J Ethnopharmacol [JOURNAL]
Sun
200 papers
Corrigendum to "Huangqi Jianzhong decoction inhibits CRC invasion through the modulation of BCLAF1-mediated glycolysis" [J. Ethnopharmacol. (2026) 121940].
Liu X, Cui Y, Liu H … +3 more , Zhang R, Zhang Y, Song H
J Ethnopharmacol · 2026 Jul · PMID 42401508 · Publisher ↗
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Cortex Phellodendri total alkaloids ameliorate ulcerative colitis by restoring intestinal barrier integrity via modulation of the ER-mitochondria axis.
Xu S, Wu X, Wan J … +9 more , Gao S, Chen L, Li H, Luo L, Wu J, Sun S, Huang C, Liu W, Hu P
J Ethnopharmacol · 2026 Jul · PMID 42401248 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Cortex Phellodendri (Huangbai), the dried bark of Phellodendron chinense C.K.Schneid. (Rutaceae), represents a classic botanical drug in Traditional Chinese Medicine (TCM) historically pre...
ETHNOPHARMACOLOGICAL RELEVANCE: Cortex Phellodendri (Huangbai), the dried bark of Phellodendron chinense C.K.Schneid. (Rutaceae), represents a classic botanical drug in Traditional Chinese Medicine (TCM) historically prescribed to "clear heat and dry dampness" for treating gastrointestinal inflammatory conditions such as dysentery. However, its multi-component cooperative mechanisms remain largely enigmatic. AIM OF THE STUDY: This study aimed to elucidate the material basis of Cortex Phellodendri total alkaloids (CPA) and investigate its systemic mechanisms and cooperative interactions in ameliorating ulcerative colitis (UC), with a specific focus on the endoplasmic reticulum (ER)-mitochondria axis. MATERIALS AND METHODS: The chemical profile of CPA was characterized using UPLC-MS/MS. In vivo efficacy and synergistic effects were evaluated in a dextran sulfate sodium (DSS)-induced colitis mouse model. The underlying molecular mechanisms were explored using DIA-based quantitative proteomics and validated via Western blotting in both colon tissues and a DSS-induced Caco-2 cellular model. RESULTS: CPA effectively ameliorated DSS-induced colitis and restored intestinal barrier integrity. Proteomic and molecular validations revealed that CPA's efficacy centers on recalibrating the ER-mitochondria axis by blunting the PKR-eIF2α-ATF4 stress cascade and rescuing mitochondrial fitness through SIRT1/3 and OPA1 upregulation. Furthermore, by utilizing its two primary pure alkaloids, berberine (BBR) and phellodendrine (PHE), as mechanistic comparators, we demonstrated that the whole CPA extract exhibits robust cooperative potentiation in silencing IKK/NF-κB signaling and upregulating Claudin-1, along with potent additive effects in suppressing organelle-specific stress. CONCLUSIONS: CPA serves as a scientifically validated, multi-target botanical therapeutic for the management of UC. The demonstrated BBR-PHE synergy provides a modern pharmacological blueprint for the traditional "Principal-Adjuvant" theory, highlighting the essential role of the coupled ER-mitochondria network in intestinal barrier restoration.
Panax quinquefolius saponins promote remyelination via orchestrating HMGCS1-NPC1-MAL-mediated lipid metabolism and rebalancing JAK-STAT signaling in a cuprizone-induced demyelination model.
Huang J, Sun L, Yue L … +4 more , Xu L, Liu H, Ma P, Xiao P
J Ethnopharmacol · 2026 Jul · PMID 42401247 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Panax quinquefolius L. is traditionally used as a "Qi-tonifying and Yin-nourishing" herb for weakness and limb flaccidity, symptoms described as "Feng fei" or flaccidity syndrome. These ma...
ETHNOPHARMACOLOGICAL RELEVANCE: Panax quinquefolius L. is traditionally used as a "Qi-tonifying and Yin-nourishing" herb for weakness and limb flaccidity, symptoms described as "Feng fei" or flaccidity syndrome. These manifestations partially resemble motor dysfunction in multiple sclerosis. Panax quinquefolius Saponins (PQS), are major bioactive constituents, but their effects on demyelination and related molecular changes remains unclear. AIM OF THE STUDY: To investigate the effects of PQS on demyelination and explore associated changes in inflammatory signaling and lipid metabolism. MATERIALS AND METHODS: PQS was qualitatively profiled by UPLC-QTOF-MS and quantitatively standardized by HPLC-DAD. Male C57BL/6N mice were randomly divided into six groups (n = 12-16/ group): Control, Model (daily intragastric administration of 330 mg/kg of cuprizone for 6 weeks), Positive control (10 mg/kg of Clemastine), and low-, medium-, and high-dose PQS groups (25, 50, or 100 mg/kg). During week 2-6, mice received drugs by daily intragastric administration. Behavioral assessments including pole test, rotarod, and open field test were performed. Myelin integrity and related molecular changes were evaluated by histological staining, immunofluorescence, transcriptomics, Western blotting, and molecular docking. RESULTS: PQS ameliorated CPZ-induced motor dysfunction in behavioral assessments (P < 0.05). PQS also attenuated myelin loss in the corpus callosum, with the high-dose group increasing myelinated areas to approximately 74% of control levels (P < 0.01). Transcriptomic and protein analyses showed that PQS downregulated JAK1/STAT3/NLRP3 inflammatory pathway. In parallel, the HMGCS1-NPC1-MAL axis was upregulated, accompanied by increased mevalonate and total cholesterol levels (P < 0.05) and reduced PLIN2 expression (P < 0.001), suggesting decreased lipid droplet accumulation and altered cholesterol metabolism.Molecular docking predicted ginsenosides Rb3, Rk3, Re, Rc, Ro, and Rf may interact with targets related to inflammatory and lipid metabolism. CONCLUSIONS: PQS supported myelin restoration, which is correlated with a modulation of the JAK-STAT signaling pathway and HMGCS1/NPC1-associated lipid homeostasis. PQS may represent a potential therapeutic lead for demyelinating diseases, although mechanisms require further validation.
The Modulation of RAGE by Natural Products and Traditional Medicines: Opening Promising Perspectives for Inflammatory Diseases.
