J Ethnopharmacol [JOURNAL]
Sun
200 papers
Tsamba-stir-fried Tiebangchui: Attenuates the toxicity of raw Tiebangchui without compromising its analgesic efficacy in Caenorhabditis elegans through TRPV channel regulation.
An Z, Wang J, Song L … +5 more , Li Y, Chi H, Huang F, Chen X, Du H
J Ethnopharmacol · 2026 Jun · PMID 42336118 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Tiebangchui (TBC) is a commonly used Tibetan medicine. However, its narrow therapeutic safety window necessitates strategies to reduce toxicity while preserving therapeutic efficacy. At pr...
ETHNOPHARMACOLOGICAL RELEVANCE: Tiebangchui (TBC) is a commonly used Tibetan medicine. However, its narrow therapeutic safety window necessitates strategies to reduce toxicity while preserving therapeutic efficacy. At present, tsamba-stir-fried TBC (TS-TBC) has become a characteristic pretreatment approach for TBC. AIM OF THE STUDY: This study aimed to preliminary explore the material basis and mechanism underlying toxicity reduction and efficacy retention in tsamba-stir-fried TBC. MATERIALS AND METHODS: First, UV, UPLC-Q-Exactive-Orbitrap-MS and HPLC were employed to characterize chemical compounds of raw TBC and TS-TBC. Subsequently, we conducted comprehensive evaluation in analgesia efficacy, basic toxicity, overall toxicity, neurotoxicity and cardiotoxic-like toxicity of using C. elegans N2. Further, network pharmacology and molecular docking approaches were adopted to screen for the potential targets of TS-TBC. To clarify the molecular mechanism of TS-TBC, we performed assays using C. elegans N2 and five mutant strains, combined with qRT-PCR detection. Finally, a compounds-phenotype-gene network was constructed via correlation analysis. RESULTS: We preliminarily identified 77 alkaloids in raw TBC and 80 alkaloids in TS-TBC. The contents of aconitine, 3-deoxyaconitine and 3-acetylaconitine decreased after processing, while the level of benzoylaconine increased. TS-TBC treatment showed to reduce toxicity of raw TBC in C. elegans N2 without compromising its analgesic efficacy. According to the result of network pharmacology and molecular docking, TRPV channel proteins were identified as potential targets of TS-TBC. In C. elegans mutant strains, deficiency in ocr-1, ocr-2, ocr-3, ocr-4, or osm-9 genes led to the loss of TS-TBC efficacy. Similarly, deletion of ocr-2 or osm-9 genes enhanced TS-TBC-induced apoptosis, while ablation of ocr-4 or osm-9 abolished its antioxidant effect. qRT-PCR validation showed that TS-TBC could downregulate the expression of ocr-2, ocr-3, and ocr-4 genes, while it exerted no significant effect on osm-9 gene. CONCLUSIONS: Our findings revealed that changes in the contents of characteristic alkaloids, rather than total alkaloids, constitute the material basis for the toxicity reduction and efficacy retention of TS-TBC, and TRPV channel proteins serve as its potential targets. These findings provide a scientific basis for the rational clinical application of processed TBC.
A comprehensive review on Jiao-tai-wan: Traditional application, pharmacokinetics, and therapeutic mechanisms in multiple disorders.
Nan F, Xu W, Wang X … +7 more , Miao Q, Sun J, Zhao R, Li X, Zhou Y, Xie X, Pang X
J Ethnopharmacol · 2026 Jun · PMID 42336117 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Jiao-tai-wan (JTW) is a renowned traditional Chinese medicine (TCM) compound formula documented in Han Shi Yi Tong in the Ming dynasty of China. It is composed of Coptidis Rhizoma (CR) and...
ETHNOPHARMACOLOGICAL RELEVANCE: Jiao-tai-wan (JTW) is a renowned traditional Chinese medicine (TCM) compound formula documented in Han Shi Yi Tong in the Ming dynasty of China. It is composed of Coptidis Rhizoma (CR) and Cinnamomi Cortex (CC) in a ratio of 10:1, and employed to alleviate the heart-kidney disharmony syndrome according to the TCM theory. At present, JTW has been extensively utilized for the treatment of multiple diseases. AIM OF THE REVIEW: This review aims to summarize current research progress on the traditional applications, bioactive components and their pharmacokinetic characteristics, as well as the pharmacological mechanisms of JTW in multiple disorders, in order to provide full-scale comprehending of JTW. METHODS: A systematic literature search was conducted using multiple well-recognized databases, namely PubMed, Web of Science, ScienceDirect, and China National Knowledge Infrastructure. Several keywords were adopted to search the literatures related to JTW, such as Jiaotaiwan, Jiaotai pill, and Jiao-tai-wan. RESULTS: The diverse alkaloids derived from CR and essential oil from CC in JTW can be absorbed into the bloodstream, peripheral tissues, and brain. These components constitute the material basis for the neuroprotective and metabolic regulatory effects of JTW. Notably, CC significantly influences the pharmacokinetic properties of coptis alkaloids within JTW. Clinical trials and preclinical studies have demonstrated that JTW can ameliorate multiple conditions including insomnia, depression, cognitive impairment, Parkinson's disease, type 2 diabetes mellitus (T2DM), and polycystic ovary syndrome (PCOS). The neuroprotective effects of JTW are primarily attributed to its regulation on neurotransmitter, inflammation of gut-brain-axis, synaptic plasticity, microglia activation, and circadian rhythm. Furthermore, JTW promotes T2DM remission by upregulating AMPK pathway and insulin signaling, and restoring gut microbiota balance. For PCOS management, JTW modulates mitochondrial dynamic and cholesterol import, thereby improving clinical outcomes. CONCLUSION: JTW serves as a promising alternative therapy for multiple nervous system diseases and metabolic disorders owing to its diverse pharmacological activities, although its clinical translation remains to be established. Further research is urgently necessary to utilize integrated systems biology approaches (such as proteomics, metabolomics, and transcriptomics) for elucidating the intricate mechanisms of JTW and uncovering the biological basis that underlies the synergistic effects of CR and CC within JTW.
