Kaempferol Research Articles

Molecular dynamics simulations, molecular docking, and kinetics study of kaempferol interaction on Jack bean urease: Comparison of extended solvation model.

Since the urease enzyme creates gastric cancer, peptic ulcer, hepatic coma, and urinary stones in millions of people worldwide, it is essential to find strong inhibitors to help patients. Natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients, the so-called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, and cosmetic applications. Kaempferol (KPF) is an antioxidant found in many fruits and vegetables. Many reports have explained the significant effects of dietary KPF in reducing the risk of chronic diseases such as cancer, ischemia, stroke, and Parkinson's. The current study aimed at investigating the inhibitory impact of KPF on Jack bean urease (JBU) using molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations to confirm the results obtained from isothermal titration calorimetry (ITC), extended solvation model, and docking software. In addition, UV-VIS spectrophotometry was used to study the kinetics of urease inhibition. Calorimetric and spectrophotometric determinations of the kinetic parameters of this inhibition indicate the occurrence of a reversible and noncompetitive mode. Also, the docking and MD results indicated that the urease had well adapted to the kaempferol in the binding pocket, thereby forming a stable complex. Kaempferol displayed low binding energy during MMPBSA calculations. The inhibitory potential of kaempferol was confirmed by experimental and simulation data, but in vivo investigations are also recommended to validate our results.

A novel kaempferol electrochemical sensor based on glass carbon electrode modified by poly (3, 4-ethylenedioxythiophene) decorated with green synthesized MIL-100(Fe)-multi- walled carbon nanotubes composites

Kaempferol (KA) belongs to the group of flavonoids with versatile biological activities, which has attracted much attention. Herein, a novel KA electrochemical sensor was proposed based on glass carbon electrode modified with MIL-100(Fe)-multi-walled-carbon nanotubes/poly(3,4-ethylenedioxythiophene) (MIL-100(Fe)-MWCNTs/PEDOT) composite, which were characterized by X-ray diffraction spectroscopy and scanning electron microscopy. MWCNTs decorated with in situ green synthesized MIL-100(Fe) showed excellent electrochemical sensing performance. For detecting KA with DPV model, the MIL-100(Fe)-MWCNTs/PEDOT/GCE showed a linear range of 50–1950 nM under optimal conditions, and the corresponding detection limit (LOD) was 13.2 nM (S/N = 3). In addition, the sensor exhibited satisfactory sensitivity and accuracy for detecting KA in real samples (XinDaKang tablet).

Kaempferol inhibits renal fibrosis by suppression of the sonic hedgehog signaling pathway

BackgroundMost chronic kidney diseases (CKDs) develop to end-stage renal disease (ESRD), which is characterized by fibrosis and permanent tissue and function loss. As a result, better and more effective remedies are essential. Kaempferol (KAE) is a common flavonoid extracted from plants. It can control the progression of kidney fibrosis and the epithelial-to-mesenchymal transition (EMT) of the renal tubular system. PurposeWe aim to investigate the effect of KAE therapy on extracellular matrix deposition and stimulation of EMT in vitro and in vivo to elucidate the treatment mechanisms regulating these effects. Study DesignChronic hypertension-induced kidney fibrosis was studied in spontaneously hypertensive rats with chronic kidney disease. Biochemical analysis, histological staining, and the expression level of relative proteins were used to assess the effect of KAE on renal function and fibrosis. The direct impact of KAE on proliferation and migration was evaluated using human renal tubular epithelial cells (HK-2) induced by transforming growth factor-β1 (TGF-β1), which can then induce EMT. The molecular mechanism of KAE was verified using co-IP assay and immunofluorescence. ResultsKAE could reduce blood pressure and decrease the extracellular matrix (ECM) components (including collagen I and collagen Ш), TGF-β1, and α-SMA in the kidneys of hypertension-induced rats with chronic kidney disease. Moreover, in HK-2 cell treated with TGF-β1, KAE administration significantly suppressed proliferation, migration, and EMT via increasing the expression of E-cadherin, while reducing the N-cadherin and α-SMA. Sufu was exceedingly repressed in HK-2 cells treated with TGF-β1. KAE inhibited the activation of Shh and Gli through increasing the expression of Sufu, thereby blocking the nuclear translocation of Gli1 in vitro. ConclusionKAE ameliorated kidney fibrosis and EMT by inhibiting the sonic hedgehog signaling pathway, thereby to attenuate the pathological progression of hypertensive kidney fibrosis.

