Natural products are effective in the treatment and the prevention of human,animal and plant diseases.Therefore,natural products may also be considered to treat fish diseases.Acori Tatarinowii Rhizoma(ATR)is a herbal ...Natural products are effective in the treatment and the prevention of human,animal and plant diseases.Therefore,natural products may also be considered to treat fish diseases.Acori Tatarinowii Rhizoma(ATR)is a herbal medicine with anti-inflammatory and antioxidant effects.However,little is known about how its active ingredients exert the beneficial effects.Here,Four effective active ingredients of ATR and their 81 targets were investigated,which affected the anti-inflammatory response.Among them,kaempferol-JUN was identified as a key regulatory module in anti-inflammatory immune responses,and kaempferol interacted with the CiJUN protein and inhibited CiJUN levels.Silencing CiJUN gene in Ctenopharyn-godon idella kidney(CIK)cells enhanced anti-inflammatory activity and resistance to Aeromonas hydrophila,whereas anti-inflammatory activity and resistance were impaired after CiJUN overexpression.The mortality rate of diseased grass carp was reduced after treatment with kaempferol,as were the inflammatory and oxidant effects.Also,grass carp showed enhanced anti-inflammatory and antioxidant effects after feeding with kaempferol.The results provide further insights into the use of kaempferol to prevent and treat fish diseases.展开更多
Alzheimer＇s disease（AD） is associated with oxidative stress, and ultimately results in cognitive deficit. Despite existing literature on the pathophysiology of AD, there is currently no cure for AD. The present stu...Alzheimer＇s disease（AD） is associated with oxidative stress, and ultimately results in cognitive deficit. Despite existing literature on the pathophysiology of AD, there is currently no cure for AD. The present study investigated the effects of kaempferol（Kmp） isolated from the extract of Mespilus germanica L.（medlar） leaves on cognitive impairment, hippocampal antioxidants, apoptosis, lipid peroxidation and neuro-inflammation markers in ovariectomized（OVX） rat models of sporadic AD. Kaempferol, as the main flavonoid of medlar extract has been previously known for anti-oxidative, anti-inflammatory and anti-neurotoxic effects. Thirty-two female Wistar rats were ovariectomized, and randomly divided into four groups： sham, OVX ＋ saline, OVX ＋ streptozotocin（STZ） ＋ saline, OVX ＋ STZ ＋ Kmp. Animals received intracerebroventricular injection of STZ（3 mg/kg, twice with one day interval） to establish models of sporadic AD. Intraperitoneal injection of Kmp（10 mg/kg） for 21 days was performed in the OVX ＋ STZ ＋ Kmp group. Spatial learning and memory of rats were evaluated using a Morris water maze. Finally, brain homogenates were used for biochemical analysis by enzyme-linked immunosorbent assay. The results showed a significant improvement in spatial learning and memory as evidenced by shortened escape latency and searching distance in Morris water maze in the OVX ＋ STZ ＋ Kmp group compared with the OVX ＋ STZ group. Kmp also exhibited significant elevations in brain levels of antioxidant enzymes of superoxide dismutase and glutathione, while reduction in tumor necrosis factor-α and malondialdehyde. Our results demonstrate that Kmp is capable of alleviating STZ-induced memory impairment in OVX rats, probably by elevating endogenous hippocampal antioxidants of superoxide dismutase and glutathione, and reducing neuroinflammation. This study suggests that Kmp may be a potential neuroprotective agent against cognitive deficit in AD.展开更多
Herein,the purpose of this study is to evaluate the effects of kaempferol on bioavailability and pharmacokinetics of nifedipine and its metabolite dehydronifedipine in rats.The experimental design is based on with or ...Herein,the purpose of this study is to evaluate the effects of kaempferol on bioavailability and pharmacokinetics of nifedipine and its metabolite dehydronifedipine in rats.The experimental design is based on with or without kaempferol in the oral and intravenous administration of nifedipine in rats.Moreover,the pharmacokinetic parameters including nifedipine and dehydronifedipine were evaluated in rats.The in vitro studies of kaempferol were investigated on P-glycoprotein(P-gp)and cytochrome P450(CYP)3A4 activity.Kaempferol reduced a 50%inhibitory concentration(IC50)of 8.6μmol·L-1 on CYP3A4 enzyme activity.Moreover,kaempferol clearly improved the cell internalization of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp.Depending on increased concentrations of kaempferol,the areas under the plasma concentration–time curve(AUC0-∞)and the peak concentration(Cmax)of nifedipine were increased after oral and intravenous administration.Moreover,the absolute bioavailability(AB)and relative bioavailability(RB)of nifedipine in the presence of kaempferol was significantly higher than those of the control group after oral and intravenous administration.Improvement of bioavailability of nifedipine by kaempferol may be mainly because of the inhibition of the P-gp-mediated efflux transporter in the small intestine and CYP3A4-mediated metabolism in the small intestine or liver,or both.展开更多
Severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)is a novel coronavirus identified at the end of 2019.It is recognized as the causative agent of coronavirus disease 2019(COVID-19).Flavonoids have been s...Severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)is a novel coronavirus identified at the end of 2019.It is recognized as the causative agent of coronavirus disease 2019(COVID-19).Flavonoids have been shown to exhibit therapeutical effect on complications related to COVID-19.The present study reviews possible therapeutic benefits of flavonoids on SARS-CoV-2.The Web of Science,PubMed,Scopus,and Google Scholar were searched using keywords:“COVID-19”,“SARS-CoV-2”,“Kaempferol”and“Quercetin”in the Title/Abstract.Relevant published articles in the English language until August 2020 were considered.Kaempferol and quercetin showed antiviral properties such as inhibition of protein kinase B and phosphorylation of protein kinase and blocking effects on a selective channel(3a channel)expressed in SARS-CoV infected cells.They also reduced the level of reactive oxygen species,expression of inducible nitric oxide synthase,pro-inflammatory mediators including TNF-α,IL-1α,IL-1β,IL-6,IL-10,and IL-12 p70,and chemokines.Kaempferol and quercetin might exert beneficial effects in the control or treatment of COVID-19 because of their antiviral,antioxidant,anti-inflammatory,and immunomodulatory effects.展开更多
OBJECTIVE To investigate the effects of kaempferol(KAE)on chronic cerebral ischemia in rats.METHODS Chronic cerebral ischemia was induced in rats by permanent occlusion of bilateral common carotid arteries(2VO).Then,t...OBJECTIVE To investigate the effects of kaempferol(KAE)on chronic cerebral ischemia in rats.METHODS Chronic cerebral ischemia was induced in rats by permanent occlusion of bilateral common carotid arteries(2VO).Then,the rats with chronic cerebral ischemia were randomly divied into three groups:model group,KAE 10 and 30 mg·kg-1group.Another group rats without occlusion of common carotid arteries were used as the sham-operation group.Memory behavior was investigated by Morris water maze test.Prehensile ability was investigated by prehensile traction test.The structure of hippocampus and cortex neurons was observed with Nissel staining.In addition,the SOD activity and MDA content in brain tissue were determined.The DJ-1protein level was determined by Western blotting.RESULTS KAE 10 and 30 mg·kg-1could significantly improve cognitive impairment and prehensile traction ability(P<0.01)induced by chronic cerebral ischemia in rats.The results of the pathological analysis also suggested that KAE could ameliorate the pathological damage induced by chronic cerebral ischemia.In addition,KAE 30 mg·kg-1significantly increased the activity of SOD(P<0.05),but had no effect on the content of MDA in rat brain tissue.Western-blotting confirmed that KAE 10 and30 mg·kg-1could increase the expression of anti-oxidation proteins DJ-1 in hippocampus(P<0.01).CONCLUSION KAE may attenuate the chronic cerebral ischemic injury in rats.展开更多
