Crocin is a plant ingredient mainly found in the extract of Crocus sativus(Saffron).This carotenoid compound has antioxidant,anti-inflammatory,antitumor,and antihypertensive properties.This review summarizes the thera...Crocin is a plant ingredient mainly found in the extract of Crocus sativus(Saffron).This carotenoid compound has antioxidant,anti-inflammatory,antitumor,and antihypertensive properties.This review summarizes the therapeutic effects of crocin.Data were retrieved from 2015 until the end of April 2025 using databases including the Web of Science,PubMed,Scopus,and Google Scholar.According to the findings of previous studies,the therapeutic effects of crocin on various organs can be attributed to its ability to scavenge free radicals,enhance antioxidant activities,reduce inflammatory reactions,and modulate the PI3K/AKT,NF-κB,and PPARγ/LXRs signaling pathways.展开更多
Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area(VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In...Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area(VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In this study, 40 male Wistar rats(200-250 g) were used in 5 experimental groups: 1) non morphine treat rats(control); 2) non morphine-treated rats with 25 mg/kg crocin carotenoid(i.p., for 21 d); 3) morphine treated rats(10 mg/kg twice a day, s.c., 21 d); 4 and 5) morphine-treated rats with 12.5 and 25 mg/kg crocin carotenoid, respectively. By the end of research, BDNF and CREB expression was determined by real-time-PCR method. ELISA analysis was also applied for assessing the serum BDNF level. Results: The data indicated that morphine treatment could cause a significant decrease in BDNF and CREB gene expression(P<0.01 and P<0.001, respectively) in brain VTA as well as serum level of BDNF(P<0.01) in comparison to control group. Treatment with 25 mg/kg crocin carotenoid caused a significant enhancement in BDNF and CREF gene expression(P<0.01 and P<0.05, respectively) and serum level of BDNF(P<0.01) in morphine-treated rats in comparison to morphine-treated group. Conclusions: Regarding to obtained results, crocin carotenoid can inhibit unfavorable effects of morphine on the neural system to some extent through enhancing BDNF and CREB gene expression in brain VTA and serum level of BDNF.展开更多
[Objectives]To explore the protection mechanism of crocin against ischemia-reperfusion injury of myocardial cells.[Methods]Newborn male SD rats were selected,left ventricular cardiomyocytes(CMs)were isolated,and a hyp...[Objectives]To explore the protection mechanism of crocin against ischemia-reperfusion injury of myocardial cells.[Methods]Newborn male SD rats were selected,left ventricular cardiomyocytes(CMs)were isolated,and a hypoxia/reoxygenation model of CMs was established to simulate the process of ischemia/reperfusion injury.The cells were randomly divided into four groups:normal cell group(control group),crocin group),hypoxia/reoxygenation group(H/R group),hypoxia/reoxygenation+crocin group(H/R+crocin group).H/R+crocin group selected the concentration of crocin 1,10,and 100μmol/L,and determined the optimal concentration of crocin by detecting the cell proliferation ability.After the cells were pretreated using the optimal concentration of crocin,the levels of superoxide anion,cell proliferation,apoptosis and Nox2 levels in each group of cells were detected.[Results]Compared with the control group,the proliferation ability of CMs after hypoxia-reoxygenation injury was reduced(P<0.05),while cell apoptosis and intracellular superoxide anion levels were significantly increased(P<0.01);the CMs pretreated with crocin can reduce the level of Nox2(P<0.01),increase the cell proliferation ability of CMs,reduce cell apoptosis,and accordingly reduce the level of superoxide anion in the cell(P<0.05).[Conclusions]Crocin protects CMs from hypoxia/reoxygenation injury through down-regulating the level of Nox2 and reducing oxidative stress injury.展开更多
