PMID: 

Eur J Pharmacol. 2019 Jul 6 ;859:172528. Epub 2019 Jul 6. PMID: 31288004

Abstract Title: 

β-Cryptoxanthin induced anti-proliferation and apoptosis by G0/G1 arrest and AMPK signal inactivation in gastric cancer.

Abstract: 

β-Cryptoxanthin has been associated with reduced-risk of some cancers. However, the mechanisms of β-cryptoxanthin still remain unclearly understood in gastric cancer (GC). In this study, we examined the effect of β-cryptoxanthin on AMPK signal in human gastric cancer cells. AGS and SGC-7901 cells were treated with β-cryptoxanthin (0-40 μM) and AGS cells were injected in BALB/c (nu/nu) mice to analyze the effect of β-cryptoxanthin on GC. We found that β-cryptoxanthin induced inhibitory effect on the cell viability in a time- and concentration-dependent manner. The number of migratedcells and protein levels of matrix metalloproteinase (MMP) -2 and MMP-9 were obviously decreased. β-Cryptoxanthin treatment induced G0/G1 arrest, and reduced the expression of Cyclin E, Cyclin D1, cyclin-dependent kinases (CDK) of CDK4 and CDK6, and increased the expression of p53 and p21 in the two GC cells. Additionally, β-cryptoxanthin induced apoptosis and increased the expression of cleaved caspase-3, -8, -9 as well as cytochrome C (cyt C). β-Cryptoxanthin induced AMP-activated protein kinase (AMPK) signal inactivation by the down-regulation of protein kinase A (PKA), p-AMPK, eukaryotic elongation factor 2 kinase (eEF2k). Furthermore, β-cryptoxanthin inhibited tumor growth through suppressing the tumor volume and weight, inducing apoptotic cells. Besides, β-cryptoxanthin induced significant reductions of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF),carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). In conclusion, our data provide the novel evidence to understand the mechanism of anti-pcancer of β-cryptoxanthin and indicate that β-cryptoxanthin can serve as a promising chemopreventive agent against gastric cancer.

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PMID: 

J Nutr. 2019 Jun 18. Epub 2019 Jun 18. PMID: 31212314

Abstract Title: 

Dietaryβ-Cryptoxanthin Inhibits High-Refined Carbohydrate Diet-Induced Fatty Liver via Differential Protective Mechanisms Depending on Carotenoid Cleavage Enzymes in Male Mice.

Abstract: 

BACKGROUND: β-Cryptoxanthin (BCX), a provitamin A carotenoid shown to protect against nonalcoholic fatty liver disease (NAFLD), can be cleaved by β-carotene-15,15'-oxygenase (BCO1) to generate vitamin A, and by β-carotene-9',10'-oxygenase (BCO2) to produce bioactive apo-carotenoids. BCO1/BCO2 polymorphisms have been associated with variations in plasma carotenoid amounts in both humans and animals.OBJECTIVES: We investigated whether BCX feeding inhibits high refined-carbohydrate diet (HRCD)-induced NAFLD, dependent or independent of BCO1/BCO2.METHODS: Six-week-old male wild-type (WT) and BCO1-/-/BCO2-/- double knockout (DKO) mice were randomly fed HRCD (66.5% of energy from carbohydrate) with or without BCX (10 mg/kg diet) for 24 wk. Pathological and biochemical variables were analyzed in the liver and mesenteric adipose tissues (MATs). Data were analyzed by 2-factor ANOVA.RESULTS: Compared to their respective HRCD controls, BCX reduced hepatic steatosis severity by 33‒43% and hepatic total cholesterol by 43‒70% in both WT and DKO mice (P 

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PMID: 

Metab Brain Dis. 2019 Jun 18. Epub 2019 Jun 18. PMID: 31214956

Abstract Title: 

Prophylactic neuroprotective propensity of Crocin, a carotenoid against rotenone induced neurotoxicity in mice: behavioural and biochemical evidence.

Abstract: 

Previously we have demonstrated the potential neuroprotective propensity of saffron and Crocin (CR) employing a Drosophila model of Parkinsonism. Rotenone (ROT) has been extensively used as a model neurotoxin to induce Parkinson's disease (PD) like symptoms in mice. In the present study, as a proof of concept we evaluated the efficacy of CR prophylaxis (25 mg/ kg bw/d, 7d) to attenuate ROT(0.5 mg/Kg bw/d,7d) -induced neurotoxic effects in male mice focussing on neurobehavioural assessments and biochemical determinants in the striatum. CR prophylaxis significantly alleviated ROT-induced behavioural alterations such as increased anxiety, diminished exploratory behaviour, decreased motor co-ordination, and grip strength. Concomitantly, we evidenced diminution of oxidative stress markers, enhanced levels of antioxidant enzyme and mitochondrial enzyme function in the striatal region. Further, varying degree of restoration of cholinergic function,dopamine and α-synuclein levels were discernible suggesting the possible mechanism/s of action of CR in this model. Based on our earlier data in flies and in worm model, we propose its use as an adjuvant therapeutic agent in oxidative stress-mediated neurodegenerative conditions such as PD.