OBJECTIVE: To study therapeutic effect of kaempferol on metabolic associated fatty liver disease(MAFLD) by network pharmacology and molecular docking combined with cell experiments. METHODS: First, use the Swiss Targe...OBJECTIVE: To study therapeutic effect of kaempferol on metabolic associated fatty liver disease(MAFLD) by network pharmacology and molecular docking combined with cell experiments. METHODS: First, use the Swiss Target Prediction database to predict the targets of kaempferol, and collect the targets of MAFLD through the Disgenet database and the Gene Cards database. Then, the common target of kaempferol and MAFLD was enriched and analyzed by the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes, and the protein-protein interaction(PPI) network was constructed through the string database to obtain the key targets, and carry out molecular docking of key targets with kaempferol;In cell experiment, oleic acid induced steatosis in Hep G2 cells, which was intervened by kaempferol, the level of triglyceride(TG) was detected, the lipid deposition was observed by oil red O staining, and the protein expression was detected by Western blot. RESULTS: The results showed that there are 33 common targets for kaempferol and MAFLD. The biological process of GO is related to the regulation of protein kinase B, cell apoptosis, inflammatory factors, lipoxygenase, etc. Its action pathway is related to the phosphatidylinositol-3-kinase and protein kinase B(PI3K-AKT) signaling pathway, hypoxia-inducible factor 1 signaling pathway, forkhead box protein O signaling pathway, AMP-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, etc., the key targets are protein kinase B(AKT1), prostaglandin G/H synthase 2, matrix metalloproteinase-9, epidermal growth factor receptor, and the molecular docking of kaempferol with the four key targets shows good binding properties. Cell experiments show that kaempferol can reduce cell TG levels, reduce lipid deposition, increase the expression of PI3K, AKT, and beclin-1, and reduce the expression of caspase-3 and nuclear factor-kappa B. Kaempferol can treat MAFLD by regulating the PI3K-AKT signaling pathway to regulate cell autophagy, apoptosis, and inflammation. CONCLUSIONS: This study shows that kaempferol can regulate lipid metabolism, reduce apoptosis, regulate inflammation and autophagy in the fatty liver cell model. It reveals the therapeutic mechanism of kaempferol on MAFLD and provides a natural product candidate for the treatment of MAFLD.展开更多
Objective:Although there have been improvements in targeted therapy and immunotherapy,the majority of lung adenocarcinoma(LUAD)patients still lack effective therapies.Consequently,it is urgent to screen for new diagno...Objective:Although there have been improvements in targeted therapy and immunotherapy,the majority of lung adenocarcinoma(LUAD)patients still lack effective therapies.Consequently,it is urgent to screen for new diagnosis biomarkers and pharmacological targets.Junctional adhesion molecule-like protein(JAML)was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD.Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD.However,the effect of kaempferol on JAML is still unknown.Methods:Small interfering RNA was used to knockdown JAML expression.The cell viability was determined using the cell counting kit-8 assay.The proliferation of LUAD cells was evaluated using the 5-ethynyl-2'-deoxyuridine incorporation assay.The migration and invasion of LUAD cells were evaluated by transwell assays.Molecular mechanisms were explored by Western blotting.Results:JAML knockdown suppressed proliferation,migration and invasion of LUAD cells,and JAML deficiency restrained epithelial-mesenchymal transition(EMT)via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway.Using a PI3K activator(740Y-P),rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway.Kaempferol also inhibited proliferation,migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway.Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells.Kaempferol exerted anticancer effects by targeting JAML.Conclusion:JAML is a novel target for kaempferol against LUAD cells.展开更多
[Objectives] To investigate the anti-tumor activity of Sedum bulbiferum Makino in vitro,and establish a HPLC method for determination of quercetin and kaempferol in S. bulbiferum. [Methods] The inhibitory activities o...[Objectives] To investigate the anti-tumor activity of Sedum bulbiferum Makino in vitro,and establish a HPLC method for determination of quercetin and kaempferol in S. bulbiferum. [Methods] The inhibitory activities of different extracts and total flavonoids of S. bulbiferum on proliferation of three kinds of cancer cells( Hep G2,EC109,SW480) were tested by MTT assay. HPLC method for determination of quercetin and kaempferol in S. bulbiferum was established. [Results]The growth and proliferation of the three kinds of cancer cells were all significantly inhibited by ethyl acetate fraction and total flavonoids isolated from S. bulbiferum. With each extraction concentration increasing,stronger anti-tumor activity was found. The linear ranges of quercetin and kaempferol were 0. 03-0. 36 μg( R = 0. 999 9) and0. 08-0. 96 μg( R = 0. 999 9),and the average recoveries were 98. 90%( RSD = 1. 15%) and 98. 27%( RSD = 1. 70%),respectively.[Conclusions]S. bulbiferum has significant anti-tumor activity in vitro. The HPLC method established was accurate,reproducible,and could be used for quality control of this crude drug.展开更多
Flavonoids play important roles in regulating plant growth and development.In this study,three kaempferol 3-O-glycosides were identi fi ed and mainly accumulated in fl owers but not in leaves or fruits of Malus.In Mal...Flavonoids play important roles in regulating plant growth and development.In this study,three kaempferol 3-O-glycosides were identi fi ed and mainly accumulated in fl owers but not in leaves or fruits of Malus.In Malus,fl ower petal color is normally white,but some genotypes have red fl owers containing anthocyanin.Anthocyanin biosynthesis appears to be in competition with kaempferol 3-O-glycosides production and controlled by the biosynthetic genes.The white fl ower Malus genotypes had better-developed seeds than the red fl ower genotypes.In fl owers,the overexpression of MYB10 in Malus domestica enhanced the accumulation of anthocyanin,but decreased that of kaempferol 3-O-glycosides.After pollination the transgenic plants showed slower pollen tube growth and fewer developed seeds.Exogenous application ofdifferent fl avonoid compounds suggested that kaempferol 3-O-glycosides,especially kaempferol 3-O-rhamnoside,regulated pollen tube growth and seed set rather than cyanidin or quercetin 3-O-glycosides.It was found that kaempferol 3-O-rhamnoside might regulate pollen tube growth through effects on auxin,the Rho of plants(ROP)GTPases,calcium and the phosphoinositides signaling pathway.With the inhibition of auxin transport,the transcription levels of Heat Shock Proteins(HSPs)and ROP GTPases were downregulated while the levels were not changed or even enhanced when blocking calcium signaling,suggesting that HSPs and ROP GTPases were downstream of auxin signaling,but upstream of calcium signaling.In summary,kaempferol glycoside concentrations in pistils correlated with auxin transport,the transcription of HSPs and ROP GTPases,and calcium signaling in pollen tubes,culminating in changes to pollen tube growth and seed set.展开更多
Two new acetylated kaempferol glycosides were isolated from the seeds of Camellia semiserrata Chi, their structures were elucidated as kaempferol-3-O-[（3-O-acetyl）-a-L-rhamnopyranosyl（1 →3）（4-O-acetyl）-α-L-rha...Two new acetylated kaempferol glycosides were isolated from the seeds of Camellia semiserrata Chi, their structures were elucidated as kaempferol-3-O-[（3-O-acetyl）-a-L-rhamnopyranosyl（1 →3）（4-O-acetyl）-α-L-rhamnopyranosyl（1→ 6）-β-D-glucopyranoside] （1） and kaempferol-3-O-[（2-O-acetyl）-α-L-rhamnopyranosyl （1 →3）（4-O-acetyl）-α-L-rhamnopyranosyl（1 →6）-β-D- gluco-pyranoside] （2） by spectral experiments （including ESI-MS, 1D- and 2D-NMR）..展开更多
