OBJECTIVE:To evaluate therapeutic mechanism of Gastrodia elata Blume and Acorus tatarinowii Schott (GEAT) herb pair in the treatment of epilepsy. METHODS:The anti-seizure effects were evaluated using the maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced acute and kindling seizures. Seizure behaviors and electroencephalography (EEG) activity were assessed. Cognitive function, hippocampal pathology, ultrastructure and key targets NLRP3, caspase-8 and BDNF were also examined. Additionally, network pharmacology and molecular docking analyses were integrated to complement the experimental findings. KEY FINDINGS:GEAT reduced the generalized seizures in the MES model. In the PTZ model, GEAT decreased the seizure stages, prolonged the latent period of epileptic seizures, and decreased the death rate. In the chronic PTZ model, GEAT significantly reduced the Racine score during the kindling process, suppressed spontaneous seizures and EEG abnormalities. It also effectively alleviated cognitive memory impairment and anxiety-like behavior. Furthermore, GEAT attenuated hippocampal neuronal loss, microglial and astrocytes activation and mitochondrial damage, and regulated BDNF, Caspase-8, NLRP3, Caspase-1 and IL-1β protein expression. CONCLUSION:GEAT exerts multi-target effects against epilepsy, associated with synergistic regulation of glial activation, neuroinflammation, and apoptosis involving the NLRP3/caspase-1/IL-1β pathway, thereby providing a robust theoretical and experimental foundation for its clinical translation.
OBJECTIVES:Lymphoma is a prevalent hematologic malignancy with complex pathogenesis involving dysregulated signaling pathways and high treatment resistance. Traditional Chinese medicine (TCM), with its multi-component and multi-target characteristics, has shown unique value in lymphoma treatment. This review systematically summarizes the latest progress in TCM-based lymphoma therapy, focusing on its anti-cancer mechanisms and clinical application prospects. METHODS:A comprehensive literature search was conducted to identify peer-reviewed studies on TCM interventions for lymphoma. Key findings were synthesized regarding the multi-target mechanisms of TCM active components, synergistic effects with conventional anti-cancer therapies, and modulation of the tumour microenvironment. Challenges in the clinical translation of TCM were also analysed. KEY FINDINGS:TCM active components (e.g. ginsenoside Rg3, triptolide, baicalin) exert multi-target effects by regulating oncogenic pathways (NF-κB, PI3K/Akt) and inducing apoptosis, autophagy, and ferroptosis. TCM formulations demonstrate synergistic effects when combined with chemotherapy and radiotherapy, while also modulating the tumour microenvironment. Major challenges include low bioavailability, insufficient targeting, and lack of standardization for compound formulations. CONCLUSION:TCM provides promising multi-target strategies for lymphoma, particularly when combined with conventional therapies. Future optimization should focus on novel drug delivery systems, multi-centre clinical trials, and integration of multi-omics and artificial intelligence technologies to standardize TCM-based protocols.
OBJECTIVES:To synthesize current evidence on the role of glycogen synthase kinase-3β (GSK-3β) in myocardial ischemia-reperfusion injury (MIRI) and evaluate its potential as a therapeutic target. METHODS:This review examines the mechanistic involvement of GSK-3β in MIRI, focusing on mitochondrial permeability transition pore opening, apoptosis, inflammation, autophagy, and associated signaling pathways. Recent pharmacological advances in GSK-3β inhibition and their translational potential were also evaluated. KEY FINDINGS:GSK-3β is a central regulator of the pathophysiological response to MIRI. Its temporal inactivation during reperfusion confers cardioprotection through pathways including PI3K/Akt and mTOR, whereas context-dependent activation may exacerbate myocardial injury. Recent GSK-3β inhibitors show therapeutic promise, although challenges including isoform selectivity and systemic toxicity remain. CONCLUSIONS:GSK-3β represents a complex yet promising therapeutic target in ischemic heart disease. Future research should prioritize precision therapies and biomarker-guided interventions to improve the clinical translation of GSK-3β-targeted strategies.
