J Ethnopharmacol [JOURNAL]
Sun
200 papers
Rexiao Kuining decoction ameliorates ulcerative colitis by restoring immune homeostasis via the protein kinase C alpha-FMS-like tyrosine kinase 3 ligand axis: multi-omics evidence.
Xiao SN, Cai T, Xia JY … +3 more , Zhou L, Cao RX, Cao B
J Ethnopharmacol · 2026 Nov · PMID 42264446 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is marked by epithelial barrier damage and immune dysregulation, and current therapies often fail to achieve both effective inflammation control and durable immune...
ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is marked by epithelial barrier damage and immune dysregulation, and current therapies often fail to achieve both effective inflammation control and durable immune restoration. Rexiao Kuining decoction (RXKND), derived from San Huang Xie Xin decoction recorded in Synopsis of Prescriptions of the Golden Chamber, has been used clinically for UC, but its mechanisms remain unclear. AIM OF THE STUDY: To investigate the therapeutic effects and mechanisms of RXKND in UC using integrative multi-omics and experimental validation. MATERIALS AND METHODS: RXKND constituents were identified by UHPLC-Q-Exactive Orbitrap MS. Network pharmacology, drug-target Mendelian randomization (MR), mediation MR, transcriptome-based machine learning, and single-cell RNA-seq were integrated to prioritize targets and pathways, followed by molecular docking and dynamics simulation. Validation was performed in DSS-induced colitis mice and LPS-stimulated dendritic cells with pathway-targeted pharmacological rescue assays. RESULTS: MR identified six genes significantly associated with UC, including PRKCA. Machine learning further highlighted five key genes (NOS3, FHIT, EDN3, SOCS1, and PRKCA) with strong diagnostic performance (AUC = 0.97 in training and 0.93 in validation). Mediation MR showed that PRKCA affected UC partly through FLT3L. Single-cell RNA-seq revealed increased PRKCA and decreased FLT3L in colonic dendritic cells from patients with UC. In vivo, RXKND alleviated DSS colitis, improved barrier integrity, reduced inflammatory cytokines, downregulated PKCα, upregulated FLT3L, and restored the Th17/Treg balance. Similar effects were observed in dendritic cells in vitro. CONCLUSIONS: RXKND may alleviate UC by suppressing PKCα, relieving its negative regulation of FLT3L, restoring immune homeostasis, and promoting mucosal repair.
Glehnia littoralis and imperatorin attenuate allergic airway inflammation via mast cell stabilization and transcriptome-defined suppression of FcεRI/TLR-MAPK/NF-κB signaling.
Park G, Kang TK, Le TT … +6 more , Jung Y, Lee G, Yoo Y, Kim M, Jung SH, Lee WB
J Ethnopharmacol · 2026 Nov · PMID 42264445 · Publisher ↗
BACKGROUND: Allergic airway inflammation is driven by mast cell activation and IgE-FcεRI signaling. Current pharmacological treatments often present limited efficacy or long-term adverse effects. Glehnia littoralis Fr. S...
BACKGROUND: Allergic airway inflammation is driven by mast cell activation and IgE-FcεRI signaling. Current pharmacological treatments often present limited efficacy or long-term adverse effects. Glehnia littoralis Fr. Schmidt ex Miq. (GL) is a traditional medicinal herb used for respiratory ailments, but its anti-allergic mechanisms remain largely undefined. PURPOSE: We aimed to evaluate the anti-allergic potential of GL and its bioactive compound, imperatorin, specifically investigating their ability to stabilize mast cells and modulate inflammatory signaling. STUDY DESIGN: This study integrated in vitro mast cell assays, an in vivo ovalbumin (OVA)-induced asthma mouse model, transcriptomic profiling (RNA-seq), and validation in human primary immune cells. METHODS: Extract screening was performed using RBL-2H3 cells. BALB/c mice were orally administered GL (50-200 mg/kg) during OVA challenge. Mechanistic assays, including RNA-seq, quantitative PCR, and immunoblotting, were conducted in bone marrow-derived mast cells (BMMCs). Human peripheral blood mononuclear cells (PBMCs) were stimulated with house dust mite (HDM) to assess translational relevance. RESULTS: GL dose-dependently inhibited mast cell degranulation and markedly reduced airway inflammation, mucus hypersecretion, and granulocyte infiltration in asthmatic mice. GL lowered serum OVA-specific IgE and partially restored TGF-β1 levels. Imperatorin was identified as the primary bioactive constituent, suppressing FcεRI- and TLR-mediated NF-κB/AP-1 and IRF signaling while reducing MAPK phosphorylation. Transcriptomics demonstrated that imperatorin reversed 186 antigen-induced genes enriched in FcεRI and inflammatory pathways. Finally, GL and imperatorin attenuated TNF-α and IL-6 production in HDM-stimulated human PBMCs. CONCLUSION: GL and imperatorin exert multi-target anti-allergic effects by stabilizing mast cells and suppressing convergent FcεRI/TLR-MAPK/NF-κB signaling, supporting their development as natural therapeutics for allergic airway diseases.
Treatment strategies and prospects for hepatic fibrosis: Application of traditional Chinese medicine polysaccharides in modulating of the TGF-β1/Smad pathway.
Guo YF, Liu Y, Zhang H … +3 more , Wang MY, Yang D, Liu W
J Ethnopharmacol · 2026 Nov · PMID 42264444 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Hepatic fibrosis (HF) is a common pathological feature of chronic liver disease, which can progress to cirrhosis and hepatocellular carcinoma. Conventional drugs typically target a single...
ETHNOPHARMACOLOGICAL RELEVANCE: Hepatic fibrosis (HF) is a common pathological feature of chronic liver disease, which can progress to cirrhosis and hepatocellular carcinoma. Conventional drugs typically target a single gene or protein, which may limit their efficacy against the complex, multifactorial nature of HF. Transforming growth factor-β1 (TGF-β1) and its downstream Smad signaling pathway play a central role in HF pathogenesis. Traditional Chinese medicine (TCM) polysaccharides, characterized by structural diversity and multi-target actions, have been shown to effectively modulate the TGF-β1/Smad pathway among other targets. Consequently, they offer a distinct advantage over single-molecule drugs and represent a promising therapeutic strategy for targeted intervention in HF. AIM OF THE STUDY: This review synthesizes the latest advances in TCM polysaccharides in the field of HF, focusing on their application in treating HF through targeting the TGF-β1/Smad pathway, and summarizes the intervention strategies of TCM polysaccharides in HF. MATERIALS AND METHODS: Through searches of databases such as PubMed, Web of Science, and ScienceDirect, relevant studies were systematically retrieved. The retrieval time range was from the establishment of the databases to January 2026. The search keywords adopted include "HF", "TCM polysaccharides", "TGF-β1/Smad pathway" and "targeted delivery", as well as their keyword combinations. By comprehensively analyzing the data from dozens of in vivo and in vitro experimental studies published in recent years, the mechanism of action is evaluated. RESULTS: Currently, therapeutic agents for HF mainly focus on regulating lipid metabolism, inflammatory responses and abnormal cell death. The transforming growth factor-β1/Smad pathway represents a key pathogenic mechanism in HF. Smad2 and Smad3 are two major downstream regulatory factors promoting TGF-β1-mediated tissue fibrosis, while Smad7 is a negative feedback regulatory factor of the TGF-β1/Smad pathway, inhibiting TGF-β1-mediated HF. Its specific anti-fibrotic mechanisms are closely associated with suppressing hepatic inflammation, inhibiting hepatic stellate cell (HSC) activation and proliferation, regulating the synthesis and secretion of pro-fibrotic factors, and modulating extracellular matrix (ECM) synthesis and degradation. CONCLUSIONS: This review primarily focuses on the molecular regulatory mechanisms of the TGF-β1/Smad signaling pathway in HF. It also summarizes TCM polysaccharides that target and modulate the TGF-β1/Smad pathway, aiming to provide reference and insights for the treatment of HF.
