-culture with pancreatic acinar cells. Changes in macrophage phenotype after KD supplementation (100, 200, and 400 μM) were analyzed using quantitative Reverse Transcription PCR (qRT-PCR) and flow cytometry. Network pharmacology and transcriptomic sequencing were utilized to identify potential targets and pathways affected by KD, with validation of key signaling pathways performed through qPCR and Western blot analysis.</div></div><div><h3>Results</h3><div>In two models of AP mice, KD at a high dose (10 mg/kg) significantly alleviated pancreatic damage. It reduced pancreatic edema, necrosis, and inflammatory cell infiltration, with a notable decrease in macrophage infiltration. Furthermore, KD (10 mg/kg) administration significantly reduced serum lipase by 53.62% in the Caerulein + LPS model and 41.14% in the NaT model, as well as amylase by 28.13% and 27.99%, respectively. Additionally, KD (10 mg/kg) administration mitigated systemic inflammation and lung injury during AP. Both <em>in vivo</em> and <em>in vitro</em> experiments demonstrated that KD (400 μM) significantly reduced the proportion of M1 macrophages. Furthermore, KD (400 μM) downregulated the mRNA expression of M1-associated genes, including <em>Nos2</em>, <em>Tnf</em>, <em>Il1b</em>, and <em>Il6</em>, in macrophages stimulated by both LPS + IFNγ and pancreatic
{"title":"Kinsenoside alleviates experimental acute pancreatitis by suppressing M1 macrophage polarization via the TLR4/STAT1 signaling pathway","authors":"Ruiyan Wang , Jing Jiang , Pengli Song , Qi Peng , Xuerui Jin , Bin Li , Jie Shen , Xiao Han , Jianbo Ni , Guoyong Hu","doi":"10.1016/j.jep.2025.119551","DOIUrl":"10.1016/j.jep.2025.119551","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Acute pancreatitis (AP) is an inflammatory disease that can progress to systemic immune responses and multi-organ damage in its severe forms. <em>Anoectochilus roxburghii</em> (Wall.) Lindl. (AR), a traditional Chinese medicinal plant, has been reported to exhibit anti-inflammatory, hypoglycemic, hepatoprotective, and analgesic properties. Kinsenoside (KD), the primary bioactive glycoside in AR, is responsible for many of its therapeutic effects. Given its anti-inflammatory and immunomodulatory properties, KD may have the potential to mitigate pancreatic inflammation in AP. However, its protective role in AP has not yet been investigated.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the protective effects of the natural active compound KD against acute pancreatitis (AP) and its associated molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>Two AP mouse models were established: one by intraperitoneal injection of caerulein combined with lipopolysaccharide (LPS) and the other by retrograde injection of sodium taurocholate (NaT) into the biliopancreatic duct. KD (2.5, 5, 10 mg/kg) was administered as a pre-treatment 1 h before the induction of AP. The severity of AP was evaluated through histopathological analysis, while macrophage infiltration and phenotypic changes in pancreatic tissues were examined using immunofluorescence staining and flow cytometry.</div><div>Bone marrow-derived macrophages (BMDMs) were polarized into the M1 phenotype through two distinct methods: stimulation with LPS and interferon-γ (IFNγ) and indirect co-culture with pancreatic acinar cells. Changes in macrophage phenotype after KD supplementation (100, 200, and 400 μM) were analyzed using quantitative Reverse Transcription PCR (qRT-PCR) and flow cytometry. Network pharmacology and transcriptomic sequencing were utilized to identify potential targets and pathways affected by KD, with validation of key signaling pathways performed through qPCR and Western blot analysis.</div></div><div><h3>Results</h3><div>In two models of AP mice, KD at a high dose (10 mg/kg) significantly alleviated pancreatic damage. It reduced pancreatic edema, necrosis, and inflammatory cell infiltration, with a notable decrease in macrophage infiltration. Furthermore, KD (10 mg/kg) administration significantly reduced serum lipase by 53.62% in the Caerulein + LPS model and 41.14% in the NaT model, as well as amylase by 28.13% and 27.99%, respectively. Additionally, KD (10 mg/kg) administration mitigated systemic inflammation and lung injury during AP. Both <em>in vivo</em> and <em>in vitro</em> experiments demonstrated that KD (400 μM) significantly reduced the proportion of M1 macrophages. Furthermore, KD (400 μM) downregulated the mRNA expression of M1-associated genes, including <em>Nos2</em>, <em>Tnf</em>, <em>Il1b</em>, and <em>Il6</em>, in macrophages stimulated by both LPS + IFNγ and pancreatic","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119551"},"PeriodicalIF":4.8,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501856","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":"Corrigendum to “Kuntai capsule for the treatment of diminished ovarian reserve: A systematic review and meta-analysis of randomized controlled trials” [J. Ethnopharmacol. 