Objective: Kaempferide and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (DTMC) are two major flavonoids found in Chromolaena odoraia Linn, leaf extract. The aim of this study was to elucidate the mechani...Objective: Kaempferide and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (DTMC) are two major flavonoids found in Chromolaena odoraia Linn, leaf extract. The aim of this study was to elucidate the mechanism by which these two flavonoids exerted their effect on adipogenesis. The inhibitory effect of kaempferide and DTMC on adipocyte differentiation and their mechanisms involving mitotic clonal expansion (MCE) and apoptosis during the early stage of adipogenesis were investigated. Methods: Confluent 3T3-L1 preadipocytes were induced to differentiate and exposed to the flavonoids during various phases of difTerentiaiion. Intracellular lipid accumulation, cell density and expression of the transcription factors peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding pro-teins a were assessed using AdipoRed, Oil red 0 and Western blot assays. Effects of both flavonoids on cell proliferation and apoptosis were also determined by carboxyfluorescein diacetate succinimidyl ester and annexin V-fluorescein isothiocyanate/propidium iodide-staining assays, respectively. Results: Kaempferide and DTMC showed significant, concentration-dependent anti-adipogenic activity and effect on cell density in the early phase of adipogenesis. The expression of the transcription factors seemed to be reduced when the treatment was prolonged or in the early phase of adipogenesis. These flavonoids interrupted MCE via inhibition of preadipocyte proliferation and induction of apoptosis. DTMC was nearly three times more potent than kaempferide in inducing apoptosis. Conclusion: Kaempferide and DTMC exerted their anti-adipogenic activity through inhibition of MCE, either by suppressing cell proliferation or by inducing apoptosis during the early phase of differentiation.展开更多
Background:Osteoarthritis(OA)is a prevalent joint disorder that significantly impairs quality of life among elderly individuals because of chronic pain and physical disability.As the global burden of OA continues to r...Background:Osteoarthritis(OA)is a prevalent joint disorder that significantly impairs quality of life among elderly individuals because of chronic pain and physical disability.As the global burden of OA continues to rise,novel therapeutic strategies are urgently needed.Kaempferide(KA),a flavonoid derived from traditional Chinese herbal medicine,is known for its anti-inflammatory properties.However,the effect of KA on the progression of OA has not been well investigated.This study aimed to explore the therapeutic potential of KA in an OA model and investigate the underlying mechanisms via transcriptomic sequencing.Methods:An in vitro OA model was established using SW1353 cells treated with interleukin-1 beta(IL-1β)and different concentrations of KA(30,60,or 90µmol/L)for 24 h.The anti-inflammatory effects of KA were assessed using quantitative real-time polymerase chain reaction(qRT-PCR),enzyme-linked immunosorbent assay(ELISA),and Western blotting.In vivo,a papain-induced OA rat model was used to evaluate the therapeutic effects of KA through histological and behavioral analyses.Transcriptomic sequencing was performed to explore the differentially expressed genes(DEGs)and related signaling pathways.Statistical analysis was conducted using one-way analysis of variance.Results:KA significantly increased cell viability in the OA chondrocyte model and downregulated the expression of inflammatory cytokines and cartilage degradation markers,with the greatest reduction observed at 90µmol/L.In vivo,KA treatment mitigated cartilage degradation and improved gait behavior in OA rats.Transcriptomic analysis revealed substantial modulation of DEGs,implicating the hypoxia-inducible factor-1(HIF-1)signaling pathway as a key mechanism.Further blocking and rescue experiments revealed that KA regulated key molecules within the HIF-1 pathway,specifically interferon-gamma(IFN-γ)and hypoxia-inducible factor 1-alpha(HIF-1α),confirming their critical roles in mediating the therapeutic effects of KA.Conclusion:KA inhibited the progression of OA by targeting the HIF-1 signaling pathway,reducing inflammation,and cartilage degradation.展开更多
基金supported by a grant from Thailand Graduate Institute of Science and Technology (TGIST) (grant number 01–54–007)National Nanotechnology Center at National Science and Technology Development Agency, Thailand
文摘Objective: Kaempferide and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (DTMC) are two major flavonoids found in Chromolaena odoraia Linn, leaf extract. The aim of this study was to elucidate the mechanism by which these two flavonoids exerted their effect on adipogenesis. The inhibitory effect of kaempferide and DTMC on adipocyte differentiation and their mechanisms involving mitotic clonal expansion (MCE) and apoptosis during the early stage of adipogenesis were investigated. Methods: Confluent 3T3-L1 preadipocytes were induced to differentiate and exposed to the flavonoids during various phases of difTerentiaiion. Intracellular lipid accumulation, cell density and expression of the transcription factors peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding pro-teins a were assessed using AdipoRed, Oil red 0 and Western blot assays. Effects of both flavonoids on cell proliferation and apoptosis were also determined by carboxyfluorescein diacetate succinimidyl ester and annexin V-fluorescein isothiocyanate/propidium iodide-staining assays, respectively. Results: Kaempferide and DTMC showed significant, concentration-dependent anti-adipogenic activity and effect on cell density in the early phase of adipogenesis. The expression of the transcription factors seemed to be reduced when the treatment was prolonged or in the early phase of adipogenesis. These flavonoids interrupted MCE via inhibition of preadipocyte proliferation and induction of apoptosis. DTMC was nearly three times more potent than kaempferide in inducing apoptosis. Conclusion: Kaempferide and DTMC exerted their anti-adipogenic activity through inhibition of MCE, either by suppressing cell proliferation or by inducing apoptosis during the early phase of differentiation.
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.82102531 and 82172410).
文摘Background:Osteoarthritis(OA)is a prevalent joint disorder that significantly impairs quality of life among elderly individuals because of chronic pain and physical disability.As the global burden of OA continues to rise,novel therapeutic strategies are urgently needed.Kaempferide(KA),a flavonoid derived from traditional Chinese herbal medicine,is known for its anti-inflammatory properties.However,the effect of KA on the progression of OA has not been well investigated.This study aimed to explore the therapeutic potential of KA in an OA model and investigate the underlying mechanisms via transcriptomic sequencing.Methods:An in vitro OA model was established using SW1353 cells treated with interleukin-1 beta(IL-1β)and different concentrations of KA(30,60,or 90µmol/L)for 24 h.The anti-inflammatory effects of KA were assessed using quantitative real-time polymerase chain reaction(qRT-PCR),enzyme-linked immunosorbent assay(ELISA),and Western blotting.In vivo,a papain-induced OA rat model was used to evaluate the therapeutic effects of KA through histological and behavioral analyses.Transcriptomic sequencing was performed to explore the differentially expressed genes(DEGs)and related signaling pathways.Statistical analysis was conducted using one-way analysis of variance.Results:KA significantly increased cell viability in the OA chondrocyte model and downregulated the expression of inflammatory cytokines and cartilage degradation markers,with the greatest reduction observed at 90µmol/L.In vivo,KA treatment mitigated cartilage degradation and improved gait behavior in OA rats.Transcriptomic analysis revealed substantial modulation of DEGs,implicating the hypoxia-inducible factor-1(HIF-1)signaling pathway as a key mechanism.Further blocking and rescue experiments revealed that KA regulated key molecules within the HIF-1 pathway,specifically interferon-gamma(IFN-γ)and hypoxia-inducible factor 1-alpha(HIF-1α),confirming their critical roles in mediating the therapeutic effects of KA.Conclusion:KA inhibited the progression of OA by targeting the HIF-1 signaling pathway,reducing inflammation,and cartilage degradation.