Ethnopharmacological evaluation of Plumbago zeylanica L. against Russell's viper envenomation: a combined computational and experimental study.
Dodakallanavar J, Harish DR, Watangi RU … +7 more , Chand J, Kundu R, Banerjee R, Desai A, Khatib NA, Hegde H, Roy S
J Ethnopharmacol · 2026 Nov · PMID 42263919 · Publisher ↗
BACKGROUND: Russell's viper envenomation (RVE) continues to result in substantial morbidity and death because of the complex effects of its venom on coagulation, inflammation, and tissue integrity, coupled with the low e...
BACKGROUND: Russell's viper envenomation (RVE) continues to result in substantial morbidity and death because of the complex effects of its venom on coagulation, inflammation, and tissue integrity, coupled with the low efficacy of conventional antivenom against local and enzyme-mediated toxicity. This study aimed to validate the antivenom properties of the Plumbago zeylanica L. hydroalcoholic methanol extract (PZE) through integrated experimental and computational approaches. MATERIALS AND METHODS: PZE was assessed using the extensive in vitro enzymatic activity of snake venom phospholipase A2 (SvPLA), fibrinolysis, hemolysis, protease and hyaluronidase activity. KEGG/Reactome and Gene Ontology (GO) analyses were used to elucidate the mechanisms at the molecular level. The in vivo studies consisted of acute toxicity, LD determination, survival assessment, and anti-myotoxic and anti-inflammatory effects in mice. RESULTS: The PZE exhibited dose-dependent inhibition of venom protease (86.83%), collagenase activity (95.41%), preserved fibrinogen integrity, and inhibited hemolysis. PZE demonstrated a positive safety profile in vivo up to 2000 mg/kg and was protective against 2xLD venom-induced mortality at 100 and 200 mg/kg, significantly extending the time to death. Network analysis identified 11 phytocompounds targeting coagulation and inflammatory pathways in envenomation, with 6-Fucosylluteolin showing strong affinity toward SvPLA and snake venom metalloproteinases (SvMPs). CONCLUSION: Although it alters key enzymatic and host regulatory pathways, PZE acts as a multitarget, system-level intervention against Russell's viper venom, showing potential as a mechanistically validated antivenom adjuvant.
An integrated multitarget screening strategy combining network pharmacology with cell membrane chromatography coupled to high-performance liquid chromatography for identifying candidate antidepressant compounds from Cyperus rotundus L.
Liu M, Wang W, Zhang Y … +9 more , Yong J, Jiang Q, Sun R, Han X, Han S, He L, Yu H, Yin J, Li Z
J Ethnopharmacol · 2026 Nov · PMID 42263918 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Cyperus rotundus L. (CR) is a traditional Chinese medicine (TCM) herb that has been used for centuries to soothe the liver, regulate Qi, and relieve emotional distress, with classical indi...
ETHNOPHARMACOLOGICAL RELEVANCE: Cyperus rotundus L. (CR) is a traditional Chinese medicine (TCM) herb that has been used for centuries to soothe the liver, regulate Qi, and relieve emotional distress, with classical indications for "Yu syndrome" encompassing depressive mood, chest distension, and dysphoria. CR is incorporated into representative TCM formulas targeting depression-related conditions, such as Yueju Pill, substantiating its ethnopharmacological relevance in mood disorder management. However, its complex chemical composition presents considerable challenges for systematic bioactive compound identification, and the specific antidepressant constituents of CR remain poorly characterized, hindering the elucidation of its antidepressant material basis and the development of related therapeutics. AIM OF THE STUDY: This study aims to establish a comprehensive multi-method strategy for the rapid screening of multi-target candidate antidepressant compounds from CR and to conduct a preliminary, in vitro evaluation of their antidepressant-relevant activity. METHODS: Headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS), headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS), and ultra-performance liquid chromatography-quadrupole Orbitrap mass spectrometry (UPLC-Q-Orbitrap-MS) were employed to comprehensively characterize the volatile and non-volatile chemical constituents of CR. On this basis, a multidimensional screening strategy integrating network pharmacology (NP) with a high-performance liquid chromatography-cell membrane chromatography (HPLC-CMC) online platform was developed to systematically identify candidate antidepressant compounds in CR. Molecular docking and surface plasmon resonance (SPR) were subsequently applied to evaluate the binding affinities between the identified candidate antidepressant compounds and their target receptors. Finally, with fluoxetine hydrochloride as a positive control, the neuroprotective effects of these compounds were assessed in a corticosterone-induced PC12 cell injury model. RESULTS: HS-GC-IMS and HS-SPME-GC-MS collectively identified 115 volatile organic compounds (VOCs), with four compounds (1,8-cineole, p-cymene, terpinen-4-ol, and α-pinene) detected by both methods. UPLC-Q-Orbitrap-MS characterized 30 non-volatile organic compounds (NVOCs). A total of seven candidate antidepressant compounds were identified that showed binding affinity for 5-Hydroxytryptamine 1 A Receptor (5-HT), 5-Hydroxytryptamine 2 A Receptor (5-HT), Dopamine D1 Receptor (DRD1), and Dopamine D2 Receptor (DRD2). Molecular docking and SPR analyses confirmed direct binding between these compounds and their target receptors. In a corticosterone-induced PC12 cell injury model, most of these compounds exhibited comparable or greater in vitro neuroprotective potency than fluoxetine hydrochloride under the tested conditions. Furthermore, cyperenone and aristolone are reported here for the first time to possess antidepressant potential. CONCLUSION: This study developed an integrated NP-HPLC-CMC screening strategy combined with HS-GC-IMS, HS-SPME-GC-MS, and UPLC-Q-Orbitrap-MS to identify seven candidate antidepressant compounds from CR targeting 5-HT, 5-HT, DRD1, and DRD2 receptors, with cyperenone and aristolone reported for the first time to possess antidepressant potential. These findings clarify the antidepressant material basis of CR and provide a reproducible framework for GPCR-targeted bioactive compound screening from TCMs, with in vivo validation of antidepressant efficacy identified as the essential next step.