OBJECTIVES:Intestinal epithelial pyroptosis drives intestinal mucosal injury in colitis. Scutellarin, a natural flavonoid, has been reported to exert anti-colitis activity. However, the mechanism by which scutellarin reverses pyroptosis in intestinal epithelial cells remains elusive. METHODS AND KEY FINDINGS:In LPS + ATP-induced NCM460 cells, scutellarin attenuated purinergic 2X7 receptor (P2RX7) expression and NOD-like receptor family pyrin domain-containing 3 (NLRP3)-mediated pyroptosis. Moreover, scutellarin suppressed K+ efflux and reactive oxygen species (ROS) generation. Scutellarin disrupted the assembly and activation of the NLRP3 inflammasome by blocking the interaction of NLRP3 with apoptosis-associated speck-like protein (ASC) and with NEK7, and by suppressing ASC oligomerization and speck formation. Molecular docking, surface plasmon resonance, and cellular thermal shift assays collectively verified the binding affinity of scutellarin to P2RX7. P2RX7 knockdown experiments further confirmed that the effect of scutellarin on K+ efflux, ROS, and pyroptosis was dependent on P2RX7 regulation. In the dextran sulfate sodium salt-induced colitis model, scutellarin significantly attenuated colitis symptoms, inflammatory responses, and intestinal barrier damage. Scutellarin significantly inhibited the expression of NLRP3, cleaved caspase-1/caspase-1, ASC, and GSDMD-N/Gasdermin D (GSDMD) in the colon. Scutellarin reduced the expression of GSDMD-N in the colonic intestinal epithelial cells (IECs). CONCLUSION:This study demonstrates that scutellarin may ameliorate colitis by suppressing pyroptosis in IECs via the P2RX7/NLRP3 pathway, offering novel insights into its therapeutic mechanism against colitis.
OBJECTIVES:Chronic inflammation, governed by epigenetic networks, underlies a broad spectrum of diseases. In this context, the long non-coding RNA maternally expressed gene 3 (MEG3) has emerged as a pivotal molecular node. This review consolidates current knowledge on MEG3, detailing its genetics, expression regulation, and core mechanisms-primarily its role as a competing endogenous RNA (posttranscriptional regulation) and as a scaffold for chromatin modifiers to modulate inflammatory pathways. KEY FINDINGS:The defining feature of MEG3 is the pronounced context-dependent duality, acting as either a protective factor or a pathogenic driver. Herein, we systematically catalog its dysregulation patterns and implications across arthritic, metabolic, respiratory, digestive, renal, cardiovascular, and cerebrovascular diseases. Furthermore, MEG3 consistently correlates with disease activity, underscoring its biomarker potential, and preclinical evidence supports MEG3 as a therapeutic target. CONCLUSIONS:Clinical translation is currently hindered by inconsistent findings arising from cellular heterogeneity and unstratified disease stages, as well as a lack of tissue-specific delivery strategies. Future research should leverage high-resolution transcriptomics technologies to dissect its precise cell-type-specific functions and enable patient stratification, while integrating molecular diagnostics, interdisciplinary collaboration, and drug design. Such efforts will be essential to harness MEG3 for developing novel diagnostic and therapeutic strategies against inflammation-associated diseases.
OBJECTIVES:Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent pain and a significant decline in quality of life. Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, exhibits significant antipyretic, analgesic, and anti-inflammatory effects. However, its low solubility in water limits its clinical applications. Objective: This study focuses on the preparation of tetrandrine nanocrystals (Tet-NCs) using ultrasound technology and evaluates their therapeutic effects and potential mechanisms in a rat model of adjuvant arthritis (AA). METHODS:The AA model was induced using Freund's complete adjuvant (FCA). Tet-NCs were prepared via ultrasound technology and administered at varying doses. The efficacy of Tet-NCs was compared with that of Tet tablets and indomethacin tablets. The assessed outcomes include joint swelling, arthritis scores, pathological changes in the joints, levels of inflammatory factors (interleukin-6, interleukin-1β, tumor necrosis factor-α, prostaglandin E2, cyclooxygenase-2, vascular endothelial growth factor A, and matrix metalloproteinase-3) in joint cavities and serum, as well as the angiogenesis in synovial tissues and the expression of key proteins-Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3). KEY FINDINGS:Experimental data indicate that the average particle size of the optimized Tet-NCs is 124.30 nm, with a polydispersity index (PDI) of 0.27. The therapeutic effects of low-dose Tet-NCs were comparable to those of Tet tablets, while medium- and high-dose Tet-NCs were significantly more effective than Tet tablets in reducing ankle joint swelling, lowering inflammatory factors levels, and protecting joint structure, and showed no statistically significant difference from indomethacin under the tested conditions. Furthermore, the expression levels of JAK1 and STAT3 in the AA model were significantly reduced by both medium- and high-dose Tet-NCs (all P < .001). CONCLUSION:This study demonstrates that Tet-NCs provide superior therapeutic effects in RA compared to conventional Tet tablets, and their mechanism of action may involve the regulation of inflammation through inhibition of the JAK1/STAT3 signaling pathway. Consequently, Tet-NCs show potential for further development as a novel anti-arthritic agent, although their clinical applicability remains to be validated in future studies. Clinical trial number: not applicable.
