J Ethnopharmacol [JOURNAL]
Sun
200 papers
Combinations of stem bark powders of Enantia chlorantha and Uvaria chamae showed antimalarial activities in mice.
Olawuni OF, Adepiti AO, Babamuyiwa BO
J Ethnopharmacol · 2026 Jun · PMID 42349770 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Enantia chlorantha Oliver (Annonaceae) and Uvaria chamae P. Beauv (Annonaceae) is widely used in African ethnomedicine for the treatment of malaria. AIM OF THE STUDY: This...
ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Enantia chlorantha Oliver (Annonaceae) and Uvaria chamae P. Beauv (Annonaceae) is widely used in African ethnomedicine for the treatment of malaria. AIM OF THE STUDY: This study investigated the antimalarial activities of E. chlorantha and U. chamae stem bark powders in order to optimize their antimalarial activity. It also aimed to assess possible herb-drug interaction with orthodox antimalarial drugs. MATERIALS AND METHODS: The single and combined [1:1 (EU1); 1:2 (EU2) and 2:1 (EU3)] powders of E. chlorantha and U. chamae were reconstituted by suspending in propylene glycol (50%). Evaluation of the chemosuppressive and curative antimalarial models was carried out by oral administration of the single (6.25-200 mg/kg) and combined (6.25-25 mg/kg) powders on mice infected with the chloroquine-sensitive Plasmodium berghei NK65 and chloroquine-resistant Plasmodium berghei ANKA, respectively. Co-administration with artesunate-amodiaquine (ACT) and chloroquine was also assessed. The n-hexane extracts of the combined powders were analyzed individually by GC-MS. RESULTS: At 200 mg/kg, E. chlorantha and U. chamae powders each gave significant chemosuppressive (86% and 83%) and curative (77% and 76%) activities, respectively. At 25 mg/kg, EU3 exhibited significant chemosuppressive activity (85.23%). At 6.25 mg/kg, EU3+CQ and EU3+ACT had chemosuppressive (77.61% and 75.87%) and curative (93.01% and 96.66%) activities, respectively. The GC-MS fingerprint of the combined powders revealed predominantly sesquiterpenes, oxygenated sesquiterpenes, fatty acid esters, and phytosterols. CONCLUSION: Antimalarial activity was enhanced with combination of the powders while additive interaction was observed with the herb-drug combinations.
A multidimensional strategy for exploring active peptides combining chemical analysis and bioassays for medicinal leeches.
Liu YF, Wang WD, Xie T … +6 more , Chen LM, Zhang QG, Lou WJ, Wang ZM, Ma Y, Gao HM
J Ethnopharmacol · 2026 Jun · PMID 42349769 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Leeches were first recorded in Shennong Bencao Jing, and they have been traditionally used to treat blood stasis-related disorders through decoction and oral administration more than 2000...
ETHNOPHARMACOLOGICAL RELEVANCE: Leeches were first recorded in Shennong Bencao Jing, and they have been traditionally used to treat blood stasis-related disorders through decoction and oral administration more than 2000 years in China. This practice involves heating and gastrointestinal transformation. However, whether it converts native constituents into pharmacologically active substances remains unresolved, representing a critical gap in understanding bioactive substance formation in traditional medicine. AIM OF THE STUDY: To elucidate the component transformation of Hirudo nipponia (HN) and Whitmania pigra (WP) during decoction and enzymolysis, and identify their effective anticoagulant and antiplatelet peptides. MATERIALS AND METHODS: A multidimensional strategy integrating decoction, enzymolysis, chemical profiling, and bioactivity evaluation was employed. Component transformation was characterized by gel permeation chromatography, protein/peptide determination, gel electrophoresis, and nano LC-MS. Anticoagulant activity was assessed using in vivo thrombosis models and coagulation assays. Bioactive peptides were prioritized by molecular prediction and validated by in vitro bioassays. RESULTS: HN and WP significantly reduced mice tail thrombosis incidence invivo (10.5% and 13.8%). Decoction and enzymatic hydrolysis induced proteins-to-peptides transformation was essential for pronounced bioactivity. In <3 kDa fractions with strongest antiplatelet effects, 23905 (HN) and 18783 (WP) peptides were identified, and among them, 70 candidates targeting thrombin and P2Y12 receptors were prioritized. Six peptides exhibited significant antiplatelet activity at 31.3 μM. Notably, the combined activity of peptides could be attributed to clinical efficacy of leeches. CONCLUSION: Leech antiplatelet activity may be primarily mediated by decoction and digestion-generated peptides rather than native constituents, providing a mechanistic basis for the efficacy of non-hematophagous WP. This strategy offers a framework for identifying bioactive substances formed during traditional practice of animal-derived medicines.
Metabolite profiling and in vitro assessment of skin-related pharmacological activities in Baccharis trimera (Less.) DC.
Gabor P, Júnior WGM, Ribeiro K … +9 more , Costa RPD, Cass QB, Severino VGP, Severino RP, Makishi GFC, Siqueira GF, Melzig MF, Weng A, Sousa LRF
J Ethnopharmacol · 2026 Jun · PMID 42349768 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis trimera (Less.) DC. (Asteraceae), commonly known as "carqueja", is a medicinal plant traditionally used in Brazil as an herbal remedy for gastrointestinal disorders. In some regi...
ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis trimera (Less.) DC. (Asteraceae), commonly known as "carqueja", is a medicinal plant traditionally used in Brazil as an herbal remedy for gastrointestinal disorders. In some regions, its aerial parts are also used to treat skin-related diseases, including wounds. Despite growing interest in discovering new cosmeceutical ingredients from traditionally used medicinal plants, knowledge of this species and its potential skin-related applications remains limited. AIM OF THE STUDY: We investigated the aerial parts of B. trimera for their anti-inflammatory, anti-aging, and skin-whitening properties. MATERIALS AND METHODS: The ethanolic extract (BtE) was fractionated via liquid-liquid extraction into hexane (BtEH), dichloromethane (BtED), ethyl acetate (BtEA), and hydroalcoholic (BtEHy) fractions. Chemical dereplication of BtE and active fractions (BtEA and BtED) was performed using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Enzyme inhibitory activity against tyrosinase and elastase was evaluated spectrophotometrically. Anti-inflammatory activity was assessed in lipopolysaccharide (LPS)-stimulated THP-1 macrophages by quantifying TNF-α, IL-1β, and IL-6 levels using ELISA. RESULTS: The crude extract inhibited elastase activity, while its fractions reduced cytokine production and enhanced tyrosinase inhibition. Among these, the dichloromethane fraction showed the most pronounced effects, including tyrosinase inhibition, reduced secretion of TNF-α, IL-1β and IL-6, and a significant decrease in LPS-induced LDH release. Twenty compounds, including flavonoids, hydroxycinnamic acid derivatives, diterpenes, phenylpropanoids, and fatty acids, were annotated in the active ethanolic extract and its fractions from Baccharis trimera, several of which have previously shown anti-inflammatory activity. After fractionation, cirsimaritin, eupatorin, and jaceosidin were found exclusively in the dichloromethane fraction and may have contributed to its anti-inflammatory activity. In addition, the anti-tyrosinase activity observed in the medium-polarity fractions may be associated with the presence of rutin, apigenin flavone glucoside, and 3-hydroxy-copalic acid. CONCLUSION: Overall, this study expands the chemical characterization of this medicinal plant and underscores its potential for skincare applications. Notably, anti-tyrosinase activity was identified in the medium-polar fractions for the first time, highlighting their potential as a source of bioactive metabolites relevant for cosmetic and skin-related applications.
Guilu Erxian oral liquid alleviates oligoasthenospermia via the mitochondria-complement-NETs network.
Yue Q, Tong K, Feng Q … +8 more , Chang H, Zhang Z, Xu X, Pan T, Xu Z, Chen L, Liu J, Liu Z
J Ethnopharmacol · 2026 Jun · PMID 42349767 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Guilu Erxian Oral Liquid (GLEX) is a traditional Chinese medicinal formula first recorded in Yi Bian, a medical classic written during the Ming Dynasty, and has been conventionally used to...
ETHNOPHARMACOLOGICAL RELEVANCE: Guilu Erxian Oral Liquid (GLEX) is a traditional Chinese medicinal formula first recorded in Yi Bian, a medical classic written during the Ming Dynasty, and has been conventionally used to treat male infertility based on its kidney tonification and is now widely recognized for its therapeutic effects against oligoasthenospermia (OAS). AIM OF THE STUDY: This study aims to investigate the impact of GLEX on cyclophosphamide (CTX)-induced OAS-like mice and to explore its underlying mechanisms, utilizing pharmacodynamics, multi-omics, and molecular biological techniques. MATERIALS AND METHODS: The chemical constituents of GLEX were identified using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The binding affinity between GLEX constituents and DJ-1 was determined by molecular docking and molecular dynamics simulations. A mouse model of OAS was induced using 60 mg/kg CTX for 5 days. ICR mice were randomly divided into seven groups: Control group, Model group, low (1.93 mL/kg)-, medium (3.86 mL/kg)-, and high (7.72 mL/kg)-dose groups of GLEX, Wu Zi Yan Zong pill group, and L-Carnitine group. Each group received consecutive gavage for 28 days. Semen quality parameters were assessed using a sperm quality analyzer, along with morphological assessment by hematoxylin and eosin (HE) staining. Serum sex hormone levels were measured using an enzyme-linked immunosorbent assay (ELISA). Gut microbiota was profiled via 16S rRNA gene sequencing. RNA-Seq and DIA proteomics were used to screen the potential pathways and targets associated with OAS pathogenesis and GLEX treatment. Subsequently, the ultrastructure of testis was examined under a transmission electron microscope. Testicular oxidative stress markers and Na-K-ATPase activity were measured by biochemical analysis and fluorescence microscopy. The Mitochondria-Complement-NETs network targets (DJ-1, UQCRQ, C3, FGG, FGA, NE-DNA, MPO-DNA, citH3, and PAD4) were assessed by immunohistochemistry detection, immunofluorescence staining, ELISA, and western blotting. RESULTS: A total of 84 components were detected by UPLC-MS/MS analysis. After merging with the 15 components predicted from the BATMAN-TCM database and screening against the TCMSP database, 13 were structurally identified. Molecular docking and molecular dynamics simulations revealed a stable binding between GLEX constituents and DJ-1. CTX-induced OAS-like mice showed markedly reduced sperm density and motility and imbalanced serum sex hormone levels, along with structural damage in testicular and epididymal tissues. GLEX effectively restored these alterations. Besides, GLEX remodeled the gut microbiota composition and function in OAS mice. Multi-omics analyses further revealed that the therapeutic mechanisms of GLEX were associated with mitochondria, energy metabolism, oxidative phosphorylation, complement and coagulation cascades, and neutrophil extracellular trap (NET) formation pathways. OAS mice performed disrupted testicular mitochondrial ultrastructure, decreased activities of Na-K-ATPase, T-SOD, GSH-Px, CAT, DJ-1, and UQCRQ, and elevated levels of ROS, MDA, C3, FGA, FGG, MPO-DNA, NE-DNA, citH3, and PAD4. GLEX significantly reversed them via the Mitochondria-Complement-NETs network, exhibiting mitochondrial protection, complement inhibition, and NETs blockade. CONCLUSION: GLEX exerts protective effects on semen quality, endocrine function, and histopathological injury of CTX-induced OAS-like mouse model, accompanied by the coordinated modulation of mitochondrial function, complement overactivation, and NETs release. These findings delineate a proposed Mitochondria-Complement-NETs network, which warrants further investigation and may inform future research on interventions for chemotherapy-related reproductive impairment.
