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
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
Saffron(Crocus sativus L.)has been traditionally used in food preparation and as a medicinal plant.It currently has numerous therapeutic properties attributed to it,such as protection against ischemia,as well as antic...Saffron(Crocus sativus L.)has been traditionally used in food preparation and as a medicinal plant.It currently has numerous therapeutic properties attributed to it,such as protection against ischemia,as well as anticonvulsant,antidepressant,anxiolytic,hypolipidemic,anti-atherogenic,anti-hypertensive,antidiabetic,and anti-cancer properties.In addition,saffron has remarkable beneficial properties,such as anti-apoptotic,anti-inflammatory and antioxidant activities,due to its main metabolites,among which crocin and crocetin stand out.Furthermore,increasing evidence underwrites the possible neuroprotective role of the main bioactive saffron constituents in neurodegenerative diseases,such as Parkinson’s and Alzheimer’s diseases,both in experimental models and in clinical studies in patients.Currently,saffron supplementation is being tested for ocular neurodegenerative pathologies,such as diabetic retinopathy,retinitis pigmentosa,age-related macular degeneration and glaucoma,among others,and shows beneficial effects.The present article provides a comprehensive and up to date report of the investigations on the beneficial effects of saffron extracts on the main neurodegenerative ocular pathologies and other ocular diseases.This review showed that saffron extracts could be considered promising therapeutic agents to help in the treatment of ocular neurodegenerative diseases.展开更多
Herbal extracts have been extensively used worldwide for their application on memory improvement, especially among aged and memory-deficit populations. In the present study, the memory loss induced by human Abeta prot...Herbal extracts have been extensively used worldwide for their application on memory improvement, especially among aged and memory-deficit populations. In the present study, the memory loss induced by human Abeta protein over-expression in fruitfly Alzheimer's disease(AD) model was rescued by multiple extracts from Gardenia jasminoides. Three extracts that rich with gardenia yellow, geniposide, and gardenoside components showed distinct rescue effect on memory loss. Further investigation on adding gardenoside into a formula of Ganoderma lucidum, Panax notoginseng and Panax ginseng(GPP) also support its therapeutic effects on memory improvement. Interestingly, the application of GPP and gardenoside did not alter the accumulation of Abeta proteins but suppressed the expression of immune-related genes in the brain. These results revealed the importance and relevancy of anti-inflammation process and the underlying mechanisms on rescuing memory deficits, suggesting the potential therapeutic use of the improved GPP formulation in improving cognition in defined population in the future.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
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
Dear Editor,Saffron is the world’s most expensive spice,often referred to as“red gold”because of its high economic value.Crocetin and its glycosylated derivatives,crocins,are carotenoid derivatives responsible for ...Dear Editor,Saffron is the world’s most expensive spice,often referred to as“red gold”because of its high economic value.Crocetin and its glycosylated derivatives,crocins,are carotenoid derivatives responsible for the color of saffron.These compounds have at-tracted attention for their pharmaceutical and health-related ef-fects,including antioxidant,anticancer,cardioprotective,neuro-protective,antidepressant,and immune-enhancing properties(Bukhari et al.,2018).The broad potential of crocetin and crocins in food,healthcare,and cosmetics has driven increasing research into their metabolically engineered production in various microorganisms and plants(Zheng et al.,2022).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
Fruits of Gardenia jasminoides（Zhizi in Chinese） have been used as dietary supplement and traditional Chinese medicine for thousands of years. Recent studies on Gardenia jasminoides reveal that the extracts or the a...Fruits of Gardenia jasminoides（Zhizi in Chinese） have been used as dietary supplement and traditional Chinese medicine for thousands of years. Recent studies on Gardenia jasminoides reveal that the extracts or the active components play an essential role in oxidative stress, inflammation, hepatoprotection,neuroprotection, anti-diabetes, antitumor and so on. Here, we reviewed G. jasminoides in the aspects of botanical identity, chemical ingredients, pharmacology and pharmacokinetics, safety and toxicity evaluation, clinical application, etc.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