Medicinal plants are rich in nutrients and phytochemicals which prevent and treat a wide range of ailments.Accumulating experimental studies exhibit that some bioactive ingredients extracted from medicinal plants have...Medicinal plants are rich in nutrients and phytochemicals which prevent and treat a wide range of ailments.Accumulating experimental studies exhibit that some bioactive ingredients extracted from medicinal plants have suitable therapeutic effects on hepatic and renal injuries.This review focuses on the hepato-and reno-protective effects of thymoquinone,crocin,and carvacrol.The relevant literature was retrieved from PubMed,Scopus,Web of Science,and Google Scholar databases from the beginning of 2015 until the end of November 2021.According to the scientific evidence,the considered phytochemicals in this review have been applied with useful therapeutic effects on hepatic and renal damage.These therapeutic effects were mainly mediated through the amelioration of oxidative stress,suppression of inflammatory responses,and inhibition of apoptosis.Intracellular signaling pathways linked to nuclear factor kappa B(NF-κB),adenosine monophosphate-activated protein kinase,c-jun N-terminal kinase,and extracellular signal-regulated kinase 1/2 and Toll-like receptors are the most important pathways targeted by these phytochemicals.Up-regulation of transcription factor Nrf2 and down-regulation of transforming growth factor-beta 1 by these natural compounds also contribute to the alleviation of hepatic and renal injuries.展开更多
Crocus sativus and its bioactive constituent crocin are well known for anti-tumor potential in different models.However, the efficacy of crocin on in-vivo melanoma metastasis is not yet reported. In this study, melano...Crocus sativus and its bioactive constituent crocin are well known for anti-tumor potential in different models.However, the efficacy of crocin on in-vivo melanoma metastasis is not yet reported. In this study, melanoma metastatic model was developed by tail vein injection of B16 F-10 cells in to C57 BL/6 mice. Metastatic mice treated with two different doses of crocin（250 and 500 μg/kg of bodyweight） for 10 days and parameters such as lung metastasis inhibition, mean survival time, lung hydroxyproline, uronic acid and hexosamine levels were analyzed after 21 days of treatment. Then blood was collected and serum gamma glutamyl transpeptidase（γ-GGT）, sialic acid,tumor necrosis factor alpha（TNF-a）, interleukin 10（IL-10）, IL-6, IL-2, and TIMP-1 levels were measured. Further, a lung histological examination was done in crocin treated metastatic mice. Subsequently hallmark metastatic parameters such as matrix metalloproteinases（MMPs）, extracellular regulated kinase 2（ERK2）, vascular endothelial growth factor（VEGF）, and K-ras gene expression were investigated in the lungs of crocin treated metastatic mice.Further, in-vitro adhesion, invasion and migration of B16 F-10 cells were examined after 24 hours of crocin（5 and 10μg/mL） treatment. Administration of crocin to tumor bearing C57 BL/6 mice reduced the lung metastasis by 85%.Elevated levels of hydroxyproline, uronic acid, hexosamine, serum sialic acid and y-GGT in metastatic control were found to be significantly reduced in crocin treated mice. Crocin also inhibited expression of MMP-2, MMP-9, ERK-2,K-ras, and VEGF. Crocin reduced the ability of B16 F-10 cells invasion（P〈0.05）, migration（P〈0.05） and adhesion by upregulating E-cadherin expression. In conclusion, crocin elicited marked anti-metastatic potential by regulating the metastasis induced biomarkers.展开更多
Saffron has many pharmacological properties in addition to being a frequently used food seasoning.Crocin and picrocrocin which accumulate in saffron stigma,are responsible for these pharmacological properties.These na...Saffron has many pharmacological properties in addition to being a frequently used food seasoning.Crocin and picrocrocin which accumulate in saffron stigma,are responsible for these pharmacological properties.These natural products have health-promoting effects for the prevention and treatment of numerous diseases,including age-related cognitive and memory disfunction.Currently,crocin and picrocrocin are obtained from saffron,considered as the spice with the highest price in the market.To develop an efficient and low-cost approach to producing these compounds with high bioactivity,biosynthetic genes isolated from saffron can be exploited in the metabolic engineering of heterologous hosts and the production of crocins in productive crop plants.Recently,we engineered tomato fruit producing crocins(Tomafran).In this study,we demonstrated that crocin-rich extract,encapsulated in chitosan or in exosomes may function as a neuroprotective strategy.Crocins contained in the Tomafran extracts and much lower doses in chitosan nanoparticles or exosomes were enough to rescue the neuroblastoma cell line SH-SY5Y after damage caused by okadaic acid.Our results confirm the neuroprotective effect of Tomafran and its exosomes that may be useful for the delay or prevention of neurodegenerative disorders such as Alzheimer’s disease.展开更多