329 (2024) 118167]","authors":"Xudong Zhang , Lina Zhang , Ling Xiong , Xia Liu , Juwen Zhang , Fanya Yu , Yun Li , Wenjing Chang , Wei Chen","doi":"10.1016/j.jep.2025.119526","DOIUrl":"10.1016/j.jep.2025.119526","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119526"},"PeriodicalIF":4.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-22DOI: 10.1016/j.jep.2025.119532
Zengfeng Pan , Caiyan Gan , Shaobin Zhi , Yali Yang , Yinmei Zhang , Lihai Li , Shengyuan Zhang , Qionghui Huang
<div><h3>Ethnopharmacological relevance</h3><div>The Gancao Xiexin decoction (GCXXD), comprising <em>Glycyrrhiza glabra</em> L., <em>Pinellia ternata</em> (Thunb.) Makino, <em>Scutellaria baicalensis</em> Georgi, <em>Zingiber officinale</em> Roscoe, <em>Panax ginseng</em> C.A.Mey. , <em>Coptis chinensis</em> Franch. , <em>Ziziphus jujuba</em> Mill. , represents a traditional Chinese medicinal formulation utilized for the treatment of ulcerative colitis (UC). Nevertheless, the potential mechanism behind GCXXD treatment for UC is not yet fully elucidated.</div></div><div><h3>Aim of the study</h3><div>Ulcerative colitis is a chronic inflammatory disorder of the gastrointestinal system distinguished by intestinal barrier destruction. Previous studies have indicated that excessive ferroptosis activation in intestinal epithelial cells (IECs) can worsen damage and focal permeability abnormalities in the colon. One of the main mechanisms of ferroptosis is lipid peroxides, which are dependent on long-chain acyl-CoA synthetase 4 (ACSL4) for the synthesis of membrane phospholipids. Recent research findings have provided evidence that GCXXD significantly reduces the symptoms of ulcerative colitis (UC) by preserving the intestinal mucosal barrier. So, we aim to demonstrate that the pharmacological mechanism of GCXXD is related to ferroptosis mediated by ACSL4 in this research.</div></div><div><h3>Materials and methods</h3><div>In this investigation, we evaluated the GSE134025 datasets and established an experimental colitis model caused by DSS and treated with a 20 mg/kg ACSL4 inhibitor (rosiglitazone). Colon pathological alterations and Alcian blue staining were used to confirm ACSL4 inhibition as a possible therapy for UC. We then examined illness symptoms, intestinal mucosa repair, and ferroptosis markers in UC mice after treated with GCXXD (9,12,15 g/kg). Transcriptome study of colon tissues revealed more about the underlying mechanism of GCXXD in the treatment of UC. Finally, we co-administered the ACSL4 upstream agonist with GCXXD in the treatment of UC to show that GCXXD reduced inflammation in UC by modifying ACSL4-induced ferroptosis.</div></div><div><h3>Results</h3><div>Through GSE134025 dataset analysis, we discovered that ACSL4 was substantially expressed in UC patients and that its inhibitors successfully reduced the clinical signs and symptoms of UC colon. Furthermore, we found that GCXXD improved colon length and body weight while increasing the expression of mucin, occuldin, and Claudin-1. It also lowered colon inflammatory cell infiltration and levels of IL-1β and TNF-α. In the meantime, GCXXD efficiently decreased ferroptosis-related indicators in colitis mice, such as MDA, Fe<sup>2+</sup>, COX2, and ACSL4, while also upregulated GPX4 expression. Using KEGG analysis of the genes that were differently expressed between the 3% DSS and GCXXD treatment group, we were able to discover important connections between the hippo signaling pathway, Ara
{"title":"Gancao Xiexin decoction attenuated experimental colitis through suppressing ACSL4-mediated ferroptosis","authors":"Zengfeng Pan , Caiyan Gan , Shaobin Zhi , Yali Yang , Yinmei Zhang , Lihai Li , Shengyuan Zhang , Qionghui Huang","doi":"10.1016/j.jep.2025.119532","DOIUrl":"10.1016/j.jep.2025.119532","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The Gancao Xiexin decoction (GCXXD), comprising <em>Glycyrrhiza glabra</em> L., <em>Pinellia ternata</em> (Thunb.) Makino, <em>Scutellaria baicalensis</em> Georgi, <em>Zingiber officinale</em> Roscoe, <em>Panax ginseng</em> C.A.Mey. , <em>Coptis chinensis</em> Franch. , <em>Ziziphus jujuba</em> Mill. , represents a traditional Chinese medicinal formulation utilized for the treatment of ulcerative colitis (UC). Nevertheless, the potential mechanism behind GCXXD treatment for UC is not yet fully elucidated.