BACKGROUND:Asthma is a chronic respiratory disease with a significant global burden. Several risk factors interact to contribute to the development of asthma. Large cross-sectional and longitudinal studies highlight a robust association between asthma and insulin resistance (IR) disorders such as metabolic syndrome, obesity, and T2DM, often leading to worse outcomes and higher morbidity. OBJECTIVE:To critically review current evidence linking IR and asthma, with emphasis on epidemiological associations, pathogenic mechanisms, and potential therapeutic implications, while identifying current knowledge gaps and translational challenges. METHODS:This narrative review was based on literature identified through PubMed, Scopus, and Google Scholar up to December 2025. Epidemiological, mechanistic, experimental, preclinical, and clinical studies relevant to the relationship between IR and asthma were evaluated, with particular attention to distinguishing preclinical findings from available clinical evidence. KEY FINDINGS:Accumulating evidence from epidemiological studies demonstrates a robust association between asthma and IR-related disorders. IR and compensatory hyperinsulinemia may contribute to asthma through multiple interconnected mechanisms, including chronic low-grade inflammation, hormonal and endothelial dysfunction, oxidative stress, glucose intolerance, alterations in the gut microbiota, and shared genetic pathways. These mechanisms may promote airway inflammation, bronchial hyperresponsiveness, and asthma heterogeneity. Emerging preclinical and limited clinical evidence suggests that lifestyle interventions and selected pharmacological therapies targeting metabolic dysfunction may improve asthma-related outcomes. However, much of the current evidence remains observational or mechanistic, and randomized clinical trials specifically evaluating asthma outcomes are scarce. CONCLUSION:IR may represent a common metabolic phenotype contributing to asthma heterogeneity and a potential therapeutic target. Nevertheless, the causal role of IR in asthma and the clinical utility of IR-targeted interventions remain incompletely established. Further prospective and interventional studies are needed to determine whether assessment and treatment of IR should be incorporated into routine asthma management.
OBJECTIVES:The aim of this study was to investigate whether different liquid formulations of a selected candidate drug could be utilized to improve oral absorption and subsequent in vivo exposure. METHODS:Polyethylene glycol 400 (PEG400) formulations with and without pH adjustment and hydroxypropyl-β-cyclodextrin (CD) formulations were prepared alongside amorphous and crystalline suspensions, the latter as micro- and nanocrystals. The suspensions of the compound were manufactured and evaluated for solubility, dissolution rate and in vivo exposure in rats, dogs, and humans, whereas the PEG400 and CD formulations were administered only to rats and/or dogs. KEY FINDINGS:Amorphous microsuspensions of the active pharmaceutical ingredient (API) demonstrated the most promising in vivo results. CD formulation resulted in significantly lower drug exposure than expected. When amorphous suspensions were administered, an absorption difference was observed between male and female rats and a greater than dose linear increase in exposure was noted between two doses in humans. CONCLUSION:This study demonstrated that amorphous suspensions of a newly selected candidate drug resulted in superior oral absorption compared with more commonly used liquid formulations of the API in all investigated species. However, progressing with an amorphous form always carries inherent risks regarding chemical and physical stability.
