The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing ...The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.展开更多
BACKGROUND Constipation,a highly prevalent functional gastrointestinal disorder,induces a significant burden on the quality of patients'life and is associated with substantial healthcare expenditures.Therefore,ide...BACKGROUND Constipation,a highly prevalent functional gastrointestinal disorder,induces a significant burden on the quality of patients'life and is associated with substantial healthcare expenditures.Therefore,identifying efficient therapeutic modalities for constipation is of paramount importance.Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms.Consequently,we postulate that hydrogen therapy,an emerging and promising intervention,can serve as a safe and efficacious treatment for constipation.AIM To determine whether hydrogen-rich water(HRW)alleviates constipation and its potential mechanism.METHODS Constipation models were established by orally loperamide to Sprague-Dawley rats.Rats freely consumed HRW,and were recorded their 24 h total stool weight,fecal water content,and charcoal propulsion rate.Fecal samples were subjected to 16S rDNA gene sequencing.Serum non-targeted metabolomic analysis,malondialdehyde,and superoxide dismutase levels were determined.Colonic tissues were stained with hematoxylin and eosin,Alcian blue-periodic acid-Schiff,reactive oxygen species(ROS)immunofluorescence,and immunohistochemistry for cell growth factor receptor kit(c-kit),PGP 9.5,sirtuin1(SIRT1),nuclear factor-erythroid-2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1,Nrf2 and HO-1.A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor,EX527,into constipated rats.NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression.RESULTS HRW alleviated constipation symptoms by improving the total amount of stool over 24 h,fecal water content,charcoal propulsion rate,thickness of the intestinal mucus layer,c-kit expression,and the number of intestinal neurons.HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism.HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway.This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats.The serum metabolites,β-leucine(β-Leu)and traumatic acid,were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1.CONCLUSION HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway,modulating gut microbiota and serum metabolites.β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.展开更多
[目的]探究缬草酸对骨折后深静脉血栓形成及Sirtuin1/NF-κB通路的影响。[方法]所有Sprague Dawley大鼠被随机分为3组(每组n=10):假手术组、模型组和缬草酸组。通过HE染色分析下腔静脉组织病理变化。通过蛋白免疫印迹分析Sirtuin1/NF-κ...[目的]探究缬草酸对骨折后深静脉血栓形成及Sirtuin1/NF-κB通路的影响。[方法]所有Sprague Dawley大鼠被随机分为3组(每组n=10):假手术组、模型组和缬草酸组。通过HE染色分析下腔静脉组织病理变化。通过蛋白免疫印迹分析Sirtuin1/NF-κB通路的变化。通过酶联免疫吸附剂测定分析炎症因子IL-6、IL-1β和TNF-α的水平。通过全自动凝血分析仪检测凝血酶原时间、活化部分凝血活酶时间、凝血酶时间。[结果]病理分析发现,缬草酸治疗后,模型组大鼠血栓染色变淡,血管再通,血管壁有少数炎症细胞。此外,缬草酸治疗后,模型组大鼠血栓重量逐渐减小(6.36±0.02 vs 11.03±0.02,P<0.05),长度逐渐缩短。此外,模型组大鼠在经过缬草酸治疗后炎症因子水平明显降低(4.67±0.08 vs 7.02±0.01;5.99±0.05 vs 11.02±0.03;5.81±0.06 vs 10.02±0.03;P<0.05),凝血酶原时间、活化部分凝血活酶时间、凝血酶时间水平明显上升。蛋白免疫印迹结果发现,与模型组相比,缬草酸组大鼠的下腔静脉组织中NF-κB p65磷酸化水平降低(0.58±0.02 vs 0.92±0.03;P<0.05),Sirtuin1水平增加(0.69±0.01 vs 0.16±0.03;P<0.05)。[结论]缬草酸能够改善下腔静脉血栓导致的病理损伤、抑制下腔静脉血栓形成,并能抑制血浆中炎症因子的水平。这一作用可能与Sirtuin1表达上调而NF-κB的抑制相关。展开更多
BACKGROUND The occurrence and development of acute liver failure(ALF)is closely related to a series of inflammatory reactions,such as the production of reactive oxygen species(ROS).Hypoxia inducible factor 1α(HIF-1α...BACKGROUND The occurrence and development of acute liver failure(ALF)is closely related to a series of inflammatory reactions,such as the production of reactive oxygen species(ROS).Hypoxia inducible factor 1α(HIF-1α)is a key factor that regulates oxygen homeostasis and redox,and the stability of HIF-1αis related to the ROS level regulated by Sirtuin(Sirt)family.The activation of Sirt1 will lead to a powerful antioxidant defense system and therapeutic effects in liver disease.However,little is known about the relationship between