Pilose antler proteins attenuate cyclophosphamide-induced myelosuppression in mice and bone marrow mesenchymal stem cells.
Gao F, Xiang X, Xie Y … +7 more , Geng Y, He Z, Zong Y, Geng J, Zhou J, Chen W, Du R
J Ethnopharmacol · 2026 Jun · PMID 42336116 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine holds that pilose antler can strengthen kidney yang, replenish essence and blood, fortify bones and muscles, as well as enhance immune function and promote hem...
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine holds that pilose antler can strengthen kidney yang, replenish essence and blood, fortify bones and muscles, as well as enhance immune function and promote hematopoiesis. However, studies on its potential to treat myelosuppression remain limited, and the underlying mechanisms and active components still require further investigation. AIM OF THE STUDY: This study aimed to evaluate the therapeutic potential of PAPs against myelosuppression and to elucidate the underlying protective mechanisms. MATERIALS AND METHODS: The protein composition of PAPs was identified by LC-MS/MS, and network pharmacology was then applied to predict the mechanisms that may underlie its effects. The protective effects of PAPs against the cytotoxic effects of CTX on bone marrow mesenchymal stem cells (BMSCs) were evaluated in terms of apoptosis, ROS level, cell cycle, cell senescence, and osteogenic differentiation in vitro. Meanwhile, the ameliorative effects of PAPs in myelosuppressed mice were observed by measuring peripheral blood routine parameters and bone marrow histopathology in vivo. RESULTS: In vitro, PAPs dose-dependently inhibited CTX-induced excessive ROS accumulation, restored SOD activity and reduced MDA content, alleviated apoptosis and senescence, and enhanced the osteogenic differentiation capacity of injured BMSCs. Immunofluorescence analysis further revealed that CTX upregulated Bax (by approximately 9.4-fold) and caspase-3 (by approximately 14.8-fold), and downregulated Bcl-2 (to approximately 0.34-fold). PAPs treatment reversed these changes, with the high-dose group reducing Bax to 0.18-fold and caspase-3 to 0.12-fold, and increasing Bcl-2 to 2.21-fold. In vivo, PAPs significantly elevated WBC, RBC, and PLT counts, as well as HGB levels, restored serum levels of SCF, TPO, EPO, and GM-CSF (to 0.69-0.80-fold of the control), and ameliorated severe bone marrow histopathological damage induced by CTX exposure. CONCLUSION: These findings suggest that PAPs alleviate chemotherapy-induced myelosuppression by activating the PI3K/AKT pathway, reducing BMSC injury and oxidative stress, improving peripheral blood parameters, and ameliorating bone marrow histopathological damage. This study not only provides modern scientific evidence supporting the traditional use of deer antler for "nourishing essence and replenishing marrow", but also provides a solid experimental basis for the further development and utilization of PAPs.
Alizarin as an NLRP3 inflammasome blocker ameliorates metabolic dysfunction-associated steatotic liver disease.
Wu C, Jiang Y, Xu Y … +5 more , Yu X, Li D, Wang Z, Zhang R, Sun M
J Ethnopharmacol · 2026 Jun · PMID 42336115 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Rubia cordifolia L. (known as Qiancao in Chinese herb) is a commonly used herbal medicine in clinical practice. It exhibits tropism to the Liver Meridian and is traditionally recognized fo...
ETHNOPHARMACOLOGICAL RELEVANCE: Rubia cordifolia L. (known as Qiancao in Chinese herb) is a commonly used herbal medicine in clinical practice. It exhibits tropism to the Liver Meridian and is traditionally recognized for its effects in cooling blood to stop bleeding and invigorating blood circulation to dispel stasis. Alizarin, its main anthraquinone component, has shown potential for clinical application. The nucleotide oligomerization domain-like receptors containing pyrin domain 3 (NLRP3) inflammasome is a promising therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to investigate the efficacy and mechanism of alizarin in treating MASLD via inhibition of the NLRP3 inflammasome. MATERIALS AND METHODS: We examined the effect of alizarin on NLRP3 inflammasome activation. The roles of alizarin in regulating NLRP3 transcription and inflammasome assembly were assessed. Its influence on lipid-induced NLRP3 activation was evaluated in mouse primary hepatocytes and Kupffer cells. The therapeutic potential of alizarin in ameliorating MASLD through NLRP3 inhibition was further verified in vivo. RESULTS: Alizarin inhibited NLRP3 inflammasome activation by reducing the cleavage of pro-IL-1β and pro-caspase-1 in mouse bone marrow-derived macrophages (BMDMs). Similar inhibitory effects were observed in BMDMs, primary hepatocytes, and Kupffer cells stimulated with LPS plus cholesterol or oleic acid/palmitic acid (OA/PA). Alizarin did not affect LPS-induced phosphorylation of P65, JNK, ERK, or P38. Mechanistically, it suppressed NLRP3 inflammasome assembly by inhibiting the interaction between NLRP3 and ASC. In a methionine-choline deficient (MCD) diet-induced mouse model of MASLD, alizarin improved liver function, reduced serum inflammatory markers, lowered histopathological inflammation scores, and attenuated liver fibrosis, likely through regulation of the NLRP3 inflammasome. CONCLUSIONS: Alizarin inhibits NLRP3 inflammasome assembly and may serve as a potential therapeutic agent for MASLD by targeting the NLRP3 inflammasome.
Guizhi-Shaoyao-Zhimu Decoction regulates the IL-17R-MAPK pathway to alleviate rheumatoid arthritis.