Gelain DP, Ojo OR, Dorcas AO … +2 more , Ajeigbe AS, Moreira JCF
J Ethnopharmacol · 2026 Jul · PMID 42401246 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional and indigenous medical systems have a long history of using medicinal plants to treat conditions now understood as chronic inflammation. This ethnopharmacological knowledge pro...
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional and indigenous medical systems have a long history of using medicinal plants to treat conditions now understood as chronic inflammation. This ethnopharmacological knowledge provides a rich resource for discovering novel anti-inflammatory agents. AIM OF THE STUDY: This review critically evaluates the evidence for the modulation of the Receptor for Advanced Glycation End-products (RAGE) signaling pathway by natural products derived from traditional medicines, aiming to connect this traditional knowledge with modern molecular pharmacology. MATERIALS AND METHODS: A comprehensive literature review was performed using the PubMed database. The search focused on keywords such as "RAGE," "natural products," and "traditional medicine" to identify studies detailing the mechanistic interactions between natural compounds and the RAGE pathway. RESULTS: Natural products, including polyphenols, terpenoids, and alkaloids, modulate the RAGE axis through several key mechanisms: (1) inhibiting the formation of Advanced Glycation End-products (AGEs); (2) directly blocking the RAGE-ligand interaction; (3) downregulating RAGE expression; and (4) suppressing downstream inflammatory signaling. Compounds like quercetin, ursolic acid, and berberine have demonstrated significant activity in various preclinical models. CONCLUSIONS: Natural products represent a profound source of multi-target RAGE modulators, offering a potential therapeutic advantage over synthetic single-target drugs. While challenges in bioavailability and clinical translation remain, the data strongly validates the ethnopharmacological approach. Future progress depends on integrating this traditional wisdom with modern technologies to unlock the full clinical potential of these compounds.
Parinari curatellifolia aqueous leaf-bark extract mitigates chronic Plasmodium berghei-induced bone loss in Wistar rats through anti-inflammatory and osteoregenerative mechanisms.
Jouonzo J, Tsofack FN, Gounoue Kamkumo R … +9 more , Nankap Tsakem JM, Fifen RN, Tcheutchoua YC, Simo-Manefeng AS, Ambamba BDA, Ngondi JL, Ndjakou BL, Sewald N, Dimo T
J Ethnopharmacol · 2026 Jul · PMID 42401245 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Chronic Plasmodium infections can promote parasite sequestration in bone tissue, leading to progressive skeletal damage and increased fracture risk. In Cameroon, Parinari curatellifolia is...
ETHNOPHARMACOLOGICAL RELEVANCE: Chronic Plasmodium infections can promote parasite sequestration in bone tissue, leading to progressive skeletal damage and increased fracture risk. In Cameroon, Parinari curatellifolia is traditionally used to treat both malaria and bone fractures. Previous studies demonstrated protective effects of an aqueous leaves and stem bark mixture extract of this plant (PCM) against acute malaria-induced bone damage. AIM OF THE STUDY: This study investigated the osteoregenerative potential of PCM extract in a chronic Plasmodium berghei ANKA-induced bone loss model in Wistar rats using in vivo and in silico approaches. MATERIALS AND METHODS: Female Wistar rats were alternately inoculated intraperitoneally with P. berghei ANKA for 28 days. They received distilled water, chloroquine sulfate (10 mg/kg), or PCM (75, 150, or 300 mg/kg) daily for 14 days. Parasitemia was monitored throughout treatment. Blood was collected for hematological evaluation, while femurs were excised for biochemical, immunological, oxidative stress, histopathological, and morphometric analyses. Drug-likeness properties and molecular docking of previously identified compounds were evaluated against NLRP3 and Plasmodium falciparum falcipain-2, using Molecular Operating Environment 14. RESULTS: Chronic Plasmodium berghei was characterized by an increase (p < 0.001) in parasitemia and femoral levels of CRP, TNF-α, IL-1β, and IL-6, with a decrease (p < 0.001) of IL-4, IL-10, and IFN-γ levels. Histological analysis revealed femoral head alterations characterized by porous cartilage and significant reductions (p < 0.001) in cartilage thickness and trabecular parameters in infected rats. PCM administration reduced (p < 0.001) parasitemia, restored bone abnormalities by increasing (p < 0.001) alkaline phosphatase activity, calcium, and phosphorus levels. PCM also reduced (p < 0.001) femoral levels of proinflammatory markers, while increasing (p < 0.001) the levels of anti-inflammatory parameters. The extract restored femoral microarchitecture compared with untreated control. Most identified compounds complied with Lipinski's rule of five and exhibited favorable predicted binding affinity toward NLRP3 receptor and falcipain-2. CONCLUSION: P. curatellifolia aqueous extract promoted bone regeneration in a model of chronic Plasmodium-induced osteoporosis. Molecular docking analyses suggested potential interactions between its phytoconstituents and NLRP3 as well as falcipain-2, providing mechanistic hypotheses that warrant further experimental validation. The extract could act through antiplasmodial, osteogenic and anti-inflammatory mechanisms, thus providing a rationale for its traditional use in the management of malaria and bone defects.
Corrigendum to "Nobiletin from Citrus reticulata Blanco alleviates pulmonary fibrosis through inhibiting the PI3K/AKT pathway and epithelial-mesenchymal transition" [J. Ethnopharmacol. 349 (2025) 119965].
Yu S, Liu K, Zhou F … +8 more , Yang X, Zhang J, Yu K, Zhu Y, Qin L, Peng T, Zhang C, He Y
J Ethnopharmacol · 2026 Jul · PMID 42399158 · Publisher ↗
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Xiongzhi Qufeng Zhitong Granule alleviates nitroglycerin-induced migraine-like nociception and central neuroinflammation by regulating the HMGB1 / TRPV1 / MAPK signaling axis.
Huang L, Zhou J, Han Y … +6 more , Mou X, Zheng Y, Liu C, Ou Y, Ding X, Han B
J Ethnopharmacol · 2026 Jul · PMID 42398658 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Chronic migraine (CM) represents a highly prevalent neuroinflammatory disorder with limited therapeutic options. Xiongzhi Qufeng Zhitong Granules (XZQF), a clinically used traditional Chin...