Diterpenoids from Tripterygium Glycosides Tablets and their anti-inflammatory activity.
Li SF, Tang PB, Fu Y … +8 more , Liu SH, Zhang LP, Ji YN, Chai WK, Zhang XY, Wang YF, Wang Q, Huo CH
J Ethnopharmacol · 2026 Jun · PMID 42349766 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Renowned in traditional medicine, Tripterygium wilfordii is historically recognized for its efficacy against inflammatory and autoimmune disorders. The modern clinical preparation, Tripter...
ETHNOPHARMACOLOGICAL RELEVANCE: Renowned in traditional medicine, Tripterygium wilfordii is historically recognized for its efficacy against inflammatory and autoimmune disorders. The modern clinical preparation, Tripterygium Glycosides Tablets (TGTs), is derived from this plant. Despite its proven clinical efficacy, the precise bioactive constituents underlying TGTs' anti-inflammatory effects remain incompletely characterized. AIM OF THE STUDY: This paper aimed to identify the phytochemical constituents in the raw material of TGTs and to examine their potential cytotoxicity and anti-inflammatory activities. MATERIALS AND METHODS: Phytochemical investigation was performed by several column chromatographic techniques. Through comprehensive spectroscopic analysis and quantum chemical calculations, the structures were elucidated. All isolates from TGTs were tested for cytotoxicity alongside anti-inflammatory effects in LPS-induced RAW264.7 cells via CCK-8, Griess, ELISA, and high-content cell painting assays. RESULTS: Ten diterpenoids were obtained, including three new abietane diterpenoids (1-3), along with seven known analogues (4-10). Compound 1 markedly suppressed NO, IL-6, and TNF-α production (IC = 2.12 ± 0.23, 3.36 ± 0.22, and 4.86 ± 0.53 μM, respectively). Compounds 2, 5, and 7 exhibited moderate inhibitory activity. High-content phenotypic screening further delineated the potential anti-inflammatory mechanisms of 1. CONCLUSION: This study validates the anti-inflammatory basis of TGTs' clinical efficacy and identifies diterpenoids, particularly compound 1, as promising lead compounds for novel anti-inflammatory drug development. These well-characterized compounds also serve as potential chemical markers for the quality assessment of T. wilfordii preparations.
Corrigendum to "Xiao-Liu Tang (XLT), a traditional Chinese medicine formula that suppresses the progression of cervical cancer by inducing apoptosis and inhibiting cell migration" [J Ethnopharmacol. (2026) 358 120966].
Dang S, Tang X, Li Q … +9 more , Wu J, Hu Y, Liu X, Cao D, Feng C, Sun Y, Huang J, Song W, Du X
J Ethnopharmacol · 2026 Jun · PMID 42342482 · Publisher ↗
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Digeda-8 formula attenuates cholestatic liver injury in rats by restoring bile acid transport and suppressing inflammation: An integrated metabolomics and proteomics approach.
Bayoude A, Yi R, Zhao Y … +4 more , Runa A, Ming M, Hu S, Jirimu B
J Ethnopharmacol · 2026 Jun · PMID 42341861 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Digeda-8 (DGD8) is a traditional polyherbal formulation with a long history of clinical use in Mongolian medicine for the treatment of hepatobiliary disorders and cholestatic conditions. D...
ETHNOPHARMACOLOGICAL RELEVANCE: Digeda-8 (DGD8) is a traditional polyherbal formulation with a long history of clinical use in Mongolian medicine for the treatment of hepatobiliary disorders and cholestatic conditions. Despite its traditional reputation, the pharmacological basis and molecular mechanisms underlying its effects against cholestatic liver injury (CLI) remain scientifically uncharacterized. AIM OF THE STUDY: This study aimed to evaluate the hepatoprotective efficacy of DGD8 against alpha-naphthylisothiocyanate (ANIT)-induced CLI in rats and to systematically elucidate its multi-target mechanisms of action using an integrated systems pharmacology approach. MATERIALS AND METHODS: A rat model of ANIT-induced CLI was established to assess the efficacy of DGD8 via biochemical markers (ALT, AST, TBA, TBIL), histopathological analysis, and immunological assessments. The chemical profile of DGD8 was characterized using HPLC-QTOF-MS/MS combined with GNPS molecular networking. To explore the underlying mechanisms, an integrated framework was employed, including metabolomics, TMT-labeled proteomics, Western blot, and immunofluorescence microscopy. Furthermore, network pharmacology integrated with human cholestasis transcriptomics and molecular docking was used to identify and validate disease-relevant molecular targets. RESULTS: DGD8 treatment, particularly at a high dose (700 mg/kg), significantly reduced ANIT-induced elevations in biochemical markers, demonstrating a protective effect in the ANIT-induced acute CLI model, with UDCA included as a reference treatment. Histopathology confirmed a marked reduction in hepatocyte necrosis and early fibrotic changes. Mechanistically, DGD8 restored dysregulated arachidonic acid and lipid metabolism, suppressed pro-inflammatory cytokines (IL-1β and TNF-α) via COX-2 inhibition, and enhanced antioxidant capacity. Proteomic analysis revealed that DGD8 activated FXR, subsequently upregulating hepatic bile acid transporters (BSEP, MRP2, OATP1A1) and the conjugation enzyme UGT1A1, thereby restoring bile acid homeostasis. Importantly, SAMHD1 and S100A16 were identified as novel therapeutic targets in CLI; their suppression by DGD8 correlated with improved hepatoprotection. Molecular docking indicated that 31 drug-like constituents, primarily alkaloids and phenolics, exhibit strong binding affinities to these key targets. CONCLUSION: DGD8 ameliorates CLI through a coordinated multi-targeted mechanism involving the suppression of COX-2-mediated inflammation, restoration of bile acid transport and detoxification via FXR activation, and modulation of novel pathogenic mediators (SAMHD1 and S100A16). This study provides a scientific validation for the traditional use of DGD8 and offers a systems-level paradigm for understanding the polypharmacological architecture of multi-herb Mongolian medicines.