We aimed to investigate whether carnosine(a natural dipeptide found in humans)and crocin(a natural product extracted from saffron and gardenia)can prevent the harmful effects of acute kidney injury(AKI)caused by glyce...We aimed to investigate whether carnosine(a natural dipeptide found in humans)and crocin(a natural product extracted from saffron and gardenia)can prevent the harmful effects of acute kidney injury(AKI)caused by glycerol-induced rhabdomyolysis with a focus on the role of the nuclear factor E2-related factor-2/heme oxygenase-1(Nrf2/HO-1)signaling pathway.Thirty-six male Wistar rats were divided into 6 groups:3 of them received saline,carnosine,and crocin IP for 7 days and the other 3 groups received the same treatment in addition to a single IM injection of 50%glycerol(10 ml/kg,divided between the two limb muscles)on 8th day.All animals were sacrificed after 24 h of the IM injection.Blood samples,muscles,and kidneys were collected for further investigations.Rhabdomyolysis was evidenced by the histopathological alterations in muscle sections and increased levels of myoglobin in kidney tissue homogenate samples.Kidney injury was characterized by increased creatinine,kidney injury molecule-1,malondialdehyde,nitric oxide,and decreased catalase activity.The injury also increased inflammatory markers and histopathological alterations in kidney sections.All these effects were corrected by pretreatment with carnosine and crocin.Both agents could also elevate HO-1 gene expression.However,both agents failed to restore the declined Nrf2 expression in glycerol-treated groups.Carnosine and crocin can effectively prevent rhabdomyolysis-induced AKI in rats through augmenting gene expression of HO-1 and antioxidant system and suppressing the generation of reactive oxygen species,lipid peroxidation,and inflammatory response.展开更多
Background:Carotenoids play important role in delay of aging process.Orange coloured tubular calyx of flowers of Nyctanthes arbor-tristis contains crocin,an apocarotenoid which forms a major component of stigma of saf...Background:Carotenoids play important role in delay of aging process.Orange coloured tubular calyx of flowers of Nyctanthes arbor-tristis contains crocin,an apocarotenoid which forms a major component of stigma of saffron.Due to presence of crocin in orange coloured tubular calyx of Nyctanthes arbor-tristis,it can be used as an economical substitute to saffron for its medicinal and cosmetic utilities.Lutein from flower petals of Tagetes patula L.,is another popular carotenoid which has antioxidant effect and many health benefits.The carotenoids are highly unstable when exposed to atmosphere.One of the ways to improve stability of these phytoconstituents,is their entrapment in phytosomes.Preparation of phytosomes will have dual advantages of improving stability as well as bioavailability of molecule.Objective:In the present study crocin and lutein rich extracts were entrapped into phytosomes to improve stability and efficacy of topical preparation.Methods:The phytosomes of Carotenoid rich extract of tubular calyx of Nyctanthes arbor-tristis L.and the petals of Tagetes patula L.(standardized for crocin and lutein content)were prepared using lipid film hydration technique and these phytosomes were then incorporated into gel base.The gel formulation was evaluated for stability as per ICH guidelines.Efficacy of formulation was evaluated by d-galactose induced aging model.Aging in skin was induced by administration of d-galactose(100 mg/kg bwsc.)to albino mice for 42 days.The gel formulation was applied topically for 42 days.Then the effect of formulation on skin aging was evaluated by estimation of biochemical parameters viz.glutathione and malondialdehyde(MDA)and histopathological studies of treated skin samples.Expression of COL type I and elastin genes in skin samples was also carried out by RT-PCR.Results:Percent entrapment(%w/w)of crocin and lutein in phytosomes were found to be 60.20%and 50.81%,respectively.Accelerated stability studies showed improvement in stability of carotenoids viz.crocin and lutein and the content of crocin and lutein in formulation was found in the range of 99.98%w/w to 99.85%w/w at the end of three months.The formulation containing extract of Phytosomes of carotenoid rich extracts of Nyctanthes arbor-tristis L.and the petals of Tagetes patula L.exhibited potent antiaging activity through significant(P<0.05)increase in dermal and epidermal layers,and increase in GSH levels of skin as compared to the untreated group.The treatment with the gel formulation revealed upregulation of collagen type I and elastin genes.There was significant reduction in lipid peroxidation as revealed through reduction in MDA levels as compared to untreated group.Conclusion:Crocin and lutein have potential to prevent skin aging via upregulation of collagen type I gene and elastin gene.Upregulation of genes resulted into increase in the thickness of epidermal and dermal layer along with reduction in oxidative stress in skin.Entrapment of carotenoid rich extracts of Nyctanthes arbor-tristis and Tagetes patula in phytosomes enhanced the stability and efficacy of the formulation.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
