Kaempferol ameliorated levodopa-induced dyskinesia in experimental rats: A role of brain monoamines, cFOS, FosB, Parkin, Pdyn, TH, and p-JNK

Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are scarce.Flavonoids reported their neuroprotective activity by ameliorating acetylcholinesterase,monoamine oxidase,and neuroinflammation.Kaempferol is anotherflavonoid bearing these potentials.Aim:To evaluate neuroprotective activity of kaempferol in dyskinetic rats.Methods:PD was developed in Sprague-Dawley rats by injecting combination of L-ascorbic acid(10µL)+6-OHDA(12µg)in medial forebrain bundle to induce neuronal damage in substantial nigra(SNr).LID was induced by administrating combination of L-dopa(20 mg/kg)+benserazide HCl(5 mg/kg)for 42 days.Rats were concomitantly treated with amantadine(40 mg/kg)or kaempferol(25,50,and 100 mg/kg,p.o.).Results:Kaempferol(50 and 100 mg/kg)markedly(p<0.05)inhibited LID-induced abnormal involuntary movements(AIMs)and alternation in motor function.Kaempferol administration considerably(p<0.05)inhibited reduced mitochondrial complex activities,serotonin and dopamine levels,Bcl-2,and Tyrosine hydroxylase protein expressions in SNr.Additionally,kaempferol considerably(p<0.05)attenuated increased cFOS,FosB,Parkin,and Pdyn mRNAs expressions,Bax,cleaved caspase-3,caspase-3,and pJNK proteins levels;DOPAC and 5-HIAA levels in SNr.A positive correlation was reported between cFOS,FosB,Parkin,Pdyn,apoptosis,and TH with AIMs.Conclusion:Kaempferol effectively attenuated L-dopa-induced AIMs and dyskinesia via amelioration of alterations in cFOS,FosB,Parkin,Pdyn,Tyrosine hydroxylase,and apoptosis in the brain SNr.

Effects of ginkgo flavone aglycone on atherosclerosis based on network pharmacology,molecular docking,and in vitro experiments

Background:Ginkgo flavone aglycones(GA),a Ginkgo(Ginkgo biloba)extract,has been proven to have good biological activity in atherosclerosis(AS)treatment.Moreover,its active compounds and the corresponding mechanism for the treatment of AS remain unclear.Methods:To evaluate and identify the potential pharmacological mechanisms of GA in AS treatment,the program Cytoscape was used to generate network mappings of the GA-AS-potential target gene.GO and KEGG enrichment analyses were performed to further investigate the potential mechanism of AS and the pharmacological properties of GA.A molecular docking approach was utilized to determine the GA components that interact with Akt.In vitro experiments were carried out to identify the anti-atherosclerotic effects of GA by targeting Akt.Results:Network pharmacological research determined that the active components of GA(quercetin,kaempferol,and isorhamnetin)correlated with AS target genes such as AKT1,EGFR,SRC,ESR1,PTGS2,MMP9,KDR,GSK3B,APP,and MMP2,respectively.GO enrichment and KEGG analysis showed that PI3K-Akt signaling may play an important role in GA treatment.Molecular docking experiments indicated that quercetin,kaempferol,and isorhamnetin integrate into the binding pockets of the most potentially beneficial GA-AS target protein(Akt).Consequently,cell experiments were conducted to support the anti-atherosclerotic activity of GA on AS by inhibiting the phosphorylation of AKT1 and its downstream signaling molecules,which regulated the proliferation of HASMCs.Conclusion:Our results detailed GA's active ingredients,potential targets,and molecular basis against AS.GA may exert anti-atherosclerotic effects by suppressing Akt phosphorylation and inhibiting the proliferation of HASMCs.It also proposed a viable approach to determining the scientific foundation and therapeutic mechanism of Chinese herbal medicine extracts in disease therapy.

Preparation, characterization and evaluation of kaempferol phospholipid complex: Improvement of its solubility and biological eff ect

Kaempferol(KA),as one of the flavonoids,has extensive pharmacological properties.However,the poor solubility of KA severely limits its clinical application.In our study,the kaempferol phospholipid complex(KA-PC)has been prepared by solvent evaporation for the enhancement of the bioavailability of KA.KA-PC was verified by scanning electron microscope characterization methods.Drug loading,solubility and long-term stability were measured.The characterization results showed that KA-PC was formed through the intermolecular interaction between KA and phospholipids.The solubility of KA-PC in water was 189 times higher than that of KA,and the solubility in n-octanol was also significantly improved.Besides,pharmacodynamic studies showed that KA-PC can significantly reduce the level of serum uric acid in mice without causing renal injury.This study expanded the clinical application of KA by preparing KA-PC.

