Inflammation plays a pivotal role in the etiology and progression of various diseases.In traditional Chinese medicine,the whole plants of Thesium chinense Turcz.and its preparations(e.g.Bairui Granules)have been emplo...Inflammation plays a pivotal role in the etiology and progression of various diseases.In traditional Chinese medicine,the whole plants of Thesium chinense Turcz.and its preparations(e.g.Bairui Granules)have been employed to manage inflammatory conditions.While flavonoids were previously considered the primary anti-inflammatory components,other potentially active constituents have been largely overlooked and not thoroughly investigated.This study presents a novel finding that the total alkaloids of T.chinense(BC-Alk)are potent active substances underlying the traditional and clinical applications of T.chinense and Bairui Granules as anti-inflammatory agents.UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids.The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide(LPS)-induced lung inflammation model in mice.Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation,attenuated the overproduction of IL-1β and the overproduction of inflammatory factors(TNF-α),and ameliorated lung tissue hyperplasia in mice in vivo.Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit(GCLM),inhibited NF-κB phosphorylation,and suppressed NLRP3 activation.Collectively,these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2,NF-κB,and NLRP3 pathways.This study provides new insights into the anti-inflammatory constituents of T.chinense and Bairui Granules.展开更多
为探讨黑果枸杞花青素(AC)对低氧诱导的H9c2心肌细胞氧化应激的潜在分子机制及其缓解作用,通过低氧(1%O2)诱导构建H9c2心肌细胞低氧模型,利用qRT-PCR与Western-blot方法分别检测常氧及低氧环境下通过AC处理后H9c2心肌细胞Nrf2、NF-κB...为探讨黑果枸杞花青素(AC)对低氧诱导的H9c2心肌细胞氧化应激的潜在分子机制及其缓解作用,通过低氧(1%O2)诱导构建H9c2心肌细胞低氧模型,利用qRT-PCR与Western-blot方法分别检测常氧及低氧环境下通过AC处理后H9c2心肌细胞Nrf2、NF-κB信号通路及其关键因子的m RNA与蛋白表达水平。结果显示,低氧环境下,Nrf2信号通路KAP1、Nrf2、HO-1、NQO1 m RNA表达量显著降低(P<0.05),Nrf2、KAP1蛋白表达量极显著降低(P<0.01),HO-1、NQO1蛋白表达量显著降低(P<0.05);与低氧组相比,低氧+AC组KAP1、Nrf2、HO-1、NQO1 m RNA和蛋白表达量均极显著升高(P<0.01)。NF-κB信号通路通过低氧诱导使IKK-α、IKK-β、NF-κB、TNF-α、COX-2 m RNA表达量与蛋白表达量极显著升高(P<0.01);与低氧组相比,低氧+AC组IKK-α、IKK-β、NF-κB、TNF-α、COX-2 m RNA表达量极显著降低(P<0.01)。添加NF-κB通路激活剂Imiquimod后与低氧组相比,低氧+imiquimod组IKK-β、NF-κB蛋白表达量极显著上调(P<0.01),IKK-α、TNF-α、COX-2蛋白表达量显著上调(P<0.05);低氧+AC+imiquimod组IKK-α、IKK-β、NF-κB、TNF-α、COX-2蛋白表达极显著下调(P<0.01)。结果表明,AC可通过上调H9c2心肌细胞Nrf2信号通路相关因子的表达,下调NF-κB信号通路相关因子的表达,抑制低氧诱导的H9c2心肌细胞氧化应激损伤,保护心肌细胞。展开更多
Objective:To examine the effect of shikonin against streptozotocin(STZ)-induced diabetic retinopathy in rats and elucidate the underlying mechanisms.Methods:Intraperitoneal administration of STZ(65 mg/kg)was used for ...Objective:To examine the effect of shikonin against streptozotocin(STZ)-induced diabetic retinopathy in rats and elucidate the underlying mechanisms.Methods:Intraperitoneal administration of STZ(65 mg/kg)was used for the induction of diabetic retinopathy in rats.Rats received oral administration of shikonin(10,20,and 30 mg/kg).The blood glucose level,insulin,body weight,and organ weight were estimated.Advanced glycation end products(AGEs)levels in serum and lens as well as protein carbonyl content of the lens were determined.The parameters related to oxidative stress and inflammation,and the levels of nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),intercellular adhesion molecule-1(ICAM-1),and vascular cell adhesion molecule 1(VCAM-1)were also measured.In addition,quantitative RT-PCR was performed to determine the mRNA expressions.Results:Shikonin treatment decreased glucose level and boosted insulin level,along with an increase in body weight and improved organ weight.It also lowered O2•−,ONOO−,serum and lens AGEs,and protein carbonyl content.Furthermore,shikonin treatment significantly alleviated oxidative stress and inflammation,as evidenced by reduced malonaldehyde,nitric oxide,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,cyclooxygenase-2,prostaglandin E2,protein carbonyl content,and nuclear factor kappa-B,and increased superoxide dismutase,glutathione,catalase,and glutathione peroxidase.Markedly decreased levels of ICAM-1 and VCAM-1,as well as heightened levels of Nrf2 and HO-1,were noticed after treatment with shikonin.Furthermore,the mRNA expressions of TNF-α,IL-1β,IL-6,ICAM-1,VCAM-1,RAGE,collagenⅣ,and fibronectin were significantly downregulated.Conclusions:Shikonin exhibits protective effects against STZ-induced diabetic retinopathy in rats via modulating the Nrf2/HO-1 and NF-κB signaling pathways.展开更多