Pang J, Chen T, Shen H … +7 more , Jiang W, Tan Y, Zhang Z, Xu J, Yang F, Liu L, Li Y
J Ethnopharmacol · 2026 Jun · PMID 42336114 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Guizhi-Shaoyao-Zhimu Decoction (GSZD), derived from Synopsis of the Golden Chamber, has been used for over two thousand years to treat joint swelling and pain disorders such as "Lijie Feng...
ETHNOPHARMACOLOGICAL RELEVANCE: Guizhi-Shaoyao-Zhimu Decoction (GSZD), derived from Synopsis of the Golden Chamber, has been used for over two thousand years to treat joint swelling and pain disorders such as "Lijie Feng" (arthralgia due to cold-dampness). It is one of the most representative traditional Chinese medicine (TCM) formulas for treating rheumatoid arthritis (RA). However, its modern pharmacological mechanism lacks systematic elaboration, and new research will better explore the underlying mechanism of its action. RESEARCH OBJECTIVES: With the collagen-induced arthritis (CIA) mouse model as the core experimental platform, this study first performed comprehensive chemical composition identification and quality control of GSZD via ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) to clarify its pharmacodynamic material basis, combined transcriptomic profiling with network pharmacology approaches, and further implemented in vitro and in vivo experimental validation including lipopolysaccharide (LPS)-stimulated macrophages and IL-17RA blockade with Brodalumab to clarify whether GSZD exerts anti-rheumatoid arthritis (RA) activity by targeting the interleukin-17 receptor (IL-17R)-MAPK signaling axis. MATERIALS AND METHODS: Sixty male SPF-grade DBA/1 mice were randomly divided into five groups: Sham, CIA, low-dose GSZD (13.24 g crude drug/kg·d), high-dose GSZD (26.48 g crude drug/kg·d), and leflunomide (10 mg/kg). Intragastric administration began 7 days after the secondary immunization and continued for 28 days. Body weight, paw thickness, and arthritis scores were monitored; spleen and thymus indices were calculated. Serum and joint tissues were collected for ELISA, qPCR, Western blot, immunohistochemistry, and histopathological staining. The chemical profile of GSZD was established by UPLC-HRMS and matched against the LuMet-TCM database. Transcriptome sequencing was performed on knee joint homogenates (CIA vs. GSZD-H, n = 3 per group) and integrated with network pharmacology (TCMSP, SwissTargetPrediction, OMIM, GeneCards, STRING, Metascape) to predict core targets. RAW264.7 macrophages were pretreated with GSZD (10-100 μg/mL) for 2 h and then stimulated with LPS (100 ng/mL) for 24 h. For IL-17RA blockade, cells were pre-incubated with Brodalumab (10 μg/mL, 30 min), followed by GSZD (100 μg/mL, 1 h) and LPS (1 μg/mL, 24 h). Molecular docking (AutoDock Vina) was used to evaluate the binding of major components to IL-17R. RESULTS: UPLC-HRMS identified 979 constituents in GSZD. Network pharmacology and transcriptomic analyses jointly predicted the IL-17R-MAPK axis as a central target. In vivo, GSZD dose-dependently attenuated arthritis symptoms, reduced spleen and thymus indices, and alleviated synovial hyperplasia and macrophage activation (decreased F4/80 and CD11b). GSZD lowered pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) and chemokines (CCL2, CCL7) in serum and joints, suppressed matrix metalloproteinases (MMP3, MMP9), and reduced cartilage/bone erosion. Immunohistochemistry confirmed that GSZD inhibited IL-17RA, ERK1/2, and phosphorylated p38 in joint tissues. In vitro, GSZD suppressed IL-17R expression and the phosphorylation of p38, ERK, and JNK in LPS-stimulated macrophages. IL-17RA blockade with Brodalumab completely abrogated the inhibitory effect of GSZD on MAPK phosphorylation and IL-1β production, confirming IL-17RA dependency. Molecular docking showed that multiple GSZD components bind directly to IL-17R. CONCLUSION: This study demonstrates that GSZD, a multi-component formula characterized by UPLC-HRMS, alleviates synovial inflammation and osteoarticular destruction by blocking the IL-17R-MAPK cascade in an IL-17RA-dependent fashion. These findings provide modern scientific evidence for the clinical application of GSZD in treating RA.
Corrigendum to "Gandouling induces GSK3β promoter methylation to improve cognitive impairment in Wilson's disease" [J. Ethnopharmacol. 334 (2024) 118493].
Tian L, Wu M, Zhao C … +3 more , Wen Y, Chen J, Dong T
J Ethnopharmacol · 2026 Jun · PMID 42331658 · Publisher ↗
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Role of an Ayurvedic formulation 'Kalyanaka Ghrita' in mild cognitive impairment: A single-patient, quasi-randomized, controlled, open-label N-of-1 trial.
Sharma S, Kaushik A, Chakrabarti SS … +1 more , Patwardhan K
J Ethnopharmacol · 2026 Jun · PMID 42331198 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Kalyanaka Ghrita (KG) is a classical Ayurvedic polyherbal formulation traditionally indicated for disorders of memory, intellect, and mental well-being. Ayurveda emphasizes individualized...