Novel uniform-sized magnetic molecularly imprinted polymers （MMIPs） were synthe- sized for selective recognition of active antitumor ingredients of kaempferol （KMF） and protoapi- genone （PA） in Macrothelypteris ...Novel uniform-sized magnetic molecularly imprinted polymers （MMIPs） were synthe- sized for selective recognition of active antitumor ingredients of kaempferol （KMF） and protoapi- genone （PA） in Macrothelypteris torresiana （M. torresiana） by surface molecular imprinting tech- nique in this study. Super paramagnetic core-sheU nanoparticles （γ-MPS-SiO2@Fe3O4） were used as seeds, KMF as template molecule, acrylamide （AM） as functional monomer, and N, N＇-methylene bisacrylamide （BisAM） as cross-linker. The prepared MMIPs were characterized by X-ray diffraction （XRD）, Fourier transform infrared spectrum fiT/R）, transmission electron microscopy （TEM） and thermo-gravimetric analysis （TGA）, respectively. The recognition capacity of MMIPs was 2.436 times of non-imprinted polymers. The adsorption results based on kinetics and isotherm analysis were in accordance with the pseudo-second-order model （R2=0.9980） and the Langmuir adsorption model （R2=0.9944）. The value of E （6.742 kJ/mol） calculated from the Dubinin-Radushkevich isotherm model suggested that the physical adsorption via hydrogen-bonding might be predominant. The Scatchard plot showed a single line （R2=0.9172） and demonstrated the homogeneous recognition sites on MMIPs for KMF. The magnetic solid phase extraction （MSPE） based on MMIPs as sorbent was established for fast and selective enrichment of KMF and its structural analogue PA from the crude extract of M. torresiana and then KMF and PA were detected by HPLC-UV. The established method showed good performance and satisfactory results for real sample analysis. It also showed the feasi- bility of MMIPs for selective recognition of active structural analogues from complex herbal extracts.展开更多
Abstract： In the present study, we developed a simple approach for the structural modifications ofkaempferol （1）. A new compound, 3,5-dihydroxy-2-（4-hydroxyphenyl）-6,8,8-tris（3-methylbut-2-en-1-yl）-4H-chromene-...Abstract： In the present study, we developed a simple approach for the structural modifications ofkaempferol （1）. A new compound, 3,5-dihydroxy-2-（4-hydroxyphenyl）-6,8,8-tris（3-methylbut-2-en-1-yl）-4H-chromene-4,7（SH）-dione （5） together with three known compounds, 8-prenylkaempferol （Z）, 6-prenylkaempferol （3） and 6,8-diprenylkaempferol （4）, were synthesized under different reaction conditions. All of derivatives were synthesized in a structural modification way for the first time. Their structures were primarily elucidated by NMR and MS analyses. Compounds 2, 3 and 5 exhibited prominent cytotoxic activity against MDA-231 （IC50 values were 9.45±0.20 μM, 7.15±0.37 μM and 6.92±0.30 μM, respectively） and MCF-7 （ICso values were 10.08±0.57 0M, 10.04±0.23 μM and 2.15±0.20 μM, respectively） breast cancer cells.展开更多
Kaempferol,a natural plant-origin flavonoid,exhibits therapeutic anti-inflammatory,antioxidant,anticancer,antidiabetic,and neuroprotective properties.Kaempferol acts within several distinct mechanisms like apoptotic i...Kaempferol,a natural plant-origin flavonoid,exhibits therapeutic anti-inflammatory,antioxidant,anticancer,antidiabetic,and neuroprotective properties.Kaempferol acts within several distinct mechanisms like apoptotic induction in cancer cells,enzymatic inhibition,signalling pathway inhibition,and downregulation in cell viability during the G2/M phase of cell division.This review summarizes the therapeutic effects of kaempferol against several health ailments.The recent progress on kaempferol obtained from fruits and vegetables as an antioxidant,anti-inflammatory,anticancer,antidiabetic,and neuroprotective agent and its mechanisms of action are also discussed.In addition,kaempferol has been reported to be present in wastes and byproducts from post-fruit and vegetable processing.Thus,a paradigm shift towards valorizing fruits and vegetable industrial wastes/byproducts to obtain bioactive kaempferol can support the circular economy pillar for generating wealth from waste and for finding a sustainable alternative source.展开更多
Pseudorabies virus(PRV),in the family Herpesviridae,is a pathogen of Aujeszky’s disease,which causes great economic losses to the pig industry.Recent outbreaks of Pseudorabies imply that new control measures are urge...Pseudorabies virus(PRV),in the family Herpesviridae,is a pathogen of Aujeszky’s disease,which causes great economic losses to the pig industry.Recent outbreaks of Pseudorabies imply that new control measures are urgently needed.The present study shows that kaempferol is a candidate drug for controlling PRV infection,as it possesses the ability to inhibit PRV replication in a dose-dependent manner in vitro.Kaempferol at a concentration of 52.40μmol L^(-1) could decrease PRV-induced cell death by 90%.With an 50%inhibitory concentration(IC50)value of 25.57μmol L^(-1),kaempferol was more effective than acyclovir(positive control)which has an IC50 value of 54.97μmol L^(-1).A mode of action study indicated that kaempferol inhibited viral penetration and replication stages,decreasing viral loads by 4-and 30-fold,respectively.Addition of kaempferol within 16 h post infection(hpi)could significantly inhibit virus replication,and viral genome copies were decreased by almost 15-fold when kaempferol was added at 2 hpi.Kaempferol regulated the NF-κB and MAPKs signaling pathways involved in PRV infection and changed the levels of the target genes of the MAPKs(ATF-2 and c-Jun)and NF-κB(IL-1α,IL-1βand IL-2)signaling pathways.The findings of the current study suggest that kaempferol could be an alternative measure to control PRV infection.展开更多
Magnetic fluorescent dual-drug nanocomposites（MFDDs） were developed with the aim of simultaneouly delivering two different anticancer drugs, kaempferol（KAE） and paclitaxel（PTX）. Firstly, Fe3O4/bovine serum albu...Magnetic fluorescent dual-drug nanocomposites（MFDDs） were developed with the aim of simultaneouly delivering two different anticancer drugs, kaempferol（KAE） and paclitaxel（PTX）. Firstly, Fe3O4/bovine serum albumin（Fe3O4/BSA） composite microspheres with physically entrapped KAE were prepared, then microspheres were modified with PTX/graphene quantum dots（PTX/GQDs） through chemically bonding, and the MFDDs were obtained. The properties of nancomposites were characterized by X-ray diffractometry, Fourier-transform infrared spectroscopy, transmission electron microscopy, vibrating sample magnetometry and X-ray fluorescence spectrometry. It was found that the superparamagnetic nanocomposites had ultrafine size（below 110 nm）, high saturation magnetization of 24.36 emu/g, and significant fluorescence. Furthermore, the cumulative in vitro release of the MFDDs exhibited controlled drug release. Cell viability experiments confirmed that the co-administration of KAE with PTX had a superior cytotoxicity to the Hela cells compared with single drug-loaded forms. Therefore, dual anticancer drug-loaded MFDDs have the potential to be used for cancer combined chemotherapy.展开更多