Metabolomics profiling and anti-colitic activity of Rudbeckia hirta aerial parts: Inhibition of NF-κB, cytokine storm, and chemokine-mediated immune cell recruitment.
Elbatanony MM, Baraka SM, Elgohary R … +1 more , El-Abd EAW
J Ethnopharmacol · 2026 Nov · PMID 42263917 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is an inflammatory disorder characterized by oxidative stress and dysregulated immune responses. Rudbeckia hirta has been traditionally utilized in Native American...
ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is an inflammatory disorder characterized by oxidative stress and dysregulated immune responses. Rudbeckia hirta has been traditionally utilized in Native American medicine for the management of inflammatory conditions and digestive ailments. OBJECTIVE: Hence, the present study was established to investigate the protective potentials of Rudbeckia hirta aerial parts methanolic extract (RHME) against colitis in rats, with comprehensive phytochemical analyses. METHODS: RHME was subjected to LC/MS/MS and GC/MS analyses to provide complete phytochemical constituents profile. Colitis was induced in rats via intrarectal administration of 4% acetic acid on day 7. RHME (100 and 200 mg/kg) or sulfasalazine (100 mg/kg) was orally administered for 7 consecutive days. To elucidate the underlying mechanisms of action of RHME, key biomarkers associated with inflammation, particularly the NF-κB and C-X-C motif chemokine signaling pathway, as well as oxidative stress parameters were assessed through performing biochemical, molecular, and immunohistochemical investigations. RESULTS: GC/MS analysis identified 30 compounds in the hexane fraction, with friedelin as the predominant constituent (37.43%), while LC/MS/MS profiling of the defatted fraction tentatively identified 64 compounds, mainly flavonoids, phenolic acid derivatives, and fatty acids. p-Coumaric acid and caffeic acid were additionally isolated by TLC. RHME was reported to be safe up to the dose 2000 mg/kg rat bw, as verified by the acute oral toxicity test. RHME (200 mg/kg) significantly alleviated colonic damage, preserving mucosal architecture and reducing inflammatory infiltration. Biochemically, RHME dose-dependently restored redox balance by decreasing malondialdehyde levels and enhancing reduced glutathione content in the colon. Furthermore, RHME exerted potent anti-inflammatory effects by suppressing NF-κB activation, consequently inhibiting release of pro-inflammatory mediators, including TNF-α, IL-6, IL-17A, and IFN-γ in the colonic tissues. It also downregulated the expression of CXCL10 gene and its receptor CXCR3, indicating reduced immune cell recruitment. CONCLUSION: RHME exhibits a multi-target protective effect against colitis through modulation of NF-κB and CXCL10/CXCR3 inflammatory pathways, alongside maintaining redox hemostatic balance. These effects are likely attributed to the synergistic action of bioactive constituents. Hence, RHME could offer a promising natural therapeutic candidate for UC.
Neuroprotective effects of aqueous extract of Pterocarpus mildbraedii Harms. on some biochemical markers in Alzheimer's disease using an AlCl-induced rat model: Integrated ADMET, network pharmacology, molecular docking, and in vivo experimental validation.
Mengue Ngadena YS, Njoupoue MB, Zemo Gamo F … +7 more , Owona PE, Bidingha A Goufani R, Bouguem Yandja PC, Akingbolabo Ogunlakin D, Bilanda DC, Chtita S, Dzeufiet Djomeni PD
J Ethnopharmacol · 2026 Nov · PMID 42263916 · Publisher ↗
ETHNOPHARMACOLOGY RELEVANCE: Neurodegenerative diseases such as Alzheimer's often lack effective conventional treatments. Phytotherapy is emerging as a promising approach to managing these conditions. Pterocarpus mildbra...
ETHNOPHARMACOLOGY RELEVANCE: Neurodegenerative diseases such as Alzheimer's often lack effective conventional treatments. Phytotherapy is emerging as a promising approach to managing these conditions. Pterocarpus mildbraedii Harms. (P. mildbraedii), a plant from the Fabaceae family, which is traditionally used to treat convulsions, headaches, and fever. This study is designed to evaluate the neuroprotective effects of the aqueous extract of Pterocarpus mildbraedii Harms. on biochemical markers of Alzheimer's disease in an AlCl-induced rat model using integrated ADMET, network pharmacology, molecular docking, and in vivo validation. METHODS: We employed network pharmacology and in silico molecular docking to identify bioactive compounds and assess their binding affinities to key proteins: VCP, MAPK1, MMP9, PTGS1, IL6, and AR. The in vivo experiment lasted 56 days, with 30 animals divided into 5 groups (n = 6 per group). They received daily oral doses of distilled water (10 mL/kg), AlCl (75 mg/kg), Donepezil (5 mg/kg) after AlCl, or P. mildbraedii bark water extract at 150 mg/kg (PM 150) and 300 mg/kg (PM 300) following AlCl. On Days 23 and 51, all animals underwent open-field and Morris water maze tests. On Day 57, animals were sacrificed, and calcium levels, oxidative markers, and neurotransmitter levels were measured in homogenates from the amygdala, hippocampus, and prefrontal cortex. Histopathological analysis of the hippocampus and amygdala was also conducted. RESULTS: In silico studies showed that the plant compounds pterocarpan and liquiritigenin bound strongly to VCP, MAPK1, and MMP9, with binding energies lower than those of reference inhibitors, indicating greater stability. In vivo, AlCl caused anxiety, locomotor issues (p < 0. 001), memory impairment (p < 0. 001), and disrupted GABA, ACh metabolism, and AChE activity. It also reduced antioxidant levels (p < 0.001), increased pro-oxidants (p < 0.001), and elevated calcium and Tau protein levels compared to the normal control. Treatment with Pterocarpus mildbraedii extract mitigated these effects, reducing anxiety and enhancing memory, locomotion, ACh, and GABA levels, as well as AChE activity. The extract notably decreased Tau protein and MDA concentrations by 80. 57% in the amygdala, 63. 80.57% in the prefrontal cortex, and 63.73. 50% in the hippocampus, and nitrites. It also significantly increased protein levels, GSH (by 6.95-fold in the amygdala, 80.48% in the prefrontal cortex, and 85.75% in the hippocampus), SOD, and catalase activities across brain regions compared with the AlCl-treated group. CONCLUSION: These findings suggest that Pterocarpus mildbraedii extract, with its antioxidant, anti-amnesic, and anxiolytic properties, offers neuroprotection and may have neuroprotective effects in Alzheimer 's-like neurotoxicity.