HIF-1αand Sirt1 in the process of ALF and the molecular mechanism.AIM To investigate whether HIF-1αmay be a target of Sirt1 deacetylation and what the effects on ALF are.METHODS Mice were administrated lipopolysaccharide(LPS)/D-gal and exposed to hypoxic conditions as animal model,and resveratrol was used as an activator of Sirt1.The cellular model was established with L02 cells stimulated by LPS.N-acetyl-Lcysteine was used to remove ROS,and the expression of Sirt1 was inhibited by nicotinamide.Western blotting was used to detect Sirt1 and HIF-1αactivity and related protein expression.The possible signaling pathways involved were analyzed by immunofluorescent staining,co-immunoprecipitation,dihydroethidium staining,and Western blotting.RESULTS Compared with mice stimulated with LPS alone,the expression of Sirt1 decreased,the level of HIF-1αacetylation increased in hypoxic mice,and the levels of carbonic anhydrase 9 and Bcl-2-adenovirus E1B interacting protein 3 increased significantly,which was regulated by HIF-1α,indicating an increase of HIF-1αactivity.Under hypoxia,the down-regulation of Sirt1 activated and acetylated HIF-1αin L02 cells.The inhibition of Sirt1 significantly aggravated this effect and the massive production of ROS.The regulation of ROS was partly through peroxisome proliferatoractivated receptor alpha or AMP-activated protein kinase.Resveratrol,a Sirt1 activator,effectively relieved ALF aggravated by hypoxia,the production of ROS,and cell apoptosis.It also induced the deacetylation of HIF-1αand inhibited the activity of HIF-1α.CONCLUSION Sirt1 may have a protective effect on ALF by inducing HIF-1α deacetylation to reduce ROS.展开更多
An increase in oxidative stress plays a key role in neurotoxicity induction and cell death, which leads to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Cyanidin-3-glucoside (C3G) i...An increase in oxidative stress plays a key role in neurotoxicity induction and cell death, which leads to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Cyanidin-3-glucoside (C3G) is a common anthocyanin and shows antioxidant activity in neuronal cells. Silent information regulator 2-related protein 1 (Sirt1) regulates antioxidant and anti-inflammatory effects. However, the effects of C3G on Sirt1 in neuronal cells remain unclear. This study evaluated the effect of C3G on Sirt1 expression and activity in human neuroblastoma (SH-SY5Y) cells. In the study, C3G increased the expression of Sirt1 and Sirt1 activity in SH-SY5Y cells. Additionally, C3G increased the expression of nuclear factor erythroid 2-related factor 2, a vital transcription factor for regulating the expression of antioxidant genes, as well as antioxidant enzymes such as superoxide dismutase and catalase. Moreover, C3G protected SH-SY5Y cells from oxidative stress. These results suggest that C3G decreased oxidative stress-induced cell injury by increasing the expression of Sirt1 and other antioxidant factors. Therefore, C3G might merit further investigation for use in attenuating the progress of neurodegenerative diseases.展开更多
Objective Safranal is a natural product from saffron(Crocus sativus L.)with anti-inflammatory and nephroprotective potential.This study aimed to explore the role of safranal in a cationic bovine serum albumin(C-BSA)-i...Objective Safranal is a natural product from saffron(Crocus sativus L.)with anti-inflammatory and nephroprotective potential.This study aimed to explore the role of safranal in a cationic bovine serum albumin(C-BSA)-induced rat model of membranous glomerulonephritis(MGN).Methods After model establishment,Sprague–Dawley rats were administered 100 or 200 mg/kg safranal by gavage.A biochemical analyser was used to measure the urine protein levels and serum levels of renal function parameters.Hematoxylin–eosin and immunofluorescence staining of kidney tissues were performed to examine histopathological changes and assess the expression of IgG,C3,and Sirt1.Western blotting was performed to measure the protein levels of podocin,nephrin,Sirt1,and