PMID: 

J Affect Disord. 2018 05 ;232:349-357. Epub 2018 Feb 26. PMID: 29510352

Abstract Title: 

affron, a standardised extract from saffron (Crocus sativus L.) for the treatment of youth anxiety and depressive symptoms: A randomised, double-blind, placebo-controlled study.

Abstract: 

BACKGROUND: Saffron has antidepressant and anxiolytic effects in adults with mild-to-moderate depression. However, this is the first study examining its mood-related effects in teenagers.METHODS: In this 8-week, randomised, double-blind, placebo-controlled study, youth aged 12-16 years, with mild-to-moderate anxiety or depressive symptoms were given tablets containing placebo or a saffron extract (affron, 14 mg b.i.d). The youth and parent versions of the Revised Child Anxiety and Depression Scale (RCADS) were used as outcome measures.RESULTS: 80 participants were enrolled and 68 completed the study. Based on youth self-reports, affronwas associated with greater improvements in overall internalising symptoms (p = 0.049), separation anxiety (p = 0.003), social phobia (p = 0.023), and depression (p = 0.016). Total internalising scores decreased by an average of 33% compared to 17% in the placebo group (p = 0.029). However, parental reports of improvements were inconsistent as mean improvements in RCADS scores were greater in the saffron group (40% vs 26%) (p = 0.026), although no other significant differences were identified. affronwas well-tolerated and there was a trend of reduced headaches in participants on the active treatment.LIMITATIONS: The use of a self-report instrument, limited study duration, single treatment dose, and non-clinical sample used in this study limit the generalisability of study findings.CONCLUSION: The administration of a standardised saffron extract (affron) for 8 weeks improved anxiety and depressive symptoms in youth with mild-to-moderate symptoms, at least from the perspective of the adolescent. However, these beneficial effects were inconsistently corroborated by parents.

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PMID: 

J Res Med Sci. 2018 ;23:16. Epub 2018 Feb 20. PMID: 29531568

Abstract Title: 

The effect of saffron (L.) hydroalcoholic extract on metabolic control in type 2 diabetes mellitus: A triple-blinded randomized clinical trial.

Abstract: 

Background: Metabolic control is a major concern in preventing diabetic complications. Saffron as a natural source of antioxidants could play a role in alleviating diabetes insults. The aim of this study was to investigate effect of saffron hydroalcoholic extract on metabolic control in type 2 diabetes (T2D) mellitus.Materials and Methods: This randomized triple blind study was included 54 T2D patients which randomly received either saffron (Group 1) or placebo (Group 2) twice daily other than routine antidiabetic treatments for 8 weeks. Serum concentration of fasting blood sugar (FBS), 2-h plasma glucose, hemoglobin A1c (HbA1c), total cholesterol, triglyceride (TG), low-density lipoprotein, and high-density lipoprotein were measured as the markers of metabolic control. Anthropometric measures and blood pressure were also measured at the baseline, every 2 weeks during the intervention and the end of the study. Data analyzed using repeated measure analysis of variance test.Results: The baseline metabolic parameters were the same in two group (>0.01). FBS serum level significantly decreased within 8 weeks in the saffron group (128.84± 31.86) as compared to the placebo (153.76 ± 41.23), (0.01).Conclusion: Saffron hydroalcoholic extract may improve blood glucose control by reducing FBS in T2D patients. However, saffron extract has no significant effect on other aspects of diabetic control in diabetic patients.

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PMID: 

Saudi J Biol Sci. 2018 May ;25(4):747-754. Epub 2016 Oct 13. PMID: 29740240

Abstract Title: 

Antifibrotic effects of crocin on thioacetamide-induced liver fibrosis in mice.

Abstract: 

Liver fibrosis is a major health concern that results in significant morbidity and mortality. Up-to-date, there is no standard treatment for fibrosis because of its complex pathogenesis. Crocin is one of the main nutraceuticals isolated from the stigma ofwith antioxidant and anti-inflammatory activities. The current study aimed at evaluating the potential antifibrotic activity of crocin against thioacetamide (TAA)-induced liver fibrosis in mice as well as the underlying mechanism using silymarin as a reference antifibrotic product. Crocin at two doses (25 and 100 mg/kg) significantly ameliorated the rise in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and total bilirubin (TB). Further, the high dose significantly protected against the increase in serum total cholesterol (TC) and triglycerides (TG). These effects were confirmed by light microscopic examinations. Crocin antioxidant activities were confirmed by the observed inhibition of reduced glutathione depletion (GSH), super oxide dismutase (SOD) exhaustion and malondialdehyde (MDA) accumulation in liver tissue. The antifibrotic effects of crocin were explored by assessing fibrosis related gene expression. Administration of crocin (100 mg/kg) hampered expression of tumor growth factor-β (TGF-β), α alpha smooth muscle actin (α-SMA) and collagen 1-α expression and significantly raised gene expression of matrix metalloproteinase-2 (MMP-2). Further,it reduced protein expression of nuclear factor-κB (NF-κB) and cyclooxygenase-2 (COX-2) as assessed immunohistochemically. These anti-inflammatory effects were confirmed by the observed protein expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Thus, it can be concludedthat crocin protects against TAA-induced liver fibrosis in mice. This can be ascribed, at least partly, to its antioxidant and anti-inflammatory effects.