Objective:The objective of this study was to explore the therapeutic effects of kaempferol(Kae)on rheumatoid arthritis(RA)and to elucidate the underlying mechanisms.Methods:The collagen-induced arthritis(CIA)model was...Objective:The objective of this study was to explore the therapeutic effects of kaempferol(Kae)on rheumatoid arthritis(RA)and to elucidate the underlying mechanisms.Methods:The collagen-induced arthritis(CIA)model was established using collagenⅡto induce RA.Mice were treated with Kae at a dose of 25 or 50 mg/kg/day via gavage.Pathological changes in the ankle joint were analyzed.Enzyme-linked immunosorbent assay(ELISA)was employed to measure the levels of inflammatory factors.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)was used to assess the expression of genes associated with the balance of regulatory T(Treg)/T helper 17(Th17)cells.Flow cytometry was utilized to determine the Treg/Th17 ratio.Furthermore,these techniques were employed to evaluate the impact of miR-34a and Foxp3 dysregulation on cellular functions in RA under the influence of Kae.Dual luciferase reporter assay was conducted to analyze the binding of miR-34a to Foxp3.Results:Treatment with Kae led to a downregulation of receptor-related orphan receptor gamma t(RORγt)and IL-17 expression,and an upregulation of Foxp3,IL-10,and TGF-βexpression in CIA mice.Kae intervention inhibited the production of proinflammatory cytokines and increased the production of anti-inflammatory cytokines.Furthermore,Kae treatment suppressed the expression of miR-34a,which was identified as a target of miR-34a.Finally,Kae regulated Treg/Th17 balance-related genes and cellular inflammation through the miR-34a/Foxp3 axis.Conclusion:The study demonstrated that Kae effectively ameliorates CIA in mice by modulating the Treg/Th17 balance and related genes via the miR-34a/Foxp3 axis.These findings suggest that Kae may serve as a promising therapeutic agent for the treatment of RA and for restoring immune homeostasis.展开更多
[Objectives] This study was conducted to determine kaempferol content in ginkgo( Ginkgo biloba L.) leaves subjected to microbial fermentation.[Methods]Bacillus licheniformis was selected for solid-state fermentation o...[Objectives] This study was conducted to determine kaempferol content in ginkgo( Ginkgo biloba L.) leaves subjected to microbial fermentation.[Methods]Bacillus licheniformis was selected for solid-state fermentation of ginkgo leaves,and the content of kaempferol in ginkgo leaves was determined by RPHPLC method. At first,methanol was used to extract flavonoid glycosides,which were then hydrolyzed by hydrochloric acid solution. HPLC was performed with Platisil ODS column C18( 150 mm ×4. 6 mm,5 μm) using mobile phase Vmethanol∶ Vwater( 0. 4% phosphoric acid solution) = 55∶45 at a flow rate of 1 ml/min,and the eluate was detected with a shimadzu HPLC ultraviolet detector at 360 nm. [Results]With kaempferol as the reference substance,the correlation coefficient was0. 999 2 in the range of 0. 001 06-0. 016 96 g/L. The content in the fermented product was less than that in the non-fermented product by 28%. [Conclusions]The method is simple,accurate,and is suitable for determination of kaempferol. This study will provide an experimental basis for the development and utilization of ginkgo.展开更多
OBJECTIVE Chloroquine is considered as a potential chemotherapy and radiotherapy sensitizer,but the anticancer effect of chloroquine alone is limited.Since we found that the flavonoid kaempferol effectively sensitizes...OBJECTIVE Chloroquine is considered as a potential chemotherapy and radiotherapy sensitizer,but the anticancer effect of chloroquine alone is limited.Since we found that the flavonoid kaempferol effectively sensitizes glioma cells to chloroquine-mediated cell death,we investigated the underlying mechanisms of glioma cell death induced by the combination of kaempferol and chloroquine.METHODS To examine the effect of kaempferol and/or chloroquine on various glioma cells,cell viability assay using calcein-AM and EthD-1was performed.The changes in the lysosomal structures following treatment with kaempferol and/or chloroquine were observed by electron microscopy and fluorescence microscopy using acridine orange or Lyso-tracker Red.The changes in cathepsin D proteins were analyzed by Western blotting,immunocytochemistry,and fluorescence microscopy using BODIPY FL-pepstatin.RESULTS Treatment with subtoxic doses of chloroquine,when combined with kaempferol,effectively induced cell death in various glioma cells,but not in normal astrocytes.While kaempferol treatment increased the numbers of lysosome,chloroquine treatment increased lysosomal masses.Combined treatment with kaempferol and chloroquine induced the expansion and subsequent rupture of lysosomes,leading to the spillage of the lysosomal contents into the cytosol.We found that while kaemfperol treatment increased the active mature forms of cathepsin D,chloroquine treatment completely blocked the processing of cathepsin D.The processing of cathepsin D was also blocked by the combined treatment,but the activity of cathepsin D,which was released from the lysosomes,was restored.The cell death induced by kaempferol and chloroquine in U251 MG cells was accompanied by mitochondrial dysfunction,ER stress,and DNA damage.CONCLUSION Disruption of lysosomal membrane integrity and a resultant release of lysosomal proteases may critically contribute to the irreparable damage of various organelles and glioma cell death by chloroquine plus kaempferol.展开更多
Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(S.aureus)infection.Functioning as the indispensable specific cellular receptor for a-toxin(Hla),a-disinteg...Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(S.aureus)infection.Functioning as the indispensable specific cellular receptor for a-toxin(Hla),a-disintegrin and metalloproteinase 10(ADAM10)is exploited to accelerate S.aureus infection through diverse mechanisms.The extraordinary contribution of ADAM10 to S.aureus pathogenesis renders it an attractive HDT target for combating S.aureus infection.Our study is the first to demonstrate the indispensable role of ADAM10 in S.aureus-induced necroptosis,and it enhances our knowledge of the role of ADAM10 in S.aureus infection.Using a fluorogenic substrate assay,we further identified kaempferol as a potent ADAM10 inhibitor that effectively protected mice from S.aureus infection by suppressing Hla-mediated barrier disruption and necroptosis.Collectively,our work presents a novel hostdirected therapeutic strategy for using the promising candidate kaempferol to treat S.aureus infection and other diseases relevant to the disordered upregulation of ADAM10.展开更多
Insulin resistance is a hallmark of type-2 diabetes(T2D)pathogenesis.Because skeletal muscle(SkM)is the major tissue for insulin-mediated glucose disposal,insulin resistance in SkM is considered a major risk factor fo...Insulin resistance is a hallmark of type-2 diabetes(T2D)pathogenesis.Because skeletal muscle(SkM)is the major tissue for insulin-mediated glucose disposal,insulin resistance in SkM is considered a major risk factor for developing T2D.Thus,the identifi cation of compounds that enhance the ability of SkM to take up glucose is a promising strategy for preventing T2D.Our previous work showed that kaempferol,a fl avonol present in many foods,improves insulin sensitivity in obese mice,however,the mechanism underlying this beneficial action remains unclear.Here,we show that kaempferol directly stimulates glucose uptake and prevents lipotoxicity-impaired glucose uptake in primary human SkM.Kaempferol stimulates Akt phosphorylation in a time-dependent manner in human SkM cells.The effect of kaempferol on glucose uptake was blunted by inhibition of glucose transporter 4,phosphoinositide 3-kinase(PI3K),or AMPK.In addition,kaempferol induced AMPK phosphorylation,and inhibition of AMPK prevented kaempferol-stimulated Akt phosphorylation.In vivo,kaempferol administration induced rapid glucose disposal accompanied with increased Akt and AMPK phosphorylation in SkM tissue of the mice.Taken together,these fi ndings suggest that kaempferol stimulates glucose uptake in SkM via an AMPK/Akt dependent mechanism,and it may be a viable therapeutic agent for insulin resistance.展开更多
基金supported by the National Key R&D Program of China(2024YFD2101002)the Key Research and Development Program of Hunan Province(2024JK2152)+3 种基金the Research Foundation of Education Bureau of Hunan Province(No.20K085)the National Natural Science Foundation of China(No.32070071)the Natural Science Foundation of Hunan Province(Nos.2021JJ30441 and 2023JJ30395)the Natural Science Foundation of Changsha(No.kq2208169).