ETHNOPHARMACOLOGICAL RELEVANCE: Kalyanaka Ghrita (KG) is a classical Ayurvedic polyherbal formulation traditionally indicated for disorders of memory, intellect, and mental well-being. Ayurveda emphasizes individualized therapeutic decision-making, which the N-of-1 trial design aligns with conceptually and methodologically, enabling systematic evaluation of traditional formulations at the single-patient level, where inter-individual variability is central. AIM OF THE STUDY: To assess the efficacy and safety of Kalyanaka Ghrita in a patient diagnosed with Mild Cognitive Impairment (MCI) using an N-of-1 trial design. MATERIALS AND METHODS: A quasi-randomized N-of-1 trial was conducted to evaluate the effects of KG in a patient with MCI. The study comprised six alternating treatment and no-treatment periods of two months each, spanning a total of 14 months. Cognitive outcomes were assessed using the Hindi Mental State Examination (HMSE) and the Clinical Dementia Rating (CDR) scales. Functional abilities were measured with the Instrumental Activities of Daily Living (IADL) scale, and affective status was evaluated using the Geriatric Depression Scale (GDS)- short form. Bayesian modeling estimated posterior probabilities and 95% highest posterior density intervals (HPDIs) for treatment effects. RESULTS: KG administration improved overall cognitive abilities, as indicated by global HMSE scores (posterior probability >97%, 95% HPDI excluding zero), with the most substantial gains in orientation (posterior probability >98%) and recall (posterior probability >93%) domains. Reduction in CDR-Sum of Boxes scores indicated strong improvement (posterior probability >98%; 95% HPDI excluded zero). Benefits were consistent in orientation and community affairs, with moderate effects on memory and judgment/problem-solving. Functional outcomes assessed using IADLs showed a probable benefit (posterior probability >80%, HPDI overlapping zero). Depressive symptoms, as measured by the GDS, decreased markedly (posterior probability = 100%; 95% HPDI -2.23 to -0.80). All safety lab parameters remained within physiological limits, confirming good tolerability of KG. CONCLUSION: KG produced measurable improvements across cognitive, functional, and affective domains in a patient with MCI, suggesting a potential role in the management of early cognitive decline. The formulation was well tolerated. The study also demonstrates the feasibility of applying an N-of-1 trial within Ayurveda. Despite limitations such as the single-patient, quasi-randomized, open-label design and absence of biomarker testing, the findings offer preliminary support for both the therapeutic potential of KG in MCI and the methodological value of N-of-1 trials in Ayurvedic research.
Efficacy and hepatotoxicity of Psoralea corylifolia L.: A meta-analysis and machine learning assessment in postmenopausal osteoporosis.
Yang H, Tang R, Ren Y … +4 more , Chen Z, Zhan T, Chen K, Fan X
J Ethnopharmacol · 2026 Jun · PMID 42331197 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia L. (P. corylifolia, also known as Cullen corylifolium (L.) Medik.) is a traditional medicinal herb used for bone-related disorders. Its broader application is constrai...
ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia L. (P. corylifolia, also known as Cullen corylifolium (L.) Medik.) is a traditional medicinal herb used for bone-related disorders. Its broader application is constrained by concerns about hepatotoxicity, creating a challenge in balancing efficacy and safety. AIM OF THE STUDY: To systematically evaluate the osteoprotective efficacy of P. corylifolia in postmenopausal osteoporosis and to explore a preliminary preclinical therapeutic window within a benefit-risk assessment framework. MATERIALS AND METHODS: Following a comprehensive search of major databases, we performed a meta-analysis coupled with Bayesian Gaussian process regression modeling. Efficacy was primarily assessed using bone mineral density, whereas alanine aminotransferase and aspartate aminotransferase, derived from separate toxicity datasets, were evaluated as safety outcomes. Mouse and rat doses were standardized to human equivalent doses (HED) for cross-species harmonization. RESULTS: A total of 23 efficacy studies and 7 toxicity studies were included. Meta-analysis showed that P. corylifolia significantly improved bone mineral density (standardized mean difference = 4.32, p < 0.001, I = 89%) and generally improved trabecular microarchitecture outcomes. Model integration suggested a favorable benefit-risk profile within a restricted range. After dose standardization of psoralen to HED for cross-species harmonization, 4.5 mg/kg for 7.0 weeks was estimated as a model-informed investigational reference pending further validation. CONCLUSIONS: This study provides meta-analytic evidence supporting the efficacy of P. corylifolia and uses Bayesian modeling to identify a preliminary, non-clinically validated investigational dose window that requires further validation in human studies.
Lonicerin from Dachaihu decoction ameliorates liver steatosis and fibrosis in MASH by inhibiting LY6D.
Xing XR, Qiu HC, Liu Y … +7 more , Tang T, Zhai YY, Tian Y, Qin FX, Zhang ZJ, Zhang P, Xu FG
J Ethnopharmacol · 2026 Jun · PMID 42331196 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Dachaihu Decoction (DCHD) is a traditional Chinese medicine formula from the Shanghan Lun. It has been used for over 1800 years to treat "Shaoyang and Yangming concurrent syndromes", which...
ETHNOPHARMACOLOGICAL RELEVANCE: Dachaihu Decoction (DCHD) is a traditional Chinese medicine formula from the Shanghan Lun. It has been used for over 1800 years to treat "Shaoyang and Yangming concurrent syndromes", which are closely related to modern liver disorders, including metabolic dysfunction-associated steatohepatitis (MASH). While DCHD has demonstrated hepatoprotective effects in preclinical studies, the specific bioactive components and mechanism of action against MASH remain elusive. AIM OF THE STUDY: To systematically identify the key active components of DCHD mediating its anti-MASH effects and to elucidate their molecular mechanisms. MATERIALS AND METHODS: The components in DCHD were characterized using high resolution-mass spectrometry (HRMS). The potential bioactive components were screened using network pharmacology. The therapeutic efficacy of candidate compounds was evaluated both in free fatty acid (FFA)-induced hepatocyte injury and activated hepatic stellate cells (HSCs) and in a high-fat diet/CCl-induced MASH mouse model. The molecular mechanism was investigated via transcriptomic profiling, drug-target interaction validation, and gene knockdown assays. RESULTS: A total of 128 components were identified from DCHD using HRMS. Lonicerin (LON), a flavonoid glycoside predominantly derived from Citrus trifoliata L., was identified as the key active component. LON significantly ameliorated steatosis, inflammation and fibrosis both in vitro and in vivo. Mechanistically, LON bound to lymphocyte antigen 6 family member D (LY6D), which was significantly upregulated during MASH progression, and dose-dependently suppressed its expression. Importantly, LY6D knockdown abolished the protective effect of LON in AML12 hepatocytes and activated HSCs, confirming LY6D as a functional target. CONCLUSIONS: This study identified LON as a key bioactive component mediating the anti-MASH effects of DCHD and revealed that it alleviated MASH progression by targeting LY6D.