Detection of total flavonoid, antioxidant activity and HPLC analysis of methanolic extract of Silybum marianum seeds

Silybum marianum considered as an ancient herb promising plants. In this work, fhese study was design to assess total flavonoids, anti-oxidant and HPLC analysis of Silybum marianum plant extract by methanol in vitro. Total flavonoids had been measured in the extract that about 201.6667±1.52753 mg/ml. anti-oxidant activity of methanolic plant extract Silybum marianum in vitro was estimated by assesment of reductive ability, in concentrations that be tested (0.02, 0.04, 0.08, 0.16, 0.32 and 0.64 mg/ml) , the absorbance had been increased significantly , results of HPLC analysis of plant contain (Ascorbic acid ,Gallic acid Catechin, Rutin, Quercetin, Apigeninand Kaemp ferol) in concentration (0.839, 0.0918, 0.628, 2.989, 0.010, 0.0680, 0.228) ppm respectivily.

Subacute 28 days oral toxicity study of kaempferol and biochanin-A in the mouse model.

The present study was undertaken to investigate the safety of kaempferol (KEM) and biochanin-A (BCA) following subacute exposure in mice. KEM and BCA were administered in three different doses by oral administration for 28 days. Evaluation of general toxicity parameters by examining the clinical signs, body weight, organ weights, haematological, biochemical, oxidative stress parameters, and histopathology was done. Administration of KEM and BCA for 28 days did not show any clinical signs of toxicity, nor any treatment-related changes in body weight and organ weights in comparison to control. The haematological parameters such as red blood cell, white blood cell, platelets count, haemoglobin (Hb) level, haematocrit, mean corpuscular haemoglobin concentration, red cell distribution width, and platelet distribution width did not show any change in the treated groups and control. Furthermore, different biochemical parameters like markers of the liver (alanine aminotransferaseand aspartate aminotransferase), kidney (creatinine and urea), and heart (creatinine kinase-myocardial band and lactate dehydrogenase) injury along with other biochemical parameters showed nonsignificant differences between treated groups and control. Results of oxidative stress parameters in treated groups showed insignificant variations with control. The level of antioxidant enzymes such as superoxide dismutase and catalase were markedly increased in the treated groups; however, these were nonsignificant in comparison to control. In histopathology, evaluation of all vital organs, such as liver, kidney, heart, and lungs, did not show any morphological abnormalities and lesions in treated groups and control. The present study suggests that KEM and BCA have no adverse effects on the general physiology in mice.

Flavonoids Ameliorate Ferroptotic Cell Death in Cardiomyocytes through ROS Scavenging and Lipid Peroxide Reduction

Myocardial ischemia‐reperfusion injury (MIRI) is a lethal disease that occurs after percutaneous intervention which may lead acute myocardial infarction patients to heart failure. Therefore, it is an important issue to find solutions for MIRI. A newly discovered cell death named ferroptosis has been associated with MIRI. Ferroptosis, which is characterized by iron‐dependent accumulation of lipid peroxide is distinct from necrosis and apoptosis. Lipophilic antioxidants like ferrostatin‐1 have been discovered to inhibit ferroptosis effectively. Flavanoids, such as Fisetin and Kaempferol (KMP), are natural compounds that are found in many edible plants. They are lipophilic antioxidants that show cardio‐protective effects through scavenging ROS, inhibiting inflammation in MIRI models. However, the effect of flavonoids in inhibiting ferroptosis associated with MIRI remains unclear. This study investigated the ability of Fisetin and KMP to attenuate ferroptosis in H9c2 cells. H9c2 cells were treated with ferroptosis inducers erastin, RSL3, and Fe‐SP. Fisetin and KMP could protect cells against ferroptosis caused by these ferroptosis inducers by ROS scavenging, lipid peroxide reduction, and decrease the mRNA levels of the ferroptosis marker Ptgs2. Thus, Fisetin and KMP play a protective role in H9c2 cells against ferroptosis which may be an effective candidate to treat MIRI.