文摘Natural products are effective in the treatment and the prevention of human,animal and plant diseases.Therefore,natural products may also be considered to treat fish diseases.Acori Tatarinowii Rhizoma(ATR)is a herbal medicine with anti-inflammatory and antioxidant effects.However,little is known about how its active ingredients exert the beneficial effects.Here,Four effective active ingredients of ATR and their 81 targets were investigated,which affected the anti-inflammatory response.Among them,kaempferol-JUN was identified as a key regulatory module in anti-inflammatory immune responses,and kaempferol interacted with the CiJUN protein and inhibited CiJUN levels.Silencing CiJUN gene in Ctenopharyn-godon idella kidney(CIK)cells enhanced anti-inflammatory activity and resistance to Aeromonas hydrophila,whereas anti-inflammatory activity and resistance were impaired after CiJUN overexpression.The mortality rate of diseased grass carp was reduced after treatment with kaempferol,as were the inflammatory and oxidant effects.Also,grass carp showed enhanced anti-inflammatory and antioxidant effects after feeding with kaempferol.The results provide further insights into the use of kaempferol to prevent and treat fish diseases.
基金supported by a grant from Research and Technology Chancellor of Guilan University of Medical Sciences,Iran(No.IR.GUMS.REC.1936.51)
文摘Alzheimer＇s disease（AD） is associated with oxidative stress, and ultimately results in cognitive deficit. Despite existing literature on the pathophysiology of AD, there is currently no cure for AD. The present study investigated the effects of kaempferol（Kmp） isolated from the extract of Mespilus germanica L.（medlar） leaves on cognitive impairment, hippocampal antioxidants, apoptosis, lipid peroxidation and neuro-inflammation markers in ovariectomized（OVX） rat models of sporadic AD. Kaempferol, as the main flavonoid of medlar extract has been previously known for anti-oxidative, anti-inflammatory and anti-neurotoxic effects. Thirty-two female Wistar rats were ovariectomized, and randomly divided into four groups： sham, OVX ＋ saline, OVX ＋ streptozotocin（STZ） ＋ saline, OVX ＋ STZ ＋ Kmp. Animals received intracerebroventricular injection of STZ（3 mg/kg, twice with one day interval） to establish models of sporadic AD. Intraperitoneal injection of Kmp（10 mg/kg） for 21 days was performed in the OVX ＋ STZ ＋ Kmp group. Spatial learning and memory of rats were evaluated using a Morris water maze. Finally, brain homogenates were used for biochemical analysis by enzyme-linked immunosorbent assay. The results showed a significant improvement in spatial learning and memory as evidenced by shortened escape latency and searching distance in Morris water maze in the OVX ＋ STZ ＋ Kmp group compared with the OVX ＋ STZ group. Kmp also exhibited significant elevations in brain levels of antioxidant enzymes of superoxide dismutase and glutathione, while reduction in tumor necrosis factor-α and malondialdehyde. Our results demonstrate that Kmp is capable of alleviating STZ-induced memory impairment in OVX rats, probably by elevating endogenous hippocampal antioxidants of superoxide dismutase and glutathione, and reducing neuroinflammation. This study suggests that Kmp may be a potential neuroprotective agent against cognitive deficit in AD.
文摘Herein,the purpose of this study is to evaluate the effects of kaempferol on bioavailability and pharmacokinetics of nifedipine and its metabolite dehydronifedipine in rats.The experimental design is based on with or without kaempferol in the oral and intravenous administration of nifedipine in rats.Moreover,the pharmacokinetic parameters including nifedipine and dehydronifedipine were evaluated in rats.The in vitro studies of kaempferol were investigated on P-glycoprotein(P-gp)and cytochrome P450(CYP)3A4 activity.Kaempferol reduced a 50%inhibitory concentration(IC50)of 8.6μmol·L-1 on CYP3A4 enzyme activity.Moreover,kaempferol clearly improved the cell internalization of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp.Depending on increased concentrations of kaempferol,the areas under the plasma concentration–time curve(AUC0-∞)and the peak concentration(Cmax)of nifedipine were increased after oral and intravenous administration.Moreover,the absolute bioavailability(AB)and relative bioavailability(RB)of nifedipine in the presence of kaempferol was significantly higher than those of the control group after oral and intravenous administration.Improvement of bioavailability of nifedipine by kaempferol may be mainly because of the inhibition of the P-gp-mediated efflux transporter in the small intestine and CYP3A4-mediated metabolism in the small intestine or liver,or both.
文摘Severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)is a novel coronavirus identified at the end of 2019.It is recognized as the causative agent of coronavirus disease 2019(COVID-19).Flavonoids have been shown to exhibit therapeutical effect on complications related to COVID-19.The present study reviews possible therapeutic benefits of flavonoids on SARS-CoV-2.The Web of Science,PubMed,Scopus,and Google Scholar were searched using keywords:“COVID-19”,“SARS-CoV-2”,“Kaempferol”and“Quercetin”in the Title/Abstract.Relevant published articles in the English language until August 2020 were considered.Kaempferol and quercetin showed antiviral properties such as inhibition of protein kinase B and phosphorylation of protein kinase and blocking effects on a selective channel(3a channel)expressed in SARS-CoV infected cells.They also reduced the level of reactive oxygen species,expression of inducible nitric oxide synthase,pro-inflammatory mediators including TNF-α,IL-1α,IL-1β,IL-6,IL-10,and IL-12 p70,and chemokines.Kaempferol and quercetin might exert beneficial effects in the control or treatment of COVID-19 because of their antiviral,antioxidant,anti-inflammatory,and immunomodulatory effects.
基金The project supported by National Natural Science Foundation of China(81473383,81573645)
文摘OBJECTIVE To investigate the effects of kaempferol(KAE)on chronic cerebral ischemia in rats.METHODS Chronic cerebral ischemia was induced in rats by permanent occlusion of bilateral common carotid arteries(2VO).Then,the rats with chronic cerebral ischemia were randomly divied into three groups:model group,KAE 10 and 30 mg·kg-1group.Another group rats without occlusion of common carotid arteries were used as the sham-operation group.Memory behavior was investigated by Morris water maze test.Prehensile ability was investigated by prehensile traction test.The structure of hippocampus and cortex neurons was observed with Nissel staining.In addition,the SOD activity and MDA content in brain tissue were determined.The DJ-1protein level was determined by Western blotting.RESULTS KAE 10 and 30 mg·kg-1could significantly improve cognitive impairment and prehensile traction ability(P<0.01)induced by chronic cerebral ischemia in rats.The results of the pathological analysis also suggested that KAE could ameliorate the pathological damage induced by chronic cerebral ischemia.In addition,KAE 30 mg·kg-1significantly increased the activity of SOD(P<0.05),but had no effect on the content of MDA in rat brain tissue.Western-blotting confirmed that KAE 10 and30 mg·kg-1could increase the expression of anti-oxidation proteins DJ-1 in hippocampus(P<0.01).CONCLUSION KAE may attenuate the chronic cerebral ischemic injury in rats.