Discovery of Kaempferol,a Novel ADAM10 Inhibitor,as a Potential Treatment for Staphylococcus aureus Infection

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.

Kaempferol improves glucose uptake in skeletal muscle via an AMPK-dependent mechanism

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.

Kaempferol and its derivatives:Biological activities and therapeutic potential

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.

Research progress and quality markers prediction analysis of Dysosma versipellis

Dysosma versipellis is the rhizome of Bajiaolian in Berberaceae.It is a unique medicinal plant in China and it was the first to be recorded in Shennong’s Classic of Materia Medica(unknown author,25–220 C.E.).It has complex chemical components as well as complex,pharmacological and toxicological effects are extensive.Based on the recent research progress,the chemical constituents,pharmacological activities and toxicological effects of Dysosma versipellis were summarized.Combined with the core concept of quality markers of traditional Chinese medicine,the prediction and analysis were carried out from the aspects of phytogenetics and the source pathway of specific chemical constituents,traditional medicinal properties,traditional efficacy,chemical composition measurability,blood components,and pharmacokinetics,in order to provide reference for further study of Dysosma versipellis.

Kaempferol attenuates cognitive deficit via regulating oxidative stress and neuroinflammation in an ovariectomized rat model of sporadic dementia

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.

Anti-viral and anti-inflammatory effects of kaempferol and quercetin and COVID-2019:A scoping review

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.

Gene set enrichment analysis of alpha-glucosidase inhibitors from Ficus benghalensis

Objective:To identify alpha-glucosidase inhibitors from Ficus benghalensis and analyze gene set enrichment of regulated protein molecules.Methods:The phytoconstituents of Ficu.s benghalen.sis were queried for inhibitors of alphaglucosidase,also identified as aldose reductase inhibitors.Druglikeness score,absorption,distribution,metabolism,excretion and toxicity profile,biological spectrum,and gene expression were predicated for each compound.Docking study was performed to predict the binding affinity with alpha-glucosidase and aldose reductase and compared with clinically proven molecules.Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed for the regulated genes to identify the modulated pathways.Results:Apigenin,3,4’,5,7-tetrahydroxy-3’-methoxyflavone,and kaempferol were identified as inhibitors of alpha-glucosidase and aldose reductase.Kaempferol was predicted to possess the highest binding affinity with both targets.The p53 signaling pathway was predicted to modulate the majority of protein molecules in diabetes mellitus.All the alpha-glucosidase inhibitors were also predicted as membrane integrity agonist and anti-mutagenic compounds.Conclusions:The current study indicates alpha-glucosidase inhibitors from Ficus benghale,nsis can act as aldose reductase inhibitors after absorption from the intestinal tract.Furthermore,these phytoconstituents are involved in the regulation of numerous protein molecules and pathways.Hence,the anti-diabetic efficacies of these compounds are due to their action on multiple protein molecules and synergistic effects which should be confirmed by future investigations.

Neuroprotective effects of kaempferol against 2VO-induced chronic cerebral ischemia in rats

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.

Screening of Anti-tumor Effective Extracts from Sedum bulbiferum Makino and HPLC Determination of Quercetin and Kaempferol in This Herbal Medicine

[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.

Isolation, Identification and Tyrosinase Inhibitory Activities of the Extractives from Allamanda cathartica

Tyrosinase inhibitory activity of the extractives from A. cathartica was examined and their new bioactivity and potent active compounds were identified. Five compounds, glabridin, new lignan, kaempferol, naringenin, and allamandicin, were isolated by a series of chromatography, and identified by NMR and LC-MS. Among them, glabridin had the high-est tyrosinase inhibitory activity (IC50:2.93 μM) which is 15 times stronger than that of kojic acid used as positive con-trol (IC50:43.7 μM). Moreover the lignan was indentified as 1-[3-(4-allyl-2,6-dimethoxyphenoxy)-4-methoxyphenyl] propane-1,2,diol which was a novel lignan.