</div></div><div><h3>Aim of the study</h3><div>Ulcerative colitis is a chronic inflammatory disorder of the gastrointestinal system distinguished by intestinal barrier destruction. Previous studies have indicated that excessive ferroptosis activation in intestinal epithelial cells (IECs) can worsen damage and focal permeability abnormalities in the colon. One of the main mechanisms of ferroptosis is lipid peroxides, which are dependent on long-chain acyl-CoA synthetase 4 (ACSL4) for the synthesis of membrane phospholipids. Recent research findings have provided evidence that GCXXD significantly reduces the symptoms of ulcerative colitis (UC) by preserving the intestinal mucosal barrier. So, we aim to demonstrate that the pharmacological mechanism of GCXXD is related to ferroptosis mediated by ACSL4 in this research.</div></div><div><h3>Materials and methods</h3><div>In this investigation, we evaluated the GSE134025 datasets and established an experimental colitis model caused by DSS and treated with a 20 mg/kg ACSL4 inhibitor (rosiglitazone). Colon pathological alterations and Alcian blue staining were used to confirm ACSL4 inhibition as a possible therapy for UC. We then examined illness symptoms, intestinal mucosa repair, and ferroptosis markers in UC mice after treated with GCXXD (9,12,15 g/kg). Transcriptome study of colon tissues revealed more about the underlying mechanism of GCXXD in the treatment of UC. Finally, we co-administered the ACSL4 upstream agonist with GCXXD in the treatment of UC to show that GCXXD reduced inflammation in UC by modifying ACSL4-induced ferroptosis.</div></div><div><h3>Results</h3><div>Through GSE134025 dataset analysis, we discovered that ACSL4 was substantially expressed in UC patients and that its inhibitors successfully reduced the clinical signs and symptoms of UC colon. Furthermore, we found that GCXXD improved colon length and body weight while increasing the expression of mucin, occuldin, and Claudin-1. It also lowered colon inflammatory cell infiltration and levels of IL-1β and TNF-α. In the meantime, GCXXD efficiently decreased ferroptosis-related indicators in colitis mice, such as MDA, Fe<sup>2+</sup>, COX2, and ACSL4, while also upregulated GPX4 expression. Using KEGG analysis of the genes that were differently expressed between the 3% DSS and GCXXD treatment group, we were able to discover important connections between the hippo signaling pathway, Ara","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119532"},"PeriodicalIF":4.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488262","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 : 2025-02-21DOI: 10.1016/j.jep.2025.119518
Júlia Maiara dos Santos , Luciana Touguinha , Raquel Bridi , Ana Cristina Andreazza , Djenifer Leticia Ulrich Bick , Carolina Bordin Davidson , André Flores dos Santos , Kolinski Alencar Machado , Fernando Joel Scariot , Longaray Ana Paula Delamare , Mirian Salvador , Catia Santos Branco
Ethnopharmacological relevance
Empirically, Ilex paraguariensis A. St. Hil, or yerba-mate, has been used by natives of South America as a stimulant. Nowadays, this plant has gained popularity due to its neuroprotective effects. However, there are few studies on the biochemical-molecular mechanisms of action involved in its effect. Aim of the study: Chemically characterize an aqueous extract of yerba mate (YME) and evaluate if it could suppress the aberrant inflammatory response related to neurodegeneration. Materials and methods: Macrophages and microglia cells were exposed to lipopolysaccharide (LPS; 100 ng/mL) plus nigericin (100 μM) or quinolinic acid (QA; 5 mM). Cellular viability, oxidative, and inflammatory markers were evaluated. Chemical matrix (HPLC - DAD), antioxidant activity, safety profile in vitro and in vivo, and an in silico docking of main targets were also assessed.
Results
Pre-treatment with YME (15 μg/mL) prevented impairments in redox metabolism and inflammatory markers in BV-2 cells. In macrophages, YME showed similar results to MCC950, an inflammasome inhibitor. YME presented 282.88 mg EAG/g total phenolic content and a redox capacity of 32.94 ± 1.30 μg/mL (IC50), and its major compounds were chlorogenic acid > rutin > ferulic acid > catechin > sinapic acid. Chlorogenic acid and rutin presented a high affinity to the MCC950 region. Additionally, YME did not cause genotoxicity and was safe in vivo.
Conclusion
YME has significantly affected macrophages and microglia by regulating the NLRP3 inflammatory pathway.