Air pollution is fourth major cause of death worldwide.Recent evidence suggests that particulate matter(PM)may affect kidneys,and the effect may be size and composition dependent.In this study,PM_(0.1),PM_(2.5),and PM...Air pollution is fourth major cause of death worldwide.Recent evidence suggests that particulate matter(PM)may affect kidneys,and the effect may be size and composition dependent.In this study,PM_(0.1),PM_(2.5),and PM_(10)were collected from ambient air and given to BALB/c male mice at 0.25 mg/m^(3) concentration in whole-body inhalation chamber for 28days(6 h/day,5 days/week)to assess their effect on kidney.Physico-chemical characterization of PM particles by SEM,ICP-MS and HPLC showed their various shapes along with the presence of metals and poly aromatic hydrocarbons(PAHs).Following PM exposure,increased serum creatinine levels were observed in animals along with dilated tubules,protein cast deposition,necrosis,immune infiltration,collagen deposition,and shrunken glomeruli in kidney.Immunofluorescence staining showed higher expressions of kidney injury molecule1(KIM-1),cystatin C,β2 microglobulin(β2M),and alpha smooth muscle actin(α-SMA)and fibronectin,suggesting renal injury and fibrosis.PM exposure also increased malondialdehyde(MDA)content and decreased superoxide dismutase 2(SOD2)activity,which in turn leads to induction of inflammation.Mechanistically,PM exposure further inhibited the nuclear factor erythroid 2-related factor 2(Nrf2)signalling and induced kelch-like ECH-associated protein 1(Keap1)and nuclear factor kappa-light-chain-enhancer of activated B(NF-κB).Interestingly,the effect of PM_(2.5)was more severe than PM_(0.1)and PM_(10),leading to higher levels of proinflammatory NF-κB and greater Nrf2 inhibition.Overall,our findings suggested that inhalation exposure to size-segregated PM can cause kidney damage and fibrosis,and PM_(2.5)showed higher toxicity than PM_(0.1)and PM_(10).展开更多
基金supported by the National Natural Science Foundation of China(No.82274065)Toxicology of Traditional Chinese Medicines,a High-Level Priority Subject in Chinese Medicine in National Administration of Traditional Chinese Medicine(No.ZYYZDXK-2023296)Cutting Edge Development Fund of Advanced Medical Research Institute(No.GYY2023QY01)。
文摘Inflammation plays a pivotal role in the etiology and progression of various diseases.In traditional Chinese medicine,the whole plants of Thesium chinense Turcz.and its preparations(e.g.Bairui Granules)have been employed to manage inflammatory conditions.While flavonoids were previously considered the primary anti-inflammatory components,other potentially active constituents have been largely overlooked and not thoroughly investigated.This study presents a novel finding that the total alkaloids of T.chinense(BC-Alk)are potent active substances underlying the traditional and clinical applications of T.chinense and Bairui Granules as anti-inflammatory agents.UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids.The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide(LPS)-induced lung inflammation model in mice.Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation,attenuated the overproduction of IL-1β and the overproduction of inflammatory factors(TNF-α),and ameliorated lung tissue hyperplasia in mice in vivo.Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit(GCLM),inhibited NF-κB phosphorylation,and suppressed NLRP3 activation.Collectively,these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2,NF-κB,and NLRP3 pathways.This study provides new insights into the anti-inflammatory constituents of T.chinense and Bairui Granules.