Identification and quantification of flavonoids in Carica papaya leaf and peroxynitrite-scavenging activity

Objective: To characterize the types, contents, and peroxynitrite-scavenging activities of flavonoids in the leaf of Carica papaya(C. papaya).Methods: Chromatographic and spectroscopic techniques along with high performance liquid chromatography quantitative analysis and peroxynitrite-scavenging assay were performed to isolate and quantify flavonoid compounds in the flavonoid-rich fraction(Bu OH fraction) derived from Me OH extract of C. papaya leaves and evaluate their peroxynitrite-scavenging activities.Results: Seven flavonoids were isolated from the leaves of C. papaya, including quercetin 3-(2~G-rhamnosylrutinoside), kaempferol 3-(2~G-rhamnosylrutinoside), quercetin 3-rutinoside, myricetin 3-rhamnoside, kaempferol 3-rutinoside, quercetin, and kaempferol. All of the substances exhibited potent activities on peroxynitrite scavenging(IC50 4.15 mmol/L), which were stronger than the positive control, L-penicillamine(6.90 mmol/L). The content of kaempferol 3-(2~G-rhamnosylrutinoside) was significantly higher than other identified compounds(123.18 mg/g Bu OH fraction and 7.23 mg/g Me OH extract).Conclusions: The results of the present study demonstrate the potent antioxidant flavonoids of C. papaya leaf, with kaempferol 3-(2~G-rhamnosylrutinoside) as the major one.

Preparation of Magnetic Molecularly Imprinted Polymers for Selective Isolation and Determination of Kaempferol and Protoapigenone in Macrothelypteris torresiana

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.

Content Comparison of Three Kinds of Flavonoids in Powders of Tartary Buckwheat of Different Parts

The contents of rutin,quercetin and kaempferol in powders of tartary buckwheat of different parts were determined by high-performance liquid chromatography( HPLC). The results showed that the contents of the three kinds of flavonoids differed greatly in the powders of tartary buckwheat of different parts. The contents of rutin and quercetin in the powder of tartary buckwheat sprouts were significantly higher than those in the powders of tartary buckwheat leaves and seeds. The content of kaempferol was highest in the powder of tartary buckwheat seeds. It indicates that high-performance liquid chromatography can be used for quality control of tartary buckwheat powder for its time saving,cost saving and accurate and reliable results. The content of rutin in the powder of tartary buckwheat sprouts was highest,suggesting that it is more suitable for the development of various foods based on tartary buckwheat powder.

A new flavonol glycoside from Hydrangea macrophylla (Thunb.) Seringe

A new kaempferol glycoside,named kaempferol 3-O-[6″-O-β-D-glucopyranosyl-6′′′-O-α-L-rhamnopy ranosyl-2′′′′-O-α-L-rhamnopyranosyl]-β-D-glucopyranoside,was isolated from Hydrangea macrophylla(Thunb.) Seringe.Its structure was establishedby spectroscopic techniques including MS,IR,UV,and 2D NMR.

ID7 Isolated from Bauhinia variegata Stem Inhibits Tumor Progression and Metastatic Mechanisms of Triple Negative Breast Cancer in Vivo

Background:The breast cancer has been the most common form of cancer among women.The triple negative subtype represents 20%of all breast cancer cases in the world and is standing out by affecting young women and being aggressive.The main cause of death of patients with cancer is due to metastasis,which can reach the liver and lungs.Objective:The activities of ID7 fraction of the stems of Bauhinia variegata L.on breast cancer,lung metastasis and liver inflammatory process were evaluated.Method:ID7 was characterized by mass-spectrometry.The viability of murine mammary cells(4T1)treated with ID7 was assessed by MTT,trypan blue and fluorescence assay and viability of BT-20,MDA-MB-231 and MCF-7 human breast cancer tumor lines by MTS.The cell migration,invasion using matrigel and adhesion were performed.The expression of cell death proteins was quanitified by western blot and the gelatinases by zimogram.The ID7 activity of the tumor(4T1)and metastatic progession in vivo was evaluated.Results:ID7 reduced the 4T1 and MDA-MB-231viability and increased the late apoptosis,inhibited the 4T1 migration and invasion,increased the 4T1 adhesion and decreased the secreted active gelatinases.ID7 also increased the expression of PARP,caspase-7 and caspase-8,RIP and TNF-R1.In vivo,the ID7 decreased the volume and weight of the tumors and decreased lung metastasis and inflammation in the liver.The characterization showed mainly the presence of oleic acid,myricetin,quercetin and kaempferol in ID7.Conclusion:Thus,it was found that ID7 fraction exhibits selective antitumor and on the mechanisms of breast cancer metastasis activity,preventing lung metastasis and inflammation in the liver.It is suggested that fatty acids and flavonoids are correlated with such activities.

Combination of kaempferol and chloroquine induces glioma cell death via expansion and subsequent rupture of lysosomes

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.

Preparation of Magnetic Fluorescent Dual-drug Nanocomposites for Codelivery of Kaempferol and Paclitaxel

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.