Suppression of STING by Acacetin attenuates renal fibrosis via balancing mitophagy and protective nucleoid-phagy.
Gao Y, Mu L, Liu C … +11 more , Zhao Y, Cai R, Zhu L, Rao F, Bao H, Chen J, Fan M, Zeng C, Yuan Z, Wei T, Cheng J
J Ethnopharmacol · 2026 Jun · PMID 42331195 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Acacetin (5,7-dihydroxy-4'-methoxyflavone) is a primary active flavonoid extracted from traditional medicinal plants such as Agastache rugosa and Saussurea involucrata. Historically, these...
ETHNOPHARMACOLOGICAL RELEVANCE: Acacetin (5,7-dihydroxy-4'-methoxyflavone) is a primary active flavonoid extracted from traditional medicinal plants such as Agastache rugosa and Saussurea involucrata. Historically, these herbs have been utilized in Traditional Chinese Medicine to clear heat, eliminate dampness, and treat inflammatory and kidney-related ailments. Despite its potent anti-inflammatory properties, the direct molecular targets of Acacetin and its specific mechanisms regarding mitochondrial quality control (MQC) in the progression of renal fibrosis (RF) remain undefined. AIM OF THE STUDY: This study aimed to evaluate the anti-fibrotic efficacy of Acacetin and elucidate whether it directly targets the cGAS-STING cascade to restore organelle homeostasis by balancing mitophagy and protective nucleoid-phagy. METHODS: Molecular dynamics (MD) simulations, microscale thermophoresis (MST), and drug affinity responsive target stability (DARTS) assays were utilized to verify the direct binding between Acacetin and STING. In vivo, wild-type (WT) and STING-knockout (STING) mice were subjected to unilateral ureteral obstruction (UUO) and folic acid nephropathy (FAN) models, and administered Acacetin (40 and 80 mg/kg/d). In vitro, human renal tubular epithelial (HK-2) cells were stimulated with TGF-β or cGAMP. Mitochondrial function, ultrastructure, and dynamic autophagic flux were evaluated using Seahorse XF analysis, transmission electron microscopy (TEM), bafilomycin A1 (BafA1) blockade, tandem fluorescence imaging, and immunofluorescence. Protein and gene expressions were measured via Western blotting and RT-qPCR. RESULTS: Biophysical assays identified Acacetin as a direct STING inhibitor that bound to the STING protein pocket (Kd = 1.57 μM) and effectively antagonized its cGAMP-induced phosphorylation. Consequently, Acacetin dose-dependently alleviated UUO- and FA-induced renal fibrogenesis, suppressed oxidative stress, and restored mitochondrial respiratory capacity. Mechanistically, Acacetin promoted a functional shift in MQC: it suppressed the initiation phase of maladaptive PINK1/Parkin-mediated "exhaustive over-mitophagy" while facilitating TFAM-LC3-associated "nucleoid-phagy" to selectively clear immunogenic leaked mitochondrial DNA (mtDNA). Crucially, the anti-fibrotic, anti-inflammatory, and MQC-restoring benefits of Acacetin were completely abolished in STING mice, establishing STING as its indispensable pharmacological target. CONCLUSION: Acacetin ameliorates renal fibrogenesis by directly inhibiting STING, thereby regulating the balance between pathological over-mitophagy and protective nucleoid-phagy. These findings validate the traditional use of Acacetin-rich herbs in treating inflammatory conditions and highlight the monomer as a promising mechanism-based therapeutic candidate for the treatment of chronic kidney disease.
A randomized controlled trial of Kangfuxin Liquid for diabetic peripheral neuropathy.
Qiao X, Liu L, Jiang Z … +2 more , Guo L, Pan Q
J Ethnopharmacol · 2026 Jun · PMID 42331194 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Kangfuxin Liquid, a traditional Chinese medicine preparation, has been widely used in the clinical practice. However, its effects on improving neuropathic symptoms and nerve conduction fun...
ETHNOPHARMACOLOGICAL RELEVANCE: Kangfuxin Liquid, a traditional Chinese medicine preparation, has been widely used in the clinical practice. However, its effects on improving neuropathic symptoms and nerve conduction function in patients with diabetic peripheral neuropathy (DPN) have not been fully elucidated. AIM OF THE STUDY: To evaluate the efficacy and safety of Kangfuxin Liquid when applied topically to the lower legs in patients with DPN. MATERIALS AND METHODS: A single-center, randomized, controlled design was employed. DPN patients were enrolled and randomly assigned in a 1:1 ratio to either the Kangfuxin Liquid group or the placebo group. All participants underwent a daily 20-min topical application for two weeks, using gauze saturated with 50 mL of the assigned solution on both lower limbs, covered with cling film. Assessments were performed at baseline and post-treatment, including the Toronto Clinical Neuropathy Score (TCSS), nerve conduction velocity (NCV), inflammatory markers (CRP, TNF-α, IL-6), and glycemic-related parameters. RESULTS: The study enrolled 73 patients (42 males [57.5%] and 31 females [42.5%]) with a mean age of 66.85 ± 8.70 years. After 2 weeks of treatment, the Kangfuxin Liquid group demonstrated significant improvements from baseline in the total TCSS score, symptom score, and sensory test score, with both the total score and symptom score being significantly lower than those in the placebo group (P < 0.05). Regarding nerve conduction, the sensory conduction velocity of the common peroneal nerve and tibial nerve increased significantly from baseline in the Kangfuxin Liquid group, and the post-treatment tibial nerve conduction velocity was superior to that of the placebo group. There were no statistically significant differences in inflammatory markers or the incidence of adverse events between the two groups. Only two cases of skin allergy were reported in the Kangfuxin Liquid group. CONCLUSIONS: Short-term use of Kangfuxin Liquid can improve symptoms and partial nerve conduction function (sensory nerve conduction velocity in the tibial nerve), in DPN patients, with a favorable safety profile.