factors involved in the NF-κB/p65 pathway.Inflammatory cytokine levels in renal homogenates were determined by ELISA.Results Safranal at 100 or 200 mg/kg reduced kidney weight(2.07±0.15 g and 2.05±0.15 g)and the kidney somatic index(0.83±0.08%and 0.81±0.08%)in MGN rats compared with those in the model group without drug administration(2.62±0.17 g and 1.05±0.1%).C-BSA increased the urine protein level to 117.68±10.52 mg/day(compared with the sham group,5.03±0.45 mg/day),caused dysregulation of renal function indicators,and induced glomerular expansion and inflammatory cell infiltration in the rat kidney samples.All the biochemical and histological changes were improved by safranal administration.Safranal at two doses also increased the fluorescence intensities of IgG(0.1±0.009 and 0.088±0.008)and C3(0.065±0.006 and 0.048±0.004)compared with those in the MGN group(0.15±0.013 and 0.086±0.008).Additionally,safranal reversed the downregulation of podocin,nephrin,and Wilms tumor protein-1(WT1)levels and reversed the high inflammatory cytokine levels in MGN rats.Mechanistically,safranal activated Sirt1 signalling to interfere with NF-κB signalling in the kidney tissues of MGN rats.Conclusions Safranal ameliorates renal damage,inflammation,and podocyte injury in MGN by upregulating SIRT1 and inhibiting NF-κB signalling.展开更多
基金supported by the Science&Technology Department of Sichuan Province(No.2019YFS0040)the Improvement Plan of“Xinglin Scholar”Scientific Research Talent,Chengdu University of Traditional Chinese Medicine(No.XKTD2022002)。
文摘The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
基金Supported by National Natural Science Foundation of China,No.82374449China Postdoctoral Science Foundation,No.2023M731782+1 种基金Jiangsu Funding Program for Excellent Postdoctoral Talent,No.2022ZB806Jiangsu Province Postgraduate Scientific Research and Innovation Plan,No.KYCX23_2136.
文摘BACKGROUND Constipation,a highly prevalent functional gastrointestinal disorder,induces a significant burden on the quality of patients'life and is associated with substantial healthcare expenditures.Therefore,identifying efficient therapeutic modalities for constipation is of paramount importance.Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms.Consequently,we postulate that hydrogen therapy,an emerging and promising intervention,can serve as a safe and efficacious treatment for constipation.AIM To determine whether hydrogen-rich water(HRW)alleviates constipation and its potential mechanism.METHODS Constipation models were established by orally loperamide to Sprague-Dawley rats.Rats freely consumed HRW,and were recorded their 24 h total stool weight,fecal water content,and charcoal propulsion rate.Fecal samples were subjected to 16S rDNA gene sequencing.Serum non-targeted metabolomic analysis,malondialdehyde,and superoxide dismutase levels were determined.Colonic tissues were stained with hematoxylin and eosin,Alcian blue-periodic acid-Schiff,reactive oxygen species(ROS)immunofluorescence,and immunohistochemistry for cell growth factor receptor kit(c-kit),PGP 9.5,sirtuin1(SIRT1),nuclear factor-erythroid-2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1,Nrf2 and HO-1.A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor,EX527,into constipated rats.NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression.RESULTS HRW alleviated constipation symptoms by improving the total amount of stool over 24 h,fecal water content,charcoal propulsion rate,thickness of the intestinal mucus layer,c-kit expression,and the number of intestinal neurons.HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism.HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway.This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats.The serum metabolites,β-leucine(β-Leu)and traumatic acid,were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1.CONCLUSION HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway,modulating gut microbiota and serum metabolites.β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.