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the Ophthalmological Network OFTARED(RD16/0008/0005,RD16/0008/0022, of the Institute of Health of Carlos III of the Spanish Ministry of Economyby the PN I+D+i 2008–2011+4 种基金by the ISCIII-Subdireccion General de Redes y Centros de Investigacion Cooperativaby the European program FEDER.SAF-2014-53779-R:from the Spanish Ministry of Economy and Competitivenessby Articulo 83 118-2017(UCM-Pharmactive Biotech)supported by a Predoctoral Fellowship(FPU17/01023)from the Spanish Ministry of Science,Innovation,and Universitiessupported by a Predoctoral Fellowship(CT42/18-CT43/18)from the Complutense University of Madrid
文摘Saffron(Crocus sativus L.)has been traditionally used in food preparation and as a medicinal plant.It currently has numerous therapeutic properties attributed to it,such as protection against ischemia,as well as anticonvulsant,antidepressant,anxiolytic,hypolipidemic,anti-atherogenic,anti-hypertensive,antidiabetic,and anti-cancer properties.In addition,saffron has remarkable beneficial properties,such as anti-apoptotic,anti-inflammatory and antioxidant activities,due to its main metabolites,among which crocin and crocetin stand out.Furthermore,increasing evidence underwrites the possible neuroprotective role of the main bioactive saffron constituents in neurodegenerative diseases,such as Parkinson’s and Alzheimer’s diseases,both in experimental models and in clinical studies in patients.Currently,saffron supplementation is being tested for ocular neurodegenerative pathologies,such as diabetic retinopathy,retinitis pigmentosa,age-related macular degeneration and glaucoma,among others,and shows beneficial effects.The present article provides a comprehensive and up to date report of the investigations on the beneficial effects of saffron extracts on the main neurodegenerative ocular pathologies and other ocular diseases.This review showed that saffron extracts could be considered promising therapeutic agents to help in the treatment of ocular neurodegenerative diseases.
基金supported by programs of Thousand Talents Program Research Park(Jiangsu,China)Provincial Innovation and Entrepreneurial Talent,Jiangsu,China(to I.F.P,)Development of Society and Technology(Kunshan City,Jiangsu,China)
文摘Herbal extracts have been extensively used worldwide for their application on memory improvement, especially among aged and memory-deficit populations. In the present study, the memory loss induced by human Abeta protein over-expression in fruitfly Alzheimer's disease(AD) model was rescued by multiple extracts from Gardenia jasminoides. Three extracts that rich with gardenia yellow, geniposide, and gardenoside components showed distinct rescue effect on memory loss. Further investigation on adding gardenoside into a formula of Ganoderma lucidum, Panax notoginseng and Panax ginseng(GPP) also support its therapeutic effects on memory improvement. Interestingly, the application of GPP and gardenoside did not alter the accumulation of Abeta proteins but suppressed the expression of immune-related genes in the brain. These results revealed the importance and relevancy of anti-inflammation process and the underlying mechanisms on rescuing memory deficits, suggesting the potential therapeutic use of the improved GPP formulation in improving cognition in defined population in the future.
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.
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 baseline funding and the Opportunity Fund Program(OFP,2023)awarded to S.A.-B.by King Abdullah University of Science and Technology(KAUST).
文摘Dear Editor,Saffron is the world’s most expensive spice,often referred to as“red gold”because of its high economic value.Crocetin and its glycosylated derivatives,crocins,are carotenoid derivatives responsible for the color of saffron.These compounds have at-tracted attention for their pharmaceutical and health-related ef-fects,including antioxidant,anticancer,cardioprotective,neuro-protective,antidepressant,and immune-enhancing properties(Bukhari et al.,2018).The broad potential of crocetin and crocins in food,healthcare,and cosmetics has driven increasing research into their metabolically engineered production in various microorganisms and plants(Zheng et al.,2022).
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supported by grants from National Natural Science Foundation of China (81373459)Chongqing Science and Technology Committee (CSTC,2015jcyjbx0064)+2 种基金Chongqing Science Found for Distinguished Young Scholars (2014jcyjjq10003)the Innovation of Science and Technology Leading Talent in Chongqing (2014kjcxljrc0018)the Innovative Research Team Development Program at the University of Chongqing (CXTDX201601031)
文摘Fruits of Gardenia jasminoides（Zhizi in Chinese） have been used as dietary supplement and traditional Chinese medicine for thousands of years. Recent studies on Gardenia jasminoides reveal that the extracts or the active components play an essential role in oxidative stress, inflammation, hepatoprotection,neuroprotection, anti-diabetes, antitumor and so on. Here, we reviewed G. jasminoides in the aspects of botanical identity, chemical ingredients, pharmacology and pharmacokinetics, safety and toxicity evaluation, clinical application, etc.