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PMID: 

Pharmacol Rep. 2019 Aug ;71(4):746-752. Epub 2019 Apr 16. PMID: 31220735

Abstract Title: 

Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats.

Abstract: 

BACKGROUND: Methotrexate (MTX) is used commonly in the treatment of various cancers and inflammatory diseases; nevertheless, the associated hepatotoxicity has limited its clinical application. Crocin (CRO) is described as a natural carotenoid with analgesic, antioxidant, and antiinflammatory properties. This study aimed to determine the effects of CRO on MTX-induced hepatotoxicity.METHODS: For pretreatment, CRO at doses of 25 and 50 mg/kg (po), as well as 20 mg/kg (ip) of MTX, was injected in rats.RESULTS: MTX led to hepatotoxicity, as confirmed by the significant increase in liver markers, histopathological changes, decreased GSH content, and reduced antioxidant enzyme activity (i.e., CAT, SOD, and GPx). It increased TNF-α, IL-1β, lipid peroxidation, and nitric oxide levels. Nevertheless, by increasing antioxidant defense in hepatic tissues and reducing oxidative stress and proinflammatory mediators, pretreatment with CRO could alleviate hepatotoxicity.CONCLUSION: CRO can inhibit MTX-induced hepatotoxicity through improving antioxidant defense and reducing oxidative stress and inflammation.

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PMID: 

Avicenna J Phytomed. 2019 Jul-Aug;9(4):347-361. PMID: 31309073

Abstract Title: 

Effect of crocin on biochemical parameters, oxidative/antioxidative profiles, sperm characteristics and testicular histopathology in streptozotocin-induced diabetic rats.

Abstract: 

Objective: Chronic hyperglycemia and overproduction of reactive oxygen species (ROS) are strong predictors of the development of reproductive complications of diabetes. The present study was conducted to determine the effects of crocin on biochemical parameters, oxidative stress, and sperm characteristics as well as testes histopathology in diabetic rats.Materials and Methods: Twenty-four rats were divided into the four groups as follows: control, untreated diabetic and two crocin (40 and 60 mg/kg/day)-treated diabetic groups. Diabetes was induced by injection of a single dose of streptozotocin (STZ, 60 mg/kg). Administration of crocin (intraperitoneally) was started three days after STZ injection and was continued until the 28day. At the end of the experiment, rats were anesthetized after weighing. Blood samples and epididymal sperm were subsequently collected to measure biochemical parameters (glucose and lipid profile), total oxidant and antioxidant status (TOS and TAS, respectively), oxidative stress index (OSI), and sperm characteristics (count, motility, and viability); also, testes were dissected out for histopathology examination.Results: Our result indicated that blood glucose, cholesterol, triglyceride, LDL cholesterol levels, as well as TOS, and OSI decreased, but body weight, sperm counts, motility and viability, as well as TAS and HDL levels increased significantly in the crocin-treated diabetic rats (P˂0.05). In testis sections from diabetic rats treated with crocin (40 and 60 mg/kg), seminiferous tubules exhibited normal shape and restoration of testis architecture was observed.Conclusion: Administration of crocin in the present study, ameliorated blood glucose, lipid abnormalities, oxidative stress, sperm characteristics and testis damage in STZ-diabetic rats.

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PMID: 

J Pharmacopuncture. 2019 Jun ;22(2):83-89. Epub 2019 Jun 30. PMID: 31338247

Abstract Title: 

Crocin Improves Oxidative Stress by Potentiating Intrinsic Anti-Oxidant Defense Systems in Pancreatic Cells During Uncontrolled Hyperglycemia.

Abstract: 

Introduction: Oxidative stress (OS) during uncontrolled hyperglycemia has a pivotal role in pancreatic dysfunction. Our study aimed to demonstrate that crocin can potentiate anti-oxidant defense systems of pancreatic cells to improve oxidative stress.Methods: Male Wistar rats were divided randomly into four groups: a normal group, a normal-treated group, a diabetic group and a diabetic-treated group (n = 6 rats per group). Diabetes was induced by a single dose of streptozotocin (45 mg/kg/IV). The treated groups received crocin daily for 8 weeks (40 mg/kg/IP). At the end of the experiment, rats were sacrificed and pancreas tissue was obtained. Subsequently, the concentrations of malondialdehyde (MDA), nitrate and glutathione as well as the enzymatic activities of catalase and superoxide dismutase (SOD) were determined in all animals. Data were analyzed by two-way ANOVA with appropriate post hoc testing and a probability value of P

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PMID: 

Front Pharmacol. 2019 ;10:440. Epub 2019 Apr 30. PMID: 31114499

Abstract Title: 

Orally Administered Crocin Protects Against Cerebral Ischemia/Reperfusion Injury Through the Metabolic Transformation of Crocetin by Gut Microbiota.