ETHNOPHARMACOLOGICAL RELEVANCE: Chronic migraine (CM) represents a highly prevalent neuroinflammatory disorder with limited therapeutic options. Xiongzhi Qufeng Zhitong Granules (XZQF), a clinically used traditional Chinese medicine, displays promising anti-migraine potential with favorable safety profiles; however, its systematic efficacy and underlying mechanisms remain poorly defined. AIM OF THE STUDY: This study aimed to investigate the protective effects of XZQF on a CM model in rats triggered by nitroglycerin (NTG) injection, and to unveil the potential mechanisms focusing on HMGB1 / TRPV1 / MAPK signaling pathway. MATERIALS AND METHODS: A CM rat model was first established, and the effects of XZQF on CM were evaluated integrating behavioral testing, enzyme-linked immunosorbent assay (ELISA), and histopathological staining analysis. Subsequently, anti-CM mechanism verification, including network pharmacological analysis, immunofluorescence, immunohistochemistry, and Western blotting, were employed to reveal the molecular mechanism of XZQF in regulating HMGB1 / TRPV1 / MAPK signaling axis to against CM. RESULTS: Both behavioral assays, ELISA test, and histopathological assessment demonstrated that XZQF significantly restored body weight and pain thresholds, reduced serum and brain levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), pain modulators (PGE2, 5-HT, β-EP), and vasoactive mediators (CGRP, VIP, NO, iNOS), while alleviating migraine-associated brain tissue damage. Network pharmacology identified core targets (STAT3, NFKB1, JUN, PTGS2, IL1B) and key bioactive components (ferulic acid, senkyunolides E/F, neocnidilide, methyleugenol), with enrichment in MAPK, PI3K-Akt, and cAMP signaling cascades. Immunofluorescence, immunohistochemistry, and Western blotting further validated that XZQF markedly suppressed the expression of CGRP, TRPV1, c-Fos, COX-2, and HMGB1, as well as the phosphorylation of MEK and MAPK. CONCLUSION: Collectively, these findings demonstrate that XZQF exerts robust analgesic, anti-inflammatory, and vasoregulatory effects against CM by blunting central neuroinflammation through the HMGB1 / TRPV1 / MAPK signaling axis. Our work establishes a mechanistic framework for understanding the anti-CM activity of XZQF and supports its further development as a therapeutic intervention for CM.
A Pholidota chinensis-derived dihydrophenanthrene acts as a bioactive constituent to trigger GPx4-mediated ferroptosis in colorectal cancer.
Kao TI, Lam SH, Chen SH … +7 more , Tsai SC, Lee CH, Hsu HT, Huang YC, Chen YL, Chen CH, Chen PJ
J Ethnopharmacol · 2026 Jul · PMID 42398657 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Pholidota chinensis Lindl. has been used as a traditional medicinal plant for heat-clearing and detoxifying purposes, as well as for inflammatory and gastrointestinal conditions. However,...
ETHNOPHARMACOLOGICAL RELEVANCE: Pholidota chinensis Lindl. has been used as a traditional medicinal plant for heat-clearing and detoxifying purposes, as well as for inflammatory and gastrointestinal conditions. However, the bioactive constituents and pharmacological mechanisms underlying the potential effects of P. chinensis in gastrointestinal disorders and colorectal carcinogenesis remain unclear. AIM OF THE STUDY: This study aimed to identify anticancer constituents from the pseudobulbs of P. chinensis and to investigate the pharmacological mechanisms of P. chinensis-derived natural products against colorectal cancer (CRC). MATERIALS AND METHODS: Through bioactivity-directed fractionation, the chromatographic fingerprint of P. chinensis pseudobulbs was analyzed, and phenanthrene-type phytochemicals were isolated and identified. The anticancer potential and pharmacological mechanisms were evaluated using human CRC cells, in silico simulations, and a zebrafish xenograft model. RESULTS: The ethyl acetate (EtOAc) fraction of P. chinensis pseudobulbs exhibited stronger anticancer activity than those of the ethanol and water fractions. A rare dihydrophenanthrene derivative, 1-(4'-hydroxybenzyl)imbricatin (3), was identified from the EtOAc fraction as a potent ferroptosis inducer. Compound 3 showed selective cytotoxicity against human CRC cells while exhibiting lower cytotoxicity toward non-tumor intestinal cells. Compound 3 triggered hallmark features of ferroptosis, including intracellular Fe accumulation, lipid peroxidation, and disruption of the GPx4-related antioxidant defense system. Cellular thermal shift assays and molecular docking further supported the interaction of compound 3 with the catalytic pocket of GPx4. Importantly, compound 3 significantly reduced tumor burden in a zebrafish CRC xenograft model. CONCLUSIONS: These findings highlight the EtOAc fraction of P. chinensis pseudobulbs as a valuable source of anticancer lead compounds and identify 1-(4'-hydroxybenzyl)imbricatin (3) as a promising dihydrophenanthrene scaffold for inducing GPx4-associated ferroptosis in CRC.
Ethyl acetate extract of Poecilobdella manillensis Lesson ameliorates ischemia stroke through inhibiting cell apoptosis and suppressing TLR4/NF-κB-mediates neuroinflammation.
Fang S, Wang T, Li Z … +5 more , Guo Q, Lan Z, Fan Q, Liu Z, Ma L
J Ethnopharmacol · 2026 Jul · PMID 42398656 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Poecilobdella manillensis Lesson is a well-recognized medicinal leech in traditional Chinese medicine and Guangxi Zhuang ethnic medicine. It has long been used to activate blood circulatio...
