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 r...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.展开更多
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 be...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.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
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
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
文摘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.
基金funded by Young and Middle Aged Teachers’Career Development Support Project of Shenyang Pharmaceutical University(ZQN2019005).
文摘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.
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.
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.
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.
