Kaempferol ameliorates PCOS by alleviating metabolic and endocrine abnormalities as well as oxidative stress.

This study explores how Kaempferol (KAE) protects against oxidative stress-induced damage by suppressing ferroptosis via the Nrf2/GPX4 axis in gastric mucosal cells. Human gastric epithelial cells (GES-1) were treated with H₂O₂ to induce oxidative damage, following pretreatment with varying doses of KAE. Cell vitality was assessed by the CCK-8 experiment, apoptosis was monitored using flow cytometry, and intracellular ROS levels and lipid peroxidation were determined by fluorescence probes. Intracellular malondialdehyde (MDA), glutathione (GSH/GSSG ratio), and Fe²⁺ were measured using biochemical assays. Expression and cellular distribution of Nrf2, GPX4, SLC7A11, and ACSL4 were assessed using Western blot analysis and immunofluorescence techniques. Additionally, the Nrf2-specific inhibitor ML385 was employed to confirm the role of the Nrf2/GPX4 axis. KAE (0-40 μM) was non-toxic and enhanced GES-1 cell viability under H₂O₂-induced stress, with optimal protection at 10 μM. It reduced ROS, lipid peroxidation, MDA, and Fe²⁺ levels, while increasing the GSH/GSSG ratio. KAE also influenced ferroptosis-associated proteins by increasing GPX4 and SLC7A11 expression while reducing ACSL4 levels. Additionally, it promoted Nrf2 nuclear translocation. These effects were attenuated by the Nrf2 inhibitor ML385, indicating involvement of the Nrf2/GPX4 axis. KAE protects against H₂O₂-induced gastric epithelial damage through activating the Nrf2/GPX4 axis, thereby lowering oxidative injury and ferroptotic processes, and offering a potential therapeutic strategy for gastric mucosal protection.

Synergistic induction of calcium overload and ROS burst by a core-shell nanoparticle for potentiated tumor suppression in breast cancer.

Kaempferol (KAE), a bioactive flavonoid, has limited solubility and stability in water. Zein-gum arabic (GA) nanoparticles (NPs) are promising carriers for KAE, but the influence of preparation methods on their structure and properties remains unclear. This study investigated the effect of preparation method on the structure and properties of KAE-loaded zein-GA NPs. The results showed that the NPs prepared by the antisolvent co-precipitation method (GA-zein-KAE) had a smaller particle size, a lower protein dispersibility index, a higher absolute zeta potential value, and greater encapsulation efficiency and loading capacity than NPs prepared by antisolvent precipitation (GA-zein/KAE). The superior performance of GA-zein-KAE likely resulted from the simultaneous solvent displacement of zein, GA, and KAE during co-precipitation, which promoted ternary synergistic co-assembly, homogeneous component distribution, and a stabilized composite matrix. Scanning electron microscopy revealed a smoother and more uniform surface for GA-zein-KAE, and X-ray diffraction demonstrated that KAE was encapsulated in an amorphous state within the NPs. Fluorescence spectroscopy and Fourier transform infrared spectroscopy confirmed hydrogen bonding, hydrophobic interactions, and electrostatic attractions among KAE, zein, and GA. The GA-zein-KAE also demonstrated superior re-dispersibility and stability across varying pH, ionic strength, thermal treatment, and storage conditions as well as higher antioxidant activity and faster KAE release in simulated intestinal fluid compared with GA-zein/KAE. The preparation method had a significant effect on the structure and properties of KAE-loaded zein-GA NPs, in which antisolvent co-precipitation promoted the ternary co-assembly of zein, GA, and KAE, yielding NPs with improved performance. © 2025 Society of Chemical Industry.

Kaempferol ameliorates renal injury by inhibiting Piezo1/HIF-1a/ROS/NLRP3 signaling in chronic kidney disease.

Efficient multi-enzyme system for icaritin production from naringenin with synchronous prenol utilization in Escherichia coli.