In vitro and in silico evaluation of the anticancer potential of ethanolic seed extract of Bryonia laciniosa against colorectal and hepatocellular cancer.
Verma D, Tiwari M
J Ethnopharmacol · 2026 Jun · PMID 42341860 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: The seed extract of Bryonia laciniosa has strong ethnopharmacological importance, supported by its longstanding use in traditional medicine. It demonstrates notable anticancer, antioxidant...
ETHNOPHARMACOLOGICAL RELEVANCE: The seed extract of Bryonia laciniosa has strong ethnopharmacological importance, supported by its longstanding use in traditional medicine. It demonstrates notable anticancer, antioxidant, and anti-inflammatory activities, highlighting its potential as a natural candidate for future cancer-focused therapeutic research. MATERIALS AND METHODS: The cytotoxic activity of ethanolic seed extract from Bryonia laciniosa was examined using established in vitro cell viability-based assays. Computational biology tools, followed by laboratory-level confirmation, were employed to determine the key molecular targets and the cellular signaling networks influenced by the extract. RESULTS: The seed extract of Bryonia laciniosa demonstrated strong growth-inhibitory effects in both colorectal and liver cancer cell models. A combination of molecular docking and laboratory analyses highlighted AKT-1 and p53 signaling as primary response points influenced by the extract's bioactive compounds. Extract exposure resulted in reduced AKT-1 protein abundance and elevated p53 expression, along with increased programmed cell death and enhanced intracellular reactive oxygen species. Collectively, the coordinated inhibition of AKT-1 and activation of p53 signaling appear to be key drivers of the extract-mediated anticancer response. CONCLUSION: Our findings offer experimental evidence supporting the traditional therapeutic application of this plant extract in cancer care. Through modulation of survival-associated signaling and apoptosis-driven mechanisms, the extract shows potential as a plant-derived therapeutic option for managing colorectal cancer and hepatocellular carcinoma. The observed biological effects underscore its value as a natural lead for future anticancer drug-discovery research. Additional work is needed to purify and characterize the active molecules and to investigate therapeutic performance in living systems using appropriate in vivo models.
Liquiritin prevents preterm labor by remodeling decidual steroid homeostasis through 11β-HSD1 inhibition.
Zhang X, Zhang W, Huang J … +5 more , Zeng H, Liu W, Wu Y, Liu L, Li Q
J Ethnopharmacol · 2026 Jun · PMID 42341859 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Licorice (Glycyrrhiza uralensis Fisch. ex DC.) is ethnobotanically indicated for stabilizing pregnancy and alleviating gestational abdominal pain. Its primary flavonoid, liquiritin (LQ), e...
ETHNOPHARMACOLOGICAL RELEVANCE: Licorice (Glycyrrhiza uralensis Fisch. ex DC.) is ethnobotanically indicated for stabilizing pregnancy and alleviating gestational abdominal pain. Its primary flavonoid, liquiritin (LQ), exhibits anti-inflammatory, antioxidant, and steroid-modulatory activities. Whether LQ prevents spontaneous preterm birth (sPTB) by rectifying placental inflammatory-metabolic imbalance remains unknown. AIM OF THE STUDY: This study investigated the pharmacological efficacy of LQ against sPTB while deciphering the molecular mechanisms. MATERIALS AND METHODS: The therapeutic efficacy of LQ was initially assessed in a lipopolysaccharide (LPS)-induced intrauterine inflammation (IUI) murine model, integrating histopathological, transcriptomic, and molecular profiling analyses. Subsequently, the molecular target of LQ was elucidated via DARTS-MS, molecular docking, CETSA-WB, and enzyme activity measurements in human decidual stromal cells (hDSCs). Target dependency was further validated through siRNA-mediated knockdown and overexpression rescue experiments. Finally, the downstream signaling mechanisms were dissected using complementary molecular analyses. RESULTS: In the LPS-induced IUI murine model, LQ markedly prolonged gestation and enhanced neonatal survival. Mechanistically, LQ recalibrated glucocorticoid-redox homeostasis by suppressing NOX2 expression and activating the Nrf2/HO-1 antioxidant axis. In primary hDSCs, integrated chemoproteomics and biochemical assays identified 11β-HSD1 as a high-affinity functional target of LQ. Mechanistic interrogation confirmed that LQ-mediated 11β-HSD1 inhibition disrupts a pro-inflammatory loop, specifically suppressing cortisol amplification and subsequent COX-2/NOX2 cascades, which in turn reduced prostaglandin production. CONCLUSION: This study demonstrates that LQ alleviates placental dysfunction by suppressing glucocorticoid excess and the associated pro-inflammatory cascade and identifies 11β-HSD1 as a direct target of LQ in hDSCs, supporting its potential as a metabolic intervention targeting steroid homeostasis for sPTB prevention.