An ultra-sensitive kaempferol electrochemical sensor based on flower-like ZIF-8 pyrolysis-derived ZnWO4/porous nanocarbon composites

Kaempferol (KA), an important polyphenolic compound, is able to combat a variety of inflammatory diseases. Here, a ZnWO4 / porous nanocarbon based electrochemical sensor has been constructed to detect KA for the first time. Innovatively, ZnWO4 has been synthesized by pyrolysis using ZIF-8 as a zinc source, while porous nanocarbon was introduced. The nanocomposites have been characterized by X-ray diffraction, X-ray photoelectron spectroscopy and scanning electron microscopy and demonstrated that Acidified ZnWO4/porous nanocarbon has been successfully prepared. Notably, the excellent catalytic properties of ZnWO4 and the great enrichment ability and conductivity of porous nanocarbon greatly enhanced the detection performance of the sensor for KA with a linear range of 0.009–0.7 μM and a LOD of 2.03 nM. In addition, the sensor has obtained satisfactory results for the detection of KA in actual natural samples (broccoli and kaempferia powder). The reaction sites and redox mechanism of KA were shown by density functional theory. Finally, the sensor is highly sensitive and stable, making it a novel detection method with extremely high potential applications.

Influence of polyphenol-metal ion-coated ovalbumin/sodium alginate composite nanoparticles on the encapsulation of kaempferol/tannin acid

In this research, ovalbumin (OVA) and sodium alginate (SA) were used as the materials to prepare OVA-SA composite carriers, which protected and encapsulated the hydrophobic kaempferol (KAE) and the hydrophilic tannic acid (TA). To achieve the purpose of targeted delivery, the TA-Fe3+ coating film was prepared. Results showed that the observation of small diffraction peaks in carriers proved the formation of TA/Fe3+ coating film on the surface of four composite nanoparticles (pOVA, pOVA-SA, pOVA-KAE-SA, and pOVA-KAE-TA-SA). The protein structure of the composite nanoparticles coated with TA/Fe3+ changed, and the order of the changes was pOVA-KAE > pOVA > pOVA-KAE-SA > pOVA-KAE-TA-SA > pOVA-SA. This phenomenon is due to the fact that the chromophore –C=O and the auxo-chromophore –OH are in the opposite position in the benzene ring of TA, and the two substituents have opposite effects and synergize, resulting in the different degrees of redshift of the composite nanoparticle λmax. Additionally, pOVA-SA had the highest α-helix content and the lowest random coils, conferring the protein structure the strongest stability. The coating of TA/Fe3+ increased the system stability and the thermal stability of the composite nanoparticles. Additionally, the carriers were endowed with antioxidant activity, and their antibacterial ability against Staphylococcus aureus and Escherichia coli was pOVA-KAE-TA-SA > pOVA-KAE-SA > pOVA-KAE > pOVA-SA > pOVA based on the difference in antibacterial diameter (D, mm) and square (S, mm2). pOVA-KAE-TA-SA had the strongest antioxidant activity and antibacterial ability, which improved the bioavailability of TA/KAE. These results provide a theoretical basis for the application of OVA-SA composite nanoparticles in the delivery of bioactive compounds.

HO-1 Upregulation by Kaempferol via ROS-Dependent Nrf2-ARE Cascade Attenuates Lipopolysaccharide-Mediated Intercellular Cell Adhesion Molecule-1 Expression in Human Pulmonary Alveolar Epithelial Cells.

