Cardioprotective of Saffron (Crocus sativus L.) treatment in patients with type 2 diabetes mellitus: a systematic review and meta-analysis / 数字中医药（英文）

Objective@#To investigate the cardioprotective effect of Saffron (Crocus sativus L.) treatment as a potential supplement on patients with type 2 diabetes mellitus (T2DM).@*Methods@#Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to analyze articles retrieved from PubMed, ScienceDirect, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and China Biology Medicine (CBM) with a publication time span from January 15, 2015 to March 20, 2023. The articles were published in English only, including randomized controlled trials (RCTs) on adult patients who were diagnosed with T2DM, and received either Saffron or placebo treatment. Meta-analysis was performed using Review Manager 5.4 software. The present study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) with a registration number as CRD42023443180.@*Results@#Seven RCTs with 455 patients were included in the study. The data revealed that Saffron treatment significantly reduced tumor necrosis factor (TNF)-α (P = 0.008) and fasting blood glucose (FBG) (P = 0.04) levels compared with what placebo did in T2DM patients. No significant differences were shown in the levels of interleukin (IL)-6, malondialdehyde (MDA), high serum C-reactive protein (hs-CRP), lipid profile, blood pressure, and body mass index (BMI) between Saffron and placebo ( P > 0.05) .@*Conclusion@#Saffron treatment has a cardioprotective effect in T2DM patients by reducing TNF-α and FBG levels. However, the potential anti-oxidant, anti-hypertensive, and anti-dyslipidaemia effects of the phytochemical need to be further investigated.

Saffron reduces the liver fibrosis in mice by inhibiting the JAK/STAT3 pathway

Purpose: Chronic inflammation in the liver is a key trigger for liver injury and fibrosis in various liver diseases. Given the anti-inflammatory and antioxidant effects of Saffron, this study aimed to investigate the pharmacological effects of Saffron on hepatic inflammation and fibrosis. Methods: The mice model of hepatic fibrosis was constructed using CCl4, and Saffron was administered at low (10 mg/kg) and high (20 mg/kg) doses by gavage. Then, the changes in liver function, liver inflammation and fibrosis markers were evaluated. The effects and mechanisms of Saffron on hepatic stellate cells were further investigated in in-vitro experiments. Results: Saffron improved liver function, reduced liver inflammation and attenuated liver fibrosis in a dose-dependent manner in hepatic fibrosis mice. Furthermore, Western blotting showed that Saffron significantly inhibited JAK/STAT3 phosphorylation in fibrotic livers. Conclusions: Saffron can attenuate liver fibrosis by inhibiting the JAK/STAT3 pathway and the activation of hepatic stellate cell, providing a theoretical basis for the development of new anti-fibrotic drugs.

Phytochemical and anti-neuropathic investigations of Crocus sativus via alleviating inflammation, oxidative stress and pancreatic beta-cells regeneration / 中草药·英文版

Objective: The aim of this study is to investigate the phytochemical and the long-term anti-neuropathic potentials of Crocus sativus cultivated in the University botanical garden, and explore its most bioactive compounds and their underlying mechanisms of action. Methods: Phytochemical analysis and bio-guided isolation-procedures including RP-HPLC and 1H and 13C NMR utilizing biological models of diabetes, inflammation, and diabetic-neuropathy were used. Cultivated saffron (S-RCED) and Spanish-saffron stigma (S-SP) alone or in combination with Camellia sinus (CS) were investigated. Results: The RP-HPLC analyses showed the presence of picrocrocin, crocin I, crocin II, crocin I’, crocin II’, and safranal (SAF) in both S-SP and S-RCED extracts with higher-concentrations. It had been shown that SAF was the most bioactive-compound in Crocus sativus. Both S-SP and S-RCED possessed significant (P < 0.05) anti-diabetic activities in acute (6 h), subchronic (8 d) and chronic (8 weeks) models. S-RCED had been proven with more hypoglycemic potentials when compared to S-SP and SAF. S-SP, S-RCED, and SAF produced significant anti-inflammatory and anti-nociceptive activities against carrageenan-induced inflammatory, hyperalgesic and tactile diabetic-neuropathy models, respectively. S-SP, S-RCED, and SAF elevated serum catalase, reduced glutathione, and insulin serum levels, ameliorated lipid peroxidation and HbA1c levels, and histopathologically regenerated the pancreatic beta-cells. Combinations with CS showed more significant efficacy than the single component. Conclusion: The oxidative stress reduction, insulin secretagogue, and pancreatic beta-cells regeneration potentials might be responsible for the mechanism underlying the anti-diabetic, anti-inflammatory and anti-diabetic neuropathy activities. Thus, the cultivated Crocus sativus might be clinically useful for protecting against many serious-disorders.