Corrigendum to "Diterpenoids of Caryopteris trichosphaera W. W. Sm. inhibiting MRSA and VRE in vitro and in vivo" [J. Ethnopharmacol. 337 (2025) 118805].
Lu QY, Wang ZJ, Bai LY … +5 more , Zu WB, Zhou ZS, Zhu YY, Zhao YL, Luo XD
J Ethnopharmacol · 2026 Jun · PMID 42259715 · Publisher ↗
Abstract loading — click title to view on PubMed.
Sini decoction inhibits colorectal cancer liver metastasis by suppressing HIF-1α-dependent exosomal integrin signaling.
Zheng X, Wang W, Zhu J … +9 more , Yang L, Du Y, Zhou H, Jiang Y, Yu Z, Tang Z, Hu D, Chai K, Chen J
J Ethnopharmacol · 2026 Nov · PMID 42259422 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Sini Decoction (SND), composed of Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, and Glycyrrhizae Radix et Rhizoma, is traditionally used to restore "Yang" and modulate immunity....
ETHNOPHARMACOLOGICAL RELEVANCE: Sini Decoction (SND), composed of Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, and Glycyrrhizae Radix et Rhizoma, is traditionally used to restore "Yang" and modulate immunity. Clinically, SND is applied as adjuvant therapy in colorectal cancer, yet its anti-metastatic mechanisms remain unclear. AIM OF THE STUDY: To clarify the bioactive constituents and mechanisms through which SND inhibits colorectal cancer liver metastasis, focusing on tumor-derived exosomes and macrophage polarization. MATERIALS AND METHODS: A murine colorectal liver metastasis model was established using luciferase-labeled mouse CT26 cell and treated with SND. Tumor burden, histology, immunohistochemistry, spectral flow cytometry, ELISA, Western blotting, immunofluorescence, and single-cell RNA sequencing were used to evaluate immune remodeling and exosomal signaling. SND-medicated serum, exosome inhibition (GW4869), and integrin αv/β5 knockdown were applied in macrophage co-culture assays. Network pharmacology, molecular docking, and CETSA identified upstream regulators. RESULTS: SND significantly reduced liver metastases, improved hepatic pathology, and decreased Ki-67 expression. SND reshaped the immune microenvironment by lowering CD206 M2 macrophages. SND suppressed tumor-derived exosome secretion and weakened exosomal ITGαvβ5-driven M2 polarization. Single-cell analysis confirmed integrin-related activation in macrophages. Network pharmacology and experiments identified HIF-1α as a key regulator of exosomal integrin loading. Aconitine directly bound and reduced HIF-1α, limiting Rab-dependent exosome biogenesis. CONCLUSION: SND inhibits colorectal cancer liver metastasis by targeting HIF-1α to suppress ITGαvβ5-enriched exosome secretion and block M2 macrophage polarization, supporting its ethnopharmacological utility against metastatic disease.
Corrigendum to "Acute and subchronic toxicity studies of polysaccharide components from Trametes robiniophila Murr (Huaier) in Sprague-Dawley rats" [J. Ethnopharmacol. 369 (2026) 121877].
Shi M, Lu Q, Gao Y … +4 more , Wu D, Zhao T, Zhao Y, Teng H
J Ethnopharmacol · 2026 Jun · PMID 42252245 · Publisher ↗
Abstract loading — click title to view on PubMed.
Screening the anti-hypoxic active components of Zanthoxylum bungeanum Maxim. seeds based on spectrum-effect relationship analysis.
Liang Z, Liu F, Wang C … +4 more , Li G, Yang A, Wang W, Yang J
J Ethnopharmacol · 2026 Nov · PMID 42252037 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum bungeanum Maxim. seeds (ZBS), as an important edible and medicinal resource, possess the efficacy of promoting diuresis, alleviating edema, and relieving dyspnea. It has been r...
ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum bungeanum Maxim. seeds (ZBS), as an important edible and medicinal resource, possess the efficacy of promoting diuresis, alleviating edema, and relieving dyspnea. It has been reported that these seeds contain unsaturated fatty acids, proteins, and alkaloids, and exhibit diverse pharmacological activities, including antiinflammatory, antioxidant and antibacterial activities. AIM OF THE STUDY: his study aimed to screen for the components responsible for the anti-hypoxic activity of ZBS using spectrum-effect relationship analysis. METHODS: GC-MS fingerprints of ZBS from 24 different origins were first established, and the common peaks were also identified. Anti-hypoxic activity was assessed using a cell injury model, in which PC12 cells were treated with 600 μM CoCl·6HO to establish a hypoxic condition. Then, the spectrum-effect relationship (SER) between the ZBS fingerprints and anti-hypoxic activity was investigated using Pearson correlation analysis, grey relation analysis (GRA), and orthogonal partial least squares (OPLS) analysis. Finally, potential anti-hypoxic components were screened via SER analysis and further validated using an in vitro assay. RESULTS: In the GC-MS fingerprint, 18 common peaks were identified from ZBS extracts collected from 24 different origins. Similarity evaluation was performed using hierarchical cluster analysis (HCA) and principal component analysis (PCA), with consistent classification results, the P7 (palmitic acid) and P13 (oleic acid) exhibited higher abundances among the common peaks. Cell experiments indicated that cell viability significantly improved after treatment with different concentrations of ZBS extract. Following the spectrum-effect relationship analysis, GRA results showed that P7, P13, and P14 had the highest correlation with anti-hypoxic activity, with correlation coefficients of 0.964, 0.974, and 0.965, respectively; Pearson correlation analysis revealed that P1, P7, P13 and P14 were significantly positively correlated with anti-hypoxic activity; OPLS results, based on variable importance in projection (VIP) values > 1, demonstrated that P6, P7, P12, and P13 were the key variables in anti-hypoxic activity. Integrating the results from the three analytical approaches, P7 and P13 exhibited a strong contribution to the anti-hypoxic activity of the seeds. Furthermore, the anti-hypoxic activity of both compounds was confirmed through in vitro assays and morphological observations. CONCLUSION: This study established the SER between the liposoluble components of ZBS and its anti-hypoxic activity using GC-MS fingerprinting combined with multivariate statistical methods. The key anti-hypoxic constituents were identified as oleic acid and palmitic acid. These findings provide a scientific basis for the development of ZBS-based anti-hypoxic functional foods and pharmaceuticals.
Mechanistic evaluation of Curcumae rhizoma-Atractylodis macrocephalae rhizoma herb pair enhancing anti-chronic hepatic injury through PI3K/AKT/mTOR signaling pathway.