{"title":"Could the inhibition of systemic NLRP3 inflammasome mediate central redox effects of yerba mate? An in silico and pre-clinical translational approach","authors":"Júlia Maiara dos Santos , Luciana Touguinha , Raquel Bridi , Ana Cristina Andreazza , Djenifer Leticia Ulrich Bick , Carolina Bordin Davidson , André Flores dos Santos , Kolinski Alencar Machado , Fernando Joel Scariot , Longaray Ana Paula Delamare , Mirian Salvador , Catia Santos Branco","doi":"10.1016/j.jep.2025.119518","DOIUrl":"10.1016/j.jep.2025.119518","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Empirically, <em>Ilex paraguariensis</em> A. St. Hil, or yerba-mate, has been used by natives of South America as a stimulant. Nowadays, this plant has gained popularity due to its neuroprotective effects. However, there are few studies on the biochemical-molecular mechanisms of action involved in its effect. <em>Aim of the study:</em> Chemically characterize an aqueous extract of yerba mate (YME) and evaluate if it could suppress the aberrant inflammatory response related to neurodegeneration. <em>Materials and methods:</em> Macrophages and microglia cells were exposed to lipopolysaccharide (LPS; 100 ng/mL) <em>plus</em> nigericin (100 μM) or quinolinic acid (QA; 5 mM). Cellular viability, oxidative, and inflammatory markers were evaluated. Chemical matrix (HPLC - DAD), antioxidant activity, safety profile <em>in vitro</em> and <em>in vivo,</em> and an <em>in silico</em> docking of main targets were also assessed.</div></div><div><h3>Results</h3><div>Pre-treatment with YME (15 μg/mL) prevented impairments in redox metabolism and inflammatory markers in BV-2 cells. In macrophages, YME showed similar results to MCC950, an inflammasome inhibitor. YME presented 282.88 mg EAG/g total phenolic content and a redox capacity of 32.94 ± 1.30 μg/mL (IC<sub>50</sub>), and its major compounds were chlorogenic acid > rutin > ferulic acid > catechin > sinapic acid. Chlorogenic acid and rutin presented a high affinity to the MCC950 region. Additionally, YME did not cause genotoxicity and was safe <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>YME has significantly affected macrophages and microglia by regulating the NLRP3 inflammatory pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119518"},"PeriodicalIF":4.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482733","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 : 2025-02-21DOI: 10.1016/j.jep.2025.119535
Jiahui Liu , Biao Qu , Sheng Wang , Linkai Qian , Feifei Liu , Xueting Zhang , Quan Zhao , Yunna Chen , Weidong Chen , Lei Wang , Sheng Zhang
Ethnopharmacological relevance
Fengshi Gutong Capsule (FSGT) is a proprietary Chinese medicine with established clinical efficacy in Rheumatoid arthritis (RA); however, its underlying mechanisms remain unclear.
Aim
This study aims to elucidate the mechanisms by which FSGT alleviates RA.
Materials and methods
A collagen-induced arthritis (CIA) rat model was employed to assess the therapeutic effects of FSGT in RA. Network pharmacology and proteomics were integrated to identify potential mechanism and molecular targets, which were further validated via Western blot analysis. Molecular docking and microscale thermophoresis (MST) were utilized to assess the binding affinities of FSGT's active components to key proteins.
Results
FSGT (280 and 840 mg/kg) alleviated CIA-induced RA in rats without significant side effects. Network pharmacology and label-free proteomic analysis displayed that FSGT exerted its therapeutic effects by modulating inflammation and bone destruction. FSGT significantly reduced serum levels of inflammatory cytokines and their protein expression in the ankle joints and synovial tissues. Additionally, FSGT attenuated bone destruction and significantly reversed the expression of bone destruction-related proteins. Molecular docking revealed that 18 active compounds in FSGT exhibited strong binding affinity for TNF-α, with hypaconitine, 18α-glycyrrhizic acid, and naringenin further validated by MST assays.
Conclusion
FSGT improved CIA-induced RA in rats by targeting TNF-α to reduce inflammation and inhibit bone destruction, offering insights into its therapeutic mechanisms in RA.