Ferroptosis, an iron-dependent regulated necrosis driven by redox imbalance, plays a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Kaempferol (KF), a bioactive flavonoid from Polygonati Rhizoma, exhibits anti-ferroptotic properties in lipid peroxidation disorders, yet its molecular mechanism against cigarette smoke extract (CSE)-induced ferroptosis in human bronchial epithelial cells (BEAS-2B) remains to be fully elucidated. Using invitro models of CSE-induced injury, we observed that KF restored cell viability and attenuated cytotoxicity by restoring redox equilibrium-significantly elevating glutathione (GSH) while reducing malondialdehyde (MDA) and labile iron pool (Fe2+) levels. Mechanistically, KF suppressed ferritinophagy via nuclear receptor coactivator 4 (NCOA4) inhibition and rescued glutathione peroxidase 4 (GPx4) activity, thereby blocking lipid peroxidation cascades. These effects were mediated through Nrf2-dependent transcriptional activation, counteracting CSE-triggered Nrf2 pathway dysregulation. Our findings reveal that KF mitigates COPD progression by coordinately targeting the Nrf2/NCOA4/GPx4 axis to inhibit ferroptosis, providing a novel therapeutic strategy for oxidative stress-driven pulmonary diseases.

Context No vaccine or effective therapy for cryptosporidiosis currently exists, except for nitazoxanide (NTZ), which has limited effectiveness in immunocompromised hosts. Kaempferol (KPF), a naturally occurring flavonoid, has various pharmacological effects and promising antiparasitic properties. Objective The current work aimed to examine the impact of KPF compared with NTZ on Cryptosporidium parvum (C. parvum) using both in silico molecular docking and in vivo studies with an experimentally infected immunocompromised mouse model. Materials and methods The present study utilized KPF and NTZ as multi-target ligands to predict, determine, and evaluate their in silico target-interacted forms, thereby demonstrating their therapeutic properties against C. parvum. Mice were immunosuppressed and divided into six groups: DEXA, Model, KPF as prophylaxis, treatment with KPF, NTZ, and a combination of KPF and NTZ. Treatment efficacy was assessed through parasitological, histopathological examination, and immunohistochemical analysis of intestinal tissues using NLRP3 protein. Results The in silico findings supported the use of KPF and NTZ as inhibitors of C. parvum growth by blocking the action of C. parvum choline and pyruvate kinases. The in vivo study demonstrated that KPF exhibits anti-cryptosporidial efficacy, particularly when combined with NTZ. The KPF+NTZ had the best results, as evidenced by a significant decrease (p < 0.001) in oocyst shedding of 83%, improved intestinal histological damage, and inhibition of the NLRP3 inflammasome pathway. Discussion and conclusion KPF demonstrated the potential to mitigate the consequences of cryptosporidiosis and serve as an adjuvant agent to NTZ by reducing the oocyst burden, alleviating intestinal inflammation, and facilitating mucosal repair.

Transient bilateral common carotid artery occlusion and reperfusion (BCCAO/R) has previously been established as an effective model for replicating early brain inflammation triggered by acute hypoperfusion and subsequent reperfusion events. Recognizing the significant role of diet and nutrition in shaping brain neuroplasticity, this investigation explored the neuroprotective impact of kaempferol (KAM), a dietary flavonoid, within a rat BCCAO/R paradigm. Adult Wistar rats received a single oral dose of KAM (40 mg) 6 h prior to surgery. Extensive lipidomic and molecular assessments were performed on frontal and temporal-occipital cortical tissues in addition to plasma samples. In the frontal cortex, KAM treatment led to increased concentrations of anti-inflammatory N-acylethanolamines – namely palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and docosahexaenoylethanolamide (DHAEA) – while diminishing levels of oxidized arachidonic acid derivatives. KAM further suppressed cyclooxygenase-2 (COX-2) protein and selectively reduced the endocannabinoid 2-arachidonoylglycerol (2-AG), reflecting alterations in arachidonic acid metabolism. These molecular effects were accompanied by elevated peroxisome proliferator-activated receptor alpha (PPARα) and cannabinoid receptors CB1R and CB2R, supporting activation of anti-inflammatory pathways at both nuclear and membrane levels. No marked changes emerged in the temporal-occipital cortex. In plasma, DHAEA levels increased in parallel with cortical findings, whereas PEA and OEA elevations were restricted to shamoperated KAM-treated subjects, implying potential central redistribution during hypoperfusion/reperfusion stress. Collectively, these results indicate that KAM confers anti-inflammatory protection by both suppressing COX-2- mediated prostanoid production and enhancing PPARα-dependent lipid signaling. This dual mechanism underscores KAM’s promise as a dietary strategy to mitigate neuroinflammation following hypoperfusion– reperfusion injury.