Annexin A2 as a therapeutic target of Artemisiae Scopariae Herba-derived quercetin in preventing malignant progression from primary sclerosing cholangitis to cholangiocarcinoma: An integrative study.
Huang W, Zhang Y, Liu K … +9 more , Li W, Li S, Zhuang M, Sun X, Gao Q, Lv X, Hu Y, Zhu W, Wen W
J Ethnopharmacol · 2026 Jun · PMID 42341858 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisiae Scopariae Herba (ASH) is traditionally used to treat cholestatic liver diseases and exhibits anti-tumour potential. Cholangiocarcinoma (CCA) and its major risk factor, primary s...
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisiae Scopariae Herba (ASH) is traditionally used to treat cholestatic liver diseases and exhibits anti-tumour potential. Cholangiocarcinoma (CCA) and its major risk factor, primary sclerosing cholangitis (PSC), lack effective therapies. AIM OF THE STUDY: In this study, we aimed to elucidate the bioactive constituents and underlying protective mechanisms of ASH in preventing malignant progression from PSC to CCA. MATERIALS AND METHODS: We identified the active constituents of ASH and their targets using multiple databases and mass spectrometry. Integrative transcriptomic analysis of public datasets determined the therapeutic targets. Machine learning and molecular docking predicted key targets, while surface plasmon resonance experimentally confirmed the primary drug-target interaction. Subsequent clinical sample analysis validated these targets. Finally, we assessed the in vitro effects of quercetin on CCA cells and utilised single-cell transcriptomics to characterise target expression within the disease microenvironment. RESULTS: Quercetin emerged as the principal bioactive constituent of ASH, with annexin A2 (ANXA2) as its key target. ANXA2 was overexpressed in CCA and PSC, which correlated with poor patient prognosis. In vitro, quercetin suppressed CCA cell malignant phenotypes and downregulated ANXA2 expression. Single-cell analysis revealed that epithelial cells, functioning as critical communication hubs, primarily overexpressed ANXA2. Functional enrichment analysis implicated pathways regulating the actin cytoskeleton and mediating bacterial infection responses. CONCLUSIONS: Quercetin likely exerts its therapeutic effects by targeting ANXA2 and modulating cholangiocyte pathogenicity. These findings highlight ANXA2 as a promising therapeutic target for treating advanced CCA and halting PSC-driven carcinogenesis.
Anti-gallstone effects of Jieshiqing Capsule and its active component verbascoside and the underlying mechanisms.
Yongbo X, Li X, Chen H … +4 more , Jiang K, Xia W, Feng Y, He M
J Ethnopharmacol · 2026 Jun · PMID 42341857 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Jieshiqing Capsule (JSQ) is a classic traditional Miao medicine with notable clinical efficacy in clearing damp-heat and promoting bile flow to eliminate gallstones. However, the lack of a...
ETHNOPHARMACOLOGICAL RELEVANCE: Jieshiqing Capsule (JSQ) is a classic traditional Miao medicine with notable clinical efficacy in clearing damp-heat and promoting bile flow to eliminate gallstones. However, the lack of a quality evaluation standard centered on its sovereign herb, together with unclear molecular mechanisms, greatly limits the modernization and broader application of this formulation. AIM OF THE STUDY: To systematically characterize the chemical basis of JSQ, elucidate the pharmacological mechanism of its core active component against cholesterol gallstones (CGS), and provide a scientific basis for improving its quality standards. MATERIALS AND METHODS: UPLC-Q-TOF-MS and HPLC were used to profile JSQ and quantify verbascoside. A CGS mouse model was established. Clinical transcriptomics, untargeted metabolomics, Western blotting and RT-qPCR were integrated to explore the mechanism. RESULTS: Among 74 annotated constituents, the primary bioactive verbascoside stably maintained 4.361-7.168 mg/g across 15 batches of JSQ. In vivo experiments confirmed that this component significantly inhibited CGS formation, ameliorated dyslipidemia, and alleviated liver injury. Integrated multi-omics analysis revealed that cytokine-cytokine receptor interaction, bile acid metabolism, and steroid biosynthesis are key pathways. Mechanistic studies demonstrated that verbascoside regulates the AGE/RAGE/NF-κB/FXR axis to exert anti-gallstone effects, downregulating the mRNA and protein expression of IL-6, IL-1β, TNF-α, and RAGE, while upregulating FXR, BSEP, NTCP, SHP, CYP7A1, CYP8B1, and NR1H3. CONCLUSIONS: Verbascoside from JSQ exerts dual anti-inflammatory and bile acid-remodeling effects via the AGE/RAGE/NF-κB/FXR axis, counteracting cholesterol gallstones. This study provides a material basis for a new quality standard centered on the sovereign herb's active component.
Paeoniae decoction attenuates chronic colitis-associated intestinal fibrosis by suppressing TGF-β/Smad-mediated epithelial-mesenchymal transition and remodeling the metabolic microenvironment.
Zhao M, Yi Q, Liang J … +8 more , Li C, Ke X, Zhao Y, Shi Y, Deng S, Wang Q, Luo X, Zhou L
J Ethnopharmacol · 2026 Jun · PMID 42341856 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniae Decoction (PD) is a classic Chinese medicine formula for treating intestinal diseases. However, its direct intervention effect on intestinal fibrosis and the underlying molecular...
ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniae Decoction (PD) is a classic Chinese medicine formula for treating intestinal diseases. However, its direct intervention effect on intestinal fibrosis and the underlying molecular mechanisms have not been fully elucidated. AIM OF THE STUDY: To evaluate the effect of PD on inflammatory bowel disease (IBD) associated intestinal fibrosis and to systematically investigate its potential molecular mechanisms utilizing integrated multi-omics. MATERIALS AND METHODS: The chemical constituents of PD were characterized and quantified utilizing ultra-high performance liquid chromatography-Quadrupole-Orbitrap mass spectrometry (LC-Q-Orbitrap-MS) and LC-MS/MS. A chronic experimental colitis-associated intestinal fibrosis mouse model lasting 56 days and involving four repeated cycles of dextran sulfate sodium (DSS) injury was established. The therapeutic efficacy of PD was evaluated through endoscopy, histopathological analysis, and collagen staining. Label-free quantitative proteomics and untargeted metabolomics and network pharmacology were employed to elucidate the target networks. In vitro mechanisms were further validated in TGF-β1-stimulated NCM460 cells using wound healing assays, immunofluorescence, and Western blotting to evaluate the epithelial-mesenchymal transition (EMT) process and the TGF-β/Smad signaling pathway. Finally, molecular docking was used to verify the direct binding of the main bioactive components of PD to the key pathway targets. RESULTS: Chemical profiling identified 16 common constituents across independent batches of PD. In vivo, PD administration significantly ameliorated intestinal fibrosis and reduced massive extracellular matrix (ECM) deposition in the mucosal and submucosal layers. Integrated omics analyses revealed that PD profoundly modulated the TGF-β signaling pathway, ECM-receptor interaction, and the Sphingolipid signaling pathway. Mechanistically, PD dose-dependently inhibited myofibroblast activation, downregulating the expression of α-SMA, Vimentin, Collagen I, and Collagen III. In vitro, PD serum suppressed TGF-β1-induced cell migration, preserved the epithelial marker E-cadherin, and inhibited the nuclear translocation of Snail by significantly decreasing the phosphorylation of Smad2 and Smad3. Furthermore, PD reversed pro-fibrotic sphingolipid metabolism and upregulated taurine and glutathione metabolism associated with antioxidant defense. CONCLUSION: PD effectively alleviates chronic colitis-associated intestinal fibrosis by inhibiting the TGF-β/Smad signaling pathway-mediated EMT process, reducing ECM deposition, and reprogramming the fibrotic metabolic microenvironment.
Screening of hepatotoxic components of Epimedium brevicornu Maxim. by liver microfluidic-organ-chip: Icariside Ⅱ induces hepatocyte apoptosis via ROS-mediated mitochondrial dysfunction and the p38 MAPK pathway.
Cui J, Yang C, Hao F … +8 more , Lin L, Jiang Z, Li F, Zhang C, Wu X, Chen J, Gao Y, Wang Y
J Ethnopharmacol · 2026 Jun · PMID 42341855 · Publisher ↗
BACKGROUND: Epimedium brevicornu Maxim., a traditional tonic Chinese herbal medicine traditionally regarded as non-toxic, is clinically widely used for the treatment of bone and reproductive system diseases. However, wit...
BACKGROUND: Epimedium brevicornu Maxim., a traditional tonic Chinese herbal medicine traditionally regarded as non-toxic, is clinically widely used for the treatment of bone and reproductive system diseases. However, with the expanded clinical application of its preparations, the number of adverse reactions such as hepatobiliary toxicity has gradually increased, thereby raising concerns about its safety. Currently, the potential toxic components of Epimedium brevicornu Maxim. remain unclear, and there is an urgent need to identify these toxic components and clarify their mechanisms using multi-dimensional models. METHODS: We developed a liver microfluidic organ chip model with a sinusoidal structure using HepaRG spheres and HUVEC. At the same time, using organ chip models and immortalized liver cell lines, we systematically evaluated the five main flavonoids in Epimedium brevicornu Maxim. to screen for potential toxic monomers and explore their mechanisms. RESULTS: First, the established liver microfluidic organ chip exhibited selective permeability and maintained stable hepatic synthetic-secretory functions for 7 days, providing a reliable platform for hepatotoxicity screening. Second, using this validated chip and an immortalized hepatocyte cell line, we identified Icariside Ⅱ as the key hepatotoxic component among five tested flavonoids, with an IC value of 15.67 μM in the cell line model. Icariside Ⅱ induces ROS overproduction, triggers mitochondrial dysfunction, and sequentially activated the intrinsic apoptotic pathway and p38 MAPK signaling, ultimately leading to hepatocyte apoptosis. CONCLUSION: To our knowledge, this study represents one of the first applications of a liver microfluidic organ chip model for screening hepatotoxic components in Epimedium brevicornu Maxim., establishing a novel methodological framework for traditional Chinese medicine safety evaluation. By systematically comparing the screening results with those obtained from traditional immortalized cell line models, we have further validated the reliability of the identified hepatotoxic components. The mechanistic verification of these components' toxic effects, including their impact on cellular redox homeostasis and mitochondrial function, provides a comprehensive understanding of Epimedium brevicornu Maxim. induced hepatotoxicity.
Investigation of the pharmacodynamic material basis and mechanism of Gexia Zhuyu Decoction in the treatment of primary dysmenorrhea with qi stagnation and blood stasis based on Chinmedomics.
Zhang Y, Wang Q, Wang X … +4 more , Yang S, Yu G, Yang D, Wu X
J Ethnopharmacol · 2026 Jun · PMID 42341854 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Gexia Zhuyu Decoction (GXZYD), a classic traditional Chinese medicine prescription, is widely used for the treatment of primary dysmenorrhea with qi stagnation and blood stasis (QBPD). How...