Curcuma Longa Abolishes Phenylephrine-Induced Contractions in Isolated Aortic Artery of Rats

Curcuma longa has biological effects. Its cardiovascular activities are yet to be scientifically studied. Objectives: To investigate the vasorelaxant effects of the aqueous extract of Curcuma longa (AECL). Methods: Aortic annuli of normotensive rats, with or without endothelium, were set up in a data storage system with nutrient solution in recipients, with scientifically recommended temperature, aeration and tension. Over contraction by Phenylephrine, the AECL (1, 3, 10, 30, 100, 300 and 1000 µg/mL) was incubated before and after incubation with atropine or L-name or indomethacin. An AECL concentration-response curve was also built over contractions caused by elevation of extracellular K+. Data were significant when p < 0.05, with GraphPad Prism 6.0 software resolutions. Results: The AECL induced 100% vasorelaxation also in the endothelium-free annuli. The part of the endothelium-dependent effect had EC50 = 4.32 ± 0.05 µg/mL. With inhibition of NO production, the EC50 increased to 126.50 ± 2.35 µg/mL; after inhibition of prostacyclin production, to 124.6 ± 0.05 µg/mL; and after muscarinic blockade, to 437.10 ± 0.2 µg/mL. Opening of K+ channels (relaxation of 56.98%) and VOCC blockade (relaxation of 31.56%) were evident. Conclusion: AECL induced significant vasorelaxation, being more significant in the presence of endothelium. The muscarinic pathway seems to be the main one involved in this effect, followed by the NO production and prostacyclin pathways. The activity in K+ channels by AECL was more significant than its VOCC blockade. The use of other models and tools to study action mechanisms will be important and elucidating

The effects of different concentrations of crocin on receptor activator of nuclear factor kappa B ligand(RANKL)–induced osteoclastogenesis / 天津医药

Objective To investigate the effects of different concentrations of crocin on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis using the monocyte-macrophage cell line RAW264.7. Methods The monocyte-macrophage cell line RAW264.7 was cultured routinely.After treatment with 0,6.25,12.5,25, 50,100,200 and 400 μmol/L crocin,cell counting kit-8(CCK-8)assay was used to analyze the viability of RAW264.7 cells to screen out the appropriate experimental concentration. RAW264.7 cells were induced by RANKL (100 ng/L) to form osteoclasts. After treated with 0, 12.5, 50 and 100 μmol/L crocin respectively, the number of osteolasts was counted by tatrate resistant acid phosphatasec (TRAP) staining. Real-time PCR was used to detect the mRNA expression levels of calcitonin receptor(CTR),nuclear factor of active T cells 1(NFATC1),C-fos and TRAP.Results No significant effects of crocin (within 0-100 μmol/L) were found on the viability of RAW264.7 cells (P>0.05). However, When crocin concentration was over 100 μmol/L,the cell proliferation was decreased,and which showed a significant inhibitory effect on proliferation (P<0.05). Thus, 0-100 μmol/L crocin was selected as the experiment concentration. The amount of differentiated osteolasts and the expression levels of CTR,NFATC1,C-fos and TRAP mRNA were decreased significantly with the increased concentrations of crocin(P<0.05).Conclusion At a certain concentration(0-100 μmol/L),the higher levels of crocin could inhibit RANKL-induced osteoclastogenesis.