The use of Crocin, derived from the flowers of Crocus sativus, is investigated as corrosion inhibitor for the AA1050, AA5083, AA5754 and AA6082 aluminum alloys in chloride ions environment. Aluminum and aluminum alloy...The use of Crocin, derived from the flowers of Crocus sativus, is investigated as corrosion inhibitor for the AA1050, AA5083, AA5754 and AA6082 aluminum alloys in chloride ions environment. Aluminum and aluminum alloys are subjected to corrosion in the aggressive environment of chlorides, so several green corrosion inhibitors, mostly of plant origin, with minimum impact on health and the environment have been examined. In this study, the inhibition efficiency of 1.25 mM Crocin in a 0.01 M NaCl corrosive solution was assessed via electrochemical corrosion techniques and gravimetric mass loss measurements of the aluminum alloys. The surface of the specimens was examined using Scanning Electron Microscopy, Energy Dispersive Spectroscopy, Stereomicroscopy and Glossiness measurements. Experimental results reveal the protective anticorrosive action of Crocin for all aluminum alloys in the sodium chloride medium.展开更多
Objective:To explore the mechanism of crocin,a major active component of Crocus sativus(Zanghonghua),in regulating amyloid beta(Aβ)generation,endoplasmic reticulum(ER)stress,and autophagy in neuronal cells,with poten...Objective:To explore the mechanism of crocin,a major active component of Crocus sativus(Zanghonghua),in regulating amyloid beta(Aβ)generation,endoplasmic reticulum(ER)stress,and autophagy in neuronal cells,with potential therapeutic applications in Alzheimer's disease(AD).Methods:Mouse neuroblastoma Neuron2a(N2a)cells stably transfected with the human amyloid precursor protein(APP)Swedish mutant was used as a cellular model for AD(N2a/APP).Control cells were vector transfected(N2a/vector).The effects of 3 different doses of crocin on reactive oxygen species(ROS)generation,cytosolic calcium,and apoptosis were evaluated by flow cytometry.Aβlevels were determined by enzyme-linked immunosorbent assay.APP processing and ER stress proteins expressions were determined by Western blot.Autophagosome formation was evaluated by autophagy detection kit and confocal microscope.Results:Crocin inhibited APP expression in N2a/APP cells and promotedα-cleavage of APP processing,while modestly reduced beta-secretase 1(BACE1)and presenilin 1(PS1,P<0.05 or P<0.01).ER stress markers,including the binding immunoglobulin protein/78-kD glucose-regulated protein(Bip/GRP78)and C/EBP homologous protein(CHOP),were elevated in N2a/APP cells compared to N2a/vector cells(P<0.05).Crocin could effectively reduce the levels of ER stress(P<0.05 or P<0.01).In addition,crocin enhanced autophagy by promoting formation of autophagosome(P<0.05 or P<0.01).Conclusion:Crocin significantly inhibited Aβgeneration by promotingα-cleavage of APP processing,inhibiting ER stressassociated unfolded protein response,and regulating autophagy.展开更多
Crocus sativus (saffron) is a globally autumn-flowering plant, and its stigmas are the most expensive spice and valuable herb medicine. Crocus specialized metabolites, crocins, are biosynthesized in distant species, G...Crocus sativus (saffron) is a globally autumn-flowering plant, and its stigmas are the most expensive spice and valuable herb medicine. Crocus specialized metabolites, crocins, are biosynthesized in distant species, Gardenia (eudicot) and Crocus (monocot), and the evolution of crocin biosynthesis remains poorly understood. With the chromosome-level Crocus genome assembly, we revealed that two rounds of lineage-specific whole genome triplication occurred, contributing important roles in the production of carotenoids and apocarotenoids. According to the kingdom-wide identification, phylogenetic analysis, and functional assays of carotenoid cleavage dioxygenases (CCDs), we deduced that the duplication, site positive selection, and neofunctionalization of Crocus-specific CCD2 from CCD1 members are responsible for the crocin biosynthesis. In addition, site mutation of CsCCD2 revealed the key amino acids, including I143, L146, R161, E181, T259, and S292 related to the catalytic activity of zeaxanthin cleavage. Our study provides important insights into the origin and evolution of plant specialized metabolites, which are derived by duplication events of biosynthetic genes.展开更多