OBJECTIVES:This study aims to investigate the neuroprotective potential of terpene-linked phloroglucinol derivatives from Eucalyptus tereticornis leaves. METHODS:Euglobals, terpene-linked phloroglucinol derivatives, were isolated using reverse-phase high-performance liquid chromatography (HPLC) and purified by recycle HPLC. Quantification was performed using quantitative 1H NMR. Neuroprotective targets were identified through the GeneCards database, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Network pharmacology integrated molecular docking were employed to identify key bioactive constituents and their targets. The neuroprotective activity of isolated euglobals and the enriched fraction was evaluated in vitro using the N2a neuronal cell line. KEY FINDINGS:High-Resolution Mass Spectrometry (HRMS) and 1H NMR confirmed the presence of euglobals in the enriched fraction of E. tereticornis leaves, with qNMR identifying euglobal-Ia2, euglobal BI-1, and robustadial A and B as major constituents. Network pharmacology and docking revealed the multitarget interactions involving PI3K-Akt, MAPK, mTOR, and NF-κB signalling pathway. In lipopolysaccharide-stimulated N2a cells, tested compounds restored neurite outgrowth, reduced intracellular and mitochondrial reactive oxygen species, suppressed IL-1β, enhanced IL-10, and modulated NF-κb/Nrf2-HO-1-SOD signalling. CONCLUSION:Network pharmacology identified euglobals as potential neuroprotective compounds. Tested compounds exhibited significant neuroprotective effects in the N2a cell line. The integrated approach combining qNMR, network pharmacology, and in vitro validation highlights euglobals as promising neuroprotective agents.
OBJECTIVES:Atherosclerosis significantly contributes to global cardiovascular mortality. Macrophage polarization and foam cell formation via oxidized low-density lipoprotein uptake are key drivers of plaque progression and instability. Targeting these processes may offer a promising therapeutic approach. This study aimed to investigate the potential therapeutic effects of Shanhuang Jiangzhi tablets (SHJZT) using apolipoprotein E-deficient mice and RAW264.7 macrophage-based experimental models. METHODS:Key assays, including oxidized low-density lipoprotein-induced foam cell formation and lipopolysaccharide (LPS)-induced macrophage polarization, were performed to elucidate the regulatory effects of SHJZT, with a particular focus on the reactive oxygen species (ROS)/Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. KEY FINDINGS:In vivo, SHJZT treatment significantly attenuated atherosclerotic lesion development, improved lipid metabolism, and enhanced reverse cholesterol transport by regulating ABCA1 and ABCG1 expression, thereby suppressing foam cell formation. Furthermore, SHJZT promoted macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Mechanistic investigations revealed that SHJZT mitigated LPS-induced ROS production and inhibited the activation of the TLR4/NF-κB signaling cascade in vitro. Specifically, SHJZT downregulated key pathway components, including TLR4, MYD88, and phosphorylated NF-κB p65, in high-fat diet-induced atherosclerosis. CONCLUSION:SHJZT exerts anti-atherosclerotic effects by modulating macrophage polarization and inhibiting foam cell formation through the suppression of ROS/TLR4/NF-κB signaling pathway.
OBJECTIVES:Epilepsy is a chronic neurological disorder affecting nearly 50 million people worldwide and is characterized by recurrent seizures caused by abnormal neuronal activity. Conventional therapies, including antiepileptic drugs, growth factors, and gene therapy, are often limited by poor blood-brain barrier (BBB) penetration, drug resistance, adverse effects, and low bioavailability. This review summarizes recent advances in nanocarrier-based drug delivery systems for improving epilepsy treatment. METHODS:A comprehensive review of peer-reviewed articles, patents, and clinical studies was conducted to evaluate lipid-based, vesicular, polymeric, dendrimer, and inorganic nanocarriers. Their formulation strategies, BBB transport mechanisms, therapeutic applications, clinical progress, and future prospects were critically analysed. KEY FINDINGS:Nanocarriers enhance the solubility, stability, bioavailability, controlled release, and brain targeting of antiepileptic drugs. Liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, dendrimers, nanoemulsions, and metallic nanoparticles have demonstrated improved BBB penetration, prolonged drug action, reduced toxicity, and enhanced seizure control in preclinical studies. Despite promising outcomes, challenges related to large-scale manufacturing, long-term safety, regulatory approval, and clinical translation remain. CONCLUSIONS:Nanomedicine represents a promising approach for overcoming the limitations of conventional epilepsy therapy by enabling efficient brain-targeted drug delivery. Further optimization, safety evaluation, and clinical validation are essential to support the successful translation of nanocarrier-based therapies into clinical practice.