文摘[目的]探究缬草酸对骨折后深静脉血栓形成及Sirtuin1/NF-κB通路的影响。[方法]所有Sprague Dawley大鼠被随机分为3组(每组n=10):假手术组、模型组和缬草酸组。通过HE染色分析下腔静脉组织病理变化。通过蛋白免疫印迹分析Sirtuin1/NF-κB通路的变化。通过酶联免疫吸附剂测定分析炎症因子IL-6、IL-1β和TNF-α的水平。通过全自动凝血分析仪检测凝血酶原时间、活化部分凝血活酶时间、凝血酶时间。[结果]病理分析发现,缬草酸治疗后,模型组大鼠血栓染色变淡,血管再通,血管壁有少数炎症细胞。此外,缬草酸治疗后,模型组大鼠血栓重量逐渐减小(6.36±0.02 vs 11.03±0.02,P<0.05),长度逐渐缩短。此外,模型组大鼠在经过缬草酸治疗后炎症因子水平明显降低(4.67±0.08 vs 7.02±0.01;5.99±0.05 vs 11.02±0.03;5.81±0.06 vs 10.02±0.03;P<0.05),凝血酶原时间、活化部分凝血活酶时间、凝血酶时间水平明显上升。蛋白免疫印迹结果发现,与模型组相比,缬草酸组大鼠的下腔静脉组织中NF-κB p65磷酸化水平降低(0.58±0.02 vs 0.92±0.03;P<0.05),Sirtuin1水平增加(0.69±0.01 vs 0.16±0.03;P<0.05)。[结论]缬草酸能够改善下腔静脉血栓导致的病理损伤、抑制下腔静脉血栓形成,并能抑制血浆中炎症因子的水平。这一作用可能与Sirtuin1表达上调而NF-κB的抑制相关。
基金Supported by National Natural Science Foundation of China,No. 82070609
文摘BACKGROUND The occurrence and development of acute liver failure(ALF)is closely related to a series of inflammatory reactions,such as the production of reactive oxygen species(ROS).Hypoxia inducible factor 1α(HIF-1α)is a key factor that regulates oxygen homeostasis and redox,and the stability of HIF-1αis related to the ROS level regulated by Sirtuin(Sirt)family.The activation of Sirt1 will lead to a powerful antioxidant defense system and therapeutic effects in liver disease.However,little is known about the relationship between HIF-1αand Sirt1 in the process of ALF and the molecular mechanism.AIM To investigate whether HIF-1αmay be a target of Sirt1 deacetylation and what the effects on ALF are.METHODS Mice were administrated lipopolysaccharide(LPS)/D-gal and exposed to hypoxic conditions as animal model,and resveratrol was used as an activator of Sirt1.The cellular model was established with L02 cells stimulated by LPS.N-acetyl-Lcysteine was used to remove ROS,and the expression of Sirt1 was inhibited by nicotinamide.Western blotting was used to detect Sirt1 and HIF-1αactivity and related protein expression.The possible signaling pathways involved were analyzed by immunofluorescent staining,co-immunoprecipitation,dihydroethidium staining,and Western blotting.RESULTS Compared with mice stimulated with LPS alone,the expression of Sirt1 decreased,the level of HIF-1αacetylation increased in hypoxic mice,and the levels of carbonic anhydrase 9 and Bcl-2-adenovirus E1B interacting protein 3 increased significantly,which was regulated by HIF-1α,indicating an increase of HIF-1αactivity.Under hypoxia,the down-regulation of Sirt1 activated and acetylated HIF-1αin L02 cells.The inhibition of Sirt1 significantly aggravated this effect and the massive production of ROS.The regulation of ROS was partly through peroxisome proliferatoractivated receptor alpha or AMP-activated protein kinase.Resveratrol,a Sirt1 activator,effectively relieved ALF aggravated by hypoxia,the production of ROS,and cell apoptosis.It also induced the deacetylation of HIF-1αand inhibited the activity of HIF-1α.CONCLUSION Sirt1 may have a protective effect on ALF by inducing HIF-1α deacetylation to reduce ROS.