基金Supported by Natural Science Foundation of Jilin Province:Study on the Pharmacodynamic Material Basis and Action Mechanism of Buyang Huanwu Decoction on Diabetic Glucolipid Metabolism Disorder Renal Injury Based on Metabolic Nuclear Receptor Pathway (No. YDZJ202201ZYTS199)the National College Students Innovation and Entrepreneurship Training Program:Study on the Mechanism of Buyang Huanwu Decoction in the Treatment of Cardiovascular Complications of Diabetes (No. 202210199020)。
文摘OBJECTIVE: To study therapeutic effect of kaempferol on metabolic associated fatty liver disease(MAFLD) by network pharmacology and molecular docking combined with cell experiments. METHODS: First, use the Swiss Target Prediction database to predict the targets of kaempferol, and collect the targets of MAFLD through the Disgenet database and the Gene Cards database. Then, the common target of kaempferol and MAFLD was enriched and analyzed by the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes, and the protein-protein interaction(PPI) network was constructed through the string database to obtain the key targets, and carry out molecular docking of key targets with kaempferol;In cell experiment, oleic acid induced steatosis in Hep G2 cells, which was intervened by kaempferol, the level of triglyceride(TG) was detected, the lipid deposition was observed by oil red O staining, and the protein expression was detected by Western blot. RESULTS: The results showed that there are 33 common targets for kaempferol and MAFLD. The biological process of GO is related to the regulation of protein kinase B, cell apoptosis, inflammatory factors, lipoxygenase, etc. Its action pathway is related to the phosphatidylinositol-3-kinase and protein kinase B(PI3K-AKT) signaling pathway, hypoxia-inducible factor 1 signaling pathway, forkhead box protein O signaling pathway, AMP-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, etc., the key targets are protein kinase B(AKT1), prostaglandin G/H synthase 2, matrix metalloproteinase-9, epidermal growth factor receptor, and the molecular docking of kaempferol with the four key targets shows good binding properties. Cell experiments show that kaempferol can reduce cell TG levels, reduce lipid deposition, increase the expression of PI3K, AKT, and beclin-1, and reduce the expression of caspase-3 and nuclear factor-kappa B. Kaempferol can treat MAFLD by regulating the PI3K-AKT signaling pathway to regulate cell autophagy, apoptosis, and inflammation. CONCLUSIONS: This study shows that kaempferol can regulate lipid metabolism, reduce apoptosis, regulate inflammation and autophagy in the fatty liver cell model. It reveals the therapeutic mechanism of kaempferol on MAFLD and provides a natural product candidate for the treatment of MAFLD.
基金supported by the National Natural Science Foundation of China(Grant No.81973630)National Clinical Key Specialty Project Foundation(Grant No.Z155080000004).
文摘Objective:Although there have been improvements in targeted therapy and immunotherapy,the majority of lung adenocarcinoma(LUAD)patients still lack effective therapies.Consequently,it is urgent to screen for new diagnosis biomarkers and pharmacological targets.Junctional adhesion molecule-like protein(JAML)was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD.Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD.However,the effect of kaempferol on JAML is still unknown.Methods:Small interfering RNA was used to knockdown JAML expression.The cell viability was determined using the cell counting kit-8 assay.The proliferation of LUAD cells was evaluated using the 5-ethynyl-2'-deoxyuridine incorporation assay.The migration and invasion of LUAD cells were evaluated by transwell assays.Molecular mechanisms were explored by Western blotting.Results:JAML knockdown suppressed proliferation,migration and invasion of LUAD cells,and JAML deficiency restrained epithelial-mesenchymal transition(EMT)via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway.Using a PI3K activator(740Y-P),rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway.Kaempferol also inhibited proliferation,migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway.Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells.Kaempferol exerted anticancer effects by targeting JAML.Conclusion:JAML is a novel target for kaempferol against LUAD cells.
文摘[Objectives] To investigate the anti-tumor activity of Sedum bulbiferum Makino in vitro,and establish a HPLC method for determination of quercetin and kaempferol in S. bulbiferum. [Methods] The inhibitory activities of different extracts and total flavonoids of S. bulbiferum on proliferation of three kinds of cancer cells( Hep G2,EC109,SW480) were tested by MTT assay. HPLC method for determination of quercetin and kaempferol in S. bulbiferum was established. [Results]The growth and proliferation of the three kinds of cancer cells were all significantly inhibited by ethyl acetate fraction and total flavonoids isolated from S. bulbiferum. With each extraction concentration increasing,stronger anti-tumor activity was found. The linear ranges of quercetin and kaempferol were 0. 03-0. 36 μg( R = 0. 999 9) and0. 08-0. 96 μg( R = 0. 999 9),and the average recoveries were 98. 90%( RSD = 1. 15%) and 98. 27%( RSD = 1. 70%),respectively.[Conclusions]S. bulbiferum has significant anti-tumor activity in vitro. The HPLC method established was accurate,reproducible,and could be used for quality control of this crude drug.
基金This work was funded by the National Key R&D Program(2018YFD1000200)the National Natural Science Foundation(31972366)of China。
文摘Flavonoids play important roles in regulating plant growth and development.In this study,three kaempferol 3-O-glycosides were identi fi ed and mainly accumulated in fl owers but not in leaves or fruits of Malus.In Malus,fl ower petal color is normally white,but some genotypes have red fl owers containing anthocyanin.Anthocyanin biosynthesis appears to be in competition with kaempferol 3-O-glycosides production and controlled by the biosynthetic genes.The white fl ower Malus genotypes had better-developed seeds than the red fl ower genotypes.In fl owers,the overexpression of MYB10 in Malus domestica enhanced the accumulation of anthocyanin,but decreased that of kaempferol 3-O-glycosides.After pollination the transgenic plants showed slower pollen tube growth and fewer developed seeds.Exogenous application ofdifferent fl avonoid compounds suggested that kaempferol 3-O-glycosides,especially kaempferol 3-O-rhamnoside,regulated pollen tube growth and seed set rather than cyanidin or quercetin 3-O-glycosides.It was found that kaempferol 3-O-rhamnoside might regulate pollen tube growth through effects on auxin,the Rho of plants(ROP)GTPases,calcium and the phosphoinositides signaling pathway.With the inhibition of auxin transport,the transcription levels of Heat Shock Proteins(HSPs)and ROP GTPases were downregulated while the levels were not changed or even enhanced when blocking calcium signaling,suggesting that HSPs and ROP GTPases were downstream of auxin signaling,but upstream of calcium signaling.In summary,kaempferol glycoside concentrations in pistils correlated with auxin transport,the transcription of HSPs and ROP GTPases,and calcium signaling in pollen tubes,culminating in changes to pollen tube growth and seed set.