Corrigendum to "A new approach for treating AD: Guifu Dihuang Pills improves brain insulin resistance by promoting NrCAM to activate the EGFR/PI3K/Akt signaling pathway" [J. Ethnopharmacol. 356 (2026) 120642].
Yu C, Liu L, Lu Z … +6 more , Chen M, Yang N, Li Z, Bai L, Li C, Zhou X
J Ethnopharmacol · 2026 Jun · PMID 42323259 · Publisher ↗
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Corrigendum to "Network pharmacology-based prediction and validation of the active ingredients and potential mechanisms of the Huangxiong formula for treating ischemic stroke" [J. Ethnopharmacol. 312 (2023) 116507].
Zhao S, Zhang P, Yan Y … +5 more , Xu W, Li J, Wang L, Wang N, Huang Y
J Ethnopharmacol · 2026 Nov · PMID 42323258 · Publisher ↗
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Cirsium japonicum Fisch. ex DC.: A review of ethnomedicine, botany, phytochemistry, pharmacology and pharmacokinetics.
Zhu X, Li Y, Wang Y … +1 more , Gu Y
J Ethnopharmacol · 2026 Jun · PMID 42323062 · Publisher ↗
RELEVANCE TO ETHNOPHARMACOLOGY: Cirsium japonicum Fisch. ex DC. (C. japonicum) is a medicinal and edible plant widely used in traditional Chinese medicine, with its applications historically documented in ancient Chinese...
RELEVANCE TO ETHNOPHARMACOLOGY: Cirsium japonicum Fisch. ex DC. (C. japonicum) is a medicinal and edible plant widely used in traditional Chinese medicine, with its applications historically documented in ancient Chinese medical texts. It is traditionally recognized for its effects in cooling the blood to arrest bleeding, dissipating blood stasis, and detoxifying to reduce swelling, and is commonly employed in the treatment of hemorrhagic conditions, sores, and abscesses. AIM OF THE REVIEW: This article aims to provide a review of ethnomedicine, botany phytochemistry, pharmacology and pharmacokinetics of C. japonicum. MATERIALS AND METHODS: A literature search on C. japonicum was conducted based on classical Chinese pharmacopoeia texts and multiple electronic databases (including Web of Science, PubMed, Elsevier, ScienceDirect, Google Scholar and CNKI). RESULTS: Botanical studies have characterized C. japonicum as a perennial herbaceous species within the genus Cirsium of the Asteraceae family. Phytochemical investigations have demonstrated that the plant contains a diverse array of structurally varied natural products, including flavonoids, phenylpropanoids, terpenoids, and other compound classes. To date, a total of 116 compounds have been isolated and identified from C. japonicum, many of which exhibit a wide spectrum of pharmacological activities, such as antioxidant, anti-inflammatory, hypoglycemic, and anticancer effects. CONCLUSION: This article comprehensively reviews the latest research advances in the Ethnomedicine, phytochemistry, pharmacological effects, and pharmacokinetics of C. japonicum aiming to provide comprehensive reference materials to support in-depth research on its active components and their potential development as modern therapeutic drugs or functional products.
Bioactive components of Mongolian medicinal Gentiana dahurica Fisch. flowers inhibit the NF-κB signaling pathway and ameliorate chronic obstructive pulmonary disease.
Wang N, Zhang W, Li J … +10 more , Bao F, Feng W, Yang Y, Zhou S, Guo Q, Song W, Chen X, Ma A, Yi L, Wang M
J Ethnopharmacol · 2026 Jun · PMID 42323061 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana dahurica Fisch. is a traditional herb widely used in Chinese and Mongolian medicine for the management of respiratory disorders such as cough, sore throat, and "lung heat". Its hi...
ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana dahurica Fisch. is a traditional herb widely used in Chinese and Mongolian medicine for the management of respiratory disorders such as cough, sore throat, and "lung heat". Its historical application provides a strong rationale for investigating its potential in the management of COPD. Its application in Mongolian medicine for 'lung heat' syndrome provides a direct ethnopharmacological basis for exploring its anti-COPD potential. AIM OF THE STUDY: This study primarily aimed to evaluate the anti-COPD effects of G. dahurica flowers and elucidate its underlying molecular mechanisms, with a particular focus on the regulatory effects of its bioactive components on inflammatory signaling pathways. MATERIALS AND METHODS: Chemical profiling was performed using HPLC-Q-Exactive-MS. A laboratory-induced COPD model was established in mice using LPS and cigarette smoke extract (CSE), followed by a 12-week treatment with G. dahurica extract. Assessments included lung function tests, histopathology, qPCR, and proteomic analysis. In vitro validation was performed on LPS-stimulated cultures, involving two distinct lung cell types: human BEAS-2B and mouse MLE-12. RESULTS: Fifty compounds were identified in the extract. Treatment significantly alleviated pulmonary inflammation and improved lung function in mice. Proteomic analysis revealed inhibition of the NF-κB signaling pathway. Additionally validated by downregulation of inflammatory genes. Isoorientin and luteolin were confirmed as key active compounds mediating these effects. CONCLUSION: G. dahurica flowers ameliorate COPD progression via suppressing the NF-κB signaling pathway, which provides a solid molecular basis for its traditional application in the treatment of respiratory disorders. These findings suggest that G. dahurica flowers hold great potential as a promising therapeutic agent for COPD intervention.
