Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength,leading to increased fragility.Buqi-Tongluo(BQTL)decoction,a traditional Chinese medicine(TCM)prescription,has yet to be f...Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength,leading to increased fragility.Buqi-Tongluo(BQTL)decoction,a traditional Chinese medicine(TCM)prescription,has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis.To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments.We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages(BMMs)at various concentrations.TRAc P experiments were conducted to examine BQTL's impact on osteoclast differentiation.RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation.Finally,in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings.This study revealed that BQTL suppressed receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity.The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity,primarily through attenuation of the MAPK,NF-κB,and Calcineurin signaling pathways.BQTL's inhibitory capacity was further examined in vivo using an ovariectomized(OVX)rat model,demonstrating a strong protective effect against bone loss.BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.展开更多
Inflammation caused by obesity,particularly in adipose tissue and the liver,can lead to insulin resistance(IR)and trigger type 2 diabetes mellitus(T2DM).It is crucial to identify therapeutic agents that alleviate IR b...Inflammation caused by obesity,particularly in adipose tissue and the liver,can lead to insulin resistance(IR)and trigger type 2 diabetes mellitus(T2DM).It is crucial to identify therapeutic agents that alleviate IR by reducing inflammation.Here,we report that isobavachromene(IB),a flavonoid derived from Psoralea corylifolia Linn.,ameliorates IR in 3T3-L1 adipocytes by inhibiting the mitogen-activated protein kinase(MAPK)and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway.We first found that IB could promote glucose uptake in 3T3-L1 adipocytes by activating the phosphoinositide 3-kinase(PI-3K)/protein kinase B(Akt)signaling pathway and was more effective than the positive control sodium orthovanadate at concentrations ranging from 25 to 100μmol/L.Additionally,IB inhibited RAW264.7 macrophage infiltration into 3T3-L1 adipocytes and suppressed the secretion of inflammatory factors from RAW264.7 macrophages,as well as the phosphorylation levels of key proteins(NF-κB p65,extracellular-signal-regulated kinase 1/2(ERK1/2),Jun N-terminal kinase(JNK),and mitogen-activated protein kinase 38(p38))in the NF-κB and MAPK signaling pathways.In summary,IB improves glucose uptake in IR adipocytes,activates the PI-3K/Akt signaling pathway,inhibits the JNK and NF-κB inflammatory signaling pathways,and reduces adipocyte inflammation,thereby improving of IR in 3T3-L1 adipocytes.展开更多
基金supported by the Natural Science Foundation of Guangdong Province,China(No.2021A1515012168)the Administration of Traditional Chinese Medicine of Guangdong Province,China(Nos.20221146 and 20241091)+5 种基金the Basic and Applied Basic Research Fund Project in Guangdong Province,China(No.2020A1515110948)the Basic and Applied Basic Research in Jointly Funded Projects of City Schools(Institutes)Projects,China(Nos.202201020500 and 202201020295)the Project of Guangzhou Science and Technology Department,China(No.202102021040)the Guangzhou Science and Technology Plan Project,China(No.2023B03J0379)the Chinese Society of Traditional Chinese Medicine Youth Talent Lifting Project(No.2022-QNRC2-B11)the Hospital Young and Middle-aged Key Talent Cultivation Project of The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine(2023-10)。
文摘Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength,leading to increased fragility.Buqi-Tongluo(BQTL)decoction,a traditional Chinese medicine(TCM)prescription,has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis.To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments.We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages(BMMs)at various concentrations.TRAc P experiments were conducted to examine BQTL's impact on osteoclast differentiation.RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation.Finally,in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings.This study revealed that BQTL suppressed receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity.The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity,primarily through attenuation of the MAPK,NF-κB,and Calcineurin signaling pathways.BQTL's inhibitory capacity was further examined in vivo using an ovariectomized(OVX)rat model,demonstrating a strong protective effect against bone loss.BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
基金supported by National Key R&D Program of China(2022YFF1100300)the Central Guidance on Local Science and Technology Development Found of Shenzhen,China(2021Szvup030).
文摘Inflammation caused by obesity,particularly in adipose tissue and the liver,can lead to insulin resistance(IR)and trigger type 2 diabetes mellitus(T2DM).It is crucial to identify therapeutic agents that alleviate IR by reducing inflammation.Here,we report that isobavachromene(IB),a flavonoid derived from Psoralea corylifolia Linn.,ameliorates IR in 3T3-L1 adipocytes by inhibiting the mitogen-activated protein kinase(MAPK)and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway.We first found that IB could promote glucose uptake in 3T3-L1 adipocytes by activating the phosphoinositide 3-kinase(PI-3K)/protein kinase B(Akt)signaling pathway and was more effective than the positive control sodium orthovanadate at concentrations ranging from 25 to 100μmol/L.Additionally,IB inhibited RAW264.7 macrophage infiltration into 3T3-L1 adipocytes and suppressed the secretion of inflammatory factors from RAW264.7 macrophages,as well as the phosphorylation levels of key proteins(NF-κB p65,extracellular-signal-regulated kinase 1/2(ERK1/2),Jun N-terminal kinase(JNK),and mitogen-activated protein kinase 38(p38))in the NF-κB and MAPK signaling pathways.In summary,IB improves glucose uptake in IR adipocytes,activates the PI-3K/Akt signaling pathway,inhibits the JNK and NF-κB inflammatory signaling pathways,and reduces adipocyte inflammation,thereby improving of IR in 3T3-L1 adipocytes.