ETHNOPHARMACOLOGICAL RELEVANCE: Poecilobdella manillensis Lesson is a well-recognized medicinal leech in traditional Chinese medicine and Guangxi Zhuang ethnic medicine. It has long been used to activate blood circulation and remove blood stasis for the treatment of ischemic stroke. Modern pharmacological research has verified its potent anticoagulant and anti-inflammatory activities. Current studies mainly focus on its polypeptide components that exert antithrombotic effects to improve cerebral ischemia, while the neuroprotective potential and related mechanisms of its small-molecule constituents remain largely unclear. AIM OF THE STUDY: This study aimed to investigate the therapeutic effects of the ethyl acetate extract (EA) of P. manillensis on cerebral ischemia-reperfusion injury and to clarify its underlying molecular mechanism. MATERIALS AND METHODS: The chemical constituents of EA were identified by UPLC-Q-TOF-MS/MS. Network pharmacology and molecular docking were used to predict and verify core targets and pathways. Neuroprotective and anti-inflammatory effects of EA were evaluated in a rat MCAO/R model, OGD/R-injured SH-SY5Y cells, and LPS-stimulated BV2 cells, using histological staining, Western blot, immunohistochemistry, and RT-qPCR. RESULTS: Seven small-molecule components were identified in EA, and 314 overlapping targets related to ischemic stroke were screened. Network analysis showed that TLR4 was the core target, and the main enriched pathways included NF-κB, Toll-like receptor, apoptosis and TNF signaling pathways. Consistent with the predicted results, EA significantly reduced cerebral infarct volume and improved neurological deficits in MCAO/R rats, and inhibited neuronal apoptosis and microglial inflammation in vivo. In vitro, EA notably improved the survival of OGD/R-injured neurons and suppressed LPS-induced inflammatory responses in BV2 cells. Meanwhile, EA markedly downregulated the expression of TLR4/NF-κB and NLRP3 inflammasome-related molecules. CONCLUSION: The present study demonstrated that EA protects against cerebral ischemia-reperfusion injury by inhibiting neuronal apoptosis and TLR4/NF-κB-mediated neuroinflammation. These findings provide a scientific basis for the traditional clinical application of P. manillensis and suggest that EA could serve as a potential therapeutic candidate for ischemic stroke.
Corrigendum to "Codonopsis pilosula (Dangshen) decoction promotes NR2F2-dependent pulmonary endothelial repair in an H9N2-induced lung injury model" [J. Ethnopharmacol. 370 (2026) 122078].
Ye Q, Liu Z, Zhang Y … +8 more , Qiao C, Guo H, Zhi Y, Zhang C, Hu G, Zhang T, Wu Y, Zhang Q
J Ethnopharmacol · 2026 Jul · PMID 42392929 · Publisher ↗
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A cell-based affinity mass spectrometry strategy for the rapid discovery of active components from Chinese herbal formulae: Chai-Gui decoction as a study case.
Zhu HJ, Xu YF, Xu C … +4 more , Yao YM, Li Q, Zhang HC, Guo LX
J Ethnopharmacol · 2026 Jul · PMID 42392552 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: As compilations of natural products, Traditional Chinese medicines (TCMs) formulae constitute a rich resource for novel drug discovery. Nevertheless, their complex composition brought abou...
ETHNOPHARMACOLOGICAL RELEVANCE: As compilations of natural products, Traditional Chinese medicines (TCMs) formulae constitute a rich resource for novel drug discovery. Nevertheless, their complex composition brought about significant challenges in identifying bioactive constituents. Chai-Gui Decoction (CGD) is a combination of two classic prescriptions commonly employed in gynecological therapeutics, and its active ingredients remain uncharacterized. AIM OF THE STUDY: This study aimed to establish a cell-based affinity mass spectrometry strategy for the rapid discovery of the active components from complex TCM formulae. This study chose CGD as an example and the G protein-coupled estrogen receptor (GPER) as a target. MATERIALS AND METHODS: A stable HEK293-T cell line overexpressing GPER-1 were established and incubated with CGD to execute ligand screening. Cell membrane fragments were harvested, and the ligand-bound components were isolated and identified by using UPLC-QTOF/MS. The theoretical binding affinities of the fished ligands for GPER were calculated via molecular docking. The compounds exhibiting the highest theoretical affinity were further managed to binding validation using a cellular thermal shift assay (CETSA), and their activity was confirmed through cell-based experiments. RESULTS: A novel fishing assay was developed, which integrated ligand-receptor binding in live cells, cell membrane extraction and lysis, and liquid chromatography-mass spectrometry identification. Seven compounds from the CGD extract demonstrated significantly higher detection levels in GPER-overexpressing cells compared to vehicle control cells. Molecular docking analyses further indicated high binding affinities between these compounds and the GPER protein. Among them, the two compounds with the highest predicted affinity, 16α-Hydroxytrametenolic acid (16α-HTA) and Alisol A, were confirmed to bind GPER by altering its thermal stability in CETSA. Subsequent cellular investigations revealed that 16α-HTA and Alisol A reduced GPER expression at a low dose and suppressed AKT phosphorylation independently of EGFR. CONCLUSIONS: The present study proposes a feasible strategy integrating cell extraction, UPLC-QTOF/MS analysis, molecular docking simulation, CETSA and cell-based experiments, which enables the effective exploration and validation of ligands for protein targets within complex mixtures.
Taohe Chengqi Decoction ameliorates APID-related local uterine inflammatory injury through modulation of inflammation, oxidative stress, and JNK/p38 MAPK-NF-κB-related signaling.
Wang YH, Wang YC, Yuan YF … +9 more , Zhang ZJ, Yan XT, He Y, Peng L, Zhang G, Gao J, Liu JP, Yan YG, Wang HY
J Ethnopharmacol · 2026 Jul · PMID 42392551 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Taohe Chengqi Decoction (THCQD), a classical formula from Shang Han Lun, is traditionally used to clear heat, purge accumulation, activate blood circulation, and dispel blood stasis in low...