Lung inflammation is a pivotal event in the pathogenesis of acute lung injury. Heme oxygenase-1 (HO-1) is a key antioxidant enzyme that could be induced by kaempferol (KPR) and exerts anti-inflammatory effects. However, the molecular mechanisms of KPR-mediated HO-1 expression and its effects on inflammatory responses remain unknown in human pulmonary alveolar epithelial cells (HPAEpiCs). This study aimed to verify the relationship between HO-1 expression and KPR treatment in both in vitro and in vivo models. HO-1 expression was determined by real time-PCR, Western blotting, and promoter reporter analyses. The signaling components were investigated by using pharmacological inhibitors or specific siRNAs. Chromatin immunoprecipitation (ChIP) assay was performed to investigate the interaction between nuclear factor erythroid-2-related factor (Nrf2) and antioxidant response elements (ARE) binding site of HO-1 promoter. The effect of KPR on monocytes (THP-1) binding to HPAEpiCs challenged with lipopolysaccharides (LPS) was determined by adhesion assay. We found that KPR-induced HO-1 level attenuated the LPS-induced intercellular cell adhesion protein 1 (ICAM-1) expression in HPAEpiCs. KPR-induced HO-1 mRNA and protein expression also attenuated ICAM-1 expression in mice. Tin protoporphyrin (SnPP)IX reversed the inhibitory effects of KPR in HPAEpiCs. In addition, in HPAEpiCs, KPR-induced HO-1 expression was abolished by both pretreating with the inhibitor of NADPH oxidase (NOX, apocynin (APO)), reactive oxygen species (ROS) (N-acetyl-L-cysteine (NAC)), Src (Src kinase inhibitor II (Srci II)), Pyk2 (PF431396), protein kinase C (PKC)α (Gö6976), p38 mitogen-activated protein kinase (MAPK) inhibitor (p38i) VIII, or c-Jun N-terminal kinases (JNK)1/2 (SP600125) and transfection with their respective siRNAs. The transcription of the homx1 gene was enhanced by Nrf2 activated by JNK1/2 and p38α MAPK. The binding activity between Nrf2 and HO-1 promoter was attenuated by APO, NAC, Srci II, PF431396, or Gö6983. KPR-mediated NOX/ROS/c-Src/Pyk2/PKCα/p38α MAPK and JNK1/2 activate Nrf2 to bind with ARE on the HO-1 promoter and induce HO-1 expression, which further suppresses the LPS-mediated inflammation in HPAEpiCs. Thus, KPR exerts a potential strategy to protect against pulmonary inflammation via upregulation of the HO-1.

Kaempferol From Penthorum chinense Pursh Attenuates Hepatic Ischemia/Reperfusion Injury by Suppressing Oxidative Stress and Inflammation Through Activation of the Nrf2/HO-1 Signaling Pathway.

The purpose of this study is to investigate the protective effect of kaempferol (KAE), the main active monomer from Penthorum chinense Pursh, on hepatic ischemia/reperfusion injury (HI/RI) and its specific mechanism. HI/RI is a common complication closely related to the prognosis of liver surgery, and effective prevention and treatment methods are still unavailable. Ischemia/reperfusion (I/R) injury is caused by tissue damage during ischemia and sustained oxidative stress and inflammation during reperfusion. Penthorum chinense Pursh is a traditional Chinese medicine widely used to treat liver disease since ancient times. Kaempferol (KAE), a highly purified flavonoid active monomer isolated and extracted from Penthorum chinense Pursh, was investigated for its protective effect on HI/RI. Our study indicates that KAE pretreatment alleviated I/R-induced transaminase elevation and pathological changes. Further analysis revealed that KAE pretreatment attenuates I/R-induced oxidative stress (as measured by the content of MDA, SOD and GSH) in vivo and reduces hypoxia/reoxygenation (H/R) -induced reactive oxygen species (ROS) generation in vitro. Meanwhile, KAE inhibits activation of NF-κB/p65 and reduces the release of pro-inflammatory factors (TNF-α and IL-6) to protect the liver from I/R-induced inflammation. Nuclear erythroid 2-related factor 2 (Nrf2) is a crucial cytoprotection regulator because it induces anti-inflammatory, antioxidant, and cytoprotective genes. Therefore, we analyzed the protein levels of Nrf2 and its downstream heme oxygenase-1 (HO-1) in the liver of mice and hepatocytes of humankind, respectively, and discovered that KAE pretreatment activates the Nrf2/HO-1 signaling pathway. In summary, this study confirmed the hepatoprotective effect of KAE on HI/RI, which inhibits oxidative stress and inflammation by activating the Nrf2/HO-1 signaling pathway.