Background: Calcineurin inhibitors (CNIs), such as tacrolimus (TAC), remain central in transplantation and autoimmune disease management; however, adverse effects, particularly hyperglycemia, frequently complicate their use. Kaempferol (KF), a flavonol with hypoglycemic and antioxidant properties, has been proposed as a potential adjunctive modulator of CNI-related toxicities. Objectives: This study investigated the mechanisms of TAC-induced hyperglycemia, focusing on oxidative stress and calcineurin B1 (CnB1) expression, and assessed the protective effects of KF. Methods: Twenty-four male Wistar rats (180 - 230 g) were randomized into three groups (n = 8/group) and treated for 30 days: (1) The TAC 0.6 mg/kg/day intraperitoneally, (2) TAC + KF 10 mg/kg/day orally, and (3) vehicle controls. Blood samples were collected at days 15 and 30 to measure TAC trough levels, glucose, and insulin by enzyme-linked immunosorbent assay (ELISA). Pancreatic tissues were analyzed for oxidative stress markers [malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH)], P-glycoprotein (P-gp), and CnB1 expression. Molecular docking (MD) was also performed to assess KF interactions with calcineurin subunits. Results: The TAC monotherapy markedly increased serum glucose (128% at day 15; 150% at day 30 vs. controls, P &lt; 0.005) and reduced insulin levels (-81% at day 15; -85% at day 30, P &lt; 0.005). The TAC also elevated pancreatic MDA (+1113%) while significantly suppressing CnB1 expression (-98.4%). Co-administration of KF significantly reduced TAC trough levels by 29% at day 30 (P &lt; 0.005), attenuated hyperglycemia (glucose reduction by 35% at day 15 and 50% at day 30 vs. TAC, P &lt; 0.005), and restored insulin levels (+143% and +350% at days 15 and 30 vs. TAC, P &lt; 0.005). In the pancreas, KF lowered MDA (-62%, P &lt; 0.001), enhanced antioxidant defenses (GSH +128%, SOD +68%), and reversed TAC-induced CnB1 suppression (+408%, P &lt; 0.01). The MD supported a moderate binding of KF to both calcineurin A (CnA) and CnB1 chains, providing a mechanistic basis for its effects. Conclusions: The MD analysis revealed that several flavonoids exhibit promising binding affinities toward CnB1, CnA, and cyclophilin. These findings suggest that flavonoids may possess potential immunomodulatory properties through modulation of the calcineurin pathway. Therefore, further comprehensive investigations — combining advanced MD, molecular dynamics simulations, and in vitro as well as in vivo experimental validation — are essential to confirm the mechanistic roles, efficacy, and safety of flavonoids as potential immunomodulatory agents.

Alzheimer's Disease (AD) is a neurological disorder characterized by progressive cognitive impairment and memory loss. In vitro artificial membrane permeability assays targeting the blood-brain barrier (BBB), such as the parallel artificial membrane permeability assay (PAMPA), are useful for pre-evaluating the BBB penetration of molecules during the early stages of drug development. Inhibitors of glycogen synthase kinase-3β (GSK-3β), casein kinase-1δ (CK-1δ), and acetylcholinesterase (AChE) exhibit neuroprotective effects, indicating a potential therapeutic approach for AD. This study aimed to assess the ability of 23 phenolic compounds derived from natural sources to penetrate the central nervous system (CNS) and examine their potential neuroprotective effects. Following the prediction of BBB penetration of the compounds by PAMPA, neuroprotective effects of CNS+ compounds were evaluated through in vitro inhibition of GSK-3β, CK-1δ, and AChE. Based on the data obtained, five flavonoids (hispidulin, nepetin, platanoside, apigenin, and kaempferol) and two furanocoumarins (isopimpinellin and bergapten) were predicted to penetrate the CNS. Apigenin (API) and kaempferol (KEM) exhibited the most potent dual inhibitory activity against CK-1δ and GSK-3β. Furthermore, API and KEM did not exhibit cytotoxic effects in SH-SY5Y cells. Molecular modeling studies, including molecular docking, molecular dynamics simulations, and dynophore analysis, were performed to understand the binding mechanism of these most potent compounds to their target enzymes. Overall, the current study offers a rational approach to designing new molecules inspired by natural compounds to treat Alzheimer's Disease.