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PMID: 

Neuropsychiatr Dis Treat. 2018 ;14:1297-1305. Epub 2018 May 21. PMID: 29849461

Abstract Title: 

Comparative efficacy and safety ofL. for treating mild to moderate major depressive disorder in adults: a meta-analysis of randomized controlled trials.

Abstract: 

Purpose: To investigate the efficacy and safety of saffron in the treatment of major depressive disorder (MDD) in comparison to placebo and synthetic antidepressants.Patients and methods: We conducted a systematic search in several electronic databases as well as manual search in bibliographies of relevant studies. We included randomized controlled trials that investigated the efficacy and safety of saffron for treating MDD in adults in comparison to either placebo or synthetic antidepressants. Primary outcome was change in scores on depressive symptoms from baseline. Secondary outcomes included remission rate, response rate, and drop-out rate for all reasons. We chose a random-effects model in order to obtain more conservative results. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated as the overall effect index by inverse variance models.Results: Seven studies were included in this meta-analysis. Overall quality of these included studies was moderate. As for the primary outcome, saffron showed more improvements in depression symptoms when compared with placebo, with an SMD of -1.22 (95% CI -1.94, -0.49,=0.001). Meanwhile, saffron was as effective as synthetic antidepressants, with an SMD of 0.16 (95% CI -0.25, 0.57,=0.44). Moderate heterogeneity existed in our analysis. Through subgroup analyses, we found that treatment dosage and duration, types of synthetic antidepressants administered in the comparison group, and outcome measures could explain most of the variance. No differences were found in remission rate, response rate, or drop-out rate.Conclusion: Saffron was effective in the treatment of MDD and had comparable efficacy to synthetic antidepressants. Saffron was also a safe drug without serious adverse events reported.

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PMID: 

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2018 Feb 8 ;34(2):173-176. PMID: 29926685

Abstract Title: 

[Effect of saffron aqueous extract on the level of blood glucose in experimental diabetes mice].

Abstract: 

OBJECTIVES: To investigate the effects of saffron aqueous extract (SE) on blood glucose, lipid and pancreatic tissue in streptozocin-induced diabetes mice.METHODS: Diabetes mellitus mice were established by intraperitoneal injection of streptozocin (60 mg/kg) for two consecutive days. The 30 well-established diabetes mice were randomly divided into three groups(=10):diabetic mellitus (DM) group, SE treated (SE) group and positive control (metformin hydrochloride, MH) group. Another ten normal mice were selected as normal control (NC) group. The mice in SE and MH groups were intragastrically administered with SE 100 mg/kg or MH 100 mg/kg once a day for 6 weeks, mice in DM and NC were given normal saline. The amount of food-intake, water consumption and body weight were measured weekly, the changes of the indicators including fasting blood glucose (FBG), oral glucose-tolerance test (OGTT), glycated serum protein (GSP), insulin (INS) and blood lipid were determined after 6 weeks of continuous administration. The pathologic changes in the pancreas tissues were detected by HE staining.RESULTS: Compared with the normal control group, the amount of food-intake, water consumption, area under the curve, FBG, GSP, and total cholesterol (TC) were significantly increased, while fasting weight, INS and high density lipoprotein cholesterol (HDL-c) were dramatically decreased in DM group. Compared with DM group, the water consumption, FBG, area under the curve and TC in SE group were starkly declined with a notable elevation of HDL-c and INS. In addition, the biopsy from DM mice showed the structure of pancreas islet was destroyed and reduced, and vascular proliferation with irregular shape. The damaged pancreas was obviously repaired by giving SE.CONCLUSIONS: The saffron aqueous extract had efficacy on blood glucose and blood lipids reduction, improvement on damaged pancreas in streptozocininduced diabetic mice, which suggested that saffron could be used for the treatment in diabetes.