Research progress of chemical components and pharmacological effects of non-medicinal parts of Crocus sativus / 中国中药杂志

The dried stigma of Crocus sativus (saffron) is a world&s precious spice and traditional medicine possessing plenty of pharmacological effects. Because the stigma represents only 7.4% of total weight of the fresh flower, when the stigma is separated from the flowers, large quantities of floral bio-residues are discarded. Accordingly, the utilization of the non-medicinal parts of saffron has drawn people&s attention. Studies showed that the non-medicinal parts of saffron were rich in flavonoids, phenolic acids, polysaccharides, et al. They were proved to have some pharmacological activities, such as antioxidant activity, antifungal activity, cytotoxicity, anti-inflammation and liver protection. The paper is to review the current research progress on the chemical components and pharmacological effects of the non-medicinal parts of saffron, which can serve as a reference for the further research and development of non-medicinal parts of saffron.

A real-time fluorescence quantitative PCR method for source identification of Crocus sativus and Carthamus tinctorius / 中国中药杂志

The specific PCR primer was designed base on ITS2 sequence in GenBank, and we developed a SYBRGreen real-time fluorescence quantitative PCR system for identification of Crocus sativus and Carthamus tinctorius source. Compared with Chinese herbal medicine DNA barcode technique, this method showed characteristics of shorter time, higher specificity and sensitivity. Using this method to detect 15 samples, 4 were C. sativus, 8 were C. tinctorius, and the other 3 samples were none of them. The result was in accordance with Chinese herbal medicine DNA barcode. This study lays the foundation for identification of related Chinese medical materials.

Neuroprotective effects of saffron on chronic focal cerebral ischemia through inhibiting glial scar formation in rats / 中国药理学与毒理学杂志

OBJECTIVE To explore the neuro-protective effects of saffron (Crocus satius L.) on chronic focal cerebral ischemia in rats.METHODS SD rats were randomly divided into 6 groups:sham control group,MCAO group,edaravone group and saffron 30,100,300 mg·kg-1groups.Focal cerebral ischemia was induced by middle cerebral artery occlusion(MCAO).Saffron was administered orally by once daily from 2 h to 42 d after ischemia. At 42 d after cerebral ischemia, neurological deficit score, spontaneous activity test,elevated plus maze test,marble burying test and novel objective recognition test were used to evaluate the effects of saffron on the behevioural change. Infarct volume, survival neuron density, activated astrocyte number, and the thickness of glial scar were also detected. GFAP expression and inflammatory cytokine contents in ischemic peripheral region were detected by Western blot and ELISA,separately.RESULTS Saffron(100,300 mg·kg-1)improved the body weight decrease, neurological deficit and spontaneous activity. Saffron (30-300 mg·kg- 1) increased the traveled distance ratio and total time in open arm, decreased the buried marble number, which indicated that saffron could ameliorate anxiety- and depression-like behaviors. Saffron (100, 300 mg·kg-1)improved the learning and memory function,which manifested by increased discrimination ratio(DR)and discrim-ination index (DI) in T2test. The results of toluidine blue found saffron treatment (100, 300 mg·kg-1) decreased the infarct volume and increased the neuron density in cortex and hippocampal.The activated astrocyte number,the thickness of glial scar and GFAP expression in ischemic peripheral region decreased after saffron. Saffron (100, 300 mg·kg-1) decreased the contents of IL-6 and IL-1β, increased the content of IL-10 in ischemic peripheral region.CONCLUSION Saffron exerted neuro-protective effects on chronic focal cerebral ischemia,which could be related with inhibiting the activation of astrocyte and glial scar,following with the decrease of inflammatory reaction.

Effect of extraction of saffron crocus on mitochondrial dynamics in ischemia/reperfusion rats / 中国药理学通报

Aim To investigate the protection mecha-nism of the extraction of the saffron crocus in ischemia/reperfusion rats. Methods Hematoxylin-eosin stai-ning, electron microscopy, and neurological assess-ments were performed in a transient middle cerebral ar-tery occlusion ( tMCAO ) rat model. The role of dy-namin-related protein 1 ( Drp1 ) and optic atrophy 1 ( Opa1 ) , the two key regulators of mitochondrial fis-sion and fusion in ischemic brain damage in vivo were observed. Results In ischemia/reperfusion rats, the extraction of the saffron crocus increased the level of protein Opa1 and decreased the level of protein Drp1 . Conclusions Inhibition of Drp1 and promotion of Opa1 , which means to maintain balancing mitochondri-al dynamics, is proposed as an efficient strategy for neuroprotection against ischemic brain damage.