Background/Objectives: Kaempferol (KAE) is used to treat gamma radiation-induced damage. However, poor water solubility of KAE restricts its application. Therefore, we developed a KAE-loaded zeolitic imidazolate framework-8 (KAE@ZIF-8) to improve the solubility and bioavailability of KAE, thereby enhancing the radioprotective effect against gamma radiation. Methods: The composite was characterized using scanning electron microscopy (SEM), nitrogen adsorption/desorption analysis, X-ray diffraction (XRD), differential scanning calorimetry (DSC), equilibrium solubility assessments, in vitro release studies, stability evaluations, and drug-loading capacity measurements. The cytotoxic effects of KAE@ZIF-8 on Caco-2 cells were assessed in vitro. Meanwhile, the bioavailability of the preparation was also investigated. Finally, the protective efficacy of KAE@ZIF-8 against total body irradiation was evaluated in C57BL/6 mice. Results: The results indicated that KAE@ZIF-8 was successfully constructed, exhibiting a uniform hexagonal crystal morphology, with KAE transitioning from a crystalline to an amorphous state. As a carrier, ZIF-8 significantly enhanced the solubility of KAE by 9.2-fold, and the cumulative release within 12 h reached approximately 89%. Meanwhile, ZIF-8 could significantly enhance the bioavailability of KAE and reduce its toxicity. We found that pretreatment with KAE@ZIF-8 prolonged mouse survival time after 9 Gy total body irradiation (TBI). Mice were scarified on the 7th day after 7 Gy TBI. Results showed that KAE@ZIF-8 exhibited an improvement of the radioprotective effects, including weight loss mitigation, spleen index increase, radiation-induced intestinal injury attenuation, and modulation expression of IL-1β, IL-6, TNF-α and TGF-β1 following radiation. Conclusions: These results suggest the potential effect of ZIF-8 as an oral drug delivery carrier for radioprotective drugs.

Taohe Chengqi Decoction (THCQD) is a traditional Chinese prescription. Clinical trials have confirmed that THCQD can be used to treat cutaneous pruritus (CP), such as chronic urticaria, by draining down stagnant heat, and meta-analysis has found that in diabetic kidney disease (DKD), it can further improve the efficiency of Western medical treatment, reduce the total amount of 24 hours urinary protein, blood creatinine, and urinary albumin excretion rate, and improve the quality of life of patients. However, the exact pharmacological mechanism by THCQD improves DKD and CP remain unclear due to the complexity of its ingredients. We used network pharmacology approaches, including multi-database search, protein–protein interaction (PPI) network construction, gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and molecular docking to elaborate the active components, signaling pathways and potential mechanisms of THCQD in the treatment of DKD and CP. 114 active ingredients and 87 intersection targets of THCQD and diseases have been found through integrated network pharmacology. And by combining the data, we found the top 5 active ingredients, including beta-sitosterol, 7,2',4'-trihydroxy-5-methoxy-3-arylcoumarin, sitosterol, kaemp ferol and naringenin. Through PPI analysis, TNF, ALB, IL1B, AKT1 and TP53 were identified as the key therapeutic targets. In addition, the underlying effect of the pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, MAPK signaling pathway and TNF signaling pathway are also suggested in the treatment. By validation of molecular docking, finding that the central therapeutic targets have good affinities with the main compounds of THCQD. This study successfully predicts the active compounds, potential targets, and signaling pathways of THCQD in the treatment of DKD and CP. These findings provided an important scientific basis for further research of the mechanism of THCQD in the treatment of DKD and CP.