ETHNOPHARMACOLOGICAL RELEVANCE: Taohe Chengqi Decoction (THCQD), a classical formula from Shang Han Lun, is traditionally used to clear heat, purge accumulation, activate blood circulation, and dispel blood stasis in lower-jiao blood accumulation and gynecological stasis-heat disorders. Acute pelvic inflammatory disease (APID) frequently affects the upper female reproductive tract during reproductive age, and its acute-stage uterine injury is closely linked to inflammatory imbalance, oxidative stress, and local tissue damage. Therefore, evaluating THCQD in an experimental model of APID-related uterine inflammatory injury may provide evidence for its potential relevance to gynecological inflammatory injury. AIM OF THE STUDY: To evaluate the effects of THCQD in a mechanical-chemical injury-induced rat model of APID-related local uterine inflammatory injury and to explore its possible association with inflammatory responses, oxidative stress, and JNK/p38 MAPK-NF-κB-apoptosis-related signaling. MATERIALS AND METHODS: A rat model was generated using endometrial mechanical injury together with intrauterine injection of phenol mucilage. Pharmacodynamic effects and potential mechanisms were assessed by biochemical assays, ELISA, histopathology, UPLC-MS/MS profiling, network pharmacology, transcriptomics, molecular docking, Western blotting, RT-qPCR, and immunohistochemistry. Cell-based validation was performed using LPS-stimulated primary rat uterine endometrial epithelial cells, H-THCQD-containing serum, and JNK/p38 MAPK inhibitors. RESULTS: THCQD improved inflammatory activation, redox imbalance, peripheral blood inflammatory cell abnormalities, and uterine pathological injury. Integrated analyses and experimental validation supported the possible involvement of JNK/p38 MAPK-NF-κB-apoptosis-related signaling in THCQD intervention. CONCLUSION: THCQD alleviated APID-related local uterine inflammatory injury, and this effect may be associated with the involvement of JNK/p38 MAPK-NF-κB-apoptosis-related signaling. These findings provide experimental evidence for the effects of THCQD on APID-related uterine inflammatory injury and support further mechanistic research on classical formulas in gynecological inflammatory injury.
Migraine Relief: Solutions from Natural Bioactive Products of Traditional Chinese Medicine.
Qin S, Luo M, Yin J … +2 more , Peng C, Li D
J Ethnopharmacol · 2026 Jul · PMID 42392550 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Migraine is a chronic and refractory primary neurological disorder that is characterized by recurrent and pulsating headache accompanied by reversible neurological or systemic symptoms, su...
ETHNOPHARMACOLOGICAL RELEVANCE: Migraine is a chronic and refractory primary neurological disorder that is characterized by recurrent and pulsating headache accompanied by reversible neurological or systemic symptoms, such as visual aura, phonophobia, and gastrointestinal symptoms. Natural bioactive products derived from traditional Chinese medicine (TCM) are regarded as promising candidates for migraine owing to multi-target and pathway synergistic effects. AIM OF THE STUDY: This paper aims to systematically evaluate the therapeutic effects of natural bioactive products from TCM on migraine, elucidate the roles of neurons, microglia, and astrocytes in the pathogenesis of migraine, and propose novel therapies for migraine from TCM. MATERIALS AND METHODS: The publications were summarized from 2015 to 2025 in the Google Scholar, PubMed, and Web of Science databases. The keywords used for the search were "migraine", "neurons", "microglia", "astrocytes", "natural products", and "TCM". The bibliometrics was used to analyze the research hotspots of literature on TCM and migraine over the past decade. The Global Burden of Disease Study 2023 and network pharmacology analysis were conducted on migraine. RESULTS: The abnormal communication between neurons and glial cells contributes to the pathological process of migraine, manifested as cortical spreading depression, neuroinflammation, and central sensitization. Correcting the vicious cycle of headache attacks to restore the disorder between neurons and glia cells is a promising strategy for migraine. TCM bioactive products, such as alkaloids, flavonoids, phenols, glycosides, etc., have been proven to relieve migraine by modulating the excitability of neurons, microglia activation, the increase in reactive astrocytes, and the abnormal cross-talk between neurons and glial cells. It is worth noting that the critical biological molecules targeted by natural bioactive products mainly include Nrf2, NF-κB, and HIF-1α signaling pathways, thereby suppressing inflammatory responses, reducing oxidative stress, ameliorating neurotransmitter disturbances, and restoring mitochondrial function in migraine. CONCLUSION: The roles of neurons and glial cells in migraine, as well as the therapeutic effects of TCM bioactive products on migraine, provide a scientific foundation for a better understanding of the pathological mechanism of migraine and are expected to promote the development of novel therapies for migraine from TCM.
Ethnopharmacological validation of the antinociceptive potential of Calotropis gigantea L. flowers: Phytochemical characterization, safety evaluation, and mechanistic insights from in vivo models.
Nazir MM, Sultana S, Rafique A … +1 more , Ashraf A
J Ethnopharmacol · 2026 Jul · PMID 42386090 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Calotropis gigantea L. is traditionally used in South and Southeast Asia for the management of pain, inflammation, cough, burns, and other disorders. However, scientific evidence supportin...
ETHNOPHARMACOLOGICAL RELEVANCE: Calotropis gigantea L. is traditionally used in South and Southeast Asia for the management of pain, inflammation, cough, burns, and other disorders. However, scientific evidence supporting its traditional use in pain management remains limited. AIM OF THE STUDY: The present study aimed to evaluate the antinociceptive activity, safety profile, phytochemical composition, and possible mechanisms underlying the antinociceptive effects of the ethanolic extract of flowers of C. gigantea (CGEE). MATERIALS AND METHODS: Phytochemical profiling was performed using qualitative screening, total phenolic and flavonoid assays, DPPH radical scavenging assay, and HPLC analysis. Acute and subacute oral toxicity studies were conducted according to OECD guidelines 423 and 407, respectively. Antinociceptive activity was evaluated using hot plate, tail flick, formalin-induced paw licking, and acetic acid-induced writhing models in rats. Mechanistic investigations were carried out using Nalbin, Atropine, Glibenclamide, and Terazosin to assess the involvement of opioidergic, cholinergic, KATP channel, and noradrenergic pathways respectively. RESULTS: Phytochemical screening revealed the presence of phenolics, flavonoids, alkaloids, glycosides, tannins, saponins, amino acids, and reducing sugars. HPLC analysis identified chlorogenic acid, quercetin, gallic acid, syringic acid, vanillic acid, and coumaric acid derivatives. The extract exhibited considerable DPPH free radical scavenging activity with an IC value of 145.77 ± 4.30 μg/mL. In addition, the extract contained high levels of phenolic and flavonoid constituents, with total phenolic content of 98.35 ± 3.12 mg gallic acid equivalents (GAE)/g extract and total flavonoid content of 65.20 ± 2.45 mg catechin equivalents (CE)/g extract. Acute and subacute toxicity studies showed no mortality or significant toxicological alterations. CGEE produced significant (p < 0.05) dose-dependent mg/kg. Mechanistic studies demonstrated the involvement of opioidergic, cholinergic, ATP-sensitive K channel, and noradrenergic pathways. CONCLUSION: The findings provide pharmacological evidence supporting the traditional use of C. gigantea in pain management. The antinociceptive effects may be associated with the synergistic action of phenolic and flavonoid constituents through modulation of multiple nociceptive pathways. CGEE also demonstrated a favorable safety profile, supporting its potential as a source of novel antinociceptive agents.