{"title":"Fengshi gutong capsules attenuates CIA-induced RA bone destruction in rats by targeting TNF-α inhibition: Integration and experimental validation of network pharmacology and proteomics","authors":"Jiahui Liu , Biao Qu , Sheng Wang , Linkai Qian , Feifei Liu , Xueting Zhang , Quan Zhao , Yunna Chen , Weidong Chen , Lei Wang , Sheng Zhang","doi":"10.1016/j.jep.2025.119535","DOIUrl":"10.1016/j.jep.2025.119535","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Fengshi Gutong Capsule (FSGT) is a proprietary Chinese medicine with established clinical efficacy in Rheumatoid arthritis (RA); however, its underlying mechanisms remain unclear.</div></div><div><h3>Aim</h3><div>This study aims to elucidate the mechanisms by which FSGT alleviates RA.</div></div><div><h3>Materials and methods</h3><div>A collagen-induced arthritis (CIA) rat model was employed to assess the therapeutic effects of FSGT in RA. Network pharmacology and proteomics were integrated to identify potential mechanism and molecular targets, which were further validated via Western blot analysis. Molecular docking and microscale thermophoresis (MST) were utilized to assess the binding affinities of FSGT's active components to key proteins.</div></div><div><h3>Results</h3><div>FSGT (280 and 840 mg/kg) alleviated CIA-induced RA in rats without significant side effects. Network pharmacology and label-free proteomic analysis displayed that FSGT exerted its therapeutic effects by modulating inflammation and bone destruction. FSGT significantly reduced serum levels of inflammatory cytokines and their protein expression in the ankle joints and synovial tissues. Additionally, FSGT attenuated bone destruction and significantly reversed the expression of bone destruction-related proteins. Molecular docking revealed that 18 active compounds in FSGT exhibited strong binding affinity for TNF-α, with hypaconitine, 18α-glycyrrhizic acid, and naringenin further validated by MST assays.</div></div><div><h3>Conclusion</h3><div>FSGT improved CIA-induced RA in rats by targeting TNF-α to reduce inflammation and inhibit bone destruction, offering insights into its therapeutic mechanisms in RA.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119535"},"PeriodicalIF":4.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482928","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 : 2025-02-21DOI: 10.1016/j.jep.2025.119533
Yan-li Li , Ting Wang , Hao Wang , Qi Wang , Cai-Hong Cai , Guo-Peng Zhu , Wen-Li Mei , Feng-Qing Xu , Hao-Fu Dai , Sheng-Zhuo Huang
Ethnopharmacological relevance
Nauclea officinalis Pierre ex Pitard, a traditional medicinal plant cherished by the Li ethnic group, is renowned for its potent anti-allergic properties in the clinic, especially in alleviating respiratory inflammations. This plant is now extensively cultivated to harness its valuable extracts for the production of traditional cough syrup.
Aim of the study
To identify the active components responsible for its anti-allergic inflammatory properties and to elucidate the underlying mechanisms of action.
Method
The structures of the compounds were meticulously elucidated using comprehensive spectroscopic analyses, including IR, UV, NMR, and MS, along with crystallography and ECD calculations. In vitro studies utilized IgE-induced RBL-2H3 cells to assess cell degranulation and the release of inflammatory mediators such as histamine, leukotrienes (LTs), and prostaglandins (PGs). Techniques such as the CCK-8 assay, enzyme-linked immunosorbent assay (ELISA), and Western blot (WB) were employed. Additionally, molecular docking methods were used to simulate and analyze the binding interactions of small molecules with their targets.
Result
Two novel monoterpene indole alkaloids were isolated: nauclofficine A, characterized by a unique 6/5/5/6/5 fused ring system, and nauclofficine B, which features an additional benzene-substituted dioxane moiety. Their structures were meticulously elucidated, and their biosynthetic pathways were hypothesized. Nauclofficine B exhibited significant inhibitory effects on cell degranulation and the release of inflammatory mediators such as histamine, leukotrienes (LTs), and prostaglandins (PGs) in IgE-induced RBL-2H3 cells. Further analysis using Western blot revealed that it significantly modulated the expression of key proteins in the IgE-mediated inflammatory signaling pathway. Molecular docking experiments suggested that its potential multi-target proteins include Lyn, FcεR, Syk, and p-Gab2, which were subsequently verified.
Conclusions
These results suggested that the wood of N. officinalis contains structurally novel alkaloids with anti-allergic inflammatory activity. The absolute configuration of the compound was accurately and reliably deduced, and the biosynthetic pathway was reasonably inferred. Their primary mechanism of action involves targeting multiple key proteins in the IgE-mediated inflammatory signaling pathway, including Lyn, FcεR, Syk, and p-Gab2.