OBJECTIVES:Targeted protein degradation (TPD) technology, with a particular emphasis on proteolysis-targeting chimeras (PROTAC), has emerged as a pivotal advancement in the field of drug discovery. However, several challenges-including the identification of suitable ligands for traditionally undruggable proteins, issues related to poor solubility and permeability, nonspecific biodistribution, and off-target toxicity-have significantly hindered their clinical translation. Peptides, recognized for their ability to serve as promising ligands for broad molecular recognition, exhibit unique potential to address these limitations in TPD applications. METHODS:Literature and related information were collected from online resources such as Google Scholar, Web of Science, PubMed, CNKI, Baidu Scholar, and X-mol. KEY FINDINGS:Recent advancements in peptide-mediated TPD have shown promise in overcoming these challenges as researchers focus on engineering highly selective peptides that enhance binding affinity for traditionally undruggable proteins while optimizing their solubility and permeability, with next-generation delivery systems also developed to reduce nonspecific biodistribution and off-target toxicity, thereby improving the therapeutic potential of peptide-based TPD approaches. CONCLUSIONS:This review summarizes recent advancements in peptide-based PROTAC development, focusing on innovative delivery strategies and methods for enhancing efficiency, while also offering insights into future prospects aimed at optimizing therapeutic precision and efficacy.
OBJECTIVES:Shikonin, a major bioactive naphthoquinone derived from Lithospermum erythrorhizon, exhibits broad pharmacological properties. However, its effects on platelet activation and arterial thrombosis, as well as the underlying mechanisms, remain unclear. METHODS:We integrated network pharmacology with comprehensive in vitro and in vivo assays. Human platelets were utilized to evaluate aggregation, dense granule release, spreading, and clot retraction following shikonin treatment. Arterial thrombosis and hemostasis were assessed in vivo via murine FeCl3-induced mesenteric injury and tail bleeding models. KEY FINDINGS:Network pharmacology analysis suggested that PI3K/Akt-related signaling may be involved in the antithrombotic effects of shikonin. In vivo, shikonin prolonged tail bleeding time and impaired arterial thrombus formation, markedly decreasing thrombus stability and triggering the continuous shedding of unstable emboli. In vitro, shikonin inhibited thrombin- and collagen-induced platelet aggregation, granule secretion, spreading, and clot retraction. Mechanistically, shikonin reduced the phosphorylation of Akt and ERK. CONCLUSION:Shikonin exerts potent antiplatelet and antithrombotic effects, which are associated with the suppression of Akt and ERK phosphorylation. These findings highlight shikonin as a promising candidate for further preclinical investigation as a novel antithrombotic therapy.
OBJECTIVES:This study aimed to develop polylactic-co-glycolic acid (PLGA) microspheres encapsulating dezocine and evaluate their efficacy in managing postoperative pain and mitigating cognitive impairment. METHODS:Dezocine-loaded PLGA microspheres (DEZ@PLGA MS) were fabricated using a single-emulsion solvent evaporation technique and were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and in vitro release studies. A rat model of open reduction and internal fixation for right hindlimb tibial plateau fracture was established in healthy male rats. Following modeling, rats were randomly divided into four groups (n = 6 per group) and received intramuscular injections of equal volumes of normal saline, blank PLGA microsphere suspension, dezocine injection (5 mg/kg), or DEZ@PLGA MS suspension (5 mg/kg). Pain thresholds of the left hind paw and cognitive behavioral tests were assessed at specified time points post-administration. After testing, rats were euthanized. Muscle tissue at the injection site was collected for hematoxylin and eosin (H&E) staining to assess inflammatory responses, and hippocampal tissue was harvested for Western blot analysis. KEY FINDINGS:The SEM results revealed spherical microspheres with a smooth surface and uniform particle size. FTIR and DSC analyses confirmed stable encapsulation of dezocine (DEZ) in the PLGA matrix, with potential intermolecular interactions and amorphous drug dispersion. In vitro release studies demonstrated a sustained release profile of DEZ from the microspheres. Animal experimental results indicated that the DEZ@PLGA MS group exhibited a significantly prolonged duration of effective analgesia compared to the dezocine injection group. Additionally, DEZ@PLGA MS improved cognitive function, as evidenced by cognitive behavioral tests and Western blot results. H&E staining confirmed no significant inflammatory responses in muscle tissue across all groups, highlighting good biocompatibility of the formulation. CONCLUSIONS:Our study demonstrated that DEZ@PLGA MS effectively manages acute postoperative pain over an extended duration and improves postoperative cognitive function.