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PMID: 

Phytomedicine. 2009 Aug ;16(8):694-702. Epub 2009 Apr 24. PMID: 19394208

Abstract Title: 

Protective effects of purified safflower extract on myocardial ischemia in vivo and in vitro.

Abstract: 

Carthamus tinctorius L. (safflower) is one of the most commonly used Chinese herbal medicines to prevent and treat cardiac disease in clinical practice. However, the mechanisms responsible for such protective effects remain largely unknown. In this study, we investigated the anti-myocardial ischemia effects of a purified extract of C. tinctorius (ECT) both in vivo and in vitro. An animal model of myocardial ischemia injury was induced by left anterior descending coronary artery occlusion in adult rats. Pretreatment with ECT (100, 200, 400, 600 mg/kg body wt.) could protect the heart from ischemia injury by limiting infarct size and improving cardiac function. In the in vitro experiment, neonatal rat ventricular myocytes were incubated to test the direct cytoprotective effect of ECT against H(2)O(2) exposure. Pretreatment with 100-400 microg/ml ECT prior to H(2)O(2) exposure significantly increased cell viability as revealed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. ECT also markedly attenuated H(2)O(2)-induced cardiomyocyte apoptosis, as detected by Annexin V and PI double labeling with flow cytometry. The intracellular level of reactive oxygen species (ROS) was shown by 2',7'-dichlorofluorescin diacetate (DCFH-DA), and ECT pretreatment significantly inhibited H(2)O(2)-induced ROS increase. We made a preliminary examination of the signaling cascade involved in ECT mediated anti-apoptotic effects. Phosphatidylinositol 3 kinase (PI3K) inhibitor (LY294002) blocked the cytoprotective effect conferred by ECT. Taken together, our findings provide the first evidence that the cardioprotective effects of ECT in myocardial ischemia operate partially through reducing oxidative stress induced damage and apoptosis. The protection is achieved by scavenging of ROS and mediating the PI3K signaling pathway.

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PMID: 

Phytother Res. 2010 Jul ;24(7):1037-41. PMID: 19960423

Abstract Title: 

Carthamus tinctorius flower extract prevents H2O2-induced dysfunction and oxidative damage in osteoblastic MC3T3-E1 cells.

Abstract: 

The flowers of Carthamus tinctorius L. (Compositae) have been widely used for enhancing blood circulation and postmenopausal disorder in women. In the present study, the potential protective effects of C. tinctorius flower extract (CFE) against reactive oxygen species (ROS) induced osteoblast dysfunction were investigated using osteoblastic MC3T3-E1 cells. The osteoblast function was assessed by measuring alkaline phosphatase activity, collagen content, calcium deposition, and RANKL production, and the oxidative status was assessed by measuring intracellular lipid peroxidation, and protein oxidation in osteoblastic MC3T3-E1 cells. A significant reduction in the alkaline phosphatase activity, collagen, and calcium deposition and an increase in the production of receptor activator of nuclear factor-kB ligand (RANKL) were observed after 0.3 mM H(2)O(2) addition. The H(2)O(2)-induced alterations were prevented by pre-incubating the osteoblasts with 2-10 microg/ml CFE for 48 h. When the oxidative stress was induced by H(2)O(2), the increased production of protein carbonyl and malondialdehyde was also reduced at the same CFE concentration. These results demonstrate that C. tinctorius flower can act as a biological antioxidant in a cell culture experimental model and protect osteoblasts from oxidative stress-induced toxicity.

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PMID: 

J Ethnopharmacol. 2010 Aug 9 ;130(3):505-13. Epub 2010 Jun 9. PMID: 20538053

Abstract Title: 

Carthamus tinctorius L. prevents LPS-induced TNFalpha signaling activation and cell apoptosis through JNK1/2-NFkappaB pathway inhibition in H9c2 cardiomyoblast cells.

Abstract: 