文摘An increase in oxidative stress plays a key role in neurotoxicity induction and cell death, which leads to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Cyanidin-3-glucoside (C3G) is a common anthocyanin and shows antioxidant activity in neuronal cells. Silent information regulator 2-related protein 1 (Sirt1) regulates antioxidant and anti-inflammatory effects. However, the effects of C3G on Sirt1 in neuronal cells remain unclear. This study evaluated the effect of C3G on Sirt1 expression and activity in human neuroblastoma (SH-SY5Y) cells. In the study, C3G increased the expression of Sirt1 and Sirt1 activity in SH-SY5Y cells. Additionally, C3G increased the expression of nuclear factor erythroid 2-related factor 2, a vital transcription factor for regulating the expression of antioxidant genes, as well as antioxidant enzymes such as superoxide dismutase and catalase. Moreover, C3G protected SH-SY5Y cells from oxidative stress. These results suggest that C3G decreased oxidative stress-induced cell injury by increasing the expression of Sirt1 and other antioxidant factors. Therefore, C3G might merit further investigation for use in attenuating the progress of neurodegenerative diseases.
基金supported by the National Natural Science Foundation of China(Nos.82474412 and 82074364)the Innovation Program of Wuhan-Basic Research in 2022(No.2022020801020506)the Natural Science Foundation of Hubei Province(No.2022CFC024).
文摘Objective Safranal is a natural product from saffron(Crocus sativus L.)with anti-inflammatory and nephroprotective potential.This study aimed to explore the role of safranal in a cationic bovine serum albumin(C-BSA)-induced rat model of membranous glomerulonephritis(MGN).Methods After model establishment,Sprague–Dawley rats were administered 100 or 200 mg/kg safranal by gavage.A biochemical analyser was used to measure the urine protein levels and serum levels of renal function parameters.Hematoxylin–eosin and immunofluorescence staining of kidney tissues were performed to examine histopathological changes and assess the expression of IgG,C3,and Sirt1.Western blotting was performed to measure the protein levels of podocin,nephrin,Sirt1,and factors involved in the NF-κB/p65 pathway.Inflammatory cytokine levels in renal homogenates were determined by ELISA.Results Safranal at 100 or 200 mg/kg reduced kidney weight(2.07±0.15 g and 2.05±0.15 g)and the kidney somatic index(0.83±0.08%and 0.81±0.08%)in MGN rats compared with those in the model group without drug administration(2.62±0.17 g and 1.05±0.1%).C-BSA increased the urine protein level to 117.68±10.52 mg/day(compared with the sham group,5.03±0.45 mg/day),caused dysregulation of renal function indicators,and induced glomerular expansion and inflammatory cell infiltration in the rat kidney samples.All the biochemical and histological changes were improved by safranal administration.Safranal at two doses also increased the fluorescence intensities of IgG(0.1±0.009 and 0.088±0.008)and C3(0.065±0.006 and 0.048±0.004)compared with those in the MGN group(0.15±0.013 and 0.086±0.008).Additionally,safranal reversed the downregulation of podocin,nephrin,and Wilms tumor protein-1(WT1)levels and reversed the high inflammatory cytokine levels in MGN rats.Mechanistically,safranal activated Sirt1 signalling to interfere with NF-κB signalling in the kidney tissues of MGN rats.Conclusions Safranal ameliorates renal damage,inflammation,and podocyte injury in MGN by upregulating SIRT1 and inhibiting NF-κB signalling.
