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      Effects of Crocin on The Pituitary-Gonadal Axis and Hypothalamic Kiss-1 Gene Expression in Female Wistar Rats

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          Abstract

          Background

          Saffron ( Crocus sativus L.) has been traditionally used as a spice for coloring and flavoring in some countries cuisine. One of the main components of saffron is Crocin. Recent research have shown that crocin has various pharmacological effects. The aim of this study was to assess the effects of crocin on the Pituitary-Gonadal axis and Kiss-1 gene expression in hypothalamus and ovarian tissue organization in female Wistar rats.

          Materials and Methods

          In this experimental study, 18 adult female Wistar rats were randomly divided into three groups. Control group received normal saline and experimental groups received two different doses of crocin (100 and 200 mg/kg) every two days for 30 days. After the treatment period, blood samples were obtained from the heart and centrifuged. Next, the serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), estrogen and progesterone hormones were measured by ELISA assay. The ovarian tissues were removed and fixed for histological investigation. The hypothalamic Kiss-1 gene expression was measured using real-time polymerase chain reaction (PCR). All data were analyzed using one-way ANOVA.

          Results

          A significant reduction (P=0.038) in the number of atretic graafian follicles (0.5 ± 0.31) was observed in rats treated with 200 mg/kg crocin. In addition, estrogen concentration in experimental groups (35.04 ± 0.85 and 36.18 ± 0.69 in crocin 100 and 200 mg/kg groups, respectively) compared to control group (38.35 ± 0.64) and progesterone concentration in rats treated with crocin 200 mg/kg (2.06 ± 0.07) compared to control group (2.16 ± 0.04), significantly decreased. Interestingly, relative expressions of Kiss-1 mRNA significantly decreased in experimental groups (0.00053 ± 0.00051 and 0.0011 ± 0.00066 in crocin 100 and 200 mg/kg groups, respectively) (P=0.000) compared to control group (1 ± 0).

          Conclusion

          Crocin, at hypothalamic level, reduces Kiss-1 gene expression and it can prevent follicular atresia and reduce serum levels of estrogen and progesterone.

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          Most cited references35

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          KiSS-1, a novel human malignant melanoma metastasis-suppressor gene.

          Microcell-mediated transfer of chromosome 6 into human C8161 and MelJuSo melanoma cell suppresses their ability to metastasize by at least 95% without affecting their tumorigenicity. This observation demonstrates that the ability to metastasize is a phenotype distinct from tumor formation and suggests that tumorigenic cells acquire metastatic capability only after accumulating additional genetic defects. These results also imply that mutations of genes on chromosome 6 are among those late genetic changes responsible for metastatic potential. They further suggest that a melanoma metastasis-suppressor gene(s) is encoded on chromosome 6 or is regulated by genes on chromosome 6. Our objective was to identify the gene(s) responsible for the suppression of metastasis in chromosome 6/melanoma cell hybrids. A modified subtractive hybridization technique was used to compare the expression of messenger RNAs (mRNAs), via an analysis of complementary DNAs (cDNAs), in metastatic cells (C8161 or MelJuSo) and nonmetastatic hybrid clones (neo6/C8161 or neo6/MelJuSo). A novel cDNA, designated KiSS-1, was isolated from malignant melanoma cells that had been suppressed for metastatic potential by the introduction of human chromosome 6. Northern blot analyses comparing mRNAs from a panel of human melanoma cells revealed that KiSS-1 mRNA expression occurred only in nonmetastatic melanoma cells. Expression of this mRNA in normal heart, brain, liver, lung, and skeletal muscle was undetectable by northern blot analysis. Weak expression was found in the kidney and pancreas, but the highest expression was observed in the placenta. The KiSS-1 cDNA encodes a predominantly hydrophilic, 164 amino acid protein with a polyproline-rich domain indicative of an SH3 ligand (binds to the homology 3 domain of the oncoprotein Src) and a putative protein kinase C-alpha phosphorylation site. Transfection of a full-length KiSS-1 cDNA into C8161 melanoma cells suppressed metastasis in an expression-dependent manner. These data strongly suggest that KiSS-1 expression may suppress the metastatic potential of malignant melanoma cells. KiSS-1 may be a useful marker for distinguishing metastatic melanomas from nonmetastatic melanomas.
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            Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents.