There are many factors influencing the growth and secondary metabolites of callus and saffron callus. In this paper, the effects of culture conditions, including culture temperatures, light levels, the carbon sourc...There are many factors influencing the growth and secondary metabolites of callus and saffron callus. In this paper, the effects of culture conditions, including culture temperatures, light levels, the carbon source and its concentration, and the preserve of regulators (mainly hormones), are studied for callus cultures. All the experiments used Murashige and Skoog (MS) solid medium as the basic medium with 10 g/L agar, pH 5.75.8. Saffron callus was cultured at 20℃ in the dark, with a sucrose concentration of 45 g/L (or starchy hydrolysate concentration of 40 g/L), but 30 g/L sucrose was best for the synthesis of crocin (for starchy hydrolysate the concentration can range from 20 to 40 g/L). To promote callus growth, the best auxin was α-naphthaleneacetic acid (NAA) and the optimum ratio of NAA (mg/L) to benzylaminopurine (BA) (mg/L) was 2∶0.25. Indole-3-acetic acid (IAA) (4 mg/L), gibberellin(GA3) (2 mg/L), and uniconazole (S-07) (1.25 mg/L) increased the crocin content remarkably as analyzed by high performance liquid chromatography (HPLC). NAA (2 mg/L) promoted the growth of saffron callus but had no benefit and may inhibit crocin synthesis while S-07 (1.25 mg/L) had the opposite effect. GA3 promoted both growth and synthesis.展开更多
Objective:To study the therapeutic effect of crocin on diabetic retinopathy(DR)in rats based on toll-like receptor 4(TLR4)/myeloid differentiation factor 88(My D88)/nuclear factor-κB(NF-κB)pathway.Methods:Thirty SPF...Objective:To study the therapeutic effect of crocin on diabetic retinopathy(DR)in rats based on toll-like receptor 4(TLR4)/myeloid differentiation factor 88(My D88)/nuclear factor-κB(NF-κB)pathway.Methods:Thirty SPF SD rats were used in the experiment,which were randomly divided into DR group,control group and crocin group,with 10 rats in each group.The DR rat model was established by feeding the rats in both the DR group and crocin group with a high glucose and high fat diet,along with intraperitoneal injection(IP)of streptozotocin.Crocin IP was administered to the rats in the crocin group,whereas the rats in the DR group and control group received an equivalent dosage of saline IP for 12 weeks.A comparison was made among the three groups regarding retinal thickness,vascular permeability,expression of TLR4/My D88/NF-κB pathway protein,levels of inflammatory factors,and levels of Bcl-2,Bax,and Bcl-2/Bax.Results:The DR group and crocins group exhibited a lower retinal thickness compared to the control group,while the crocins group displayed a higher thickness than the DR group.The DR group and crocins group had higher retinal vascular permeability than the control group,and the crocins group had lower retinal vascular permeability than the DR group(P<0.05).TLR4,My D88,and P-NF-κB relative expressions were higher in the DR and crocin groups than in the control group,whereas TLR4,My D88,and P-NF-κB relative expressions were lower in the crocin group than in the DR group(P<0.05).The DR group and crocin group exhibited elevated levels of inflammatory cytokines compared to the control group,while the crocin group displayed decreased levels in comparison to the DR group(P<0.05).The DR group and crocin group exhibited lower levels of Bcl-2 and Bcl-2/Bax compared to the control group,whereas the control group displayed higher levels of Bax.The crocin group exhibited elevated levels of Bcl-2 and Bcl-2/Bax compared to the DR group,whereas the DR group displayed diminished levels of Bax(P<0.05).Conclusion:Crocin has the potential to enhance the retinal thickness and vascular permeability of DR rats,and the inhibition of the TLR4/My D88/NF-κB pathway by crocin could play a crucial role in impeding the advancement of DR.展开更多