Research progress on biosynthetic pathway of apo-carotenoids in Crocus sativus / 中草药

The apo-carotenoid compounds represented by crocins are the main medicinal components of Crocus sativus, which have extensive anti-oxidation, anti-inflammatory, anti-atherosclerosis, anticancer, antidepressant, and other pharmacological activities. Biosynthetic pathways of apo-carotenoids in C. sativus include the traditional upstream route of the synthesis of geranylgeranyl pyrophosphate to zeaxanthin starting from mevalonate, and downstream pathway for the specific synthesis of crocetin and crocin by cleavage of zeaxanthin. This article reviews the recent research of key enzymes involved in the metabolism of apo-carotenoids in C. sativus, which facilitates further analysis of downstream pathways for the synthesis of apo-carotenoid derivatives such as crocin, and further provides a theoretical basis for the use of metabolic engineering methods to increase the production of crocins and other pharmacodynamic substances.

Cardioprotective Effect of Crocin Combined with Voluntary Exercise in Rat: Role of Mir-126 and Mir-210 in Heart Angiogenesis / Efeito Cardioprotetor de Crocina Combinado com Exercício Voluntário em Ratos: Papel do Mir-126 e Mir-210 na Angiogênese Cardíaca

Abstract Background: Crocin is reported to have a wide range of biological activities such as cardiovascular protection. Recent epidemiologic studies have shown that exercise reduces cardiovascular morbidity and mortality in the general population. Objective: The aim of this study was to evaluate the effect of crocin and voluntary exercise on miR-126 and miR-210 expression levels and angiogenesis in the heart tissue. Methods: Animals were divided into 4 groups: control, exercise, crocin, and exercise-crocin. Animals received oral administration of crocin (50 mg/kg) or performed voluntary exercise alone or together for 8 weeks. Akt, ERK1/2 protein levels, miR-126 and miR-210 expression were measured in the heart tissue. Immunohistochemical method was used to detect CD31 in the heart tissue. Results: Akt and ERK1/2 levels of the heart tissue were higher in crocin treated group and voluntary exercise trained group after 8 weeks. Combination of crocin and exercise also significantly enhanced Akt and ERK1/2 levels in the heart tissue. MiR-126, miR-210 expression and CD31 in the heart increased in both crocin and voluntary exercise groups compared with control group. In addition, combination of exercise and crocin amplified their effect on miR-126 and miR-210 expression, and angiogenesis. Conclusion: Crocin and voluntary exercise improve heart angiogenesis possibly through enhancement of miR-126 and miR-210 expression. Voluntary exercise and diet supplementation with crocin could have beneficial effects in prevention of cardiovascular disease.

Resumo Fundamentos: A crocina tem uma vasta gama de atividades biológicas, tais como a proteção cardiovascular. Estudos epidemiológicos recentes demonstraram que o exercício reduz a morbidade e a mortalidade cardiovasculares na população em geral. Objetivo: O objetivo deste estudo foi avaliar o efeito da crocina e do exercício voluntário nos níveis de expressão miR-126 e miR-210 e na angiogênese no tecido cardíaco. Métodos: Os animais foram divididos em 4 grupos: controle, exercício, crocina e exercício-crocina. Os animais receberam a administração oral de crocina (50 mg/kg) ou realizaram exercício voluntário sozinhos ou em conjunto durante 8 semanas. Os níveis de proteína Akt, ERK1/2, e a expressão de miR-126 e miR-210 foram medidos no tecido cardíaco. O método imunohistoquímico foi utilizado para detectar CD31 no tecido cardíaco. Resultados: Os níveis de Akt e ERK1/2 do tecido cardíaco foram maiores no grupo tratado com crocina e no grupo de exercício voluntário após 8 semanas. A combinação de crocina e exercício também aumentou significativamente os níveis de Akt e ERK1/2 no tecido cardíaco. A expressão de MiR-126, miR-210 e CD31 no coração aumentou tanto em no grupo de crocina como no grupo de exercício voluntário em comparação com o grupo de controle. Além disso, a combinação de exercício e crocina amplificou seu efeito na expressão de miR-126 e miR-210 e angiogênese. Conclusão: A Crocina e o exercício voluntário melhoram a angiogênese cardíaca possivelmente através do aumento da expressão de miR-126 e miR-210. O exercício voluntário e a suplementação dietética com crocina podem ter efeitos benéficos na prevenção de doenças cardiovasculares.