Antipyretic activity of Phanera strychnifolia stem extract in yeast-induced febrile rats: A plasma metabolomics study.
Kongkiatpaiboon S, Yimsoo T, Kotsaouppara N … +5 more , Tayana N, Schinnerl J, Mahavorasirikul W, Taychaworaditsakul W, Ampawong S
J Ethnopharmacol · 2026 Jul · PMID 42386089 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Phanera strychnifolia is a medicinal plant species distributed in Thailand and the Malay Peninsula. Its stem has been traditionally used for detoxification and reducing fever. AIM OF THE S...
ETHNOPHARMACOLOGICAL RELEVANCE: Phanera strychnifolia is a medicinal plant species distributed in Thailand and the Malay Peninsula. Its stem has been traditionally used for detoxification and reducing fever. AIM OF THE STUDY: This study aimed to evaluate the antipyretic activity of P. strychnifolia stem extract and to elucidate fever associated metabolic alterations using an integrated pharmacological and metabolomics approach. MATERIAL AND METHODS: Antipyretic effects were evaluated in male Wistar rats with baker's yeast-induced fever. Animals were orally administered P. strychnifolia stem extract at doses of 100, 250, and 500 mg/kg, with paracetamol used as a reference drug. Rectal temperature was monitored for 6 h post-treatment. Untargeted plasma metabolomics was performed using LC-MS/MS, and multivariate analyses were applied to characterize fever- and treatment-associated metabolic changes. RESULTS: Phanera strychnifolia stem extract, containing astilbin (9.0% w/w), produced a significant, dose-dependent reduction in rectal temperature; the highest dose (500 mg/kg) showed the most pronounced antipyretic effect, with a response approaching that of paracetamol without inducing hypothermia. Metabolomic analysis revealed that fever induction caused pronounced, system-wide metabolic reprogramming involving energy metabolism, lipid signaling, amino acid utilization, and cellular stress-related pathways. Exploratory PCA and PLS-DA visualizations suggested separation between pyretic and normal metabolic profiles, with partial overlap among some treatment groups. Paracetamol and P. strychnifolia treatment showed a partial movement of metabolic profiles toward the non-pyretic group, particularly at the higher extract dose. CONCLUSION: Phanera strychnifolia stem extract exhibited significant antipyretic activity and was associated with partial modulation of fever-associated metabolic alterations in a yeast-induced fever model. The findings provide scientific evidence supporting its traditional use in fever management.
Trifluoro-icaritin mitigates spared nerve injury-induced neuropathic pain by upregulating spinal α7nAChR through suppressing ferroptosis.
Luo F, Zhong Y, Meng L … +5 more , Chen X, Li W, Wei T, Ma H, Huang C
J Ethnopharmacol · 2026 Jul · PMID 42386088 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium spp. has served as a traditional analgesic herbal medicine in Chinese medicine for over two thousand years. Its active metabolite, icariin (ICT), along with its fluorinated deriv...
ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium spp. has served as a traditional analgesic herbal medicine in Chinese medicine for over two thousand years. Its active metabolite, icariin (ICT), along with its fluorinated derivative, trifluoro-icaritin (ICTF), has been shown in our previous research to alleviate neuropathic pain induced by spared nerve injury (SNI) through an α7 nicotinic acetylcholine receptor (α7nAChR)-dependent pathway. AIM OF THE STUDY: Neuropathic pain remains a significant and unresolved health issue. Ferroptosis has recently been identified as a key, yet insufficiently explored, aspect, and the interaction between ferroptosis and the spinal cholinergic anti-inflammatory receptor α7nAChR remains entirely unknown. This study aims to investigate whether ferroptosis serves as a critical mechanistic link between α7nAChR and the analgesic effects of ICTF. MATERIALS AND METHODS: A spared nerve injury (SNI) rat model was established to investigate neuropathic pain. Pain-related behaviors were assessed through paw withdrawal threshold (PWT) and CatWalk gait analysis. Western blotting and immunofluorescence were employed to detect protein expression and co-localization. Moreover, transcriptomic sequencing of spinal cord tissue was conducted to identify candidate pathways. To establish causality, two independent reverse validation approaches were utilized, including the administration of the ferroptosis agonist Erastin and intrathecal injection of adeno-associated virus to knock down α7nAChR. RESULTS: Transcriptomic analysis revealed a significant enrichment of ferroptosis-associated gene signatures in SNI rat spinal cords, characterized by marked upregulation of pro-ferroptotic genes, including Cybb, Sat1, and Hmox1. Concurrently, SNI markedly decreased neuronal expression of α7nAChR and the ferroptosis-inhibitory enzyme GPX4. Treatment with ICTF (5.0 mg/kg, intraperitoneally), the optimal dosage screened in our prior study, effectively counteracted these alterations, accompanied by attenuation of iron overload, lipid peroxidation, and oxidative stress within the spinal cord.. Reverse validation further demonstrated that Erastin abolished the analgesic and motor-improving effects of ICTF, while concurrently suppressing α7nAChR and GPX4 expression. Moreover, α7nAChR knockdown produced comparable effects, negating ICTF-mediated benefits and further reducing GPX4 levels. CONCLUSION: We found that spinal ferroptosis is markedly activated in SNI rats, thereby exacerbating neuroinflammation and mechanical allodynia. Importantly, ferroptosis suppresses the expression of α7nAChR, while ICTF interrupts this vicious cycle by upregulating α7nAChR, inhibiting ferroptosis-related iron accumulation, lipid peroxidation, and the downregulation of GPX4, ultimately alleviating SNI-induced neuropathic pain. This study offers a scientific interpretation of the traditional use of Epimedium-derived active compounds for treating neuropathic pain at the modern molecular mechanism level.
Senkyunolide a from danggui buxue decoction protects podocytes against diabetic nephropathy via the mir-223-3p/nlrp3 inflammasome axis.
Lv Z, Yu J, Bian D … +3 more , Yao S, Zhang J, Guo D
J Ethnopharmacol · 2026 Jul · PMID 42386087 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue Decoction (DBD), a classical Traditional Chinese Medicine (TCM) formula comprising Astragalus membranaceus (Fisch.) Bunge (Astragali Radix) and Angelica sinensis (Oliv.) Diel...
ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue Decoction (DBD), a classical Traditional Chinese Medicine (TCM) formula comprising Astragalus membranaceus (Fisch.) Bunge (Astragali Radix) and Angelica sinensis (Oliv.) Diels (Angelicae Sinensis Radix) in a 5:1 ratio, has been traditionally used to treat "Xiaoke" (wasting-thirst syndrome) and is increasingly applied as an adjunctive therapy for diabetic nephropathy (DN). DN is a major microvascular complication of diabetes mellitus for which effective curative therapies remain limited. Although DBD has demonstrated promising clinical efficacy in the prevention and management of DN, its pharmacologically active constituents and underlying mechanisms of action have yet to be fully elucidated. AIM OF THE STUDY: This study aimed to comprehensively profile the blood-entering bioactive constituents of DBD, identify the core active compound through integrated UPLC-Q-TOF-MS/MS and network pharmacology analyses, and elucidate the molecular mechanisms by which the core constituent protects against high glucose-induced podocyte injury, with particular focus on the miR-223-3p/NLRP3 inflammasome axis. MATERIALS AND METHODS: UPLC-Q-TOF-MS/MS was employed to globally characterize the chemical constituents of Danggui Buxue Decoction (DBD), and the absorbed components and in vivo metabolites were identified in a DN rat model. Network pharmacology combined with target intersection analysis was used to identify the core active constituents. Subsequently, PPI network construction, GO functional annotation, and KEGG pathway enrichment analyses were performed to elucidate the underlying molecular mechanisms. In a high glucose-induced MPC5 podocyte model, CCK-8, TUNEL, and JC-1 assays were conducted to evaluate the cytoprotective effects of the major active constituents. Furthermore, Western blotting, qRT-PCR, and dual-luciferase reporter assays were performed to clarify the regulatory mechanism of the miR-223-3p/NLRP3 axis. RESULTS: UPLC-Q-TOF-MS/MS identified a total of 1584 chemical constituents in DBD, among which 249 absorbed components and 155 in vivo metabolites were detected in the plasma of DN model rats. Network pharmacology analysis identified senkyunolide A (SA) as the core active constituent, which targeted 33 NLRP3 inflammasome-related proteins, covering the entire activation cascade of this pathway. PPI network construction and enrichment analyses further revealed that SA-associated targets were involved in key biological processes at the systems level, including oxidative stress and PI3K-Akt/NF-κB signaling pathways. In vitro experiments demonstrated that SA at a concentration of 50 μmol/L significantly ameliorated high glucose-induced podocyte injury, apoptosis, and mitochondrial dysfunction. Mechanistically, SA upregulated miR-223-3p expression, thereby directly inhibiting NLRP3 inflammasome activation, which in turn suppressed Caspase-1 cleavage and GSDMD-mediated pyroptosis. Meanwhile, SA maintained mitochondrial dynamic homeostasis and energy metabolism by regulating DRP1 phosphorylation, upregulating OPA1 and MFN2, and activating the PGC-1α/MnSOD pathway, ultimately exerting multi-level protective effects on podocytes. CONCLUSIONS: SA is identified as the core bioactive constituent of DBD responsible for its therapeutic effects in DN. SA exerts multi-level renoprotective effects by upregulating miR-223-3p, suppressing NLRP3 inflammasome activation and GSDMD-mediated pyroptosis, and maintaining mitochondrial dynamic homeostasis via the PGC-1α/MnSOD pathway. These findings provide a scientific basis for the rational application of DBD in the clinical prevention and treatment of diabetic nephropathy and highlight the miR-223-3p/NLRP3 axis as a promising therapeutic target.
Metabolic profiling of Piper regnellii (Piperaceae) and its dual anti-inflammatory and anti-urolithiatic effects.
de Oliveira Silva D, Costa LPM, Salem PPO … +9 more , Katchborian-Neto A, da Silva PRS, Viana GS, da Silva JS, Murgu M, Dias DF, Edrada-Ebel R, Chagas-Paula DA, Soares MG
J Ethnopharmacol · 2026 Jun · PMID 42379540 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Piper regnellii ("Pariparoba"), is a shrub widely employed in traditional medicine, particularly in the form of leaf infusions or decoctions. These preparations are traditionally used for...
ETHNOPHARMACOLOGICAL RELEVANCE: Piper regnellii ("Pariparoba"), is a shrub widely employed in traditional medicine, particularly in the form of leaf infusions or decoctions. These preparations are traditionally used for the treatment of wounds, infections, edema, skin lesions, pain, and other inflammatory conditions. AIM OF THE STUDY: Building upon traditional reports of P. regnellii associated with inflammatory conditions, this study combined chemical profiling and bioactivity assays to evaluate its inhibitory effects on key inflammatory mediators (PGE and LTB), alongside its effects on the reduction of calcium oxalate (CaOx) crystals. MATERIALS AND METHODS: The anti-urolithiatic activity of P. regnellii infusion was evaluated using urine containing calcium oxalate (CaOx) crystals at concentrations of 0.5, 1.0, and 1.5 mg/mL. The results were compared to negative and positive controls (sodium citrate and Cystone®). Anti-inflammatory activity was assessed using an ex vivo human whole blood assay, evaluating key inflammation mediators, prostaglandin E (PGE) and leukotriene B (LTB). The infusion's chemical profile was determined by UHPLC-ESI-HRMS in positive ion mode, using a gradient chromatographic method. Data were processed using MZmine software, and chemical annotation was performed utilizing in-house and online databases. RESULTS: In the ex vivo anti-inflammatory assay, infusion samples significantly reduced LTB and PGE levels with significant statistical differences compared to the negative control (p≤0.05). The infusion demonstrated inhibition percentages of 57.4% and 75.1% for the release of LTB and PGE, respectively. In the in vitro anti-urolithiatic evaluation, all tested concentrations of P. regnellii showed statistically significant differences compared to the negative control (p≤0.05), with the highest concentration (1.5 mg/mL) demonstrating the strongest crystal reduction capacity (90.4%) and a calculated IC value of 0.21 mg/mL for anti-urolithiatic activity. Metabolic profiling of the aqueous extract revealed the presence of multiple bioactive compounds. The predominant classes of annotated compounds found on P. regnellii infusion were flavonoids, and other classes of compounds were also found. From all detected metabolites, 12 could be annotated at level 2 of confidence. CONCLUSIONS: This study provides scientific evidence supporting the traditional use of P. regnellii infusion related to inflammatory conditions. Additionally, the evaluation of its anti-urolithiatic effects expands the preliminary pharmacological insights into this species. Collectively, these findings suggest that P. regnellii may represent a promising source of bioactive compounds for the development of multitarget strategies addressing both inflammatory processes and urolithiasis-associated mechanisms.
Saururus chinensis (Lour.) Baill.: A comprehensive review of botany, traditional uses, phytochemistry, pharmacology, quality control, pharmacokinetics, and toxicology.
Zhao R, Zhang J, Tian X … +5 more , Wang C, Shan G, Kuang H, Yang L, Jiang H
J Ethnopharmacol · 2026 Jun · PMID 42379539 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Saururus chinensis (Lour.) Baill. is a traditional medicinal herb widely used in East Asia, with a long history of use in traditional Chinese medicine and traditional Korean medicine. It i...
ETHNOPHARMACOLOGICAL RELEVANCE: Saururus chinensis (Lour.) Baill. is a traditional medicinal herb widely used in East Asia, with a long history of use in traditional Chinese medicine and traditional Korean medicine. It is traditionally used to clear heat, detoxify, promote diuresis, and reduce swelling, particularly for damp-heat-related disorders. Given its long-standing ethnomedicinal use, S. chinensis has considerable potential for further development. AIM OF THE REVIEW: Although studies on S. chinensis have increased rapidly, no comprehensive systematic review dedicated to this species is available. This review summarizes its botany, traditional uses, phytochemistry, pharmacology, quality control, pharmacokinetics, and toxicity, with the aim of evaluating its therapeutic potential and identifying current research gaps. MATERIALS AND METHODS: Relevant literature is systematically retrieved from PubMed, Web of Science, CNKI, and other major databases. The collected studies are screened, organized, and comprehensively analyzed. RESULTS: A total of 232 compounds have been identified from S. chinensis, with lignans as the predominant class of constituents. Available studies indicate that S. chinensis exhibits antitumor, anti-inflammatory, cardiovascular-protective, neuroprotective, multiorgan-protective, metabolic-regulatory, antioxidant, antimicrobial, skin-protective, anti-asthmatic, anti-allergic, and bone-protective activities. However, several issues remain, including unclear toxic mechanisms, the lack of a well-defined safe dosage range, insufficient understanding of synergistic effects, low bioavailability, and incomplete quality control. CONCLUSIONS: S. chinensis shows considerable potential for further development. Future studies should address these issues to support the safe, effective, and standardized development and application of this medicinal plant.
Xin-Zi-Sheng-Wan decoction alleviates hyperuricemia-associated renal injury by inhibiting RIPK1/RIPK3/MLKL-mediated necroptosis.
Chen J, Zhu L, Huang W … +8 more , Wang Z, Gao Y, Fan M, Qiao H, Bao H, Zeng C, Wang F, Cheng J
J Ethnopharmacol · 2026 Jun · PMID 42379538 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Xin-Zi-Sheng-Wan Decoction (XZSWD) is a modified formulation derived from the classical prescription Zi-Sheng Pill, which was recorded in Xian Xing Zhai Yi Xue Guang Bi Ji from the Ming Dy...
ETHNOPHARMACOLOGICAL RELEVANCE: Xin-Zi-Sheng-Wan Decoction (XZSWD) is a modified formulation derived from the classical prescription Zi-Sheng Pill, which was recorded in Xian Xing Zhai Yi Xue Guang Bi Ji from the Ming Dynasty. Traditionally, this formula is used to eliminate "turbid stagnation" and restore metabolic balance. Contemporary ethnopharmacological evidence indicates that XZSWD can reduce uric acid (UA) levels and ameliorate renal injury, although the molecular mechanism underlying these effects remains incompletely understood. AIM OF THE STUDY: The aim of this study was to determine whether XZSWD mitigates hyperuricemia-associated renal injury and to elucidate the underlying mechanisms, with a particular focus on RIPK1/RIPK3/MLKL-mediated necroptosis and oxidative stress in vivo and in vitro. METHODS: UPLC-QTOF/MS was used to profile XZSWD constituents. A hyperuricemia mouse model was established in C57BL/6J mice using hypoxanthine plus potassium oxonate, followed by XZSWD or febuxostat treatment; serum UA, Cr, and BUN and renal histopathology were assessed, together with Western blot and immunofluorescence. RNA-seq (GSE300922), network pharmacology, and molecular docking were performed to identify key targets and pathways. In vitro, HK-2 cells were treated with tumor necrosis factor-alpha (TNF-α), necroptosis inhibitors, apoptosis inhibitors and XZSWD-medicated serum, and cell viability and Annexin V-FITC/PI flow cytometry were conducted. RESULTS: XZSWD lowered serum UA and improved renal function, alleviating tubular injury and fibrosis in hyperuricemic mice. RNA-Seq and network analyses implicated TNF signaling and necroptosis. In HK-2 cells, XZSWD improved viability, reduced reactive oxygen species (ROS) accumulation, and suppressed RIPK1/RIPK3/MLKL phosphorylation, consistent with inhibition of necroptotic cell death. CONCLUSIONS: XZSWD ameliorates hyperuricemia-associated renal injury by attenuating TNF-α-driven RIPK1/RIPK3/MLKL-mediated necroptosis and oxidative stress.
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