OBJECTIVES:Norisoboldine (NOR), an isoquinoline alkaloid from Radix Linderae, has known anti-inflammatory properties, but its role in colorectal cancer remains unclear. METHODS:HCT-15, SW480, and HT-29 cells were treated with NOR and assessed via MTT, Western blotting, zymography, wound-healing, invasion assays, and STAT3 loss/gain-of-function experiments. Molecular docking explored NOR-STAT3 interaction. KEY FINDINGS:NOR showed limited cytotoxicity at the concentrations used for mechanistic experiments. NOR decreased the expression of mesenchymal and metastasis-associated proteins, including Vimentin, Twist, Snail, CXCR4, CXCR7, MMP-2, and MMP-9, while increasing E-cadherin and Occludin levels. NOR also reduced gelatinolytic activity and attenuated CXCL12-enhanced migration and invasion. In parallel, NOR decreased phosphorylation of STAT3 and its upstream kinases JAK1, JAK2, and Src, and reduced nuclear accumulation of STAT3. STAT3 knockdown lowered CXCR4, CXCR7, and Snail expression, whereas STAT3 overexpression produced the opposite pattern; NOR partly reversed these changes. Docking analysis suggested that NOR may interact with the SH2 domain of STAT3, although this requires biochemical validation. CONCLUSION:NOR attenuates epithelial-mesenchymal transition and invasive phenotypes in colorectal cancer cells via JAK/STAT3 suppression, positioning it as a candidate anti-metastatic modulator. Further in vivo and target-engagement studies are warranted.
OBJECTIVES:Muntingia calabura L. has long been utilized in traditional therapies, with various plant parts (fruits, leaves, and stem bark) used to treat a range of conditions, including diabetes, inflammatory disorders, and respiratory diseases. This review aims to provide a comprehensive synthesis of current knowledge on M. calabura, including its chemical constituents, biological activities, and emerging applications. METHODS:A comprehensive literature search was conducted using several electronic databases, including PubMed, Web of Science, SciFinder, and ScienceDirect. The search strategy employed keywords such as "M. calabura", "M. calabura", "Jamaican cherry", "botanical characteristics", "distribution", "phytoconstituents", "biological activities", "toxicological profiles", and "green-synthesized nanoparticles". KEY FINDINGS:Based on the synthesis of available literature, a total of 98 flavonoids have been characterized, alongside 22 phenolic compounds, 25 terpenoids, 7 tocopherol derivatives, and other secondary metabolites, demonstrating the diversity of phytochemical constituents from M. calabura. Pharmacological investigations have revealed a wide range of bioactivities, including antidiabetic, anti-inflammatory, antioxidant, antimicrobial, gastroprotective, hepatoprotective, cardioprotective, anticancer, wound-healing, respiratory-supportive, anti-obesity, immunomodulatory, renoprotective, metabolic, and antidepressant effects. Additionally, recent studies highlight its potential as a green bioconstituent for eco-friendly nanoparticle synthesis, extending its relevance to environmental technologies.
OBJECTIVE:We aim to evaluate the influence of A. conyzoides essential oil on uterine contractility, considering hormonal status and potential mechanisms of action. METHODS:Uterine strips from mice at different estrous stages or after ovariectomy were mounted in an organ bath, and contractile responses were evoked by potassium chloride (KCl, 80 mM) following pre-incubation with increasing concentrations of the essential oil, in the presence or absence of nifedipine, a calcium channel blocker. KEY FINDINGS:The oil significantly reduced both phasic and tonic components of KCl-induced contractions (P < .01), demonstrating marked relaxant activity. These effects were consistent across estrous cycle stages but were more pronounced in ovariectomized mice. Nifedipine failed to block the oil's inhibitory action, although a potentiation was observed in the tonic phase during estrus (pIC50; -4671 vs -5734; P < .01). CONCLUSION:A. conyzoides essential oil modulates uterine contractility partly through calcium-independent pathways. This mechanism potentially involves broader smooth muscle signaling mechanisms. The study showcases the therapeutic potential of A. conyzoides in managing uterine hyperactivity and related reproductive disorders.