            Radical scavenging activity is involved in aging processes, antiinflammatory, anticancer and wound healing activity. Hence, in the present study the DPPH radical scavenging activity of a natural product that possesses biological properties, an extract of Crocus sativus L. (saffron), grown in Crocos, Kozani (Greece), and some of its bioactive constituents (crocin, safranal) was studied. It was shown that a methanol extract of Crocus sativus exhibited high antioxidant activity, although it contains several active and inactive constituents. In trying to approximate a structure-activity relationship, two bioactive constituents of saffron extract were tested, namely crocin and safranal. Crocin showed high radical scavenging activity (50% and 65% for 500 and 1,000 ppm solution in methanol, respectively), followed by safranal (34% for 500 ppm solution). All the tested samples showed high radical scavenging activity, probably due to the ability to donate a hydrogen atom to the DPPH radical.Thus, saffron grown in Greece can be used promisingly in functional foods, drinks with antioxidant activity, in pharmaceutical and cosmetic preparations for their antioxidant activity and probably for their antiaging activity. Saffron can also be used internally in the form of powder or other pharmacotechnical formulae as a food supplement with antioxidant properties.
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              Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice

              Background Crocus sativus L. (saffron) is used in folk medicine, for example as an antiedematogenic agent. We aimed to evaluate the antinociceptive and anti-inflammatory activity of saffron extracts in mice. Results We used aqueous and ethanolic maceration extracts of Crocus sativus L. stigma and petals. Antinociceptive activity was examined using the hot plate and writhing tests. The effect of extracts against acute inflammation was studied using xylene induced ear edema in mice. The activity of the extracts against chronic inflammation was assessed by formalin-induced edema in the rat paw. In the hot plate tests, intraperitoneal injection of both extracts showed no significant antinociceptive activity in mice. The extracts exhibited antinociceptive activity against acetic acid induced writhing. Naloxone partially blocked only the antinociceptive activity of the stigma aqueous extract. Only the stigma extracts showed weak to moderate effect against acute inflammation. In chronic inflammation, both aqueous and ethanolic stigma extracts, as well as ethanolic petal extract, exerted anti-inflammatory effects. Conclusions We conclude that aqueous and ethanolic extracts of saffron stigma and petal have an antinociceptive effect, as well as acute and/or chronic anti-inflammatory activity.
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                Author and article information

                Journal
                Int J Fertil Steril
                Int J Fertil Steril
                Royan Institute
                International Journal of Fertility & Sterility
                Royan Institute
                2008-076X
                2008-0778
                Apr-Jun 2018
                15 January 2018
                : 12
                : 1
                : 56-60
                Affiliations
                [1 ]Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
                [2 ]National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
                Author notes
                [*Corresponding Address: ]P.O.Box: 1477893855Department of BiologyScience and Research BranchIslamic Azad University TehranIran Email: kazem_parivar@ 123456yahoo.comIntroduction
                Article
                Int-J-Fertil-Steril-12-56
                10.22074/ijfs.2018.5139
                5767933
                29334208
                ccd34464-2384-453e-b734-b648e88afb06
                Any use, distribution, reproduction or abstract of this publication in any medium, with the exception of commercial purposes, is permitted provided the original work is properly cited

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 December 2016
                : 5 February 2017
                Categories
                Original Article
                Genetics
                Pharmacognosy
                Custom metadata
                Zohrabi D, Parivar K, Sanati MH, Hayati Roodbari N. Effects of crocin on the pituitary-gonadal axis and hypothalamic Kiss-1 gene expression in female wistar rats. Int J Fertil Steril. 2018; 12(1): 56-60. doi: 10.22074/ijfs.2018.5139

                crocin,folliculogenesis,gonadal steroid hormones,gonadotropins,kiss-1

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