Mao J, Li Y, Yang M … +9 more , Li M, Guo Q, Dong W, Zhu W, Zeng L, Jiang W, Yao C, Mao C, Lu T
J Ethnopharmacol · 2026 Nov · PMID 42252036 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Chronic hepatic injury is a liver disease that poses a threat to human health with increasing morbidity. Chinese herb pairs are the fundamental and concise form of traditional Chinese medi...
ETHNOPHARMACOLOGICAL RELEVANCE: Chronic hepatic injury is a liver disease that poses a threat to human health with increasing morbidity. Chinese herb pairs are the fundamental and concise form of traditional Chinese medicine (TCM) prescriptions, which can effectively explain their underlying concepts. Curcumae rhizoma (Ezhu) and Atractylodis macrocephalae rhizoma (Baizhu) herb-pair (PW) have been frequently used in TCM prescriptions for hundreds of years, which derived from the renowned traditional Chinese medical classic "Yixue Zhongzhong Canxi Lu", primarily to treat liver-related conditions such as hypochondriac pain, abdominal mass, amassment and accumulation that are closely associated with liver diseases including hepatic injury and hepatic fibrosis in modern medicine. As a classic drug pair of invigorating Qi and promoting blood circulation, they align with the TCM syndrome characteristics of chronic hepatic injury with qi deficiency and blood stasis. However, the specific mechanism of the therapeutic effects of PW against chronic hepatic injury remains unclear. AIM OF THE STUDY: The study aimed to assess the enhanced efficacy, underlying targets, and the potential mechanism of PW in treating chronic hepatic injury. MATERIALS AND METHODS: UPLC-MS/MS analysis was performed to identify the active components of PW. Subsequently, the therapeutic efficacy as well as latent action mechanisms of PW upon chronic hepatic injury were examined in vivo study in rats with chronic hepatic injury and in vitro in LX-2 cells. A network pharmacology method was used to prognosticate the mechanisms by which PW treats chronic hepatic injury. Integrated application of pharmacokinetic analysis and metabolomics approaches was employed to identify and characterize critical active ingredients and regulatory signaling pathways. Western blot assays and molecular docking were conducted to reveal the primary mechanisms of action. RESULTS: Totally 1059 metabolites were identified, including 662 detected in positive ion mode and additional 397 detected in negative ion mode. Network pharmacology suggested that the protective effect against chronic hepatic injury of PW may be closely relevant to PI3K/AKT/mTOR signaling pathway. Pharmacodynamics assessment indicated that PW effectively inhibited chronic HI progression in vivo compared with the two herbs alone. PW significantly improved lipid deposition, hepatic function, inflammation and histopathological injury. Additionally, PW significantly decreased the serum AST, ALT and ALP activity levels and effectively reduced the expression level of α-SMA in the liver, significantly inhibited the phosphorylation level of the PI3K/AKT/mTOR pathway. The results of pharmacokinetics and tissue distribution studies showed that PW may increase the concentration of potential bioactive compounds like Curcumol, Curdione, Germacrone, Furanodiene, Atractylenolide III and Atractylon, thereby enhancing the effect of anti-chronic hepatic injury. Combined metabolomics and WB analysis of rat liver tissue revealed that the enhanced anti-chronic hepatic injury effect of PW may be associated with PI3K/AKT/mTOR signaling pathway. Experiments on LX-2 cells indicated that the combination of Curdione and Atractylolide III exerted a hepatoprotective effect by reducing the phosphorylation levels of proteins in the PI3K/AKT/mTOR pathway. CONCLUSION: PW significantly increases the plasma exposure of potential active compounds and the liver distribution level. It emerges as a potential therapeutic strategy for chronic HI, thereby exerting an enhanced anti-chronic hepatic injury effect accompanying fibrotic lesions through the modulation of PI3K/AKT/mTOR signaling pathway.
Huo-Xue-Xiao-Zhong Decoction prevents thrombus formation of deep vein thrombosis by targeting SOAT2 to modulate the AKT and ERK pathways.
Li J, Yang L, Wang R … +6 more , Liu Y, Ye G, Wen L, Long W, Li F, Song E
J Ethnopharmacol · 2026 Nov · PMID 42252035 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Huo-Xue-Xiao-Zhong Decoction (HXXZ), a traditional Chinese medicine formulation comprising 14 herbal components, has demonstrated significant efficacy and favorable safety profiles in clin...
ETHNOPHARMACOLOGICAL RELEVANCE: Huo-Xue-Xiao-Zhong Decoction (HXXZ), a traditional Chinese medicine formulation comprising 14 herbal components, has demonstrated significant efficacy and favorable safety profiles in clinical trials for the prevention of deep vein thrombosis (DVT). However, the underlying molecular mechanisms responsible for its therapeutic effects remain to be elucidated. AIM OF THE STUDY: This study aims to investigate the molecular mechanisms through which HXXZ prevents thrombus formation in DVT. MATERIALS AND METHODS: The chemical profile of HXXZ was characterized using HPLC-Q-TOF-MS. Therapeutic efficacy was evaluated in a mouse model of DVT (n = 8 per group) and in a TNF-α-induced human umbilical vein endothelial cell (HUVEC) injury model. A multi-faceted approach integrating network pharmacology, molecular docking, and transcriptomic analysis was employed to identify potential targets of HXXZ. Following gain- and loss-of-function experiments, levels of inflammation-related, coagulation-related, and endothelial injury markers were assessed using ELISA, Western blotting, and immunofluorescence staining. RESULTS: HPLC-Q-TOF-MS analysis identified 38 major constituents in HXXZ. In vivo, treatment with moderate to high doses of HXXZ significantly reduced thrombus length and mass, while modulating levels of IL-1β, IL-6, NO, vWF, P-Selectin, FXI, FVIII, TM, PC, eNOS, EPCR, and ICAM-1 in plasma and thrombus tissue. In vitro, HXXZ attenuated TNF-α-induced apoptosis and endothelial dysfunction, and reduced total cholesterol, cholesteryl ester, and free cholesterol levels in HUVECs. Network pharmacology revealed 181 active compounds and 53 DVT-related targets, with enrichment in the PI3K-AKT and MAPK pathways. Molecular docking confirmed favorable binding potential interactions between HXXZ constituents and AKT1, ERK2, KLF11, and KLF15. Transcriptomic analysis identified CD14, SOAT2, and MCL1 as key genes modulated by HXXZ. Functional studies demonstrated that SOAT2 knockdown enhanced the protective effects of HXXZ on HUVECs, whereas SOAT2 overexpression produced opposing effects. CONCLUSIONS: HXXZ prevents thrombus formation in DVT through a multi-component, centered on the downregulation of SOAT2 and consequent suppression of the AKT-ERK pathway, revealing a previously unrecognized pharmacological target for DVT management.
Steamed Panax notoginseng saponins ameliorate cyclophosphamide-induced anemia by promoting erythroid progenitor proliferation via the cAMP/PI3K/AKT/cGMP pathway.