OBJECTIVES:Gastric ulcer is a pathological condition marked by mucosal lesions resulting from a decrease in protective factors and increased Pro-inflammatory cytokines and ROS. Elevated levels of GLP-1, an incretin hormone released from gastrointestinal cells, have been shown to attenuate gastric ulcer area. METHODS:Rats were randomly assigned in equal numbers (n = 6) to the experimental groups and pretreated with liraglutide at doses of 50 and 100 μg/kg for 14 days. Then gastric ulcers were induced by oral gavage of 99% ethanol. We investigated the protective effects of liraglutide, a GLP-1 agonist, on ethanol-induced gastric ulcer in rats. KEY FINDINGS:Our results showed that pretreatment with 50 and 100 μg/kg liraglutide decreased ulcer area, Pro-inflammatory cytokines such as TNFα, IL-1β, and NFκB, and oxidant malondialdehyde levels in the ethanol-induced groups, while increasing levels of the protective factor PGE2 and antioxidant factor GSH. Furthermore, male rats tended to have more ulcer areas in their gastric tissues compared to female rats. However, no gender-dependent differences were observed in any parameters, excluding PGE2 levels. CONCLUSION:The present study demonstrates that liraglutide administration prior to ethanol exposure may attenuate gastric mucosal damage through enhancement of the defensive barrier as well as antioxidant and anti-inflammatory actions.
OBJECTIVES:To elucidate the therapeutic mechanism of Qufengzhitong Pills (QFZTP) in the treatment of rheumatoid arthritis (RA). METHODS:Blood-absorbed active components of QFZTP and its potential therapeutic targets for RA were screened via liquid chromatography-tandem mass spectrometry (LC-MS/MS) and network pharmacology. Core targets were analyzed using protein-protein interaction networks, with key pathways identified via Gene Ontology/Kyoto Encyclopedia of Genes and Genomes enrichment. Molecular docking was performed for major components and core targets. An IL-1β-induced MH7A cell-based RA model was established; CCK-8, ELISA (IL-6/TNF-α), wound-healing/Transwell, flow cytometry, EdU, and western blot (PI3K/AKT/NF-κB/MAPK pathways) were used to assess cell viability, cytokines, migration, apoptosis, proliferation, and protein expression. KEY FINDINGS:LC-MS/MS identified 92 active components in rat serum, and network pharmacology identified 369 potential QFZTP targets for RA, enriched mainly in TNF signaling, PI3K/AKT, MAPK, and apoptosis pathways. Core components (crocetin, epigallocatechin, bergapten) showed stable binding (<-5.0 kcal/mol) to AKT1, EGFR, and PI3K, occupying similar active pockets as native inhibitors. In vitro, QFZTP-containing serum significantly reduced IL-1β-induced MH7A cell viability; inhibited IL-6/TNF-α secretion (comparable to native QFZTP solution); attenuated migration/proliferation; induced apoptosis; downregulated EGFR, p-PI3K, p-AKT, p-p38, p-NF-κB, and Bcl-2; and up-regulated Bax. CONCLUSION:QFZTP synergistically regulates the PI3K/AKT, NF-κB, and MAPK pathways to inhibit synovial cell proliferation and migration, induce apoptosis, and attenuate inflammation. This study provides a robust theoretical and experimental basis for its clinical application in RA.
BACKGROUND:While nephrotoxicity remains the most recognized adverse effect of cisplatin, hepatotoxicity is increasingly acknowledged as a significant clinical concern. OBJECTIVE:This study evaluated the hepatoprotective effect of dapagliflozin (DAPA), a selective sodium-glucose cotransporter-2 inhibitor, focusing on its modulation of the PI3K/Akt-Nrf2/HO-1 signaling pathway. METHODS:Male Wistar albino rats received oral dapagliflozin (5 or 10 mg/kg/day) for 14 days, with a single intraperitoneal injection of cisplatin (7.5 mg/kg) administered on Day 7. Biochemical, molecular, and histopathological assessments were conducted. RESULTS:Cisplatin induced marked hepatic injury, evidenced by body weight loss, hepatomegaly, hyperglycemia, impaired liver function, oxidative stress, inflammation, and apoptosis dysregulation. Dapagliflozin pretreatment significantly and dose-dependently mitigated these effects. It reduced lipid peroxidation and nitric oxide levels while enhancing antioxidant defenses, including Nrf2, heme oxygenase-1, and superoxide dismutase. Additionally, dapagliflozin restored PI3K/Akt signaling, suppressed NF-κB-mediated inflammatory responses, and normalized apoptotic balance. Histological findings corroborated biochemical results, showing preservation of hepatic architecture, particularly at the higher dose. CONCLUSIONS:Dapagliflozin exerts significant hepatoprotective effects against cisplatin-induced toxicity via antioxidant, anti-inflammatory, and cytoprotective mechanisms, supporting its potential as an adjunct to improve cisplatin safety.