Preparation of a new component group of Ginkgo biloba leaves and investigation of the antihypertensive effects in spontaneously hypertensive rats

Ginkgo (Ginkgo biloba L.) is a traditional economic tree species in China. Ginkgo biloba extract (GBE) is widely used in combination to treat hypertension and complications in clinical practice. However, the antihypertensive effect of GBE alone is weak and it is also difficult to study the mechanism because of its complex composition. This study was to prepare a new component group of Ginkgo biloba leaves (GBLCG) with clear chemical structures, and to investigate its effect on reducing blood pressure and improving myocardial hypertrophy in spontaneously hypertensive rats with GBE and amlodipine as positive controls. The results showed that total flavonoid aglycones (TFAs) of GBLCG was mainly composed of quercetin (QCT), kaempferol (KMF) and isorhamnetin (ISR); Total terpenoid lactones (TTLs) of GBLCG might be a novel cocrystal composed of Ginkgolide A (GA), Ginkgolide B (GB) Ginkgolide C (GC), Ginkgolide J (GJ) and bilobalide (BB). The hypotensive activity of GBLCG (4.4 mg/kg) group was better than that of GBE group (p < 0.05), and the effect of improving myocardial hypertrophy was better than that of amlodipine besylate group (p < 0.01). GBLCG might reduce blood pressure and improve myocardial hypertrophy by promoting the synthesis and release of NO in endothelial cells, reducing oxidative stress, inhibiting platelet aggregation and promoting lesion circulation. Eventually, we hope to introduce GBLCG as a new drug for hypertension.

Protective Effect of Kaempferol and Its Nanoparticles on 5-Fluorouracil-Induced Cardiotoxicity in Rats.

Background Fluorouracil (5-FU) is the third most common chemotherapeutic agent used in the treatment of solid tumors. 5-FU-associated cardiotoxicity ranks the second causes of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Kaempferol (KPF), a common flavonoid, possessing anti-inflammatory, antiapoptotic, antioxidative properties, and its protective effects on cardiovascular disease has been reported in various studies. The current study is aimed at appraising the effect of KPF and KPF nanoparticles (NPs) on 5-FU-induced cardiotoxicity in rats. Methods Thirty Male Wistar rats were divided into five groups as follows: control, 5-FU, 5-FU+10 mg/kg vitamin C, 5-FU+ 1 mg/kg KPF, and 5-FU+ 1 mg/kg KPF-NPs. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-FU (100 mg/kg). The control group received normal saline, and the treatment groups received KPF and KPF-NPs with an intraperitoneal injection for 14 days. Each heart histopathological lesions were given a score of 0 to 3 in compliance with the articles for statistical analysis. Results 5-FU resulted in a significant cardiotoxicity represented by an increase in cardiac enzymes, MDA (malondialdehyde) levels, COX-2 (cyclooxygenase-2) expression, and histopathological degenerations. 5-FU treatment also decreased body weight, TAC (total antioxidant capacity) values, VEGF (vascular endothelial growth factor) expression, blood cells, and hemoglobin (Hb) levels. Treatment with KPF and KPF-NPs reduced oxidative stress, cardiac enzymes, COX-2 expression, and VEGF expression. The number of blood cells, Hb levels, and histopathological degenerations, in cardiac tissue also body weight of animals, increased, followed by treatment with KPF and KPF-NPs. Conclusion Our results demonstrated that treatment with KPF and KPF-NPs significantly improved cardiotoxicity induced by 5-FU in rats.

Kaempferol and Apigenin suppresses the stemness properties of TNBC cells by modulating Sirtuins.