Abstract: 

Our pilot study suggested that orally administered crocin was hardly absorbed into circulatory system, but it was effective against cerebral ischemic/reperfusion (I/R) injury. The pharmacologically active component and targeting site of crocin remain elusive. In this study, the cerebral-protective effect of crocin was evaluated on a rat transient middle cerebral artery occlusion (MCAO) model. Our data showed that oral administration of crocin had better effectiveness in cerebral protection than an intravenous injection. Neither crocin nor its metabolite crocetin were determined in the brain of cerebral I/R rats, indicating a target site of periphery. Abundant crocetin was detected in plasma after oral administration instead of intravenous injection of crocin. Meanwhile, orally administered crocetin showed similar cerebral protection to that of crocin, but this exciting effect was not clearly observed by intravenous administration of crocetin, indicating the importance of crocetin in gut. Moreover, orally administered crocin showed less cerebral-protective effect in pseudo germ-free (pGF) MCAO rats.andexperiments confirmed that crocin could be deglycosylated to crocetin in gut content of normal rats, rather than that of pGF rats, indicating that gut microbiota facilitated the transformation of crocin into crocetin, which played a key role in the activation of the pharmacological effect. Metabolomic study revealed that microbial-host co-metabolic molecules were significantly perturbed after oral administration of crocin, indicating a regulation on intestinal ecosystem. It was further suggested that gut microbiota may be the potential target of the cerebral-protective effect of crocin.

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PMID: 

Iran J Basic Med Sci. 2019 Apr ;22(4):334-344. PMID: 31223464

Abstract Title: 

Immunoregulatory and anti-inflammatory properties of(Saffron) and its main active constituents: A review.

Abstract: 

The medicinal uses of saffron, the dried stigmas ofL., have very long history in food coloring agent, and flavoring agent as well as traditional medicine for the treatment of several diseases.is rich in carotenoids that affect immunity. This review summarizes the putative immunoregulatory effects of saffron and its active its derivatives including crocin, crocetin and safranal. In modern studies, its active constituents including protective effects, anti-inflammatory activities and molecular mechanisms of saffron on thimmune system have been demonstrated. Furthermore, the beneficial effects of saffron on inhibition of serum levels nuclear transcription factorκB (NF-κB) p65 unit, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and some interleukin (IL) such as IL-1β, IL-6, IL-12, IL-17A were reported. Furthermore, saffron has been known as the antagonist of NF-κB and the agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ). In addition, saffron down-regulates the key pro-inflammatory enzymes such as myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phospholipase A2, and prostanoids. This review summarizes the protective roles ofand its constituents against the pathogenesis of immune diseases and understanding a better management of these problems. Taken together, the main bioactive constituents of saffron may have health-promoting with important benefits in immune-related disorders. Finally, our study indicates that these bioactive constituents can affect both cellular and humoral immunity functions.

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PMID: 

Prev Nutr Food Sci. 2019 Jun ;24(2):103-113. Epub 2019 Jun 30. PMID: 31328113

Abstract Title: 

Health Benefits of Carotenoids: A Role of Carotenoids in the Prevention of Non-Alcoholic Fatty Liver Disease.

Abstract: 

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases with a prevalence of ~25% worldwide. NAFLD includes simple hepatic steatosis, non-alcoholic steatohepatitis, fibrosis, and cirrhosis, which can further progress to hepatocellular carcinoma. Therefore, effective strategies for the prevention of NAFLD are needed. The pathogenesis of NAFLD is complicated due to diverse injury insults, such as fat accumulation, oxidative stress, inflammation, lipotoxicity, and apoptosis, which may act synergistically. Studies have shown that carotenoids, a natural group of isoprenoid pigments, prevent the development of NAFLD by exerting antioxidant, lipid-lowering, anti-inflammatory, anti-fibrotic, and insulin-sensitizing properties. This review summarizes the protective action of carotenoids, with primary focuses on astaxanthin, lycopene,β-carotene, β-cryptoxanthin, lutein, fucoxanthin, and crocetin, against the development and progression of NAFLD.

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PMID: 

Food Chem. 2019 Jun 29 ;299:125102. Epub 2019 Jun 29. PMID: 31279126

Abstract Title: 

Chemical compositions andα-glucosidase inhibitory effects of anthocyanidins from blueberry, blackcurrant and blue honeysuckle fruits.

Abstract: 

The chemical compositions andα-glucosidase inhibitory activities of anthocyanins extracted from blueberry, blackcurrant and blue honeysuckle fruits and their acid hydrolysates (anthocyanidins) were analysed. Those anthocyanins were glycosidic anthocyanins that converted to anthocyanidins during acid hydrolysis, leading to increases in their α-glucosidase inhibitory activities (expressed as ICvalues) from 0.232, 0.152 and 0.188 to 0.113 to 0.005 and 0.025 mg/mL. The potential inhibitory mechanism of these anthocyanidins was then investigated through inhibition kinetics, fluorescence quenching and docking simulations. The results showed the following: 1) all anthocyanidins were mixed-type inhibitors of α-glucosidase and they bind more tightly to free α-glucosidase as compared to the α-glucosidase-substrate complex; 2) anthocyanidin inhibition of α-glucosidase was a static procedure, presumably driven by hydrophobic associations and hydrogen bonding; and 3) all anthocyanidins were inserted into the active site of α-glucosidase and avoidedthe entrance of p-nitrophenyl-a-D-glucopyranoside. This study is valuable for anthocyanidins as potential α-glucosidase inhibitors.

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