目的利用网络药理学、分子对接技术和细胞实验验证,探讨藏红花素改善阿尔茨海默病(Alzheimer’s disease,AD)的作用机制。方法运用Super-PRED、DisGenet、Genecards、Uniprot、STRING数据库构建藏红花素与AD的相互作用网络,导入Cytoscap...目的利用网络药理学、分子对接技术和细胞实验验证,探讨藏红花素改善阿尔茨海默病(Alzheimer’s disease,AD)的作用机制。方法运用Super-PRED、DisGenet、Genecards、Uniprot、STRING数据库构建藏红花素与AD的相互作用网络,导入Cytoscape软件根据连接程度筛选枢纽基因,并进行基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,应用Autodock vina软件进行分子对接验证。体外采用脂多糖(lipopolysaccharide,LPS)诱导BV2小胶质细胞炎症模型,给予藏红花素干预后,采用CCK-8法检测细胞活力,qRT-PCR检测肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、IL-6 m RNA表达,Western blotting检测磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)/糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)通路相关蛋白表达。结果网络药理学结果显示,藏红花素可能通过调控PI3K-Akt信号通路、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路等,作用于热休克蛋白90AA1(heat shock protein 90 alpha family class A member 1,HSP90AA1)、核因子-κB(nuclear factor-κB,NF-κB)、Toll样受体4(Tolllike receptor 4,TLR4)、磷脂酰肌醇3-激酶调节亚基1(phosphatidylinositol 3-kinase regulatory subunit 1,PIK3R1)、磷脂酰肌醇3-激酶催化亚基α(phosphatidylinositol 3-kinase catalytic subunitα,PIK3CA)、E1A结合蛋白p300(E1A-binding protein p300,EP300)等靶点,发挥治疗AD的作用。分子对接结果显示藏红花素与PIK3R1靶点对接效果良好。细胞实验结果显示,藏红花素显著抑制LPS诱导的BV2细胞中炎症因子表达(P<0.05、0.01),促进PI3K、Akt、GSK-3β的磷酸化(P<0.05)。结论藏红花素具有改善小胶质细胞极化、抗神经炎症的作用,其作用机制与激活PI3K/Akt/GSK-3β通路有关。展开更多
文摘Crocin is a plant ingredient mainly found in the extract of Crocus sativus(Saffron).This carotenoid compound has antioxidant,anti-inflammatory,antitumor,and antihypertensive properties.This review summarizes the therapeutic effects of crocin.Data were retrieved from 2015 until the end of April 2025 using databases including the Web of Science,PubMed,Scopus,and Google Scholar.According to the findings of previous studies,the therapeutic effects of crocin on various organs can be attributed to its ability to scavenge free radicals,enhance antioxidant activities,reduce inflammatory reactions,and modulate the PI3K/AKT,NF-κB,and PPARγ/LXRs signaling pathways.
基金supported by a grant from the Rafsanjan University of Medical Sciences(20/341/1395)
文摘Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area(VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In this study, 40 male Wistar rats(200-250 g) were used in 5 experimental groups: 1) non morphine treat rats(control); 2) non morphine-treated rats with 25 mg/kg crocin carotenoid(i.p., for 21 d); 3) morphine treated rats(10 mg/kg twice a day, s.c., 21 d); 4 and 5) morphine-treated rats with 12.5 and 25 mg/kg crocin carotenoid, respectively. By the end of research, BDNF and CREB expression was determined by real-time-PCR method. ELISA analysis was also applied for assessing the serum BDNF level. Results: The data indicated that morphine treatment could cause a significant decrease in BDNF and CREB gene expression(P<0.01 and P<0.001, respectively) in brain VTA as well as serum level of BDNF(P<0.01) in comparison to control group. Treatment with 25 mg/kg crocin carotenoid caused a significant enhancement in BDNF and CREF gene expression(P<0.01 and P<0.05, respectively) and serum level of BDNF(P<0.01) in morphine-treated rats in comparison to morphine-treated group. Conclusions: Regarding to obtained results, crocin carotenoid can inhibit unfavorable effects of morphine on the neural system to some extent through enhancing BDNF and CREB gene expression in brain VTA and serum level of BDNF.
文摘[Objectives]To explore the protection mechanism of crocin against ischemia-reperfusion injury of myocardial cells.[Methods]Newborn male SD rats were selected,left ventricular cardiomyocytes(CMs)were isolated,and a hypoxia/reoxygenation model of CMs was established to simulate the process of ischemia/reperfusion injury.The cells were randomly divided into four groups:normal cell group(control group),crocin group),hypoxia/reoxygenation group(H/R group),hypoxia/reoxygenation+crocin group(H/R+crocin group).H/R+crocin group selected the concentration of crocin 1,10,and 100μmol/L,and determined the optimal concentration of crocin by detecting the cell proliferation ability.After the cells were pretreated using the optimal concentration of crocin,the levels of superoxide anion,cell proliferation,apoptosis and Nox2 levels in each group of cells were detected.[Results]Compared with the control group,the proliferation ability of CMs after hypoxia-reoxygenation injury was reduced(P<0.05),while cell apoptosis and intracellular superoxide anion levels were significantly increased(P<0.01);the CMs pretreated with crocin can reduce the level of Nox2(P<0.01),increase the cell proliferation ability of CMs,reduce cell apoptosis,and accordingly reduce the level of superoxide anion in the cell(P<0.05).[Conclusions]Crocin protects CMs from hypoxia/reoxygenation injury through down-regulating the level of Nox2 and reducing oxidative stress injury.