Study on specific chromatograms of Crocus sativus and authenticity identification / 中草药

Objective: To establish the method for the specific chromatograms analysis of Crocus sativus, so as to distinguish the active constituents between saffron and gardenia. Methods: HPLC with ZorBax XDB-C18 column was used, the mobile phase was a linear gradient of methanol containing 0.5% acetic acid and water containing 0.5% acetic acid in 45 min, the detection wavelength was set at 254 nm and the flow-rate was 1.0 mL/min. Results: Multi batches of samples were analyzed to establish the specific chromatograms. Eight marked peaks were separated. The methodological evaluation showed that the method had a good repeatability. The active constituents between saffron and gardenia could be significantly distinguished by this method. Conclusion: The method is simple, rapid, and accurate with good reproducibility and can be used for the quality control and identification of C. sativus.

Rapid molecular identification of saffron (Crocus sativus L.) based on specific PCR / 中国药学杂志

OBJECTIVE: To establish a rapid molecular method for identifying saffron (Crocus sativus L.) and its adulterants by PCR: amplification using specific primers and fluorescent dyes detection. METHODS: The chloroplast barcode was sequenced and analyzed to find the SNPs between saffron and its adulterants. Specific primers were designed for the SNPs, the PCR reaction systems were built and optimized, and fluorescent dyes method was used to identify PCR products. RESULTS: A 421 bp saffron identification band based on the psbA-trnH barcode sequence was screened when 100 × SYBR Green I was added into the optimized PCR product under the following condition; initial denaturation at 90℃ for 1 min, denaturation at 90℃ for 5 s, annealing at 58℃ for 5 s, 26 cycles; the saffron (Crocus sativus L.) showed strong green fluorescence under 365 nm UV lamp whereas adulterants did not. CONCLUSION: Fast site-specific PCR can rapidly identify saffron and its adulteration.

Effect of saffron (Crocus sativus L.) on sodium valporate induced cytogenetic and testicular alterations in albino rats / 대한해부학회지

The present study investigated the cytogenetic and testicular damage induced by the antiepileptic drug, sodium valporate (SVP) in albino rats and the effect of saffron aqueous extracts. Treating rats with SVP caused a significant increase in the chromosomal aberrations either structural or numerical and decreased the mitotic index. Besides, animals administered SVP showed DNA damage appeared in the single strand breaks (comet assay). Testis of SVP-treated rats showed many histopathological changes. A significant decrease in seminiferous tubules and their epithelial heights diameters and inhibition of spermatogenesis was recorded. In addition, the number of sperm head abnormalities was increased. Biochemical results revealed an increase in malondialdhyde (MDA) which is lipid peroxidation marker and a significant decrease in the level of serum antioxidant enzyme, catalase (CAT) and reducing antioxidant power (RAP). Animals given SVP and saffron showed an improvement in chromosomal aberrations, mitotic index, DNA damage and testicular alterations caused by SVP. Moreover, MDA decreased and CAT and RAP increased. It is concluded from the present results that the ameliorative effects of saffron extract against SVP-induced cytogenetic and testicular damage in albino rats may be due to the presence of one or more antioxidant components of saffron.

Research progress on chemical constituents of Crocus sativus and their pharmacological activities / 中草药

Crocus sativus (saffron), widely used in food industry as coloring or flavoring agent, is widely cultivated in Iran and other countries, such as Greece, Italy, Spain, India, China, and Japan. But modern pharmacological studies have shown its potential to promote health. In this paper, chemical constituents and pharmacological activities of saffron are systematically reviewed. More than 100 compounds were isolated from saffron, primarily including terpenes, flavonoids, anthraquinones and so on. Pharmacological references showed that it had the treatment effects on diseases, such as mental disorder, neurodegenerative disease, learning and memory dysfunctions, cardiovascular disease, atherosclerosis, hyperlipidemia, diabetes, hypertension, ulcer, fatty liver, epilepsy, and convulsions. This review provides a reference for the further research and development of saffron.