基金financially supported by the National Natural Science Foundation of China(No.30772714)
文摘Two new acetylated kaempferol glycosides were isolated from the seeds of Camellia semiserrata Chi, their structures were elucidated as kaempferol-3-O-[（3-O-acetyl）-a-L-rhamnopyranosyl（1 →3）（4-O-acetyl）-α-L-rhamnopyranosyl（1→ 6）-β-D-glucopyranoside] （1） and kaempferol-3-O-[（2-O-acetyl）-α-L-rhamnopyranosyl （1 →3）（4-O-acetyl）-α-L-rhamnopyranosyl（1 →6）-β-D- gluco-pyranoside] （2） by spectral experiments （including ESI-MS, 1D- and 2D-NMR）..
基金supported by grants from the National Natural Science Foundation of China(No.21105032)Doctoral Program Fund of Ministry of Education of China(No.20110142120031)
文摘Novel uniform-sized magnetic molecularly imprinted polymers （MMIPs） were synthe- sized for selective recognition of active antitumor ingredients of kaempferol （KMF） and protoapi- genone （PA） in Macrothelypteris torresiana （M. torresiana） by surface molecular imprinting tech- nique in this study. Super paramagnetic core-sheU nanoparticles （γ-MPS-SiO2@Fe3O4） were used as seeds, KMF as template molecule, acrylamide （AM） as functional monomer, and N, N＇-methylene bisacrylamide （BisAM） as cross-linker. The prepared MMIPs were characterized by X-ray diffraction （XRD）, Fourier transform infrared spectrum fiT/R）, transmission electron microscopy （TEM） and thermo-gravimetric analysis （TGA）, respectively. The recognition capacity of MMIPs was 2.436 times of non-imprinted polymers. The adsorption results based on kinetics and isotherm analysis were in accordance with the pseudo-second-order model （R2=0.9980） and the Langmuir adsorption model （R2=0.9944）. The value of E （6.742 kJ/mol） calculated from the Dubinin-Radushkevich isotherm model suggested that the physical adsorption via hydrogen-bonding might be predominant. The Scatchard plot showed a single line （R2=0.9172） and demonstrated the homogeneous recognition sites on MMIPs for KMF. The magnetic solid phase extraction （MSPE） based on MMIPs as sorbent was established for fast and selective enrichment of KMF and its structural analogue PA from the crude extract of M. torresiana and then KMF and PA were detected by HPLC-UV. The established method showed good performance and satisfactory results for real sample analysis. It also showed the feasi- bility of MMIPs for selective recognition of active structural analogues from complex herbal extracts.
基金National Key Technology R&D Program“New Drug Innovation”of China(Grant No.2013ZX09103002-006)National Natural Science Foundation of China(Grant No.81673590)
文摘Abstract： In the present study, we developed a simple approach for the structural modifications ofkaempferol （1）. A new compound, 3,5-dihydroxy-2-（4-hydroxyphenyl）-6,8,8-tris（3-methylbut-2-en-1-yl）-4H-chromene-4,7（SH）-dione （5） together with three known compounds, 8-prenylkaempferol （Z）, 6-prenylkaempferol （3） and 6,8-diprenylkaempferol （4）, were synthesized under different reaction conditions. All of derivatives were synthesized in a structural modification way for the first time. Their structures were primarily elucidated by NMR and MS analyses. Compounds 2, 3 and 5 exhibited prominent cytotoxic activity against MDA-231 （IC50 values were 9.45±0.20 μM, 7.15±0.37 μM and 6.92±0.30 μM, respectively） and MCF-7 （ICso values were 10.08±0.57 0M, 10.04±0.23 μM and 2.15±0.20 μM, respectively） breast cancer cells.
文摘Kaempferol,a natural plant-origin flavonoid,exhibits therapeutic anti-inflammatory,antioxidant,anticancer,antidiabetic,and neuroprotective properties.Kaempferol acts within several distinct mechanisms like apoptotic induction in cancer cells,enzymatic inhibition,signalling pathway inhibition,and downregulation in cell viability during the G2/M phase of cell division.This review summarizes the therapeutic effects of kaempferol against several health ailments.The recent progress on kaempferol obtained from fruits and vegetables as an antioxidant,anti-inflammatory,anticancer,antidiabetic,and neuroprotective agent and its mechanisms of action are also discussed.In addition,kaempferol has been reported to be present in wastes and byproducts from post-fruit and vegetable processing.Thus,a paradigm shift towards valorizing fruits and vegetable industrial wastes/byproducts to obtain bioactive kaempferol can support the circular economy pillar for generating wealth from waste and for finding a sustainable alternative source.
基金This work was supported by the Program of Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System(SCCXTD-2020-18)the Science and Technology Project of Sichuan Province,China(2018NZ0043,2018NZ0064 and 2018HH0076).
文摘Pseudorabies virus(PRV),in the family Herpesviridae,is a pathogen of Aujeszky’s disease,which causes great economic losses to the pig industry.Recent outbreaks of Pseudorabies imply that new control measures are urgently needed.The present study shows that kaempferol is a candidate drug for controlling PRV infection,as it possesses the ability to inhibit PRV replication in a dose-dependent manner in vitro.Kaempferol at a concentration of 52.40μmol L^(-1) could decrease PRV-induced cell death by 90%.With an 50%inhibitory concentration(IC50)value of 25.57μmol L^(-1),kaempferol was more effective than acyclovir(positive control)which has an IC50 value of 54.97μmol L^(-1).A mode of action study indicated that kaempferol inhibited viral penetration and replication stages,decreasing viral loads by 4-and 30-fold,respectively.Addition of kaempferol within 16 h post infection(hpi)could significantly inhibit virus replication,and viral genome copies were decreased by almost 15-fold when kaempferol was added at 2 hpi.Kaempferol regulated the NF-κB and MAPKs signaling pathways involved in PRV infection and changed the levels of the target genes of the MAPKs(ATF-2 and c-Jun)and NF-κB(IL-1α,IL-1βand IL-2)signaling pathways.The findings of the current study suggest that kaempferol could be an alternative measure to control PRV infection.
基金Funded by the Natural Science Fund of Jiangsu Overseas Research&Training Program for University Prominent Young&Middle-aged Teachers and Presidentsthe Natural Science Fund of Jiangsu Province(No.BK20130094)+1 种基金the Enterpriseuniversities Cooperative Innovation Fund of Jiangsu Province(No.BY2014016)the National Natural Science Foundation of China(No.51103066)
文摘Magnetic fluorescent dual-drug nanocomposites（MFDDs） were developed with the aim of simultaneouly delivering two different anticancer drugs, kaempferol（KAE） and paclitaxel（PTX）. Firstly, Fe3O4/bovine serum albumin（Fe3O4/BSA） composite microspheres with physically entrapped KAE were prepared, then microspheres were modified with PTX/graphene quantum dots（PTX/GQDs） through chemically bonding, and the MFDDs were obtained. The properties of nancomposites were characterized by X-ray diffractometry, Fourier-transform infrared spectroscopy, transmission electron microscopy, vibrating sample magnetometry and X-ray fluorescence spectrometry. It was found that the superparamagnetic nanocomposites had ultrafine size（below 110 nm）, high saturation magnetization of 24.36 emu/g, and significant fluorescence. Furthermore, the cumulative in vitro release of the MFDDs exhibited controlled drug release. Cell viability experiments confirmed that the co-administration of KAE with PTX had a superior cytotoxicity to the Hela cells compared with single drug-loaded forms. Therefore, dual anticancer drug-loaded MFDDs have the potential to be used for cancer combined chemotherapy.