文摘Medicinal plants are rich in nutrients and phytochemicals which prevent and treat a wide range of ailments.Accumulating experimental studies exhibit that some bioactive ingredients extracted from medicinal plants have suitable therapeutic effects on hepatic and renal injuries.This review focuses on the hepato-and reno-protective effects of thymoquinone,crocin,and carvacrol.The relevant literature was retrieved from PubMed,Scopus,Web of Science,and Google Scholar databases from the beginning of 2015 until the end of November 2021.According to the scientific evidence,the considered phytochemicals in this review have been applied with useful therapeutic effects on hepatic and renal damage.These therapeutic effects were mainly mediated through the amelioration of oxidative stress,suppression of inflammatory responses,and inhibition of apoptosis.Intracellular signaling pathways linked to nuclear factor kappa B(NF-κB),adenosine monophosphate-activated protein kinase,c-jun N-terminal kinase,and extracellular signal-regulated kinase 1/2 and Toll-like receptors are the most important pathways targeted by these phytochemicals.Up-regulation of transcription factor Nrf2 and down-regulation of transforming growth factor-beta 1 by these natural compounds also contribute to the alleviation of hepatic and renal injuries.
文摘Crocus sativus and its bioactive constituent crocin are well known for anti-tumor potential in different models.However, the efficacy of crocin on in-vivo melanoma metastasis is not yet reported. In this study, melanoma metastatic model was developed by tail vein injection of B16 F-10 cells in to C57 BL/6 mice. Metastatic mice treated with two different doses of crocin（250 and 500 μg/kg of bodyweight） for 10 days and parameters such as lung metastasis inhibition, mean survival time, lung hydroxyproline, uronic acid and hexosamine levels were analyzed after 21 days of treatment. Then blood was collected and serum gamma glutamyl transpeptidase（γ-GGT）, sialic acid,tumor necrosis factor alpha（TNF-a）, interleukin 10（IL-10）, IL-6, IL-2, and TIMP-1 levels were measured. Further, a lung histological examination was done in crocin treated metastatic mice. Subsequently hallmark metastatic parameters such as matrix metalloproteinases（MMPs）, extracellular regulated kinase 2（ERK2）, vascular endothelial growth factor（VEGF）, and K-ras gene expression were investigated in the lungs of crocin treated metastatic mice.Further, in-vitro adhesion, invasion and migration of B16 F-10 cells were examined after 24 hours of crocin（5 and 10μg/mL） treatment. Administration of crocin to tumor bearing C57 BL/6 mice reduced the lung metastasis by 85%.Elevated levels of hydroxyproline, uronic acid, hexosamine, serum sialic acid and y-GGT in metastatic control were found to be significantly reduced in crocin treated mice. Crocin also inhibited expression of MMP-2, MMP-9, ERK-2,K-ras, and VEGF. Crocin reduced the ability of B16 F-10 cells invasion（P〈0.05）, migration（P〈0.05） and adhesion by upregulating E-cadherin expression. In conclusion, crocin elicited marked anti-metastatic potential by regulating the metastasis induced biomarkers.
基金supported by grants BIO2016-77000-R,PIB2020-114761RB-I00 and FJC2021-046632-I(to M.E.)from the Ministerio de Ciencia e Innovación(MCIN),SBPLY/17/180501/000234,and SBPLY/21/180501/000012 from the Junta de Comunidades de Castilla-La Mancha(co-financed European Union FEDER funds)to LGG and OA.
文摘Saffron has many pharmacological properties in addition to being a frequently used food seasoning.Crocin and picrocrocin which accumulate in saffron stigma,are responsible for these pharmacological properties.These natural products have health-promoting effects for the prevention and treatment of numerous diseases,including age-related cognitive and memory disfunction.Currently,crocin and picrocrocin are obtained from saffron,considered as the spice with the highest price in the market.To develop an efficient and low-cost approach to producing these compounds with high bioactivity,biosynthetic genes isolated from saffron can be exploited in the metabolic engineering of heterologous hosts and the production of crocins in productive crop plants.Recently,we engineered tomato fruit producing crocins(Tomafran).In this study,we demonstrated that crocin-rich extract,encapsulated in chitosan or in exosomes may function as a neuroprotective strategy.Crocins contained in the Tomafran extracts and much lower doses in chitosan nanoparticles or exosomes were enough to rescue the neuroblastoma cell line SH-SY5Y after damage caused by okadaic acid.Our results confirm the neuroprotective effect of Tomafran and its exosomes that may be useful for the delay or prevention of neurodegenerative disorders such as Alzheimer’s disease.