Sirtuins (SIRTs) overexpression serves as a potential therapeutic target for TNBC because it is associated with bioactivities of cancer stem cells (CSCs), resistance to chemotherapy, and metastasis. Irrespective of the availability of synthetic SIRT inhibitors, new SIRT inhibitors with enhanced potency and lesser side effects serve as current unmet needs. Therefore, bioactive dietary compounds; kaempferol (KMP) and apigenin (API) were investigated for their anti-SIRTs potential. We observed KMP and API inhibits cellular proliferation by DNA damage and S-phase cell cycle arrest in TNBC Cells. They also suppress stemness properties in TNBCs as observed in experiments of mammosphere formation and clonogenic potential. Our mechanistic approach indicated that KMP and API inhibited SIRT3 and SIRT6 proteins, as evidenced by our in silico and in vitro experiment. Collectively, our studies suggest that KMP and API are promising candidates to be further developed as sirtuin modulators against TNBCs.

Horseradish peroxidase catalyzed grafting of chitosan oligosaccharide with different flavonols: structures, antioxidant activity and edible coating application.

Enzymatic catalyzed grafting of oligosaccharides with polyphenols is a safe and environmentally friendly approach to simultaneously enhance the bioactivity of oligosaccharides and the solubility of polyphenols. In this study, chitosan oligosaccharide (COS) was grafted with three different flavonols including myricetin (MYR), quercetin (QUE) and kaempferol (KAE) by horseradish peroxidase (HRP) catalysis. The structures, antioxidant activity and edible coating application of COS-flavonol conjugates were investigated. The total phenol content of COS-MYR, COS-QUE and COS-KAE conjugates was 59.89, 68.37 and 53.77 mg gallic acid equivalents g-1 , respectively. Thin layer chromatography showed the conjugates did not contain ungrafted flavonols. COS-flavonol conjugates showed ultraviolet absorption peak at about 294 nm, corresponding to the A-ring of flavonols. Fourier-transform infrared spectra of conjugates confirmed the formation of Schiff-base and Michael-addition products. The proton-nuclear magnetic resonance spectrum of COS-KAE conjugate exhibited phenyl proton signals of KAE. X-ray diffraction patterns of conjugates showed some diffraction peaks of flavonols. COS-flavonol conjugates presented rough and porous morphologies with sheet-like and/or blocky structures. The conjugates showed higher water solubility, free radical scavenging activity and reducing power than flavonols. Moreover, fish gelatin/COS-flavonol conjugate coatings effectively prolonged the shelf life of refrigerated largemouth bass (Micropterus salmoides) fillets from 5 days to 7-8 days. COS-flavonol conjugates prepared by HRP catalysis have great potentials as novel antioxidant agents. © 2022 Society of Chemical Industry.

Kaempferol increases intracellular ATP content in C2C12 myotubes under hypoxic conditions by suppressing the HIF-1α stabilization and/or by enhancing the mitochondrial complex IV activity

Kaempferol (KMP) has numerous important biological functions, and we recently showed that it remarkably increased intracellular adenosine triphosphate (ATP) content in C2C12 myotubes under hypoxic conditions. Since intracellular ATP is generated by aerobic energy metabolism or anaerobic glycolysis, hypoxia inducible factor-1α (HIF-1α) has been shown to be associated with metabolic remodeling and causes metabolic shift from aerobic energy metabolism to anaerobic glycolysis in response to hypoxic conditions. Here, we investigate the effects of KMP under hypoxic conditions on the stabilization of HIF-1α in C2C12 myotubes and its underlying molecular mechanisms. Constitutive HIF-1α protein expression was observed in C2C12 myotubes, and its expression under hypoxic conditions was remarkably suppressed by KMP by reducing its stability; thus, resulting in an increase in ATP content. Furthermore, KMP strikingly increased the ubiquitination of HIF-1α and promoted its degradation via the ubiquitin proteasome system. Inhibition of HIF-1α by KMP resulted in the abrogation of the expression of glycolytic enzymes such as lactate dehydrogenase A and pyruvate dehydrogenase kinase isozyme 1. In addition, the metabolome profiling showed that KMP promoted oxidative energy production, while the mitochondrial complex activity assay indicated that KMP increased the activity of mitochondrial complex IV. Finally, we showed that KMP inhibited HIF-1α expression and increased intracellular ATP content in the soleus muscle of rats. Taken together, these results suggest that KMP increases intracellular ATP content under hypoxic conditions by suppressing the HIF-1α stabilization and/or by enhancing the mitochondrial complex IV activity in muscle.