文摘Objective:The objective of this study was to explore the therapeutic effects of kaempferol(Kae)on rheumatoid arthritis(RA)and to elucidate the underlying mechanisms.Methods:The collagen-induced arthritis(CIA)model was established using collagenⅡto induce RA.Mice were treated with Kae at a dose of 25 or 50 mg/kg/day via gavage.Pathological changes in the ankle joint were analyzed.Enzyme-linked immunosorbent assay(ELISA)was employed to measure the levels of inflammatory factors.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)was used to assess the expression of genes associated with the balance of regulatory T(Treg)/T helper 17(Th17)cells.Flow cytometry was utilized to determine the Treg/Th17 ratio.Furthermore,these techniques were employed to evaluate the impact of miR-34a and Foxp3 dysregulation on cellular functions in RA under the influence of Kae.Dual luciferase reporter assay was conducted to analyze the binding of miR-34a to Foxp3.Results:Treatment with Kae led to a downregulation of receptor-related orphan receptor gamma t(RORγt)and IL-17 expression,and an upregulation of Foxp3,IL-10,and TGF-βexpression in CIA mice.Kae intervention inhibited the production of proinflammatory cytokines and increased the production of anti-inflammatory cytokines.Furthermore,Kae treatment suppressed the expression of miR-34a,which was identified as a target of miR-34a.Finally,Kae regulated Treg/Th17 balance-related genes and cellular inflammation through the miR-34a/Foxp3 axis.Conclusion:The study demonstrated that Kae effectively ameliorates CIA in mice by modulating the Treg/Th17 balance and related genes via the miR-34a/Foxp3 axis.These findings suggest that Kae may serve as a promising therapeutic agent for the treatment of RA and for restoring immune homeostasis.
基金Supported by Guilin Science and Technology Bureau Project(20100305)Guangxi"2011 Collaborative Innovation Center"-Zhuang Yao Medicine Collaborative Innovation Center Project(G2013[20])
文摘[Objectives] This study was conducted to determine kaempferol content in ginkgo( Ginkgo biloba L.) leaves subjected to microbial fermentation.[Methods]Bacillus licheniformis was selected for solid-state fermentation of ginkgo leaves,and the content of kaempferol in ginkgo leaves was determined by RPHPLC method. At first,methanol was used to extract flavonoid glycosides,which were then hydrolyzed by hydrochloric acid solution. HPLC was performed with Platisil ODS column C18( 150 mm ×4. 6 mm,5 μm) using mobile phase Vmethanol∶ Vwater( 0. 4% phosphoric acid solution) = 55∶45 at a flow rate of 1 ml/min,and the eluate was detected with a shimadzu HPLC ultraviolet detector at 360 nm. [Results]With kaempferol as the reference substance,the correlation coefficient was0. 999 2 in the range of 0. 001 06-0. 016 96 g/L. The content in the fermented product was less than that in the non-fermented product by 28%. [Conclusions]The method is simple,accurate,and is suitable for determination of kaempferol. This study will provide an experimental basis for the development and utilization of ginkgo.
基金The project supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIP)〔2011-0030043(SRC)〕a grant of the Korean Health Technology R&D Progect,Ministry of Health&Welfare(HI14C2230)
文摘OBJECTIVE Chloroquine is considered as a potential chemotherapy and radiotherapy sensitizer,but the anticancer effect of chloroquine alone is limited.Since we found that the flavonoid kaempferol effectively sensitizes glioma cells to chloroquine-mediated cell death,we investigated the underlying mechanisms of glioma cell death induced by the combination of kaempferol and chloroquine.METHODS To examine the effect of kaempferol and/or chloroquine on various glioma cells,cell viability assay using calcein-AM and EthD-1was performed.The changes in the lysosomal structures following treatment with kaempferol and/or chloroquine were observed by electron microscopy and fluorescence microscopy using acridine orange or Lyso-tracker Red.The changes in cathepsin D proteins were analyzed by Western blotting,immunocytochemistry,and fluorescence microscopy using BODIPY FL-pepstatin.RESULTS Treatment with subtoxic doses of chloroquine,when combined with kaempferol,effectively induced cell death in various glioma cells,but not in normal astrocytes.While kaempferol treatment increased the numbers of lysosome,chloroquine treatment increased lysosomal masses.Combined treatment with kaempferol and chloroquine induced the expansion and subsequent rupture of lysosomes,leading to the spillage of the lysosomal contents into the cytosol.We found that while kaemfperol treatment increased the active mature forms of cathepsin D,chloroquine treatment completely blocked the processing of cathepsin D.The processing of cathepsin D was also blocked by the combined treatment,but the activity of cathepsin D,which was released from the lysosomes,was restored.The cell death induced by kaempferol and chloroquine in U251 MG cells was accompanied by mitochondrial dysfunction,ER stress,and DNA damage.CONCLUSION Disruption of lysosomal membrane integrity and a resultant release of lysosomal proteases may critically contribute to the irreparable damage of various organelles and glioma cell death by chloroquine plus kaempferol.
基金supported by the National Natural Science Foundation of China(U22A20523,32172912,and 32102722)the Interdisciplinary Integration and Innovation Project of Jilin University(JLUXKJC2021QZ04)。
文摘Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(S.aureus)infection.Functioning as the indispensable specific cellular receptor for a-toxin(Hla),a-disintegrin and metalloproteinase 10(ADAM10)is exploited to accelerate S.aureus infection through diverse mechanisms.The extraordinary contribution of ADAM10 to S.aureus pathogenesis renders it an attractive HDT target for combating S.aureus infection.Our study is the first to demonstrate the indispensable role of ADAM10 in S.aureus-induced necroptosis,and it enhances our knowledge of the role of ADAM10 in S.aureus infection.Using a fluorogenic substrate assay,we further identified kaempferol as a potent ADAM10 inhibitor that effectively protected mice from S.aureus infection by suppressing Hla-mediated barrier disruption and necroptosis.Collectively,our work presents a novel hostdirected therapeutic strategy for using the promising candidate kaempferol to treat S.aureus infection and other diseases relevant to the disordered upregulation of ADAM10.
基金partially supported by grants from Diabetes Action Research and Education Foundation。
文摘Insulin resistance is a hallmark of type-2 diabetes(T2D)pathogenesis.Because skeletal muscle(SkM)is the major tissue for insulin-mediated glucose disposal,insulin resistance in SkM is considered a major risk factor for developing T2D.Thus,the identifi cation of compounds that enhance the ability of SkM to take up glucose is a promising strategy for preventing T2D.Our previous work showed that kaempferol,a fl avonol present in many foods,improves insulin sensitivity in obese mice,however,the mechanism underlying this beneficial action remains unclear.Here,we show that kaempferol directly stimulates glucose uptake and prevents lipotoxicity-impaired glucose uptake in primary human SkM.Kaempferol stimulates Akt phosphorylation in a time-dependent manner in human SkM cells.The effect of kaempferol on glucose uptake was blunted by inhibition of glucose transporter 4,phosphoinositide 3-kinase(PI3K),or AMPK.In addition,kaempferol induced AMPK phosphorylation,and inhibition of AMPK prevented kaempferol-stimulated Akt phosphorylation.In vivo,kaempferol administration induced rapid glucose disposal accompanied with increased Akt and AMPK phosphorylation in SkM tissue of the mice.Taken together,these fi ndings suggest that kaempferol stimulates glucose uptake in SkM via an AMPK/Akt dependent mechanism,and it may be a viable therapeutic agent for insulin resistance.