LC-MS/MS phytochemical analysis, in vivo acute toxicity, and anti-inflammatory evaluation of hydromethanolic root extract of Deverra scoparia Coss. & Durieu: Molecular docking and molecular dynamics simulation against the COX-2 enzyme.
Karbab A, Charef N, Jaber AM … +6 more , Ouhida S, Ouksel L, Djabi F, Sanabrah A, Arrar L, Mubarak MS
J Ethnopharmacol · 2026 Jun · PMID 42323060 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Deverra scoparia Coss. & Durieu (D. scoparia) has been used locally in traditional medicine for decades to treat inflammatory diseases. About 24.47% of people use this plant in traditional...
ETHNOPHARMACOLOGICAL RELEVANCE: Deverra scoparia Coss. & Durieu (D. scoparia) has been used locally in traditional medicine for decades to treat inflammatory diseases. About 24.47% of people use this plant in traditional folk medicine. AIM OF THE STUDY: LC-MS/MS phytochemical analysis of the hydromethanolic root extract (HMRE) was performed to evaluate qualitative and quantitative phytochemical constituents. We evaluated the in vivo acute toxicity, anti-inflammatory and anti-nociceptive efficacy, in silico activity against the COX-2 enzyme, and molecular dynamics simulation studies. MATERIAL AND METHODS: Phytochemical analysis was performed using HMRE via LC-MS/MS, whereas the acute toxicity of HMRE was assessed in accordance with OECD Guideline 425. Furthermore, the extract's anti-inflammatory activity was evaluated using xylene- and croton oil-induced ear edema and carrageenan-induced paw edema, and its antinociceptive activity was assessed in a mouse model. Molecular docking was used for in silico analysis of COX-2, along with molecular dynamics simulations. RESULTS: LC-MS/MS phytochemical analysis of HMRE identified 20 compounds, including phenolic acids, flavonoids, and other secondary metabolites, collectively contributing to its diverse pharmacological potential. The extract showed no signs of acute oral toxicity (LD50 > 5 g/kg BW) and was considered safe. Each dose of samples (100, 300, and 600 mg/kg) was administered orally and produced effective inhibition in both edema models (xylene- and croton oil-induced) in mice. Three doses of HMRE (100, 250, and 500 mg/kg) were administered orally and displayed a significant anti-inflammatory influence in the carrageenan-induced rat paw edema after 3 h. At a dose of 500 mg/kg, HMRE significantly decreased writhing in the acetic acid-induced writhing model. Molecular docking analysis indicated a strong binding affinity of major phytoconstituents toward the COX-2 enzyme. The molecular dynamics simulation indicated that rutin forms a more stable, more tightly bound complex with the protein than naringin. CONCLUSIONS: The present results support the medicinal use of D. scoparia in folk medicine and as a supplementary reference for natural anti-inflammatory medication. The identification of phenolic constituents, supported by in silico and molecular dynamics simulations, suggests the therapeutic potential of HMRE and warrants further investigation into their pharmacological mechanisms of action.
Multi-omics characterization of glucose-lipid metabolic remodeling associated with Gymnema sylvestre (Retz.) R.Br. ex Sm. treatment in a type 2 diabetic mouse model.
Zeng Z, Liu Y, Xiao G … +7 more , Jia C, Wu M, Li Y, Jiang J, Zhang J, Xu A, Bi X
J Ethnopharmacol · 2026 Jun · PMID 42323059 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Gymnema sylvestre (Retz.) R.Br. ex Sm. is a traditional herb widely used in Indian and Chinese ethnomedicine for diabetes and obesity management. Although its hypoglycemic and hypolipidemi...
ETHNOPHARMACOLOGICAL RELEVANCE: Gymnema sylvestre (Retz.) R.Br. ex Sm. is a traditional herb widely used in Indian and Chinese ethnomedicine for diabetes and obesity management. Although its hypoglycemic and hypolipidemic effects have been extensively reported, a system-level understanding of how G. sylvestre modulates glucose-lipid metabolism has not been fully elucidated. AIM OF THE STUDY: The study aimed to explore metabolic alterations associated with G. sylvestre intervention in type 2 diabetes mellitus using an integrated multi-omics strategy. MATERIALS AND METHODS: A type 2 diabetic mouse model was induced using a high-fat diet plus streptozotocin. Mice received graded doses of G. sylvestre extract for six weeks. Metabolic parameters, oxidative stress indices, and liver histopathology were assessed. Proteomic and metabolomic profiling coupled with integrative bioinformatics identified pathway-level metabolic alterations related to G. sylvestre treatment, with selected targets further examined by Western blot analysis. RESULTS: G. sylvestre treatment significantly improved glycemic control and lipid profiles, as shown by decreased fasting blood glucose, total cholesterol, triglycerides, and low-density lipoprotein cholesterol, along with enhanced insulin sensitivity and hepatic glycogen storage. Integrated multi-omics analysis revealed coordinated alterations in 160 proteins and 43 metabolites, predominantly associated with glucose-lipid metabolism, including energy homeostasis and lipid metabolic regulation-associated pathways. Five proteins associated with lipid and energy metabolism were identified, including fatty acid synthase (FAS), carnitine palmitoyltransferase 1A (CPT1A), acetyl-CoA carboxylase alpha (ACACA), fatty acid-binding protein 5 (FABP5), and 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3), together with metabolites involved in linoleic acid and glycerophospholipid metabolism, were identified as representative molecular features associated with G. sylvestre treatment. CONCLUSION: This study provides integrative multi-omics evidence of coordinated glucose-lipid metabolic remodeling associated with G. sylvestre treatment in type 2 diabetes mellitus. By combining ethnopharmacological context with integrated multi-omics analyses, the results offer scientific support for the traditional application of G. sylvestre in metabolic disorder management.
Chrysin reprograms microglial metabolism and function via targeting SYK to alleviate the symptoms of Alzheimer's disease.