Xu C, Cui H, Fang Q … +3 more , Wang H, Tu P, Cui X
J Ethnopharmacol · 2026 Nov · PMID 42250832 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Steamed Panax notoginseng has long been used in traditional medicine to enrich the blood, and its principal constituents are saponins. This traditional blood-enriching property suggests it...
ETHNOPHARMACOLOGICAL RELEVANCE: Steamed Panax notoginseng has long been used in traditional medicine to enrich the blood, and its principal constituents are saponins. This traditional blood-enriching property suggests its potential value in treating chemotherapy-induced anemia. AIM OF THE STUDY: To elucidate the underlying mechanism and identify the key active components through which steamed Panax notoginseng saponins (SPNS) ameliorate cyclophosphamide-induced anemia. MATERIALS AND METHODS: A model of anemia was established by intraperitoneal injection of cyclophosphamide combined with acetylphenylhydrazine. Cell proliferation was evaluated by examining peripheral blood and HE-stained bone marrow sections. Our multiomics analysis revealed hematopoiesis-related pathways, and surface plasmon resonance (SPR) confirmed saponin binding to target proteins. The proliferative effect of individual saponins on erythrocytes was validated in zebrafish with fluorescently-labeled red blood cells. Cellular damage was assessed by flow cytometry and electron microscopy. The expression of hemoglobin-related genes and signaling pathway proteins was detected by real-time PCR and Western blotting, respectively. RESULTS: The cAMP and PI3K/AKT signaling pathways were significantly enriched in the SPNS group. The ginsenosides Rk and Rh were bound strongly to G protein-coupled receptors (GPCRs) and guanylate cyclase (GC), while F was bound to integrin α5 (ITGA5). All three ginsenosides enhanced erythrocyte proliferation in zebrafish. SPNS also repaired cyclophosphamide (CTX)-induced damage in K-562 cells, promoted the expression of hemoglobin-related genes, and increased the phosphorylation of key proliferative pathway proteins. CONCLUSIONS: SPNS mitigates cyclophosphamide-induced anemia by activating the cAMP/PI3K/AKT/cGMP pathway, an effect that is likely mediated by its active components Rk, Rh, and F, thereby promoting erythropoiesis, inhibiting apoptosis, and restoring hematopoietic function. This study provides valuable insights into clinical applications of the active ingredients of SPNS.
Isomucronulatol 7-O-glucoside attenuates post-AMI monocyte/macrophage cardiac recruitment via HIF-1α/THBS1-mediated immunometabolic adhesion.
Sun X, Wang H, Wan Y … +13 more , Gu Y, Yang M, Chen T, Yi S, Qian Y, Yang Z, Zhang M, Ouyang Y, Weng H, Du Z, Wang W, Li C, Gao S
J Ethnopharmacol · 2026 Nov · PMID 42250831 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix (Huangqi) is widely used in the clinical management of ischemic heart disease and heart failure, where it improves patient outcomes and quality of life. Isomucronulatol-7-O...
ETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix (Huangqi) is widely used in the clinical management of ischemic heart disease and heart failure, where it improves patient outcomes and quality of life. Isomucronulatol-7-O-glucoside (IM-7G) is a key bioactive flavonoid derived from Huangqi, but its precise pharmacological mechanisms remain incompletely understood. OBJECTIVE: This study aimed to elucidate the mechanisms underlying early cardiac recruitment and adhesion of monocyte/macrophage (Mo/Mφ) subsets following acute myocardial infarction (AMI), and to identify the molecular targets and therapeutic effects of early IM-7G intervention. METHODS: Single-cell RNA sequencing was performed on cardiac arterial blood from ST-segment elevation myocardial infarction (STEMI) patients and cardiac immune cells from AMI mice to delineate Mo/Mφ transcriptional states. Putative downstream targets of Hif1a were predicted using an in silico "virtual knockout" approach and validated in myeloid-specific Hif1a conditional knockout (cKO) mice. Echocardiography, flow cytometry, and surface plasmon resonance analyses were conducted to evaluate the therapeutic efficacy and underlying mechanisms of IM-7G in AMI model of mice. RESULTS: AMI induced profound immune remodeling characterized by myeloid immigration, enhanced glycolysis, and upregulation of Hif1a expression in Mo/Mφ populations. In cardiac macrophages, Hif1a-mediated glycolysis was further elevated, and Thbs1 was identified as a key downstream effector. Myeloid-specific Hif1a deletion significantly improved cardiac function and reduced Ly6CF4/80THBS1 Mo/Mφ infiltration into the myocardium, indicating that HIF-1α promotes immune cell adhesion and cardiac recruitment via THBS1. Moreover, IM-7G treatment markedly improved cardiac function, suppressed inflammatory cytokines, and reduced HIF-1αTHBS1 Mo/Mφ infiltration. Mechanistically, IM-7G directly bound HIF-1α, inhibiting activation of the HIF-1α/THBS1 axis. These effects were absent in Hif1a cKO mice, confirming that the pharmacological action of IM-7G is HIF-1α-dependent. CONCLUSION: HIF-1α-mediated glycolytic reprogramming regulates Mo/Mφ migration and adhesion via THBS1, establishing a potential "immunometabolic-adhesion" axis in AMI pathology. Targeted intervention with IM-7G effectively attenuates inflammation and improves cardiac function, providing a promising therapeutic strategy for AMI.
Revealing the enhancing mechanism and material basis of bile-processed Coptidis Rhizoma in anti-anxiety from perspective of cross organ regulation.
Chen L, Yuan S, Wang R … +8 more , Chen L, Zhang B, Zhang Z, Zhao Y, Feng W, Zheng X, Li K, Zhou N
J Ethnopharmacol · 2026 Nov · PMID 42250830 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Coptidis Rhizoma (CR) is a typical cold-attribute herb with potential anti-anxiety properties. Bile is of cold nature and can also interfere with the central nervous system. Bile-processed...