ETHNOPHARMACOLOGICAL RELEVANCE: Gexia Zhuyu Decoction (GXZYD), a classic traditional Chinese medicine prescription, is widely used for the treatment of primary dysmenorrhea with qi stagnation and blood stasis (QBPD). However, its pharmacodynamic material basis remains unclear. AIM OF THE STUDY: This study aimed to assess the therapeutic effects of GXZYD on QBPD, and to elucidate its core pharmacodynamic material basis and targets using the Chinmedomics strategy. MATERIALS AND METHODS: The therapeutic effects of GXZYD were evaluated in a rat model of QBPD established by unpredictable stimuli combined with estrogen and progesterone intervention. Metabolic biomarkers in the QBPD model rats were analyzed using metabonomics, while the blood-absorbed constituents of GXZYD were characterized by serum pharmacochemistry. Correlation analysis, network analysis and molecular docking were performed to screen the key pharmacodynamic substances, metabolic biomarkers, and targets. In addition, the regulatory effects of these components on the identified targets were investigated through in vitro experiments. RESULTS: GXZYD significantly prolonged writhing latency, reduced writhing times, and improved the levels of prostaglandin F2α (PGF), prostaglandin E2 (PGE), thromboxane B2 (TXB), 6-keto-prostaglandin F1α (6-keto-PGF) and calcium signaling pathway-related proteins in QBPD model rats. Metabonomics revealed that 32 metabolic biomarkers were differentially regulated by various doses of GXZYD. Serum pharmacochemical analysis characterized 184 compounds derived from GXZYD that were absorbed into the blood. Correlation analysis pinpointed 15 pharmacodynamic substances associated with both the metabolic biomarkers and pharmacodynamic indicators. Among them, paeoniflorin, hesperidin, neohesperidin, luteolin, and daidzein were identified as the key active components. In vitro experiments demonstrated that these key components exert their therapeutic effects by modulating the protein expression of cytochrome P450 19A1 (CYP19A1), estrogen receptor 1 (ESR1), and matrix metalloproteinase 2 (MMP2) in human endometrial epithelial cells. CONCLUSIONS: This study clarified the pathogenesis of QBPD and the pharmacodynamic basis of GXZYD. The findings indicate that the key pharmacodynamic substances may alleviate QBPD by targeting CYP19A1, ESR1, and MMP2 in endometrial epithelial cells, thereby regulating the release of prostaglandins. These results provide a theoretical foundation for the modern interpretation and clinical application of this classical formula.
Targeting HDAC2 with bruceine D epigenetically restores SMAD3 expression via H4K16ac enrichment to suppress malignant progression in EGFR-TKI-resistant lung adenocarcinoma.
Wang K, Wu Z, Lu B … +7 more , Tao X, Chen P, Lu T, Gao M, Zhang H, Song Y, Ke X
J Ethnopharmacol · 2026 Jun · PMID 42341853 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are a cornerstone therapy for lung adenocarcinoma (LUAD), but their efficacy is often limited by primary or acquired...
ETHNOPHARMACOLOGICAL RELEVANCE: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are a cornerstone therapy for lung adenocarcinoma (LUAD), but their efficacy is often limited by primary or acquired resistance. Natural bioactive compounds such as bruceine D (BD) may offer alternative strategies for patients with EGFR-TKI resistance; however, the mechanism underlying BD's effects in resistant LUAD remains unclear. AIM OF THE STUDY: This study aimed to determine whether BD suppresses malignant phenotypes of primary and acquired EGFR-TKI-resistant LUAD cells and to elucidate the shared molecular mechanisms. MATERIALS AND METHODS: Using H1975 (primary resistant) and PC-9/OR (acquired resistant) cells, cytotoxicity assays determined optimal BD concentration. Antitumor effects were evaluated in vitro via functional assays and in vivo using a xenograft mouse model. Integrative approaches including network pharmacology, Mendelian randomization, molecular docking, and dynamics simulations identified potential targets, with functional rescue experiments. CPTAC, Western blot, mRNA-seq, and CUT&Tag explored epigenetic mechanisms, validated by rescue. RESULTS: BD suppressed proliferation, migration, invasion, and induced intrinsic apoptosis in both resistant cells in vitro and in vivo. HDAC2 was identified as a direct binding target. BD binding to HDAC2 increased H4K16ac enrichment at the SMAD3 promoter, upregulating SMAD3. Rescue experiments confirmed that the HDAC2/H4K16ac/SMAD3 axis mediates the antitumor effects of BD. Clinical samples and database analyses suggested diagnostic, prognostic, and therapeutic potential for H4K16ac, HDAC2, and SMAD3. CONCLUSION: This study reveals for the first time a common mechanism by which the BD/HDAC2/H4K16ac/SMAD3 axis regulates malignant phenotypes in EGFR-TKI-resistant LUAD, offering a novel natural compound-based therapy.
Targeting post-translational modifications by traditional Chinese medicine in cerebral ischemia-reperfusion injury: Recent advances.
Gu Y, Jiang L, Qi C … +4 more , Lei J, Li J, Bai B, Jiang X
J Ethnopharmacol · 2026 Jun · PMID 42341852 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Globally, ischemic stroke is a major contributor to global mortality. Cerebral ischemia-reperfusion injury (CIRI) occurs as a pathophysiological event subsequent to blood flow restoration,...
ETHNOPHARMACOLOGICAL RELEVANCE: Globally, ischemic stroke is a major contributor to global mortality. Cerebral ischemia-reperfusion injury (CIRI) occurs as a pathophysiological event subsequent to blood flow restoration, which accelerates the transmission of pathological signals and exacerbates damage. Current medical interventions still carry certain risks. Traditional Chinese medicine (TCM), characterized by its multi-component and multi-target nature, offers distinctive advantages including multi-constituent profiles, pleiotropic targeting capabilities, and broad-spectrum regulatory characteristics. In clinical practice, TCM enables individualized treatment based on syndrome differentiation and pharmacological regulation, forming a disease management chain encompassing prevention, treatment, and functional rehabilitation, thereby demonstrating significant promise in the treatment of CIRI. AIM OF THE STUDY: This review systematically examines how TCM formulas, active components, and characteristic TCM therapies regulate post-translational modifications (PTMs) to prevent and treat CIRI. The regulatory mechanisms involved include phosphorylation, acetylation, ubiquitination, and lactylation, thereby offering novel perspectives for treatment of CIRI. MATERIALS AND METHODS: Relevant literature was systematically retrieved from databases such as PubMed, Web of Science, CNKI, and Wanfang Database by employing search terms associated with stroke, CIRI, post-translational modifications, phosphorylation, acetylation, ubiquitination, and lactylation. The search covered relevant literature published between 2015 and 2025. The scientific names of medicinal plants were confirmed through the Medicinal Plant Names Services (MPNS, http://mpns.kew.org). RESULTS: By regulating PTMs, including phosphorylation, acetylation, ubiquitination, and lactylation, TCM formulas, individual herbs, and monomeric compounds exert suppressive effects on the development and progression of CIRI. CONCLUSION: PTMs represent key therapeutic targets in the treatment of CIRI. TCM demonstrates efficacy in counteracting CIRI. However, further exploration is needed to investigate the downstream targets of PTMs regulated by TCM and to elucidate the specific regulatory sites of PTMs during the development and progression of CIRI. Additionally, attention should be given to evaluating the potential adverse effects of TCM and closely monitoring individual variations in clinical application. Elucidating the complex regulatory networks and therapeutic targets of PTMs following CIRI remains a high priority.
Corrigendum to "Marsdenia tenacissima extract potentiates the anti-lung cancer efficacy of gefitinib through dual regulation of the Wnt pathway and ferroptosis" [J. Ethnopharmacol. 359 (2026) 121121].
Yang L, Ren A, Wang X … +8 more , Chen S, Ni S, Wang Y, Li X, Liao Q, Li J, Su X, Sun R
J Ethnopharmacol · 2026 Jun · PMID 42336698 · Publisher ↗
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Corrigendum to "Yiqi Huoxue formula promotes post-myocardial infarction angiogenesis by modulating mitochondria-associated membranes (MAMs) and calcium homeostasis via the cGMP/PKG signaling pathway" [J. ethnopharmacol. 2026 (370) 121936].
Hui Du T
J Ethnopharmacol · 2026 Jun · PMID 42336697 · Publisher ↗
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Corrigendum to "Combination of Cornus officinalis Siebold and Moutan officinalis (L.) Lindl. alleviates the metabolic disorders of MAFLD through regulating IRE1α/ASK1/JNK pathway mediated endoplasmic reticulum stress" [J. Ethnopharmacol. 369 (2026) 121890].
Liao W, Li Y, Huang X … +5 more , Shu J, Zhao F, Ma Y, Shan J, Hang A
J Ethnopharmacol · 2026 Jun · PMID 42336696 · Publisher ↗
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Sanguisorba officinalis L. polysaccharides: A review of structural characteristics, pharmacological activities, structure-activity relationships and applications.
Meng W, Caijiao L, Yizhi C … +3 more , Lihong W, Pan H, Xinpeng Y
J Ethnopharmacol · 2026 Jun · PMID 42336119 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Sanguisorba officinalis L. (S. officinalis) is a traditional Chinese medicine used to cool blood and stop bleeding, and its polysaccharides are among the important active components respon...
ETHNOPHARMACOLOGICAL RELEVANCE: Sanguisorba officinalis L. (S. officinalis) is a traditional Chinese medicine used to cool blood and stop bleeding, and its polysaccharides are among the important active components responsible for its efficacy. The anti-inflammatory, wound-healing, hemostatic, and immune-regulatory activities of S. officinalis polysaccharides align precisely with its traditional efficacy in cooling blood, promoting hemostasis, detoxifying, and astringing sores, providing modern scientific support for its medicinal value. AIM OF THE REVIEW: This paper comprehensively reviews the extraction, structural characteristics, pharmacological activities, structure-activity relationships, future application potential, and challenges of S. officinalis polysaccharides. MATERIALS AND METHODS: Key terms including "Sanguisorba officinalis L.", "S. officinalis" and "Sanguisorba officinalis L. polysaccharide" were systematically searched in databases such as PubMed, Web of Science, and Google Scholar (2000-2026) to ensure the comprehensiveness and accuracy of the retrieved literature. RESULTS: S. officinalis polysaccharides are mainly composed of glucose, galacturonic acid, arabinose, and galactose. The glycosidic bond types include →4)-α-Glcp, →4)-GalAp, and highly branched arabinogalactan. Some polysaccharide components have a triple helix conformation, which provides a basis for their pharmacological activities. CONCLUSIONS: This paper systematically reviews the research progress of S. officinalis polysaccharides, summarizing the qualitative correlations between structural characteristics and pharmacological activities. Existing studies are predominantly in vitro, and the structure-activity relationships lack quantitative analysis, while in vivo efficacy and safety data remain insufficient. On this basis, future research should focus on quantitative structure-activity relationships studies, as well as pharmacokinetic and safety evaluations, to facilitate the development and utilization of S. officinalis polysaccharides.
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