Research on the Mechanism of Kaempferol for Treating Senile Osteoporosis by Network Pharmacology and Molecular Docking.

Kaempferol (KP), as a natural anti-inflammatory compound, has been reported to have curative effects on alleviating senile osteoporosis (SOP), which is an inflammation-related musculoskeletal disease, but the molecular mechanisms remain unclear due to scanty relevant studies. We predicted the targets of KP and SOP, and the common targets of them were subsequently used to carry out PPI analysis. Moreover, we adopted GO and KEGG enrichment analysis and molecular docking to explore potential mechanisms of KP against SOP. There were totally 152 KP-related targets and 978 SOP-related targets, and their overlapped targets comprised 68 intersection targets. GO enrichment analysis showed 1529 biological processes (p < 0.05), which involved regulation of inflammatory response, oxidative stress, regulation of bone resorption and remodeling, osteoblast and osteoclast differentiation, etc. Moreover, KEGG analysis revealed 146 items including 44 signaling pathways (p < 0.05), which were closely linked to TNF, IL-17, NF-kappa B, PI3K-Akt, MAPK, estrogen, p53, prolactin, VEGF, and HIF-1 signaling pathways. By means of molecular docking, we found that kaempferol is bound with the key targets' active pockets through some connections such as hydrogen bond, pi-alkyl, pi-sigma, pi-pi Stacked, pi-pi T-shaped, and van der Waals, illustrating that kaempferol has close combination with the key targets. Collectively, various targets and pathways involve in the process of kaempferol treatment against SOP through regulating inflammatory response, oxidative stress, bone homeostasis, etc. Moreover, our study first reported that kaempferol may regulate core targets' expression with involvement of inflammatory response, oxidative stress, and bone homeostasis, thus treating SOP.

Kaempferol ameliorate the prognosis of Aspergillus fumigatus keratitis by reducing fungal load and inhibiting the Dectin-1 and p38 MAPK pathway

Fungal keratitis is one of leading reasons for blindness in the world, which causes corneal blindness mainly due to excessive inflammatory responses. Kaempferol (KAE) is a natural flavonoid which has potent anti-inflammatory effects. However, whether KAE plays protective roles in fungal keratitis and the potentially protective mechanisms are unrevealed. Here we first investigated the anti-inflammatory and antifungal effects of KAE on Aspergillus fumigatus (A. fumigatus) keratitis in C57BL/6 mice. We found that treatment of KAE ameliorated the severity of keratitis, inhibited macrophages and neutrophils recruitment, depressed corneal fungal load, and declined the expression of TLR4 and Dectin-1 in A. fumigatus infected mice corneas. And in activated hyphae or Curdlan stimulated macrophages, pretreatment of KAE also significantly decreased the mRNA and protein expression of IL-1β, TNF-α, MIP-2 and the phosphorylated-p38 (p-p38)/p38 MAPK ratio. In summary, KAE ameliorated the prognosis of fungal keratitis in C57BL/6 mice by reducing corneal fungal load, depressing the inflammatory cells recruitment, and downregulating the expression of inflammatory factors, and those effects depended on the inhibition of Dectin-1 and p38 MAPK pathway.

Hydroxy Pentacyclic Triterpene Acid, Kaempferol, Inhibits the Human 5-Hydroxytryptamine Type 3A Receptor Activity