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We aimed to investigate whether carnosine(a natural dipeptide found in humans)and crocin(a natural product extracted from saffron and gardenia)can prevent the harmful effects of acute kidney injury(AKI)caused by glycerol-induced rhabdomyolysis with a focus on the role of the nuclear factor E2-related factor-2/heme oxygenase-1(Nrf2/HO-1)signaling pathway.Thirty-six male Wistar rats were divided into 6 groups:3 of them received saline,carnosine,and crocin IP for 7 days and the other 3 groups received the same treatment in addition to a single IM injection of 50%glycerol(10 ml/kg,divided between the two limb muscles)on 8th day.All animals were sacrificed after 24 h of the IM injection.Blood samples,muscles,and kidneys were collected for further investigations.Rhabdomyolysis was evidenced by the histopathological alterations in muscle sections and increased levels of myoglobin in kidney tissue homogenate samples.Kidney injury was characterized by increased creatinine,kidney injury molecule-1,malondialdehyde,nitric oxide,and decreased catalase activity.The injury also increased inflammatory markers and histopathological alterations in kidney sections.All these effects were corrected by pretreatment with carnosine and crocin.Both agents could also elevate HO-1 gene expression.However,both agents failed to restore the declined Nrf2 expression in glycerol-treated groups.Carnosine and crocin can effectively prevent rhabdomyolysis-induced AKI in rats through augmenting gene expression of HO-1 and antioxidant system and suppressing the generation of reactive oxygen species,lipid peroxidation,and inflammatory response.
基金supported by National Medicinal Plant Board(NMPB),Dept.of Ayush,Government of India.(Project No.R&D/MS 04/2010).
文摘Background:Carotenoids play important role in delay of aging process.Orange coloured tubular calyx of flowers of Nyctanthes arbor-tristis contains crocin,an apocarotenoid which forms a major component of stigma of saffron.Due to presence of crocin in orange coloured tubular calyx of Nyctanthes arbor-tristis,it can be used as an economical substitute to saffron for its medicinal and cosmetic utilities.Lutein from flower petals of Tagetes patula L.,is another popular carotenoid which has antioxidant effect and many health benefits.The carotenoids are highly unstable when exposed to atmosphere.One of the ways to improve stability of these phytoconstituents,is their entrapment in phytosomes.Preparation of phytosomes will have dual advantages of improving stability as well as bioavailability of molecule.Objective:In the present study crocin and lutein rich extracts were entrapped into phytosomes to improve stability and efficacy of topical preparation.Methods:The phytosomes of Carotenoid rich extract of tubular calyx of Nyctanthes arbor-tristis L.and the petals of Tagetes patula L.(standardized for crocin and lutein content)were prepared using lipid film hydration technique and these phytosomes were then incorporated into gel base.The gel formulation was evaluated for stability as per ICH guidelines.Efficacy of formulation was evaluated by d-galactose induced aging model.Aging in skin was induced by administration of d-galactose(100 mg/kg bwsc.)to albino mice for 42 days.The gel formulation was applied topically for 42 days.Then the effect of formulation on skin aging was evaluated by estimation of biochemical parameters viz.glutathione and malondialdehyde(MDA)and histopathological studies of treated skin samples.Expression of COL type I and elastin genes in skin samples was also carried out by RT-PCR.Results:Percent entrapment(%w/w)of crocin and lutein in phytosomes were found to be 60.20%and 50.81%,respectively.Accelerated stability studies showed improvement in stability of carotenoids viz.crocin and lutein and the content of crocin and lutein in formulation was found in the range of 99.98%w/w to 99.85%w/w at the end of three months.The formulation containing extract of Phytosomes of carotenoid rich extracts of Nyctanthes arbor-tristis L.and the petals of Tagetes patula L.exhibited potent antiaging activity through significant(P<0.05)increase in dermal and epidermal layers,and increase in GSH levels of skin as compared to the untreated group.The treatment with the gel formulation revealed upregulation of collagen type I and elastin genes.There was significant reduction in lipid peroxidation as revealed through reduction in MDA levels as compared to untreated group.Conclusion:Crocin and lutein have potential to prevent skin aging via upregulation of collagen type I gene and elastin gene.Upregulation of genes resulted into increase in the thickness of epidermal and dermal layer along with reduction in oxidative stress in skin.Entrapment of carotenoid rich extracts of Nyctanthes arbor-tristis and Tagetes patula in phytosomes enhanced the stability and efficacy of the formulation.
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.