文摘The use of Crocin, derived from the flowers of Crocus sativus, is investigated as corrosion inhibitor for the AA1050, AA5083, AA5754 and AA6082 aluminum alloys in chloride ions environment. Aluminum and aluminum alloys are subjected to corrosion in the aggressive environment of chlorides, so several green corrosion inhibitors, mostly of plant origin, with minimum impact on health and the environment have been examined. In this study, the inhibition efficiency of 1.25 mM Crocin in a 0.01 M NaCl corrosive solution was assessed via electrochemical corrosion techniques and gravimetric mass loss measurements of the aluminum alloys. The surface of the specimens was examined using Scanning Electron Microscopy, Energy Dispersive Spectroscopy, Stereomicroscopy and Glossiness measurements. Experimental results reveal the protective anticorrosive action of Crocin for all aluminum alloys in the sodium chloride medium.
基金Supported by the University of Macao (No.MYRG-2022-00248-ICMS).
文摘Objective:To explore the mechanism of crocin,a major active component of Crocus sativus(Zanghonghua),in regulating amyloid beta(Aβ)generation,endoplasmic reticulum(ER)stress,and autophagy in neuronal cells,with potential therapeutic applications in Alzheimer's disease(AD).Methods:Mouse neuroblastoma Neuron2a(N2a)cells stably transfected with the human amyloid precursor protein(APP)Swedish mutant was used as a cellular model for AD(N2a/APP).Control cells were vector transfected(N2a/vector).The effects of 3 different doses of crocin on reactive oxygen species(ROS)generation,cytosolic calcium,and apoptosis were evaluated by flow cytometry.Aβlevels were determined by enzyme-linked immunosorbent assay.APP processing and ER stress proteins expressions were determined by Western blot.Autophagosome formation was evaluated by autophagy detection kit and confocal microscope.Results:Crocin inhibited APP expression in N2a/APP cells and promotedα-cleavage of APP processing,while modestly reduced beta-secretase 1(BACE1)and presenilin 1(PS1,P<0.05 or P<0.01).ER stress markers,including the binding immunoglobulin protein/78-kD glucose-regulated protein(Bip/GRP78)and C/EBP homologous protein(CHOP),were elevated in N2a/APP cells compared to N2a/vector cells(P<0.05).Crocin could effectively reduce the levels of ER stress(P<0.05 or P<0.01).In addition,crocin enhanced autophagy by promoting formation of autophagosome(P<0.05 or P<0.01).Conclusion:Crocin significantly inhibited Aβgeneration by promotingα-cleavage of APP processing,inhibiting ER stressassociated unfolded protein response,and regulating autophagy.
基金This work was supported by the National Natural Science Foundation of China(81973424,82073966,82204346)the CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2021-I2M-1-029,China)+2 种基金the National Key R&D Program of China(2023YFC3504800)the Fundamental Research Funds for the Central public welfare research institutes(ZZ16-YQ-047,ZZ16-ND-10-02,China)the Key Scientific Research Foundation of the Higher Education Institutions of Anhui Province,China(KJ2021A0235).
文摘Crocus sativus (saffron) is a globally autumn-flowering plant, and its stigmas are the most expensive spice and valuable herb medicine. Crocus specialized metabolites, crocins, are biosynthesized in distant species, Gardenia (eudicot) and Crocus (monocot), and the evolution of crocin biosynthesis remains poorly understood. With the chromosome-level Crocus genome assembly, we revealed that two rounds of lineage-specific whole genome triplication occurred, contributing important roles in the production of carotenoids and apocarotenoids. According to the kingdom-wide identification, phylogenetic analysis, and functional assays of carotenoid cleavage dioxygenases (CCDs), we deduced that the duplication, site positive selection, and neofunctionalization of Crocus-specific CCD2 from CCD1 members are responsible for the crocin biosynthesis. In addition, site mutation of CsCCD2 revealed the key amino acids, including I143, L146, R161, E181, T259, and S292 related to the catalytic activity of zeaxanthin cleavage. Our study provides important insights into the origin and evolution of plant specialized metabolites, which are derived by duplication events of biosynthetic genes.
文摘There are many factors influencing the growth and secondary metabolites of callus and saffron callus. In this paper, the effects of culture conditions, including culture temperatures, light levels, the carbon source and its concentration, and the preserve of regulators (mainly hormones), are studied for callus cultures. All the experiments used Murashige and Skoog (MS) solid medium as the basic medium with 10 g/L agar, pH 5.75.8. Saffron callus was cultured at 20℃ in the dark, with a sucrose concentration of 45 g/L (or starchy hydrolysate concentration of 40 g/L), but 30 g/L sucrose was best for the synthesis of crocin (for starchy hydrolysate the concentration can range from 20 to 40 g/L). To promote callus growth, the best auxin was α-naphthaleneacetic acid (NAA) and the optimum ratio of NAA (mg/L) to benzylaminopurine (BA) (mg/L) was 2∶0.25. Indole-3-acetic acid (IAA) (4 mg/L), gibberellin(GA3) (2 mg/L), and uniconazole (S-07) (1.25 mg/L) increased the crocin content remarkably as analyzed by high performance liquid chromatography (HPLC). NAA (2 mg/L) promoted the growth of saffron callus but had no benefit and may inhibit crocin synthesis while S-07 (1.25 mg/L) had the opposite effect. GA3 promoted both growth and synthesis.