AIM OF THE STUDY: Severe and potentially fatal hypotension and cardiac contractile dysfunction are common symptoms in patients with sepsis. In our previous study, we found that estradiol and estrogen-receptor alpha have cardio-protective effects in myocardial cells exposed to LPS. Estradiol supplementation has been shown to induce breast and cervical cancers. Flos Carthami, the flower of Carthamus tinctorius L. (Compositae) is an important traditional Chinese medicine used for the treatment of heart disease and inflammation, and therefore might be a potential alternative to Estradiol in the prevention of heart damage. This study investigated the effect of Flos Carthami (FC(EtOH)) ethanolic extract on LPS-induced apoptosis in H9c2 cardiomyoblast cells.MATERIALS AND METHODS: H9c2 cells induced apoptosis with LPS administration (1 microg/mL). H9c2 cells were divided into five groups: Control, LPS (1 microg/mL), and three FC(EtOH) (31.25, 62.5,and 125 microg/mL). We detected apoptosis using MTT, LDH, TUNEL assay. JC-1 staining and Western blot were used to detect pro-apoptosis proteins, anti-apoptosis proteins, MAPK proteins (JNK, ERK, and P38), and NFkappaB expression.RESULTS: FC(EtOH) (62.5 microg/mL) inhibited LPS-induced apoptosis by suppressing JNK1/2 activity, which resulted in the reduction of both IkappaB degradation and NFkappaB activation. In addition, FC(EtOH) led to the activation of anti-apoptotic proteins, Bcl-2 and Bcl-xL, the stabilization of the mitochondria membrane and the down-regulation of extrinsic and intrinsic pro-apoptotic proteins, such as TNFalpha, active caspase-8, t-Bid, Bax, active caspases-9, and -3.CONCLUSIONS: Carthamus tinctorius L. possesses the ability to suppress JNK activity and inhibit LPS-induced TNFalpha activation and apoptosis in H9c2 cardiomyoblast cells. Carthamus tinctorius L could potentially serve as a cardio-protective agent against LPS-induced apoptosis.

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PMID: 

J Ethnopharmacol. 2011 Jan 27 ;133(2):524-30. Epub 2010 Oct 20. PMID: 20969944

Abstract Title: 

Anti-inflammatory action of methanol extract of Carthamus tinctorius involves in heme oxygenase-1 induction.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: The methanol extracts of Carthamus tinctorius (MEC) have long been used in traditional medicine as anti-inflammatory agent, however, the molecular mechanism by which MEC shows anti-inflammatory action is not investigated.AIM OF THE STUDY: Induction of heme oxygenase-1 (HO-1) by many medicinal herbs has been reported excellent anti-inflammatory action. Thus, the aim of the study is to explore whether anti-inflammatory action of MEC is related with HO-1 induction in RAW 264.7 cells.MATERIALS AND METHODS: The present study was designed to investigate as to MEC induces HO-1 expression so that it reduces inflammation by suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in cells activated with lipopolysaccharide (LPS).RESULTS: Expression of HO-1 protein by MEC in macrophages was increased in a concentration- and time-dependent manner. Treatment with MEC significantly inhibited upregulation of both iNOS and COX-2 in LPS-activated macrophages and consequently reduced production of NO and PGE(2), respectively. The reduced expression of iNOS and COX-2 by MEC was reversed by siHO-1 RNA transfection. In addition, NF-E2-related factor (Nrf2) was translocated from cytosol to nucleus by MEC. The binding of NF-κB as well as NF-κB luciferase activity was also significantly diminished by MEC. Finally, tumor necrosis factor (TNF)-α-mediated VCAM-1 expression in endothelial cell was significantly inhibited by MEC.CONCLUSIONS: The present results show that MEC induces HO-1 expression via Nrf2 translocation and inhibits NF-κB activity, which may be responsible for anti-inflammatory action. Therefore, we propose that anti-inflammatory action of MEC involves at least HO-1 induction.

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PMID: 

Phytother Res. 2012 May ;26(5):722-6. Epub 2011 Oct 24. PMID: 22021176

Abstract Title: 

Potentα-glucosidase inhibitors from safflower (Carthamus tinctorius L.) seed.

Abstract: 

As part of the search for naturally derivedα-glucosidase inhibitors, the chemical components isolated from safflower seed (Carthamus tinctorius L.) were evaluated. The compounds active as α-glucosidase inhibitors were serotonin derivatives (e.g. N-p-coumaroyl serotonin (1) and N-feruloyl serotonin (2)). These compounds showed a potent inhibitory activity, the 50% inhibitory concentration (IC(50) ) values were calculated as 47.2 µm (1) and 99.8 µm (2) while that of the reference drugs acarbose and 1-deoxynojirimycin were evaluated as 907.5 µm and 278.0 µm, respectively. Regarding the structure of the serotonin derivative, the existence of the hydroxyl group at 5-position in the serotonin moiety and the linkage of cinnamic acid and serotonin are essential for α-glucosidase inhibitory activities. These results are helpful for the proper use of safflower seed as traditional medicine for the treatment of diabetes, moreover, itcould serve to develop medicinal preparations as supplements and functional foods for diabetes. In particular, the serotonin compounds could be used as a lead compound for a new potential α-glucosidase inhibitor derived from the plant.

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