{"title":"Nauclofficines A and B, two novel monoterpenoid indole alkaloids from the Li folk herb Nauclea officinalis with anti-allergic inflammatory effects on RBL-2H3 cells","authors":"Yan-li Li , Ting Wang , Hao Wang , Qi Wang , Cai-Hong Cai , Guo-Peng Zhu , Wen-Li Mei , Feng-Qing Xu , Hao-Fu Dai , Sheng-Zhuo Huang","doi":"10.1016/j.jep.2025.119533","DOIUrl":"10.1016/j.jep.2025.119533","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Nauclea officinalis</em> Pierre ex Pitard, a traditional medicinal plant cherished by the Li ethnic group, is renowned for its potent anti-allergic properties in the clinic, especially in alleviating respiratory inflammations. This plant is now extensively cultivated to harness its valuable extracts for the production of traditional cough syrup.</div></div><div><h3>Aim of the study</h3><div>To identify the active components responsible for its anti-allergic inflammatory properties and to elucidate the underlying mechanisms of action.</div></div><div><h3>Method</h3><div>The structures of the compounds were meticulously elucidated using comprehensive spectroscopic analyses, including IR, UV, NMR, and MS, along with crystallography and ECD calculations. In vitro studies utilized IgE-induced RBL-2H3 cells to assess cell degranulation and the release of inflammatory mediators such as histamine, leukotrienes (LTs), and prostaglandins (PGs). Techniques such as the CCK-8 assay, enzyme-linked immunosorbent assay (ELISA), and Western blot (WB) were employed. Additionally, molecular docking methods were used to simulate and analyze the binding interactions of small molecules with their targets.</div></div><div><h3>Result</h3><div>Two novel monoterpene indole alkaloids were isolated: nauclofficine A, characterized by a unique 6/5/5/6/5 fused ring system, and nauclofficine B, which features an additional benzene-substituted dioxane moiety. Their structures were meticulously elucidated, and their biosynthetic pathways were hypothesized. Nauclofficine B exhibited significant inhibitory effects on cell degranulation and the release of inflammatory mediators such as histamine, leukotrienes (LTs), and prostaglandins (PGs) in IgE-induced RBL-2H3 cells. Further analysis using Western blot revealed that it significantly modulated the expression of key proteins in the IgE-mediated inflammatory signaling pathway. Molecular docking experiments suggested that its potential multi-target proteins include Lyn, FcεR, Syk, and p-Gab2, which were subsequently verified.</div></div><div><h3>Conclusions</h3><div>These results suggested that the wood of N. officinalis contains structurally novel alkaloids with anti-allergic inflammatory activity. The absolute configuration of the compound was accurately and reliably deduced, and the biosynthetic pathway was reasonably inferred. Their primary mechanism of action involves targeting multiple key proteins in the IgE-mediated inflammatory signaling pathway, including Lyn, FcεR, Syk, and p-Gab2.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119533"},"PeriodicalIF":4.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482932","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 : 2025-02-21DOI: 10.1016/j.jep.2025.119534
Genil Dantas de Oliveira , Mariana França de Moraes , Magna Maria Lima Araújo , Dilma Maria de Brito Melo Trovão , José Iranildo Miranda de Melo , Wêndeo Kennedy Costa , Maria Tereza dos Santos Correia , Alisson Macário de Oliveira , Samuel Paulo Cibulski , Harley da Silva Alves
Ethnopharmacological relevance
Doyerea emetocathartica is a Cucurbitaceae known as ''cabeça de negro'' and used by North-eastern Brazil and South-eastern Mexico communities to treat rheumatism, inflammation and pain. Despite ethnopharmacological reports, there is currently a lack of evidence about its chemical composition, toxicity and pharmacological effects.
Aim of the study
This study aimed to investigate the chemical composition of the aqueous extract of D. emetocathartica stems (DEAQ), evaluate its acute oral toxicity, mutagenicity and its anti-inflammatory profile in mice.
Material and methods
The DEAQ chemical composition was evaluated through HPLC-MS/MS. Acute oral toxicity was assessed for 14 days after the oral administration of DEAQ in a single dose of 2000 mg kg−1. The mutagenic assessment was carried out through micronucleus test in mice. The DEAQ anti-inflammatory activity was evaluated at doses of 25, 50 and 100 mg kg−1 throught models of carrageenan-induced paw edema, peritonitis and air pouch.
Results
Using HPLC-MS/MS the cayaponoside D2 was identified as the most abundant compound in DEAQ. Oral DEAQ administration showed no signs of toxicity or mutagenicity. All tested DEAQ doses had anti-edematogenic effects, decreased the migration of total leukocytes and neutrophils and decreased the levels of TNF-α and IL-1β.
Conclusions
The in vivo tests results indicated that DEAQ showed strong anti-inflammatory activity, with possible cayaponoside D2 involvement, highlighting the absence of toxicity and genotoxicity for the dose and route used. Furthermore, the study provides chemical and pharmacological evidences about the therapeutic use of D. emetocathartica in folk medicine.