文摘为探讨黑果枸杞花青素(AC)对低氧诱导的H9c2心肌细胞氧化应激的潜在分子机制及其缓解作用,通过低氧(1%O2)诱导构建H9c2心肌细胞低氧模型,利用qRT-PCR与Western-blot方法分别检测常氧及低氧环境下通过AC处理后H9c2心肌细胞Nrf2、NF-κB信号通路及其关键因子的m RNA与蛋白表达水平。结果显示,低氧环境下,Nrf2信号通路KAP1、Nrf2、HO-1、NQO1 m RNA表达量显著降低(P<0.05),Nrf2、KAP1蛋白表达量极显著降低(P<0.01),HO-1、NQO1蛋白表达量显著降低(P<0.05);与低氧组相比,低氧+AC组KAP1、Nrf2、HO-1、NQO1 m RNA和蛋白表达量均极显著升高(P<0.01)。NF-κB信号通路通过低氧诱导使IKK-α、IKK-β、NF-κB、TNF-α、COX-2 m RNA表达量与蛋白表达量极显著升高(P<0.01);与低氧组相比,低氧+AC组IKK-α、IKK-β、NF-κB、TNF-α、COX-2 m RNA表达量极显著降低(P<0.01)。添加NF-κB通路激活剂Imiquimod后与低氧组相比,低氧+imiquimod组IKK-β、NF-κB蛋白表达量极显著上调(P<0.01),IKK-α、TNF-α、COX-2蛋白表达量显著上调(P<0.05);低氧+AC+imiquimod组IKK-α、IKK-β、NF-κB、TNF-α、COX-2蛋白表达极显著下调(P<0.01)。结果表明,AC可通过上调H9c2心肌细胞Nrf2信号通路相关因子的表达,下调NF-κB信号通路相关因子的表达,抑制低氧诱导的H9c2心肌细胞氧化应激损伤,保护心肌细胞。
文摘Objective:To examine the effect of shikonin against streptozotocin(STZ)-induced diabetic retinopathy in rats and elucidate the underlying mechanisms.Methods:Intraperitoneal administration of STZ(65 mg/kg)was used for the induction of diabetic retinopathy in rats.Rats received oral administration of shikonin(10,20,and 30 mg/kg).The blood glucose level,insulin,body weight,and organ weight were estimated.Advanced glycation end products(AGEs)levels in serum and lens as well as protein carbonyl content of the lens were determined.The parameters related to oxidative stress and inflammation,and the levels of nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),intercellular adhesion molecule-1(ICAM-1),and vascular cell adhesion molecule 1(VCAM-1)were also measured.In addition,quantitative RT-PCR was performed to determine the mRNA expressions.Results:Shikonin treatment decreased glucose level and boosted insulin level,along with an increase in body weight and improved organ weight.It also lowered O2•−,ONOO−,serum and lens AGEs,and protein carbonyl content.Furthermore,shikonin treatment significantly alleviated oxidative stress and inflammation,as evidenced by reduced malonaldehyde,nitric oxide,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,cyclooxygenase-2,prostaglandin E2,protein carbonyl content,and nuclear factor kappa-B,and increased superoxide dismutase,glutathione,catalase,and glutathione peroxidase.Markedly decreased levels of ICAM-1 and VCAM-1,as well as heightened levels of Nrf2 and HO-1,were noticed after treatment with shikonin.Furthermore,the mRNA expressions of TNF-α,IL-1β,IL-6,ICAM-1,VCAM-1,RAGE,collagenⅣ,and fibronectin were significantly downregulated.Conclusions:Shikonin exhibits protective effects against STZ-induced diabetic retinopathy in rats via modulating the Nrf2/HO-1 and NF-κB signaling pathways.
基金supported by the institutional fund MLP004 and Science and Engineering Research Board(SERB)(No.CRG/2021/002625)financial assistance from DBT-JRF,Department of Biotechnology,Gov of India,New Delhi India(DBT/2018/1111)。
文摘Air pollution is fourth major cause of death worldwide.Recent evidence suggests that particulate matter(PM)may affect kidneys,and the effect may be size and composition dependent.In this study,PM_(0.1),PM_(2.5),and PM_(10)were collected from ambient air and given to BALB/c male mice at 0.25 mg/m^(3) concentration in whole-body inhalation chamber for 28days(6 h/day,5 days/week)to assess their effect on kidney.Physico-chemical characterization of PM particles by SEM,ICP-MS and HPLC showed their various shapes along with the presence of metals and poly aromatic hydrocarbons(PAHs).Following PM exposure,increased serum creatinine levels were observed in animals along with dilated tubules,protein cast deposition,necrosis,immune infiltration,collagen deposition,and shrunken glomeruli in kidney.Immunofluorescence staining showed higher expressions of kidney injury molecule1(KIM-1),cystatin C,β2 microglobulin(β2M),and alpha smooth muscle actin(α-SMA)and fibronectin,suggesting renal injury and fibrosis.PM exposure also increased malondialdehyde(MDA)content and decreased superoxide dismutase 2(SOD2)activity,which in turn leads to induction of inflammation.Mechanistically,PM exposure further inhibited the nuclear factor erythroid 2-related factor 2(Nrf2)signalling and induced kelch-like ECH-associated protein 1(Keap1)and nuclear factor kappa-light-chain-enhancer of activated B(NF-κB).Interestingly,the effect of PM_(2.5)was more severe than PM_(0.1)and PM_(10),leading to higher levels of proinflammatory NF-κB and greater Nrf2 inhibition.Overall,our findings suggested that inhalation exposure to size-segregated PM can cause kidney damage and fibrosis,and PM_(2.5)showed higher toxicity than PM_(0.1)and PM_(10).