Li L, Gu Y, Luo X … +3 more , Wang J, Jia Y, Yan T
J Ethnopharmacol · 2026 Nov · PMID 42322864 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Alpiniae Oxyphyllae Fructus, first documented in Bencao Shiyi, is a classical traditional Chinese herb traditionally used to warm the kidney, invigorate the spleen, consolidate essence and...
ETHNOPHARMACOLOGICAL RELEVANCE: Alpiniae Oxyphyllae Fructus, first documented in Bencao Shiyi, is a classical traditional Chinese herb traditionally used to warm the kidney, invigorate the spleen, consolidate essence and relieve chronic diarrhea. Guided by the TCM theory that kidney essence nourishes brain marrow, modern studies have confirmed its notable neuroprotective and anti-neuroinflammatory activities. BACKGROUND: Neuroinflammation is a key pathological hallmark of Alzheimer's disease (AD), and spleen tyrosine kinase (SYK) serves as a critical signaling regulator. Our previous work confirmed that Alpiniae Oxyphyllae Fructus extract (AE) exerts notable neuroprotection; nevertheless, its blood-brain barrier-permeable components and detailed mechanisms remain poorly clarified. OBJECTIVE: The purpose of this study is to identify the main active components in AE and clarify its mechanism of improving AD pathology by regulating the SYK signaling pathway. METHODS: A preliminary dose-finding study with two AE doses (180 mg/kg, 360 mg/kg) was performed via open field test and inflammatory indexes to select the optimal dose for subsequent experiments. Behavioral assays assessed AE-related neurobehavioral improvements. LC-QTOF-MS/MS identified brain-permeable components, while network pharmacology combined with GEO database analysis screened potential targets and underlying mechanisms. Molecular docking was applied to filter SYK-binding candidates, further validated by molecular dynamics simulation and Cellular thermal shift assay (CETSA). In vivo, a piceatannol-induced SYK inhibition model was established to verify whether the candidate component alleviated LPS-triggered behavioral deficits in mice in a SYK-dependent manner. In vitro, BV2 microglia were used to detect microglial polarization, Aβ phagocytosis and migration through qRT-PCR, glucose/ATP/lactate measurement, wound healing assay and immunofluorescence staining. RESULTS: Chrysin was identified as the primary brain-permeable constituents targeting SYK. In AD mice, it significantly ameliorated cognitive deficits and reduced Aβ accumulation. Mechanistically, Chrysin modulated the SYK/BTK/PLCγ2 and NF-κB axes to trigger a microglial M1-to-M2 phenotypic shift. This phenotypic transition is accompanied by metabolic reprogramming-shifting from glycolysis to oxidative phosphorylation, thereby notably enhancing microglial migration capacity and Aβ phagocytosis. These neuroprotective effects were confirmed to be SYK-dependent. CONCLUSION: Chrysin is the primary brain-permeable constituent of AE. that targets SYK to restore microglial metabolic homeostasis, offering a promising therapeutic strategy for AD.
Corrigendum to "Screening of antithrombotic components from Typhae Pollen by a multidimensional evaluation strategy" [J. Ethnopharmacol. 369 (2026) 121868].
Kuang YJ, Weng ZB, Chen QQ … +5 more , Zhu BZ, Li F, Xiao PT, Liu EH, all author
J Ethnopharmacol · 2026 Jun · PMID 42321090 · Publisher ↗
Abstract loading — click title to view on PubMed.
Multi-herb formulations modulating gut microbiota: A systematic review and data-driven analysis.
Cho MS, Lee IS, Kim J … +3 more , Park JW, Kim J, Ko SJ
J Ethnopharmacol · 2026 Nov · PMID 42320776 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Multi-herb formulations, characterized by their complex synergistic compositions, are widely used in traditional medicine to modulate the gut microbiota. However, identifying reproducible...
ETHNOPHARMACOLOGICAL RELEVANCE: Multi-herb formulations, characterized by their complex synergistic compositions, are widely used in traditional medicine to modulate the gut microbiota. However, identifying reproducible herb-microbiota associations across disparate clinical settings remains a significant methodological challenge. AIM OF THE STUDY: This study aims to systematically synthesize human clinical evidence to map the modulation patterns of multi-herb formulations on the gut microbiota and to identify the herbal components associated with reported directional microbial shifts. MATERIALS AND METHODS: We conducted a systematic review and data-driven analysis of 29 clinical trials involving 954 participants in multi-herb formulation groups. To integrate findings from heterogeneous clinical settings, we employed a binarization strategy focused on statistically significant directional shifts (+1 for increase, -1 for decrease). An extreme gradient boosting (XGBoost) learning framework combined with SHapley Additive exPlanations (SHAP) was used to deconstruct these formulations and explore the predictive importance of individual constituents. To ensure the highest level of scientific integrity and prevent data leakage, the model's generalizability was rigorously validated using Leave-One-Study-Out (LOSO) cross-validation at the independent study level. RESULTS: The LOSO validation yielded a mean accuracy of 0.84 and a macro F1-score of 0.42, indicating limited but informative cross-study pattern recognition despite the inherent heterogeneity of clinical data. Our analysis identified recurrent directional associations: formulas containing Scutellaria baicalensis Georgi were associated with reported reductions in genus-level taxa such as Escherichia-Shigella within neuropsychiatric disease contexts. Formulas containing Zingiber officinale Roscoe were associated with reported increases and decreases in selected genus-level taxa across heterogeneous disease contexts. CONCLUSIONS: This study provides a comprehensive, evidence-based map of how multi-herb formulations modulate the human gut microbiota. By prioritizing rigorous validation and accounting for the complexity of synergistic preparations, we have identified hypothesis-generating patterns that transcend individual study variations. These findings provide a realistic foundation for future high-resolution metagenomic research and the development of standardized ethnopharmacological therapies.
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