Monoamine serotonin is a major neurotransmitter that acts on a wide range of central nervous system and peripheral nervous system functions and is known to have a role in various processes. Recently, it has been found that 5-HT is involved in cognitive and memory functions through interaction with cholinergic pathways. The natural flavonoid kaempferol (KAE) extracted from Cudrania tricuspidata is a secondary metabolite of the plant. Recently studies have confirmed that KAE possesses a neuroprotective effect because of its strong antioxidant activity. It has been confirmed that KAE is involved in the serotonergic pathway through an in vivo test. However, these results need to be confirmed at the molecular level, because the exact mechanism that is involved in such effects of KAE has not yet been elucidated. Therefore, the objective of this study is to confirm the interaction of KAE with 5-HT3A through electrophysiological studies at the molecular level using KAE extracted from Cudrania tricuspidata. This study confirmed the interaction between 5-HT3A and KAE at the molecular level. KAE inhibited 5-HT3A receptors in a concentration-dependent and voltage-independent manner. Site-directed mutagenesis and molecular-docking studies confirmed that the binding sites D177 and F199 are the major binding sites of human 5-HT3A receptors of KAE.

The Effect of Kaempferol on Autophagy and Nrf-2 Signaling in a Rat Model of Aβ1-42-induced Alzheimer’s Disease

Background: Numerous pieces of evidence support that oxidative stress is a key factor in the pathogenesis of neurodegenerative diseases, like Alzheimer’s Disease (AD). Suppression of oxidative stress is an attractive strategy and flavonoids as potent natural antioxidants are extremely noticeable. Objectives: In this study, the effects of Kaempferol (KMP) were evaluated on passive avoidance memory, hippocampal Nrf-2, and beclin-1 expression in a rat model of Aβ1-42 –induced AD. Materials &amp; Methods: Forty male Wistar rats weighing 200-250 g were divided into five groups (n=8); sham-operated, AD model, and KMP treatment (5, 7.5, 10 mg/kg, i.p. for three weeks). Animals received an intracerebroventricular injection of amyloid-beta (1-42) to establish an AD model. Passive avoidance memory of rats was evaluated using a shuttle box on day 21; Step-Through Latency (STL) and time spent in The Dark Compartment (TDC) were recorded. Then, hippocampus homogenates were used for biochemical and molecular analysis by real-time PCR, western blot, and ELISA. Results: It was found that KMP improved memory evidenced by increased STL (P≤0.05) and decreased TDC (p≤0.01). KMP also increased the levels of Total Antioxidant Capacity (TAC) in the hippocampus of rats (P≤0.05). In addition, KMP enhanced the expression of Nrf-2 mRNA (P≤0.001) and beclin-1 protein in the hippocampus tissues (P≤0.001). Conclusion: Overall, it is suggested that the memory-improving effect of KMP is mediated, at least in part, by enhancing Nrf-2 and TAC. KMP is also able to induce autophagy through the expression of beclin-1.

THE EFFECT OF KAEMPFEROL, ETHYL-pMETHOXYCINNAMATE, AND THE ETHANOL EXTRACT OF Kaempferia galanga RHIZOME ON THE PRODUCTION OF PROSTAGLANDIN BY In-vitro AND In-silico STUDY

Cyclooxygenases (COX) catalyze the biosynthesis of prostaglandins from arachidonic acid, the substrate. COX has two isoforms which are targets of non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs exhibit their antiinflammatory activity by blocking the conversion of arachidonic acid to prostaglandins. Overall, NSAIDs are well tolerated, especially when used short-term, nevertheless due to their global use, they are frequently involved in adverse drug reactions. Kaempferia galanga has been traditionally used to cure various inflammatory-related disorders by consuming the boiled rhizome tea or applying the rhizome powder paste topically on the inflamed site. This plant has been proven to contain flavonoids and polyphenolic compounds that are considered to have pharmacological activities. This work studied the effect of kaempferol (KAE), ethyl-p-methoxycinnamate (EPMC), and K. galanga rhizome ethanolic extract (EKG) on prostaglandin production and compared the results with that of celecoxib and triamcinolone acetonide by in vitro and in silico technique. Results revealed that both KAE and EPMC could occupy the catalytic site of COX-2 by building hydrogen bonds with important amino acid residues. Moreover, in vitro study confirmed that lower concentrations of EKG could reduce the production of prostaglandin PGG2, while higher concentration does not. It is proven that KAE inhibits the production of prostaglandin PGG2 in both concentration and time-dependent manners. Taken together, the EKG can be further developed as a COX-2 inhibitor drug.