BackgroundExosomes (EXOs), small vesicles secreted by cells, and kaempferol (KMP) as a natural flavonoid have anti-inflammatory and anti-oxidant activities. Here, we investigated the therapeutic potential of combination therapy of mesenchymal stem cell (MSC)-derived EXOs with KMP in a cuprizone (CPZ)-induced demyelination model.MethodsForty-five male C57BL/6J mice were used in this study. KMP was administered intracerebroventricularly and EXOs were delivered intranasally. Behavioral tests, tissue analyses, and molecular assays measured working memory, cognitive function, motor function, myelin integrity, oxidative stress, and inflammation.ResultsBehavioral assessments using Y-maze, novel arm discrimination, and wire hang tests revealed that the combination therapy significantly improved working memory, spatial recognition, and motor endurance compared to KMP or EXOs treated groups. Histological analyses demonstrated marked prevention of demyelination, as evidenced by enhanced myelin integrity on FluoroMyelin and Black-Gold II staining. At the molecular level, the combined treatment up regulated the antioxidant genes expression and regulated the activity of key antioxidant enzymes, while simultaneously reducing lipid peroxidation. Glial activation and pro-inflammatory cytokine genes expression were also reduced in the EXO + KMP treated mice.ConclusionsThese findings suggest that combination therapy with EXOs and KMP improves myelin repair by targeting oxidative stress and neuroinflammation in a CPZ-induced demyelination model.

Mitochondrial physiology and beyond: Mechanistic insights into kaempferol actions.

Mechanism and potential targets of kaempferol alleviating photothrombotic stroke via integrating experimental validation, network pharmacology, and molecular docking.

Kaempferol attenuated LPS-induced microglial neurotoxicity by promoting mitophagy to inhibit mtDNA-mediated NLRP3 inflammasome activation.

Structure-activity relationship of (poly)phenols on human salivary α-amylase: A stepwise in vitro/in silico analysis of interfacial inhibition.

Pancreatic neuroendocrine tumors (pNETs) represent a diverse category of neoplasms originating from pancreatic neuroendocrine cells. Although these tumors generally exhibit a relatively indolent nature, they often metastasize early in their course, significantly affecting patient outcomes. Sulfatinib (SULF) is associated with considerable toxicity and resistance challenges, leading to many patients failing to achieve long-term disease management. In contrast, Kaempferol (KMP), a naturally occurring phytochemical, has shown considerable promise in anti-tumor treatments. Our study revealed that the combination of SULF and low-dose KMP enhances the sensitivity of pNET cells to SULF. Moreover, this combination demonstrated a synergistic effect on angiogenesis inhibition, observed in both in vitro and in vivo environments. Additionally, we confirmed this synergistic anti-tumor effect using a subcutaneous tumor model of pNETs. Transcriptome sequencing identified CALCA as a key molecule in the synergistic inhibition of pNETs proliferation by SULF and KMP. In summary, our findings provide novel insights into combination therapy for pNETs while elucidating the mechanistic role of CALCA in the modulation of angiogenesis. This research establishes a foundation for the development of vascular-targeted combination therapeutic strategies for the treatment of pNETs.

Previous research has demonstrated that the transient bilateral common carotid artery occlusion and reperfusion (BCCAO/R) effectively models early brain inflammation resulting from sudden hypoperfusion and subsequent reperfusion. According to studies showing that diet and nutrition strongly influence brain neuroplasticity, in this study we evaluated whether kaempferol (KAM), a dietary flavonoid, offers neuroprotection in a rat BCCAO/R model. Adult Wistar rats were gavage fed a single dose of KAM (40 mg) six hours before surgery. Comprehensive lipidomic and molecular analyses were conducted on samples from the frontal and temporal-occipital cortices, as well as the plasma. In the frontal cortex, KAM elevated anti-inflammatory N-acylethanolamines palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and docosahexaenoylethanolamide (DHAEA) and reduced oxidized arachidonic acid metabolites. KAM also downregulated cyclooxygenase- 2 (COX-2) protein and selectively decreased the endocannabinoid 2-arachidonoylglycerol (2-AG), showing a shift in AA metabolism. These molecular changes correlated with increased levels of peroxisome proliferator-activated receptor alpha (PPARα) and cannabinoid receptors CB1R and CB2R, supporting activation of both nuclear and membrane-bound anti-inflammatory pathways. No significant changes were observed in the temporal-occipital cortex. In plasma, DHAEA levels increased similarly to those in the cortex. However, rises in PEA and OEA were detected only in sham-operated KAM-treated animals, suggesting possible central redistribution under hypoperfusion/reperfusion stress. In summary, these findings demonstrate that KAM exerts dual anti-inflammatory effects by inhibiting COX-2-mediated prostanoid synthesis and promoting PPARα-driven lipid signaling. This dual mechanism highlights the potential of KAM as a dietary intervention to reduce neuroinflammation associated with hypoperfusion–reperfusion challenges.