ETHNOPHARMACOLOGICAL RELEVANCE: Coptidis Rhizoma (CR) is a typical cold-attribute herb with potential anti-anxiety properties. Bile is of cold nature and can also interfere with the central nervous system. Bile-processed CR (BCR) exhibits synergistically enhanced anti-anxiety performance. However, the underlying mechanism and material basis for this synergism are not clear. AIM OF THE STUDY: To decipher the enhanced anti-anxiety mechanism and material basis of BCR from the perspective of cross-organ regulation. METHODS: A rat model of anxiety with sthenic heat syndrome was established to systematically evaluate the enhanced anti-anxiety efficacy of BCR in terms of anxiety behaviour, liver metabolism, and histopathology. Subsequently, the gut microbiome sequencing and untargeted metabolomics of the brain, liver, and serum were performed to explore the mechanism of BCR and CR in regulating the gut-liver-brain axis. In vivo and in vitro molecular biology experiments were performed to further clarify the mechanisms underlying the differential efficacy of BCR and CR. Finally, supramolecular self-assembly simulation and tissue distribution in target organs were carried out to predict the material basis for the enhanced efficacy of BCR. RESULTS: BCR performed better than CR in improving the anxiety behaviour and liver metabolism and in alleviating cerebral injury in the rat model of anxiety. The results of gut microbiome and metabolomic analyses indicated that BCR was superior to CR in reshaping the gut microbiota composition and correcting the metabolic disorders in the brain, liver, and serum. Mechanistically, multiomic analysis revealed that BCR and CR (especially BCR) could block the TLR4/NF-κB pathway in the colon, attenuate hepatic inflammation, improve the integrity of the intestinal mucosa and blood-brain barrier, and inhibit the NLRP3/Caspase-1/IL-1β pathway in the brain, thereby blocking the transmission of inflammation along the gut-liver-brain axis and exerting anti-anxiety effects. BCR and CR (particularly BCR) could suppress the overactivation of ammonia-induced MAPK/NF-κB/iNOS pathway and overexpression of glutamine synthetase in the brain, consequently maintaining the normal morphology and glutamate uptake function (GLAST and GLT-1 activities) of astrocytes, alleviating neuronal apoptosis caused by glutamate excitotoxicity (GluN2B), and ultimately blocking the transmission of neurotoxicity along the gut-liver-brain axis to relieve anxiety. The alkaloid-bile acid supramolecules assembled during the decoction of BCR enabled more alkaloids and bile acids to be distributed in the brain and liver, providing material support for the enhanced effect of BCR. CONCLUSIONS: BCR was superior to CR in blocking the transmission of inflammation and neurotoxic substances along the gut-liver-brain axis and, hence, exerted stronger efficacy in alleviating neuroinflammation and improving neuronal survival in the rat model of anxiety. The alkaloid-bile acid supramolecules may provide the material foundation. This study fully considers the characteristic of traditional Chinese medicine being able to exert therapeutic effects through multiple pathways, providing novel avenues for research on the processing mechanism.
Aurantio-obtusin ameliorates prediabetes in a gut microbiota-dependent manner via regulating LPS-TLR4 axis and Akt/GLUT4 signaling.
Chen X, Li M, Xia M … +4 more , Yang Y, Liu R, Ma L, Luo M
J Ethnopharmacol · 2026 Nov · PMID 42248376 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Cassiae Semen, the dried seeds of Cassia obtusifolia L., has traditionally been used in East Asian medicine to manage metabolic disorders, including hyperglycemia and dyslipidemia. Auranti...
ETHNOPHARMACOLOGICAL RELEVANCE: Cassiae Semen, the dried seeds of Cassia obtusifolia L., has traditionally been used in East Asian medicine to manage metabolic disorders, including hyperglycemia and dyslipidemia. Aurantio-obtusin (AO), a bioactive anthraquinone compound, exhibits diverse pharmacological activities, derived from Cassiae Semen, a traditional herb used for metabolic disorders; however, its protective efficacy against prediabetes remains poorly understood. AIM OF THE STUDY: This study aimed to investigate the effects of AO on prediabetes and to elucidate the underlying mechanisms, with particular emphasis on gut microbiota-mediated regulation of metabolic homeostasis. MATERIALS AND METHODS: Mice were subjected to prediabetes by a combination of a high-fat diet and streptozotocin. Metabolic parameters, liver function, oxidative stress, inflammatory responses, insulin signaling, and gut microbiota composition were assessed. Fecal microbiota transfer and models simulating antibiotic-induced germ-free conditions were utilized to investigate the function of gut microbiota. RESULTS: AO exhibited a marked improvement in glucose tolerance, lipid profiles, and insulin sensitivity among prediabetic mice. Furthermore, AO demonstrated a protective effect against liver damage, as suggested by the notable reductions in serum levels of alanine aminotransferase and aspartate aminotransferase. Oxidative stress was markedly suppressed, as indicated by decreased malondialdehyde levels, along with enhanced antioxidant defenses, including superoxide dismutase, catalase, and reduced glutathione. Additionally, AO preserved intestinal barrier integrity, reduced endotoxemia, and suppressed Toll-like receptor 4-mediated inflammatory signaling, accompanied by restoration of the PI3K/Akt/GLUT4 pathway. Notably, depletion of gut microbiota completely abolished the metabolic benefits of AO. CONCLUSION: Collectively, this study substantiates the ethnomedical value of Cassiae Semen, demonstrating that AO improves prediabetes through the regulation of intestinal barrier function, oxidative stress, inflammation, and insulin signaling, which is dependent on gut microbiota.
Yiqi Huoxue formula promotes post-myocardial infarction angiogenesis by modulating mitochondria-associated membranes (MAMs) and calcium homeostasis via the cGMP/PKG signaling pathway.
Du T, Zhang Y, Wang H … +5 more , Xie W, Liang C, Guo J, Zheng C, Guo S
J Ethnopharmacol · 2026 Nov · PMID 42248375 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Therapeutic angiogenesis represents a promising strategy for recovery following myocardial infarction (MI). Yiqi Huoxue Formula (YQHX), a well-known traditional Chinese medicinal prescript...
ETHNOPHARMACOLOGICAL RELEVANCE: Therapeutic angiogenesis represents a promising strategy for recovery following myocardial infarction (MI). Yiqi Huoxue Formula (YQHX), a well-known traditional Chinese medicinal prescription, is widely utilized in clinical practice to treat myocardial ischemia and enhance cardiac performance in patients with MI. This study aims to elucidate the regulatory role of YQHX on mitochondria-associated membranes (MAMs) via the cGMP/PKG signaling pathway in promoting post-MI angiogenesis and restoring cardiac function. MATERIALS AND METHODS: An in vivo MI model was established via left anterior descending (LAD) coronary artery ligation in rats, and an in vitro model was developed using hypoxia-induced injury in human umbilical vein endothelial cells (HUVECs). The effects of YQHX on cardiac function and HUVEC behaviors (proliferation, migration, and tube formation) were evaluated. Myocardial histopathology and endothelial damage were assessed using HE/Masson staining and biochemical assays. Angiogenesis in the infarct border zone was visualized by platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) immunofluorescence. Ultrastructural changes in MAMs, the endoplasmic reticulum (ER), and mitochondria were observed via transmission electron microscopy (TEM). Intracellular reactive oxygen species (ROS) and calcium (Ca ) levels were detected using fluorescent probes. Transcriptomic sequencing was performed to identify key therapeutic pathways, followed by validation of the cGMP/PKG axis and MAMs-associated proteins (including cGMP, PKG, IP3R2, GRP75, FUNDC1, VDAC1, CYPD, and MCU) using ELISA, Western blotting, and immunofluorescence. RESULTS: Echocardiography and biochemical analysis demonstrated that high-dose YQHX demonstrated comparable efficacy to the first-line clinical drug Perindopril in preserving cardiac function and mitigating myocardial injury. Immunofluorescence revealed that while the infarct border zone in the MI group exhibited disordered and dysfunctional capillary proliferation, YQHX treatment promoted the formation of organized and functional microvessels. TEM revealed significant disruption of MAMs ultrastructure post-MI. Furthermore, the colocalization of IP3R2 and VDAC1 was markedly reduced in MI tissues and hypoxic HUVECs, an effect that was reversed by YQHX. Transcriptomic analysis identified the cGMP/PKG pathway as a pivotal mechanism. Activation of this pathway by YQHX restored MAMs structural integrity and rescued impaired cytosolic Ca signaling, as confirmed by TEM, Western blotting, triple-labeling immunofluorescence, and calcium assays. Consequently, YQHX-mediated MAMs repair enhanced HUVEC proliferation, migration, and angiogenic capacity. CONCLUSION: This study demonstrates that MI/hypoxia impairs endothelial function by disrupting the structural and functional integrity of MAMs. YQHX effectively preserves MAMs architecture and restores intracellular Ca signaling via the cGMP/PKG signaling axis, thereby promoting post-MI angiogenesis and improving cardiac performance. These findings identify a novel therapeutic target for MI and highlight the unique advantages of traditional Chinese medicine formulas in modulating subcellular organelle interactions. However, given the inherent variability of botanical materials, these mechanistic findings are based on a single validated batch, and future multi-batch standardizations are warranted.