{"title":"Anti-inflammatory and non-toxic effects of Doyerea emetocathartica aqueous extract in mice","authors":"Genil Dantas de Oliveira , Mariana França de Moraes , Magna Maria Lima Araújo , Dilma Maria de Brito Melo Trovão , José Iranildo Miranda de Melo , Wêndeo Kennedy Costa , Maria Tereza dos Santos Correia , Alisson Macário de Oliveira , Samuel Paulo Cibulski , Harley da Silva Alves","doi":"10.1016/j.jep.2025.119534","DOIUrl":"10.1016/j.jep.2025.119534","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Doyerea emetocathartica</em> is a Cucurbitaceae known as ''cabeça de negro'' and used by North-eastern Brazil and South-eastern Mexico communities to treat rheumatism, inflammation and pain. Despite ethnopharmacological reports, there is currently a lack of evidence about its chemical composition, toxicity and pharmacological effects.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the chemical composition of the aqueous extract of <em>D. emetocathartica</em> stems (DEAQ), evaluate its acute oral toxicity, mutagenicity and its anti-inflammatory profile in mice.</div></div><div><h3>Material and methods</h3><div>The DEAQ chemical composition was evaluated through HPLC-MS/MS. Acute oral toxicity was assessed for 14 days after the oral administration of DEAQ in a single dose of 2000 mg kg<sup>−1</sup>. The mutagenic assessment was carried out through micronucleus test in mice. The DEAQ anti-inflammatory activity was evaluated at doses of 25, 50 and 100 mg kg<sup>−1</sup> throught models of carrageenan-induced paw edema, peritonitis and air pouch.</div></div><div><h3>Results</h3><div>Using HPLC-MS/MS the cayaponoside D<sub>2</sub> was identified as the most abundant compound in DEAQ. Oral DEAQ administration showed no signs of toxicity or mutagenicity. All tested DEAQ doses had anti-edematogenic effects, decreased the migration of total leukocytes and neutrophils and decreased the levels of TNF-α and IL-1β.</div></div><div><h3>Conclusions</h3><div>The <em>in vivo</em> tests results indicated that DEAQ showed strong anti-inflammatory activity, with possible cayaponoside D<sub>2</sub> involvement, highlighting the absence of toxicity and genotoxicity for the dose and route used. Furthermore, the study provides chemical and pharmacological evidences about the therapeutic use of <em>D. emetocathartica</em> in folk medicine.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119534"},"PeriodicalIF":4.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483243","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 : 2025-02-21DOI: 10.1016/j.jep.2025.119530
Mingyun Wang , Jingwen Zhou , Ling Li , Tong Zhang , Yiqiong Pu
<div><h3>Ethnopharmacological relevance</h3><div>Paeonol has often been used as an anti-inflammatory agent in gastrointestinal diseases. However, as a primary paeonol-originated herb, the effects of <em>Cynanchum paniculatum</em> (CP) extracts have rarely been reported in the study on gastrointestinal inflammation models.</div></div><div><h3>Aim of the study</h3><div>The study aims to investigate the anti-inflammatory effects of different CP extracts, including the volatile extract (CP-VE), and its aqueous extract (CP-AE), based on their different contents of paeonol.</div></div><div><h3>Methods</h3><div>The contents of paeonol in the extracts were detected by HPLC. The anti-inflammatory effects of CP-VE, CP-AE and their combination (CP-VA), were compared on lipopolysaccharide (LPS)-induced macrophage RAW264.7 cells, with which the primary mechanisms were investigated in MAPK/NF-κB signaling pathway. Additionally, the effects of CP-VE at different dosages were further investigated on <em>Helicobacter pylori</em> (<em>Hp</em>)-infected gastrointestinal mucosal damaged zebrafish.</div></div><div><h3>Results</h3><div>The content of paeonol in CP-VE was 93.29%, while that in CP-AE was 0.03%. The cellular study showed that the levels of IL-1β, IL-6, TNF-α and reactive oxygen species (ROS) were significantly decreased in the CP-extract groups when compared with the model group, while their levels of IL-10 and nitric oxide (NO) were significantly increased. Compared with the LPS group, p-P65, p-JNK, p-ERK and NLRP3 protein expression was decreased in the CP-extract groups with different degrees, where CP-VA exhibited the most pronounced inhibitory activities on the phosphorylation of the proteins (<em>p</em> < 0.001, <em>p</em> < 0.01). CP-AE and CP-VE demonstrated the similar inhibition of ERK and P65 phosphorylation, while CP-AE showed slightly superior inhibition of P38, and NLRP3 than CP-VE did (<em>p</em> < 0.05, <em>p</em> < 0.01). The zebrafish study indicated that the CP-VE groups showed obvious reductions in the gastrointestinal tract areas, the fluorescence intensities and gastrointestinal neutrophil counts in a dose-dependence style, when compared with the model group. The histopathological results also indicated that CP-VE showed significant effects on the pathologic structure of the intestinal mucosa.