文摘Objective:To study the therapeutic effect of crocin on diabetic retinopathy(DR)in rats based on toll-like receptor 4(TLR4)/myeloid differentiation factor 88(My D88)/nuclear factor-κB(NF-κB)pathway.Methods:Thirty SPF SD rats were used in the experiment,which were randomly divided into DR group,control group and crocin group,with 10 rats in each group.The DR rat model was established by feeding the rats in both the DR group and crocin group with a high glucose and high fat diet,along with intraperitoneal injection(IP)of streptozotocin.Crocin IP was administered to the rats in the crocin group,whereas the rats in the DR group and control group received an equivalent dosage of saline IP for 12 weeks.A comparison was made among the three groups regarding retinal thickness,vascular permeability,expression of TLR4/My D88/NF-κB pathway protein,levels of inflammatory factors,and levels of Bcl-2,Bax,and Bcl-2/Bax.Results:The DR group and crocins group exhibited a lower retinal thickness compared to the control group,while the crocins group displayed a higher thickness than the DR group.The DR group and crocins group had higher retinal vascular permeability than the control group,and the crocins group had lower retinal vascular permeability than the DR group(P<0.05).TLR4,My D88,and P-NF-κB relative expressions were higher in the DR and crocin groups than in the control group,whereas TLR4,My D88,and P-NF-κB relative expressions were lower in the crocin group than in the DR group(P<0.05).The DR group and crocin group exhibited elevated levels of inflammatory cytokines compared to the control group,while the crocin group displayed decreased levels in comparison to the DR group(P<0.05).The DR group and crocin group exhibited lower levels of Bcl-2 and Bcl-2/Bax compared to the control group,whereas the control group displayed higher levels of Bax.The crocin group exhibited elevated levels of Bcl-2 and Bcl-2/Bax compared to the DR group,whereas the DR group displayed diminished levels of Bax(P<0.05).Conclusion:Crocin has the potential to enhance the retinal thickness and vascular permeability of DR rats,and the inhibition of the TLR4/My D88/NF-κB pathway by crocin could play a crucial role in impeding the advancement of DR.
文摘目的利用网络药理学、分子对接技术和细胞实验验证,探讨藏红花素改善阿尔茨海默病(Alzheimer’s disease,AD)的作用机制。方法运用Super-PRED、DisGenet、Genecards、Uniprot、STRING数据库构建藏红花素与AD的相互作用网络,导入Cytoscape软件根据连接程度筛选枢纽基因,并进行基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,应用Autodock vina软件进行分子对接验证。体外采用脂多糖(lipopolysaccharide,LPS)诱导BV2小胶质细胞炎症模型,给予藏红花素干预后,采用CCK-8法检测细胞活力,qRT-PCR检测肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、IL-6 m RNA表达,Western blotting检测磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)/糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)通路相关蛋白表达。结果网络药理学结果显示,藏红花素可能通过调控PI3K-Akt信号通路、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路等,作用于热休克蛋白90AA1(heat shock protein 90 alpha family class A member 1,HSP90AA1)、核因子-κB(nuclear factor-κB,NF-κB)、Toll样受体4(Tolllike receptor 4,TLR4)、磷脂酰肌醇3-激酶调节亚基1(phosphatidylinositol 3-kinase regulatory subunit 1,PIK3R1)、磷脂酰肌醇3-激酶催化亚基α(phosphatidylinositol 3-kinase catalytic subunitα,PIK3CA)、E1A结合蛋白p300(E1A-binding protein p300,EP300)等靶点,发挥治疗AD的作用。分子对接结果显示藏红花素与PIK3R1靶点对接效果良好。细胞实验结果显示,藏红花素显著抑制LPS诱导的BV2细胞中炎症因子表达(P<0.05、0.01),促进PI3K、Akt、GSK-3β的磷酸化(P<0.05)。结论藏红花素具有改善小胶质细胞极化、抗神经炎症的作用,其作用机制与激活PI3K/Akt/GSK-3β通路有关。