Huangqi Jianzhong decoction inhibits CRC invasion through the modulation of BCLAF1-mediated glycolysis.
Liu X, Cui Y, Liu H … +3 more , Zhang R, Zhang Y, Song H
J Ethnopharmacol · 2026 Nov · PMID 42248374 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Jianzhong decoction (HQJZ) is a well-known traditional Chinese medicine used to treat gastrointestinal diseases because of its beneficial effects on Qi and the spleen. Its potentia...
ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Jianzhong decoction (HQJZ) is a well-known traditional Chinese medicine used to treat gastrointestinal diseases because of its beneficial effects on Qi and the spleen. Its potential effect on gastric cancer has also been well demonstrated, but its multitarget mechanisms in the treatment of CRC remain unclear, limiting its scientific development. AIM OF THE STUDY: This study aimed to clarify the role and specific mechanism of HQJZ in combating CRC and identify the key proteins it modulates and the specific mechanism involved. MATERIALS AND METHODS: We performed cellular function experiments to validate the effects of HQJZ on CRC cell activity, apoptosis, proliferation, migration and invasion. Network pharmacology was combined with differential proteomics to identify key modulated proteins. Western blot, immunofluorescence and lactic acid assays were used to clarify the specific mechanism involved. RESULTS: The suppressive effects of HQJZ on the proliferation, migration and invasion of CRC cells were verified. By combining network pharmacology and differential proteomics, we identified BCL2-associated transcription factor 1 (BCLAF1) as one of the key proteins involved in the inhibition of the CRC malignant phenotype by HQJZ. Mechanistic studies revealed that HQJZ associating with BCLAF1 to inhibit glycolytic metabolism and lactic acid production in CRC cells and increase programmed cell death ligand 1 (PD-L1) expression on CRC cell membranes. CONCLUSIONS: We reveal that HQJZ inhibits CRC malignancy. Modulating and inhibiting BCLAF1-mediated glycolysis to increase PD-L1 expression on CRC cell membranes may affect the sensitivity of CRC cells to immunotherapy, but further study is needed. Our study provides new insights into the treatment of CRC by HQJZ.
Comparative study on the efficacy and underlying mechanisms of Lonicerae Japonicae Flos and Lonicerae Flos in Shuanghuanglian formula against acute lung injury.
Yuan Q, Chen F, Xiao Q … +7 more , Zhang Z, Liu C, Xia J, He W, Pan X, He F, Xiao M
J Ethnopharmacol · 2026 Nov · PMID 42242602 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: ALI and its severe form, ARDS, are characterized by high mortality and a lack of effective treatments. The classic heat-clearing and detoxifying TCM formula, Shuanghuanglian, is a potentia...
ETHNOPHARMACOLOGICAL RELEVANCE: ALI and its severe form, ARDS, are characterized by high mortality and a lack of effective treatments. The classic heat-clearing and detoxifying TCM formula, Shuanghuanglian, is a potential intervention. However, its principal herb Lonicerae Japonicae Flos is often substituted with Lonicerae Flos, and the differences in their chemical profiles and the pharmacological effects of Shuanghuanglian formulations containing these two herbs remain to be clarified. AIM OF THE STUDY: This study aimed to compare the therapeutic efficacy of Lonicerae Japonicae Flos and Lonicerae Flos in Shuanghuanglian formula against acute lung injury (ALI) and to investigate the potential underlying mechanisms of action. MATERIALS AND METHODS: Ultra-performance liquid chromatography (UPLC) was employed to characterize the chemical composition of Shuanghuanglian extracts prepared from Lonicerae Japonicae Flos (default material, SHL-D) and Lonicerae Flos (alternative material, SHL-A), respectively. Network pharmacologyanalysis was conducted to predict potential targets and signaling pathways. The predictions were validated using a lipopolysaccharide (LPS)-induced ALI murine model. In vivo validation was conducted through LPS-induced ALI model, evaluating lung histopathological scores, detecting inflammatory factors such as TNF-α, IL-6, IL-1β, and Western blot analysis of phosphorylation levels of key proteins in NF-κB and MAPKs signaling pathways. RESULTS: UPLC analysis revealed lower total phenolic acid content in SHL-D compared to SHL-A. Network pharmacology predicted potential involvement of IL1β, TNF, and IL6 related signaling networks, along with signaling pathways including NF-κB and MAPKs, in the protective effects of the two extracts against acute lung injury. In vivo experiments demonstrated that both SHL-D and SHL-A significantly attenuated lung histopathological damage and reduced pro-inflammatory cytokine levels, exhibiting similar overall protective effects within the parameters evaluated in this study. Nevertheless, the two extracts displayed distinct downstream signaling responses: SHL-D more potently suppressed NF-κB pathway protein phosphorylation and p38 MAPK phosphorylation, while SHL-A demonstrated more obvious advantages in reducing JNK phosphorylation and downregulating apoptosis-related protein expressions such as p53 and Caspase-3. CONCLUSION: In the classical Shuanghuanglian compound formulation, formulations containing Lonicerae Japonicae Flos and those containing Lonicerae Flos showed similar overall therapeutic effects against LPS-ALI, yet exhibited distinct downstream signaling profiles associated with inflammation and apoptosis, providing preliminary experimental evidence for their rational application in Shuanghuanglian compound preparations.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe