J Ethnopharmacol [JOURNAL]
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200 papers
Jinhuang San alleviates plasma cell mastitis by restoring Th17/Treg balance through the HTR7/IL-6/JAK2/STAT3 axis.
Meng Z, Liu M, Weng X … +3 more , Wu L, Wu H, Xue R
J Ethnopharmacol · 2026 Oct · PMID 42242601 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Jinhuang San (JHS) is a traditional topical medication for "mastitis". It is currently used in the treatment of plasma cell mastitis (PCM), but its mechanism remains unclear. AIM OF THE ST...
ETHNOPHARMACOLOGICAL RELEVANCE: Jinhuang San (JHS) is a traditional topical medication for "mastitis". It is currently used in the treatment of plasma cell mastitis (PCM), but its mechanism remains unclear. AIM OF THE STUDY: This study aimed to investigate the therapeutic mechanism of JHS in PCM through chemical characterization, immune microenvironment analysis, and experimental validation. MATERIALS AND METHODS: The chemical constituents of JHS were characterized by UPLC-Q-Orbitrap-MS/MS. A PCM-like mouse model was established by intraductal injection of human PCM-derived breast tissue homogenate emulsified with complete Freund's adjuvant. JHS was topically administered for 7 consecutive days. Transcriptomic sequencing and public single-cell RNA-seq data were integrated to profile the immune microenvironment. A macrophage-CD4 T cell co-culture system was established, and LP-44 (a selective HTR7 agonist) together with recombinant IL-6 was used for mechanistic validation. An in silico HTR7 perturbation analysis was also performed. RESULTS: 30 major constituents were identified in JHS. Single-cell reanalysis indicated prominent macrophage infiltration and Th17/Treg imbalance in PCM. Molecular docking suggested potential interactions between several identified constituents and HTR7. In vivo and in vitro experiments showed that JHS reduced HTR7 expression, decreased IL-6 production, and attenuated JAK2/STAT3 phosphorylation; these effects were partially reversed by LP-44 or recombinant IL-6. Virtual HTR7 knockout altered immune-related genes (IL-6, JAK2, STAT3, FOXP3) and enriched Th17 pathways. CONCLUSION: JHS alleviated experimental PCM and restored Th17/Treg balance, potentially through modulation of the HTR7/IL-6/JAK2/STAT3 axis in macrophages. These findings provide an experimental basis for further clinical evaluation of JHS in PCM.
Comprehensive phytochemical and pharmacological investigation of Cynoglossum clandestinum desf. ethanolic leaf extract: In vitro, In vivo, and In silico assessment of antioxidant, anti-inflammatory, and antidepressant properties.
Hmamou A, El Khomsi M, Bendaoud A … +5 more , Khibech O, Bouakline H, Laftouhi A, Idrissi AM, Lahkimi A
J Ethnopharmacol · 2026 Nov · PMID 42242600 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Cynoglossum clandestinum Desf. (C. clandestinum Desf.) is a wild Moroccan medicinal species traditionally used for wounds, burns, microbial infections, and inflammatory skin disorders. AIM...
ETHNOPHARMACOLOGICAL RELEVANCE: Cynoglossum clandestinum Desf. (C. clandestinum Desf.) is a wild Moroccan medicinal species traditionally used for wounds, burns, microbial infections, and inflammatory skin disorders. AIM OF THE STUDY: This work aimed to characterize the phytochemical composition of the ethanolic leaf extract of C. clandestinum Desf. and to evaluate its antioxidant, anti-inflammatory, and antidepressant-like activities using in vitro, in vivo, and in silico approaches. MATERIALS AND METHODS: Leaves were macerated in absolute ethanol to obtain a reproducible ethanol-soluble fraction. Total phenolic and flavonoid contents were determined, and major compounds were identified by HPLC-DAD. Antioxidant activity was assessed by DPPH radical scavenging and total antioxidant capacity assays. Anti-inflammatory activity was evaluated in the carrageenan-induced paw edema model, and antidepressant-like activity was assessed in the forced swimming test in rats. Major identified compounds were further examined by ADMET prediction and molecular docking. RESULTS: The extract contained 51.25 ± 1.06 mg GAE/g of total phenolics and 41.14 ± 1.81 mg QE/g of total flavonoids. HPLC-DAD identified six major phenolics, with quercetin-3-glucoside (12.08%) and epicatechin (10.17%) as the most abundant compounds. The extract showed strong antioxidant activity (DPPH IC = 0.290 ± 0.03 μg/mL; TAC = 295.83 ± 6.71 mg AAE/g), dose-dependent anti-inflammatory activity (63.64% edema inhibition at 400 mg/kg at T6), and a significant reduction in immobility time in the forced swimming test. Docking suggested quercetin-3-glucoside as the best xanthine oxidase binder, whereas quercetin showed the highest affinity for COX-2 and MAO-A. CONCLUSION: The ethanolic leaf extract of C. clandestinum Desf. is rich in bioactive phenolics and shows promising antioxidant, anti-inflammatory, and antidepressant-like effects. Quercetin-3-glucoside appears to be the main antioxidant-oriented lead, whereas quercetin is the most promising anti-inflammatory and antidepressant-oriented lead. Further studies on isolated compounds, toxicity, and pharmacokinetics are required.
Bakuchiol, a potentially toxic component in Fructus psoraleae, causes liver damage in vitro by affecting the homeostasis of the liver GABA signalling system.
Xu Y, Wu Y, Zhang H … +5 more , Li X, Yang Z, Li Y, Yin F, Li W
J Ethnopharmacol · 2026 Nov · PMID 42242599 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Psoraleae (FP) is an herbal medicine widely used in East Asia. Nevertheless, numerous reports have documented its toxicity, including adverse reactions involving the liver, kidney,...
ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Psoraleae (FP) is an herbal medicine widely used in East Asia. Nevertheless, numerous reports have documented its toxicity, including adverse reactions involving the liver, kidney, and skin. The underlying toxic components and mechanisms remain unclear, which severely limits its clinical application. AIM OF THE STUDY: This study aimed to identify potentially toxic components in FP and to further elucidate their mechanism of toxicity. MATERIALS AND METHODS: Potentially toxic components in FP were rapidly screened using a zebrafish model. Potential hepatotoxicity-related targets and pathways were identified by integrating network toxicology with molecular docking, and the candidate targets were subsequently validated. RESULTS: Fifteen components of FP were evaluated for acute toxicity in zebrafish. Bakuchiol, bavachinin and corylifolinin - the three compounds exhibiting the highest c/LC values - adversely affected normal hepatic function in zebrafish and induced oxidative stress responses. Bakuchiol was further identified as the component with the greatest hepatotoxic potential and was demonstrated to disrupt the homeostasis of the γ-aminobutyric acid (GABA) signalling system in the liver at 1, 5 and 10 μM by altering Cl levels and upregulating GABA receptor expression. Moreover, the GABA receptor antagonist flumazenil was able to counteract bakuchiol-induced hepatotoxicity. CONCLUSION: Bakuchiol, by virtue of its high content and potent toxicity, is a potential hepatotoxic component of FP. It disrupts hepatic GABA system homeostasis by affecting Cl channel and GABA receptor expression.
Corrigendum to "Danlong Oral Liquid alleviates airway remodeling in asthma by targeting the S1PR2/ROCK1/YAP signaling pathway in airway smooth muscle cells" [J. Ethnopharmacol. 362 (2026) 121347].
Zhou M, Xiang M, Li Y … +2 more , Wang Z, Lin J
J Ethnopharmacol · 2026 Nov · PMID 42236378 · Publisher ↗
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Rosmarinic acid in Suhuang antitussive capsule alleviates cough variant asthma by targeting EGFR.
Sun J, Jiang H, Tian Q … +4 more , Sui Y, Chen L, Wang Y, Tan N
J Ethnopharmacol · 2026 Nov · PMID 42235719 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Suhuang antitussive capsule (SH) is one of the commercially available traditional Chinese medicines (TCMs) used clinically for cough variant asthma (CVA). Over the past decade, our laborat...
ETHNOPHARMACOLOGICAL RELEVANCE: Suhuang antitussive capsule (SH) is one of the commercially available traditional Chinese medicines (TCMs) used clinically for cough variant asthma (CVA). Over the past decade, our laboratory has systematically investigated the pharmacological properties of SH and established its potent antitussive, anti-inflammatory, expectorant, and antiasthmatic activities. In preliminary screening, rosmarinic acid (RA) detected in SH showed anti-CVA activity in vitro. AIM OF THE STUDY: This study aimed to investigate the efficacy and mechanism of RA, as an active component of SH, for alleviating CVA. MATERIALS AND METHODS: Ovalbumin/aluminum hydroxide (OVA/Al(OH)) sensitization and challenge created a CVA rat model. Complementary in vitro models were generated by lipopolysaccharide (LPS) stimulation of BEAS-2B and RAW264.7 cells. Therapeutic efficacy was evaluated by cough assay, histopathology, and immune cell counts. Mechanisms were examined by Western blotting, immunofluorescence, and immunohistochemistry. Network pharmacology identified EGFR as a key target. Molecular docking, CETSA, and DARTS assays were performed to validate direct RA-EGFR engagement, and agonist rescue experiments tested EGFR-dependent efficacy. RESULTS: RA markedly alleviated key CVA-associated phenotypes in vivo, supporting RA as an antitussive component of SH. Consistently, RA attenuated LPS-driven inflammatory activation in BEAS-2B and RAW264.7 cells in vitro. RA downregulated EGFR and suppressed downstream EGFR/ERK and AKT/NF-κB signaling, accompanied by reduced inflammatory responses and improved pathological changes for CVA; these effects were reversed by EGFR agonist stimulation. CONCLUSION: This study demonstrates that RA exerts its therapeutic effect against CVA by inhibiting EGFR, thereby establishing it as a key antitussive component of SH.
Broussochalcone A alleviates cognitive impairment in scopolamine-induced mice as a potent β-amyloid aggregation inhibitor and changes blood and brain metabolite profiles.
Oh JM, Jeong WK, Son HJ … +11 more , Kwon YJ, Kim SY, Oh TW, Ji M, Baek M, Shin WH, Kim HJ, Choi B, Kim SH, Paik MJ, Kim H
J Ethnopharmacol · 2026 Nov · PMID 42235718 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Broussonetia papyrifera (BP) has been used for traditional medicine in amelioration of cognitive decline. Accumulation of β-amyloid (Aβ) plaques majorly contributed to the pathogenesis of...
ETHNOPHARMACOLOGICAL RELEVANCE: Broussonetia papyrifera (BP) has been used for traditional medicine in amelioration of cognitive decline. Accumulation of β-amyloid (Aβ) plaques majorly contributed to the pathogenesis of Alzheimer's disease (AD). AIM OF THE STUDY: This study aimed to investigate the role of broussochalcone A (BCA), a bioactive constituent of BP, in alleviation of cognitive impairment via Aβ aggregation inhibition in model mice. METHODS: We screened a potent Aβ aggregation inhibitor from a herbal library and analyzed its effect on improving cognitive functions in model mice and principal protein expression. In addition, we compared the metabolite profiling of blood and tissues. We used the aggregation inhibition assay to screen 960 herbal compounds using Aβ-, and a leading compound was selected based on drug-like properties. Animal behavioral tests including the Morris water maze were performed using scopolamine (SCO)-treated mice. Western blotting and histopathological analysis were performed. Key compounds in the blood, hippocampus, and cortex were analyzed to compare the metabolic profiles. RESULTS: BCA was a potent Aβ aggregation inhibitor (IC = 1.75 ± 0.021 μM) with a predicted binding energy of -6.405 kcal/mol, and nontoxic to MDCK and SH-SY5Y cells. Molecular dynamics simulation revealed that the atomic contact numbers of BCA with Aβ were highly fluctuated during 100 ns; however, the transient contacts might prevent the aggregation. Cognitive function was significantly improved in BCA-treated mice in behavioral tests. Western blotting and histopathological analysis demonstrated that BCA treatment attenuated apoptosis, preserved hippocampal pyramidal neuron integrity, and alleviated SCO-induced spatial memory impairment. Metabolite profiling demonstrated that BCA modulated the metabolic pathways related to energy metabolism, redox homeostasis, amino acid turnover, and lipid metabolism in the serum and brain tissues, partially attenuating SCO-associated metabolic alterations. CONCLUSIONS: BCA is a potent Aβ aggregation inhibitor and exhibits significant cognitive improvement, as well as neuroprotective effects, decreasing inflammation, and retaining neuron structures. In addition, BCA induced distinct metabolic alterations in the serum and brain tissues compared to SCO. These results strongly support the use of BCA as a promising candidate for the amelioration of cognitive impairment and application to AD therapeutics.
Standardized ethanolic extract of the Thai herbal compress Ya-Pra-Kob: Phytochemical profiling, anti-inflammatory activity, and skin permeation potential.
Kaewkenma R, Sakloetsakun D, Laophongphit A … +1 more , Tuntiyasawasdikul S
J Ethnopharmacol · 2026 Oct · PMID 42235717 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: The Thai herbal compress Ya-Pra-Kob (YPK) has traditionally been used in Thai traditional medicine to relieve musculoskeletal pain and promote rehabilitation. However, its preparation proc...
ETHNOPHARMACOLOGICAL RELEVANCE: The Thai herbal compress Ya-Pra-Kob (YPK) has traditionally been used in Thai traditional medicine to relieve musculoskeletal pain and promote rehabilitation. However, its preparation process is time-consuming and lacks standardization. AIM OF THE STUDY: This study aimed to develop a standardized ethanolic extract of the YPK formulation and evaluate its phytochemical profile, safety, pharmacological activity, skin penetration behavior, and stability. MATERIALS AND METHODS: Active compounds in the YPK extract were characterized and standardized using validated HPLC and GC-MS methods. Cytotoxicity and genotoxicity were assessed using the MTT assay and Ames test, respectively. Anti-inflammatory activity was evaluated by measuring the inhibition of nitric oxide and prostaglandin E production in LPS-stimulated RAW264.7 cells. Skin penetration was investigated using an ex vivo porcine ear skin model. RESULTS: The optimized extract contained high levels of bioactive compounds, including phenylbutenoid derivatives and curcuminoids (0.58-3.07 mg/g extract). The extract demonstrated significant antioxidant and anti-inflammatory activities, including suppression of inflammatory gene expression, with low cytotoxicity and no mutagenic effects. Skin permeation studies revealed limited transdermal absorption, with most active compounds retained within the skin layers. CONCLUSION: The standardized YPK extract exhibits promising safety, biological activity, and skin retention properties, supporting its potential as a topical herbal ingredient. These findings provide comprehensive scientific evidence to support the modernization and integration of traditional Thai herbal compresses into healthcare applications.
Traditional herbal medicine Hyangsapyeongwi-san inhibits alcohol-induced gastric injury in mice by regulating NLRP3 inflammasome signaling.
Huh E, Ju IG, Kim SH … +9 more , Kang M, Lee S, Park H, Choi M, Choi S, Park SH, Lee H, Jang YP, Oh MS
J Ethnopharmacol · 2026 Oct · PMID 42235716 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Hyangsapyeongwi-san (HPS), known as Xiangsha Pingwei San in Chinese medicine, is a classical herbal formula composed of ten medicinal herbs that has been traditionally used in traditional...
ETHNOPHARMACOLOGICAL RELEVANCE: Hyangsapyeongwi-san (HPS), known as Xiangsha Pingwei San in Chinese medicine, is a classical herbal formula composed of ten medicinal herbs that has been traditionally used in traditional Korean medicine and East Asian medicine for centuries to treat gastrointestinal disorders associated with digestive impairment, including functional dyspepsia and gastritis. In traditional Korean medicine theory, these conditions correspond to "dampness-heat accumulation" and "qi stagnation" patterns affecting the spleen and stomach. HPS is formulated to "eliminate dampness, strengthen the spleen, and regulate qi circulation"-a traditional rationale for which the present study provides molecular evidence by demonstrating suppression of key inflammatory signaling pathways underlying gastric mucosal injury. AIM OF STUDY: This study aimed to investigate the gastroprotective effects of HPS against acute gastric injury and to elucidate its underlying molecular mechanisms, with a focus on NLRP3 inflammasome activation. MATERIALS AND METHODS: Male ICR mice were administered HPS (75 or 300 mg/kg) or ranitidine (40 mg/kg) orally once daily for 4 days prior to HCl/ethanol-induced gastric injury. Gastric damage, NLRP3 inflammasome components, inflammatory cytokines, signaling pathways, and apoptosis markers were assessed. Anti-inflammatory effects were further evaluated in TNF-α-stimulated MKN45 gastric epithelial cells. RESULTS: HPS dose-dependently reduced gastric damage scores and preserved mucosal architecture. High-dose HPS significantly suppressed IL-1β protein, IL-1β mRNA, and TNF-α mRNA expression. HPS inhibited NLRP3 inflammasome activation by reducing NLRP3 and caspase-1 levels, suppressed AKT and NF-κB p65 phosphorylation, and prevented apoptosis. In gastric epithelial cells, HPS attenuated IL-6 and IL-8 expression without cytotoxicity. CONCLUSION: HPS protects against acute gastric injury through NLRP3 inflammasome inhibition via the AKT/NF-κB pathway, providing molecular evidence that supports its traditional use for digestive disorders.
Re Du Ning exerts anti-influenza activity by counteracting viral NS1-mediated suppression of host type I interferon signaling.
Ke S, Chen R, Wang J … +6 more , Bi X, Zhang D, Liu Y, Chen Z, Liu Y, Geng Z
J Ethnopharmacol · 2026 Nov · PMID 42235715 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Re Du Ning (RDN) injection is a modern Chinese herbal formulation with heat-clearing, wind-dispersing, and detoxifying properties. It is clinically used for the treatment of influenza-rela...
ETHNOPHARMACOLOGICAL RELEVANCE: Re Du Ning (RDN) injection is a modern Chinese herbal formulation with heat-clearing, wind-dispersing, and detoxifying properties. It is clinically used for the treatment of influenza-related high fever and upper respiratory tract infections, with validated clinical efficacy and a favorable safety profile. Although its anti-inflammatory activity has been extensively documented, the antiviral effects of RDN against influenza A virus (IAV) remain controversial, and the underlying mechanisms are not fully elucidated. AIM OF THE STUDY: To investigate the mechanisms and active constituents through which RDN exerts anti-influenza activity by counteracting viral nonstructural protein 1 (NS1)-mediated suppression of host type I interferon (IFN-I) signaling. MATERIALS AND METHODS: The anti-IAV efficacy of RDN was evaluated by monitoring mortality, body weight, lung index, pulmonary viral load, and histopathological changes. qRT-PCR and Western blotting were used to quantify IFN-α/β and interferon-stimulated genes (ISG15, MX1, OAS1, and PKR) at defined time points in vivo, as well as to assess the activation of the IFNAR1/IFNAR2-JAK1/TYK2-STAT1/STAT2 signaling pathway. The contribution of STAT1 and STAT2 to the antiviral effects of RDN was examined using siRNA-mediated knockdown. The effects of NS1 on IFN-I signaling and the inhibitory role of RDN were assessed by evaluating interferon-stimulated response element (ISRE)-luciferase reporter activation, JAK1/TYK2-STAT1/STAT2 phosphorylation, STAT1/STAT2 nuclear translocation, and NS1-associated protein complexes. Chromatographic profiles of RDN and its polarity fractions were obtained by HPLC, and peak constituents were identified by HPLC-Q-TOF-MS/MS. Anti-NS1 constituents were identified using spectrum-effect relationship analysis and subsequently validated. RESULTS: RDN provided significant protection against IAV infection in mice, reducing mortality, attenuating body weight loss, lowering lung index and viral load, and alleviating lung injury. After infection, IFN-α/β expression remained consistently lower in the RDN (H) group than in the model group. In contrast, ISG15, MX1, OAS1, and PKR levels in the RDN (H) group were comparable to those in the model group on days 1 and 2 post-infection, whereas ISG15 and MX1 were markedly elevated on day 4. Consistently, STAT1 and STAT2 phosphorylation was transiently increased on day 4 relative to the model group. siRNA-mediated knockdown of STAT1 or STAT2 reduced, but did not abolish, the anti-IAV activity of RDN. RDN dose-dependently inhibited NS1 (A/Puerto Rico/8/34, PR8)-mediated suppression of ISRE-luciferase activity. NS1 suppressed phosphorylation of JAK1, TYK2, STAT1, and STAT2 and impaired STAT1/STAT2 nuclear translocation. RDN mitigated NS1-mediated suppression of STAT1 and STAT2 phosphorylation and nuclear translocation both in vitro and in vivo. No detectable association was observed between NS1 and either exogenously expressed STAT1 or STAT2; however, NS1 was found to associate with exogenously expressed JAK1 and TYK2, and these associations were attenuated by RDN. Chlorogenic acid was identified as one of the major contributing constituents that weakened the NS1-JAK1 association and mitigated NS1-mediated suppression of STAT1/STAT2 phosphorylation. By contrast, neochlorogenic acid alleviated NS1-mediated inhibition of STAT1 phosphorylation but did not significantly affect NS1-JAK1 or NS1-TYK2 associations. CONCLUSIONS: This study demonstrates that RDN exerts significant anti-IAV activity. JAK1 and TYK2 may be previously underappreciated host kinases associated with PR8 NS1. RDN partially restored host IFN-I-JAK/STAT-ISG antiviral signaling, potentially by attenuating NS1-JAK1/TYK2 associations. Chlorogenic acid was identified as one of the major constituents contributing to the anti-NS1 activity of RDN. These findings provide mechanistic insight into the host-directed antiviral activity of RDN.
Mechanistic investigation of Guizhi Gancao decoction in alleviating isoproterenol-induced chronic heart failure via inhibition of sarcoplasmic/endoplasmic (SR/ER) reticulum Ca-ATPase 2a ubiquitination.
Li R, Yang S, Tang Y … +9 more , Shan X, Zhao P, Guo W, Xu M, Zhang C, Liao W, Lu R, Guo S, Chen H
J Ethnopharmacol · 2026 Nov · PMID 42235714 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Chronic heart failure (CHF) remains a leading cause of mortality globally, with limited therapeutic options targeting its underlying pathological mechanisms. Guizhi Gancao Decoction (GGD),...
ETHNOPHARMACOLOGICAL RELEVANCE: Chronic heart failure (CHF) remains a leading cause of mortality globally, with limited therapeutic options targeting its underlying pathological mechanisms. Guizhi Gancao Decoction (GGD), a classic traditional Chinese medicine formula, has been used for centuries to treat cardiovascular diseases, but its molecular mechanisms in CHF remain elusive. AIM OF THE STUDY: This study aimed to investigate the therapeutic effects of GGD on isoproterenol (ISO)-induced CHF in mice and explore its underlying mechanisms, focusing on the cAMP/PKA signaling pathway, ubiquitin-proteasome system (UPS), and calcium handling. METHODS: A CHF model was established by subcutaneous injection of ISO in C57BL/6 mice. Cardiac function and structural remodeling were evaluated using echocardiography, histopathology (hematoxylin-eosin staining, Masson staining), and molecular markers (ANP, BNP). Serum metabolomics combined with western blotting was used to identify key signaling pathways. Co-immunoprecipitation (Co-IP) and mass spectrometry (MS) were employed to explore protein-protein interactions. Molecular docking and in vitro calcium transient assays validated the functional relevance of key targets. RESULTS: GGD treatment significantly improved ISO-induced cardiac dysfunction, as evidenced by increased ejection fraction (EF), fractional shortening (FS), and reduced left ventricular internal diameters (LVIDs/d). Pathological hypertrophy and fibrosis were attenuated by GGD, particularly at low doses, with downregulated ANP/BNP expression. Metabolomic profiling identified the cAMP/PKA pathway as a critical target, where GGD normalized ISO-induced upregulation of PKA regulatory (RI-α/β) and catalytic (α/β/γ) subunits. Five active ingredients in GGD (e.g., 4-hydroxy cinnamic acid, 18α-glycyrrhetinic acid) exhibited strong binding affinity to PKA. Co-IP-MS revealed PKA interaction with proteasome-related proteins (Psma2, Psmb5, Ube2d3), and GGD inhibited ISO-enhanced PKA-proteasome binding, restoring UPS homeostasis. Importantly, GGD reduced ubiquitin-mediated degradation of SERCA2a, preserved calcium transient dynamics, and improved cardiomyocyte contractility, an effect mimicked by the proteasome inhibitor MG132. CONCLUSION: GGD alleviates ISO-induced CHF by modulating the cAMP/PKA pathway, inhibiting PKA-proteasome interactions, and preserving SERCA2a-dependent calcium cycling. These findings highlight GGD as a promising therapeutic agent for CHF via targeting UPS-mediated SERCA2a degradation. However, because the present study was conducted using a single batch of GGD, the findings should be considered preliminary and require further validation across multiple batches of herbal materials.
Extract of Agathis dammara and its active monomer araucarone attenuate metabolic dysfunction-associated steatotic liver disease by targeting carboxylesterase 2.
Peng A, Wang R, Yu Z … +5 more , Li Y, Ma Z, Hu Y, Qiu Y, Qi R
J Ethnopharmacol · 2026 Nov · PMID 42235713 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, yet effective therapeutic options remain limited. Dysregulated lipid...
ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, yet effective therapeutic options remain limited. Dysregulated lipid metabolism plays an important role in MASLD progression, making it a promising target for intervention. In Malaysia, the resin extract of Agathis dammara (Lamb.) Rich. & A.Rich. (AD) is traditionally used as a health supplement to regulate metabolism and treat inflammatory diseases. Araucarone (AO) is the most abundant monomeric component in AD. However, the therapeutic efficacy of AD and AO against MASLD, as well as their underlying mechanisms of action, remains unknown. AIM OF THE STUDY: The study aimed to clarify the inhibitory effects of AD and AO against MASLD, elucidate their mechanisms of action, and identify their primary molecular target, thereby providing a novel and effective strategy for the treatment of MASLD. METHODS: We evaluated the anti-steatotic effects of AD and AO using in vitro (oleic acid-induced steatosis in LO2 cells and primary mouse hepatocytes) and in vivo (high-fat diet [HFD]- and methionine-choline-deficient diet [MCD]- induced MASLD mice) models. Oil red O staining and lipid quantification were applied to evaluate the severity of hepatic steatosis, while Western blotting and qPCR analyses were used to detect changes in protein or gene expression within the metabolism-related pathways. Proteomics, molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assays (CETSA) were employed to identify the direct target of AO. Functional validation was performed via siRNA knockdown. RESULTS: AD and AO significantly attenuated hepatic steatosis in both in vitro and in vivo models by inhibiting lipid synthesis (via LXRα/SREBP-1c downregulation) and promoting fatty acid oxidation (via PPARα activation). Mechanistically, AO directly bound to carboxylesterase 2 (CES2), enhancing its protein stability and enzymatic activity. CES2 knockdown abolished the lipid-lowering effects of AO, confirming CES2 as the primary functional target. Furthermore, AO increased intracellular free fatty acids (FFAs), which acted as signaling molecules to modulate both the LXRα and PPARα pathways. CONCLUSION: This study identifies AO as the first small-molecule CES2 agonist capable of ameliorating MASLD, highlighting its potential as a novel therapeutic strategy and providing a foundation for further drug development.
Phytochemical screening and safety evaluation of Sedum reflexum L. aerial parts extract: Acute and subacute toxicity in a rat model.
Taher RF, El-Mosallamy AEMK, El-Sammad NM … +3 more , Bastawy N, Ali ME, Hassan SK
J Ethnopharmacol · 2026 Nov · PMID 42235712 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Sedum L. species have long been used in traditional medicine for treating wounds, burns, pain, and ulcers. AIM: This study aims to thoroughly analyze the phytochemical composition and toxi...
ETHNOPHARMACOLOGICAL RELEVANCE: Sedum L. species have long been used in traditional medicine for treating wounds, burns, pain, and ulcers. AIM: This study aims to thoroughly analyze the phytochemical composition and toxicological profile of the methanolic extract of the aerial parts of Sedum reflexum L. (SRM). MATERIALS AND METHODS: Phytochemical profiling was performed using HPLC‒ESI‒MS/MS to characterize the chemical constituents of SRM. For the acute toxicity evaluation, the rats received a single oral dose of SRM at 2000 mg/kg, followed by 14-days observation period. Subacute toxicity was evaluated by daily oral administration of SRM at doses of 150, 300, and 600 mg/kg for 28 days. RESULTS: The analysis using HPLC-ESI-MS/MS identified a total of 59 compounds in SRM. No treatment-related adverse effects or mortality was observed following single or repeated doses, indicating an LD50 above 2000 mg/kg. Compared to the control groups, there were no significant changes in body weight, relative organ weight, food and water intake, or biochemical and hematological parameters in either toxicity study. Histopathological assessments revealed no structural abnormalities in vital organs. CONCLUSION: Based on the current findings, the no-observed -adverse- effect level (NOAEL) for SRM has been determined at 300 mg/kg. However, to establish a more comprehensive safety profile, further long-term studies are recommended.
Water-soluble anthocyanins from Vaccinium myrtillus L. alleviate diabetic kidney disease by targeting ALOX15-mediated lipid peroxidation.
Sun J, Ding X, Zhang YH … +8 more , Fan HM, Shi YL, Yan CY, Huang RT, Liu FN, He RK, He RR, Sun WY
J Ethnopharmacol · 2026 Nov · PMID 42229624 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic kidney disease (DKD) is a major diabetic complication with limited therapeutic options. Vaccinium myrtillus L. (bilberry) has a long history in European traditional medicine for t...
ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic kidney disease (DKD) is a major diabetic complication with limited therapeutic options. Vaccinium myrtillus L. (bilberry) has a long history in European traditional medicine for treating microvascular disorders, inflammatory conditions, and urinary system ailments. As a traditional medicinal food rich in water-soluble anthocyanins, it has been reported to exert nephroprotective effects; however, its bioactive constituents and molecular mechanisms remain poorly defined. AIM OF THE STUDY: This study aimed to investigate the renoprotective effects of a water-soluble anthocyanin-rich bilberry extract (VmE) in DKD, to identify its bioactive components, and to elucidate the underlying molecular mechanisms. MATERIALS AND METHODS: A high-fat diet/streptozotocin-induced DKD mouse model was employed. The chemical profile of VmE was characterized by LC-MS. Renal function, histopathology, and metabolomics were evaluated. Integrated network pharmacology, molecular docking, microscale thermophoresis (MST), and molecular dynamics (MD) simulations were conducted to identify and validate key molecular targets. RESULTS: VmE dose-dependently improved renal function, ameliorated tubulointerstitial injury, and restored metabolic homeostasis. Delphinidin-3-O-glucoside (Dp3Glc) and cyanidin-3-O-glucoside (Cy3Glc) were identified as the major anthocyanins. Both MST and MD simulations confirmed that Dp3Glc and Cy3Glc directly bind to arachidonate 15-lipoxygenase (ALOX15). This interaction inhibited ALOX15-mediated lipid peroxidation, resulting in reduced malondialdehyde (MDA) accumulation and iron overload, as well as restored glutathione (GSH) homeostasis, thereby attenuating ferroptosis in renal tubular cells. CONCLUSIONS: VmE through its major anthocyanins Dp3Glc and Cy3Glc, alleviates DKD by directly targeting ALOX15 and suppressing lipid peroxidation-driven ferroptosis. These findings establish a pharmacological basis for developing VmE as a standardized nutraceutical for DKD management, bridging traditional use with modern mechanistic evidence.
MS/MS-based molecular networking for exploring the chemical diversity of Chiliadenus montanus (Vahl.) brullo and Chiliadenus candicans (Delile) brullo and their anti-ulcer potential via modulation of Nrf2/ICAM-1 in rats.
Shaheen AM, Abdel-Sattar E, El-Kashoury EA … +5 more , Tawfik WA, Mohamed TA, Hegazi NM, Salama AA, Hegazy MF
J Ethnopharmacol · 2026 Oct · PMID 42229623 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Chiliadenus montanus and Chiliadenus candicans are two closely related species that are traditionally used for treating gastric ailments and peptic ulcers; however, their therapeutic effic...
ETHNOPHARMACOLOGICAL RELEVANCE: Chiliadenus montanus and Chiliadenus candicans are two closely related species that are traditionally used for treating gastric ailments and peptic ulcers; however, their therapeutic efficacy lacks scientific validation. AIM OF THE STUDY: This study aims to investigate the gastroprotective potential of both species through comprehensive metabolite profiling, in-vivo biological evaluation, and molecular docking studies. METHODS: Methylene chloride: methanol (1:1) and 70% methanolic extracts from the aerial parts of both C. montanus and C. candicans are subjected to ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) analysis. After this, the gastroprotective efficacy of the extracts is evaluated in an ethanol-induced gastric ulcer model in rats at 200 and 400 mg/kg. Histopathological examination of gastric tissue for all extracts and molecular docking study for the most active extract was established. RESULTS: UPLC-HRMS/MS allowed for the annotation of 217 metabolites, with only 30 metabolites previously reported in the studied species, and one potentially new compound annotated as dihydroxy costic acid O- caffeic acid hexoside, reported for the first time. Both plant extracts significantly attenuate ulcer indices and mitigate gastric inflammation through modulation of the Nrf2/ICAM-1 signaling pathway. Additionally, the extracts demonstrate potent antioxidant and anti-inflammatory activities. CONCLUSION: Both C. montanus and C. candicans show outstanding ulcer protective potential; these effects are attributed to high content of cinnamic acid derivatives, flavonoids, and terpenoid constituents as shown through LC/MS analysis. These findings provide scientific evidence for its traditional use as an herbal tea in the treatment of gastric ulcers by Bedouins in Saint Catherine.
Network toxicology and biolayer interferometry validation reveal the mechanism of Stelleropsis tianschanica Pobed.-induced hepatotoxicity.
Meng X, Jiang WL, Shi LL … +2 more , Ma ZL, Huang XJ
J Ethnopharmacol · 2026 Oct · PMID 42229622 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Stelleropsis tianschanica Pobed. is a perennial herb belonging to the genus Stelleropsis in the family Thymelaeaceae of the order Myrtales, and possesses certain toxicity. In the Zhaosu re...
ETHNOPHARMACOLOGICAL RELEVANCE: Stelleropsis tianschanica Pobed. is a perennial herb belonging to the genus Stelleropsis in the family Thymelaeaceae of the order Myrtales, and possesses certain toxicity. In the Zhaosu region of Xinjiang, it is used medicinally as an expectorant and analgesic, and for the treatment of chronic bronchitis, cough, asthma, and skin diseases. However, beyond its therapeutic efficacy, the potential hepatotoxicity of Stelleropsis tianschanica Pobed. poses a threat to human health. Currently, research regarding its hepatotoxicity remains limited. AIM OF THE STUDY: This study aims to integrate network toxicology, Bio-Layer Interferometry (BLI), and in vitro experiments to systematically explore the toxicological material basis and potential molecular mechanisms underlying liver injury induced by Stelleropsis tianschanica Pobed. MATERIALS AND METHODS: In vivo acute toxicity studies and in vitro cell experiments were employed to determine the hepatotoxic parts of Stelleropsis tianschanica Pobed. Combined with LC-MS/MS analysis, network toxicology prediction, and molecular docking technology, the material basis and potential targets of hepatotoxicity were preliminarily screened. LC-MS/MS combined with Bio-Layer Interferometry (BLI) was applied, using core targets as "bait," to affinity-fish and identify active ingredients from the drug system. Finally, relevant signaling pathways were verified via in vitro cell experiments to reveal the molecular mechanism of hepatotoxicity. RESULTS: In vivo and in vitro evaluations demonstrated that the root parts of Stelleropsis tianschanica Pobed possessed significantly higher toxicity than the aerial parts, characterized by severe liver lesions and elevated transaminases. It may induce hepatotoxic effects by targeting the EGFR-PI3K/AKT-mitochondrial pathway. Daphnoretin, Umbelliferone, and Formononetin were identified as the potential toxic material basis responsible for its hepatotoxicity.
Hydrolysable tannins from Pelargonium graveolens overcome bacterial virulence and resistance through membrane and motility disruption.
El-Otmani N, Blank T, Teufel R … +1 more , Potterat O
J Ethnopharmacol · 2026 Nov · PMID 42229621 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Pelargonium graveolens L'Hér. (Geraniaceae) is traditionally used for the treatment of microbial infections. Its flowers exhibit antibacterial activity, but the bioactive constituents and...
ETHNOPHARMACOLOGICAL RELEVANCE: Pelargonium graveolens L'Hér. (Geraniaceae) is traditionally used for the treatment of microbial infections. Its flowers exhibit antibacterial activity, but the bioactive constituents and their modes of action against multidrug-resistant (MDR) pathogens remain insufficiently characterised. AIM OF THE STUDY: This study aimed to identify the antibacterial compounds from P. graveolens flowers and to elucidate their in vitro effects on virulence-related bacterial phenotypes against clinically relevant MDR bacteria. MATERIALS AND METHODS: A methanolic flower extract was subjected to HPLC-based activity profiling, followed by preparative chromatographic purification. The gallotannins obtained from the active fractions were then evaluated against Gram-positive and Gram-negative MDR clinical isolates harbouring mecA/C, erm, bla-like, bla resistance genes and Panton-Valentine leukocidin (PVL). Antibacterial activity (MIC, IC), biofilm formation, motility (swimming, swarming), efflux pump activity, membrane permeability and depolarization were assessed using biochemical, fluorescence-based and microscopic assays including cryogenic transmission electron microscopy (cryo-TEM). RESULTS: Penta-, hexa-, hepta-, octa- and nonagalloylglucose were identified as the main antibacterial constituents with broad-spectrum activity observed for pentagalloylglucose and higher-order gallotannins. Mechanistic investigations showed that at a concentration of 250 μg/mL, gallotannins significantly impaired bacterial motility, reduced biofilm formation under the tested experimental conditions in a strain-dependent manner, enhanced membrane permeability and depolarization, and strongly inhibited efflux pump activity, exceeding the response induced by the reference proton motive force disruptor carbonyl cyanide 3-chlorophenylhydrazone (CCCP) in some strains. CONCLUSIONS: Gallotannins from P. graveolens exhibited multiple in vitro antibacterial and anti-virulence-related effects, including disruption of membrane-associated functions, motility and efflux-mediated resistance, highlighting their potential as complementary antimicrobial candidates against toxin-producing MDR pathogens and setting the stage for further studies on cytotoxicity towards mammalian cells and selectivity to confirm their therapeutic relevance.
Systemic and topical use of herbal drugs vary by plant organ and chemosensory properties in De MateriaMedica.
Leonti M, Casu L, Cabras S
J Ethnopharmacol · 2026 Nov · PMID 42229620 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Botanical drugs can be used for internal and external applications while some are only applied for either. Aspects such as effectiveness, toxicity organoleptic properties such as shape, te...
ETHNOPHARMACOLOGICAL RELEVANCE: Botanical drugs can be used for internal and external applications while some are only applied for either. Aspects such as effectiveness, toxicity organoleptic properties such as shape, texture, colour, taste and smell can theoretically affect exclusive modes of application. AIM OF THE STUDY: Ethnomedicinal field studies often quantify plant organs mentioned for therapy and give stereotype explanations for their frequency of use without considering taxonomy, therapeutic applications or other factors. We tested for the effect of topical versus systemic applications as well as for the effect of drug shape on gustatory and olfactory perception. MATERIAL AND METHODS: We used therapeutic recommendations of 675 herbal drugs reported in Dioscorides' De Materia Medica. Drugs were assessed by a chemosensory tasting panel in 3843 individual trials. Statistical analysis relies on Generalized Linear Models, like Log-linear and logistic models. RESULTS: Drugs exclusively used topically had a higher share of leaves and herbs compared to those exclusively used systemically. Leaves and herbs were of significantly higher olfactory intensity and complexity but had lower gustatory intensity with respect to more three-dimensional plant drugs. CONCLUSIONS: The higher share of leaves and herbs among drugs exclusively used topically could be influenced by structural and textural properties making them more convenient products for this sort of application but also by stronger olfactory signals relating these drugs to the outside world and the exterior part of the human body. Considering the often-uncritical reporting of plant use patterns in ethnomedical surveys we suggest additional context and nuanced analyses including taxonomy, therapeutic categories, mode of applications and chemosensory qualities when reporting the frequencies of plant parts used.
Shengyang Xiehuo formula regulates lipid droplet-mitochondrial interaction via TNF-α/PPARγ axis to treat chronic atrophic gastritis.
Guo Y, Zhi Z, Wang R … +8 more , Du P, Wang J, Zhang X, Jia X, Cai Y, Du Y, Fang C, Yang Q
J Ethnopharmacol · 2026 Oct · PMID 42229619 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Chronic atrophic gastritis (CAG) is a common and frequently occurring disease of the digestive system. Shengyang Xiehuo Formula (SYXHF) is a classical prescription originating from Li Dong...
ETHNOPHARMACOLOGICAL RELEVANCE: Chronic atrophic gastritis (CAG) is a common and frequently occurring disease of the digestive system. Shengyang Xiehuo Formula (SYXHF) is a classical prescription originating from Li Dongyuan's "Treatise on Spleen and Stomach". In recent years, SYXHF has garnered widespread attention for its therapeutic effects on chronic atrophic gastritis, although its specific mechanisms of action require further investigation. AIM OF THE STUDY: This study employed a combined approach integrating network pharmacology, molecular docking, molecular dynamics simulations, and in vitro/in vivo experimental validation to investigate the therapeutic efficacy of SYXHF on CAG and its underlying mechanisms. MATERIALS AND METHODS: This study analyzed the active components of SYXHF through ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and employed network pharmacology, molecular docking, and molecular dynamics simulation techniques to identify and validate the interactions between the active components of SYXHF and disease targets. The N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) combined with ranitidine compound modeling approach was utilized to induce CAG model in mice, thereby verifying the therapeutic efficacy of SYXHF. MNNG-induced injured gastric mucosal epithelial cells were employed to investigate how SYXHF mediates the TNF-α/PPARγ axis to influence lipid droplet-mitochondrial interactions. RESULTS: UPLC-MS/MS revealed that the main active components of SYXHF include quercetin, decursin, berberine, isoferulic acid, kaempferol, calycosin, baicalin, β-sitosterol, and saikosaponin A. Network pharmacology analysis identified a total of 211 active SYXHF compounds and 373 potential targets. Key targets included STAT3, TP53, JUN, AKT1, IL-6, TNF, and PPARG. Molecular docking and molecular dynamics simulations further validated the interaction relationships between compounds quercetin, kaempferol, and target proteins TNF and PPARG. In vitro and in vivo experiments demonstrated that SYXHF inhibits the PLIN2/ACSL1 interaction by modulating the TNF-α/PPARγ axis, effectively alleviating inflammation, suppressing lipid droplet-mitochondrial interaction, promoting lipid droplet lipolysis to mitigate gastric mucosal pathological damage, and thereby inhibiting the progression of CAG. CONCLUSION: SYXHF inhibits the interaction between PLIN2 and ACSL1 via the TNF-PPARG pathway, regulating lipid droplet-mitochondrial interaction to promote lipid droplet lipolysis, which may represent a novel approach to halt the progression of CAG.
Rosavin mitigates hepatic fibrosis via KLF14-mediated suppression of P2X7 receptor-dependent inflammatory signaling cascades.
Wang WL, Xu ZY, Wang ZH … +3 more , Guo X, Liu XK, Song J
J Ethnopharmacol · 2026 Nov · PMID 42225163 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola crenulata (Hook. f. & Thomson) H. Ohba is a medicinal plant known for its prominent hepatoprotective and immunomodulatory properties. Rosavin (RSV), a phenylpropanoid glycoside is...
ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola crenulata (Hook. f. & Thomson) H. Ohba is a medicinal plant known for its prominent hepatoprotective and immunomodulatory properties. Rosavin (RSV), a phenylpropanoid glycoside isolated from its roots, exhibits regulatory effects on hepatic inflammation. AIM OF THE STUDY: This study elucidates the hepatoprotective activity of RSV and its underlying mechanism in hepatic fibrosis. MATERIALS AND METHODS: C57BL/6 mice were pretreated with thioacetamide (TAA) prior to RSV administration. RNA sequencing analyzed related signaling pathways. Hepatocyte inflammatory injury models were established by treating LX-2 with TGF-β, and HepG2 with TNF-α. Murine peritoneal macrophages (MPMs) were stimulated in vitro with LPS/ATP. To evaluate the functional role of Kruppel-like factor 14 (KLF14), siKLF14 was transfected into LX-2, HepG2, and MPMs. Dual-luciferase reporter assays verified the interaction between KLF14 and the P2X7r promoter. RESULTS: RNA sequencing identified the NOD-like receptor/neutrophil extracellular traps (NETs) signaling pathway is essential for RSV-mediated hepatoprotection against TAA-induced liver injury in mice. RSV upregulated KLF14 expression while downregulating the P2X7r-NLRP3 pathway and its target genes. Silencing of KLF14 by siRNA markedly upregulated P2X7r expression at both mRNA and protein levels in mouse liver, thereby aggravating hepatic inflammatory responses. Deficiency of KLF14 in LX-2, HepG2, and MPMs impaired the inhibitory effect of RSV on the P2X7r-NLRP3 pathway. KLF14 might bind to the P2X7r promoter. Additionally, RSV reduced pyroptosis in MPMs, attenuating the inflammatory. CONCLUSIONS: RSV attenuated the inflammatory response via the KLF14-P2X7r/NLRP3 pathway and inhibited fibrogenesis, suggesting RSV as a potential therapeutic agent for hepatic fibrosis.
Polygonum chinense L. extracts regulate OxInflammation through Nrf2/HO-1/NF-κB signaling pathways.
Guo Y, Cui C, Yang L … +3 more , Yang X, Wu W, Huang X
J Ethnopharmacol · 2026 Oct · PMID 42219072 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum chinense L. (PCL) has long been used in traditional medicine for the management of inflammatory and infection-related conditions, yet the pharmacological basis for these uses rem...
ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum chinense L. (PCL) has long been used in traditional medicine for the management of inflammatory and infection-related conditions, yet the pharmacological basis for these uses remains incompletely defined, particularly in livestock-relevant immune cells exposed to oxidative-inflammatory injury. AIM OF THE STUDY: This study aimed to investigate the antioxidant and anti-oxidative stress-induced inflammatory activities of PCL. ethanol extract and to clarify the underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated porcine alveolar macrophages (PAMs). MATERIALS AND METHODS: The PCL extract was primarily characterized by UHPLC-MS/MS. Antioxidant activity was evaluated by DPPH, ABTS, FRAP and superoxide anion scavenging assays. Preliminary inflammation-related screening and in vitro compatibility were assessed using protein denaturation, erythrocyte membrane stabilization, protease inhibition, hemolysis, CCK-8, LDH, and nitric oxide assays. Intracellular ROS, MDA, SOD, GSH and T-AOC were measured in LPS-induced PAMs, while RT-qPCR, western blotting, confocal microscopy and ML385 intervention were used to examine the involvement of the Nrf2/HO-1 and NF-κB pathways. RESULTS: UHPLC assay revealed 38 tentatively constituents in the PCL extract. The PCL extract showed strong in vitro antioxidant activity, significant inhibition of protein denaturation and protease activity, excellent erythrocyte safety, and cell viability was not significantly affected at concentrations below 50 μg/mL in PAMs. It markedly reduced LPS-induced LDH leakage, NO release, ROS accumulation and MDA production, while restoring SOD, GSH and T-AOC levels. In addition, it upregulated Nrf2 and HO-1 expression and suppressed NF-κB activation and the transcription of TNF-α, IL-1β and IL-6. These effects were partially reversed by the Nrf2 inhibitor ML385. CONCLUSIONS: These findings indicated that PCL ethanol extract exerted significant antioxidative and anti-inflammatory effects in vitro. Its effects were associated with activation of the Nrf2/HO-1 pathway and inhibition of NF-κB signaling, consistent with its traditional use and supporting its potential for further investigation as a natural agent for oxidative stress-related inflammatory conditions.
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