Molecular identification of viral pathogens in Crocus sativus / 中草药

Objective: To investigate the viral pathogens in cultivated Crocus sativus. Methods: Viral pathogen identification was carried out by the observation of virus particle morphology and cytopathology as well as the detection of DAS-ELISA, RT-PCR, and sequencing. Results: Linear virus particles of 600-900 nm in length were observed in C. sativus by negative staining under transmission electron microscope (TEM). Bundles of linear virus particles, cylindrical inclusion bodies of subdivision II, and amorphous inclusion bodies were observed in the cells of C. sativus under TEM after ultrathin-section. These observations resembled the cytopathology of infectious Bean yellow mosaic virus (BYMV). Positive result of DAS-ELISA was obtained from the leaves of C. sativus by using monoclonal antiserum against BYMV capsid protein. Positive result of RT-PCR induced by the Potyvirus specific primers (Sprimer and M4) was also obtained. Sequencing after RT-PCR revealed that the viral sequence in this diseased C. sativus had a homology of 99% with the BYMV sequence. Conclusion: The pathogenic virus of this C. sativus disease is identified as BYMV.

Web of science-based visual analysis of citations in papers on saffron crocus / 中华医学图书情报杂志

The distribution of years, active regions, high production authors and core journals in papers on saffron crocus was analyzed using HistCite.The main methods in research of saffron crocus were described according to its chronological chart generated by the Pajek-generated matrix with its development history revealed.

Studies on the Pharmacological Effects of Crocus(Crocus sativus LINNE). Changes in Prostaglandin Levels, Platelet Aggregation, Blood Viscosity and Laboratory Data throughout the Menstrual Cycle / 日本東洋医学雑誌

In order to determine the pharmacological effects of Crocus (traditionally classified as an herb helpful in eliminating Blood Stagnation), the 11-dehydro TXB₂, platelet aggregation, blood viscosity and laboratory data of 12 healthy sexually mature females were examined during the menstrual, follicle and corpus luteum phases before the test substance was administered. Compared with the follicle or corpus luteum phases, higher levels of 11-dehydro TXB₂ and increased mean cell volume (MCV) were found during the menstrual phases. This suggested that the increase in blood viscosity may be due to a lowering of erythrocyte deformation resulting from increased mean cell volume. From the fact that the highest endometrial PGE₂ value was exhibited during the menstrual Phase, PGE₂ was thought to be involved in the MCV increase. Next, plain hot water was administered to the six cases in the control group (for four weeks), and Crocus infusion administered to the other six cases (for four weeks), after which a comparative study was made of their indicators. The significant lowering of the MCV and blood viscosity during the menstrual phase upon Crocus administration suggested that an improvement in erythrocyte deformation brought about by decreased MCV played a role in the reduction of blood viscosity. Moreover, a decrease in 11-dehydro TXB₂ was observed during the low blood estrogen follicle phase. It has been reported that there is an overall increase in blood viscosity and acceleration of platelet and thrombin synthesis associated with the disease state known as “Blood Stagnation”. From the clear effects of Crocus upon these indicators, its effectiveness as an herb useful in eliminating Blood Stagnation in healthy sexually mature females was indicated.

HPLC fingerprint analysis of Crocus sativus L. and comparative study on its different sources / 中成药

AIM: To establish the method of fingerprint analysis of Crocus sativus L. and compare their HPLC-FPS of eight kinds of Crocus sativus L. from different sources. METHODS: HPLC with ZORBAX SB-C 18 column was used, the mobile phase was a linear gradient of methanol containing 1% acetic acid and water containing 1% acetic acid in 40min, the detection wavelength at 312nm. RESULTS: 12 marker peaks were separated. The methodological evaluation showed that the method had a good repeatability, and the marker peak area ratio of different samples were different. CONCLUSION: This method is simple and accurate with good reproducibility and can be used for a quality control for Crocus sativus L.