</div></div><div><h3>Conclusion</h3><div>The results showed that CP-VE (40 μg/mL) and CP-AE (700 μg/mL) showed similar significantly anti-inflammatory activity on LPS-induced macrophage RAW 264.7 cells, which indicated that the activity might be not fully related with paeonol content. It is also speculated that both CP-VE and CP-AE may exert their anti-inflammatory effects via inhibiting the MAPK/NF-κB pathways. CP-extracts are expected to be potential anti-inflammatory agents from natural source in gastrointestinal inflammation-related indications, among which CP-AE need to be further investigated on its pharmacological material ba
{"title":"The anti-inflammatory effects of paeonol from Cynanchum paniculatum extracts on LPS-induced macrophage RAW 264.7 cells and Helicobacter pylori-infected gastrointestinal mucosal damaged zebrafish","authors":"Mingyun Wang , Jingwen Zhou , Ling Li , Tong Zhang , Yiqiong Pu","doi":"10.1016/j.jep.2025.119530","DOIUrl":"10.1016/j.jep.2025.119530","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Paeonol has often been used as an anti-inflammatory agent in gastrointestinal diseases. However, as a primary paeonol-originated herb, the effects of <em>Cynanchum paniculatum</em> (CP) extracts have rarely been reported in the study on gastrointestinal inflammation models.</div></div><div><h3>Aim of the study</h3><div>The study aims to investigate the anti-inflammatory effects of different CP extracts, including the volatile extract (CP-VE), and its aqueous extract (CP-AE), based on their different contents of paeonol.</div></div><div><h3>Methods</h3><div>The contents of paeonol in the extracts were detected by HPLC. The anti-inflammatory effects of CP-VE, CP-AE and their combination (CP-VA), were compared on lipopolysaccharide (LPS)-induced macrophage RAW264.7 cells, with which the primary mechanisms were investigated in MAPK/NF-κB signaling pathway. Additionally, the effects of CP-VE at different dosages were further investigated on <em>Helicobacter pylori</em> (<em>Hp</em>)-infected gastrointestinal mucosal damaged zebrafish.</div></div><div><h3>Results</h3><div>The content of paeonol in CP-VE was 93.29%, while that in CP-AE was 0.03%. The cellular study showed that the levels of IL-1β, IL-6, TNF-α and reactive oxygen species (ROS) were significantly decreased in the CP-extract groups when compared with the model group, while their levels of IL-10 and nitric oxide (NO) were significantly increased. Compared with the LPS group, p-P65, p-JNK, p-ERK and NLRP3 protein expression was decreased in the CP-extract groups with different degrees, where CP-VA exhibited the most pronounced inhibitory activities on the phosphorylation of the proteins (<em>p</em> < 0.001, <em>p</em> < 0.01). CP-AE and CP-VE demonstrated the similar inhibition of ERK and P65 phosphorylation, while CP-AE showed slightly superior inhibition of P38, and NLRP3 than CP-VE did (<em>p</em> < 0.05, <em>p</em> < 0.01). The zebrafish study indicated that the CP-VE groups showed obvious reductions in the gastrointestinal tract areas, the fluorescence intensities and gastrointestinal neutrophil counts in a dose-dependence style, when compared with the model group. The histopathological results also indicated that CP-VE showed significant effects on the pathologic structure of the intestinal mucosa.</div></div><div><h3>Conclusion</h3><div>The results showed that CP-VE (40 μg/mL) and CP-AE (700 μg/mL) showed similar significantly anti-inflammatory activity on LPS-induced macrophage RAW 264.7 cells, which indicated that the activity might be not fully related with paeonol content. It is also speculated that both CP-VE and CP-AE may exert their anti-inflammatory effects via inhibiting the MAPK/NF-κB pathways. CP-extracts are expected to be potential anti-inflammatory agents from natural source in gastrointestinal inflammation-related indications, among which CP-AE need to be further investigated on its pharmacological material ba","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119530"},"PeriodicalIF":4.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478621","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 : 2025-02-21DOI: 10.1016/j.jep.2025.119537
Ralf Weiskirchen
{"title":"Critical comment on \"Inhibitory effects of Raddeanin a on hepatocellular carcinoma cells\"","authors":"Ralf Weiskirchen","doi":"10.1016/j.jep.2025.119537","DOIUrl":"10.1016/j.jep.2025.119537","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119537"},"PeriodicalIF":4.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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