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|ImageFile=Cinobufagin.png |
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|ImageSize=240 |
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| verifiedrevid = 379637995 |
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|IUPACName= |
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|OtherNames=Cinobufagin |
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| ImageFile=Cinobufagin.png |
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| ImageSize=240 |
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| IUPACName=3β-Hydroxy-14,15β-epoxy-5β-bufa-20,22-dienolid-16β-yl acetate |
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| SystematicName=(1''R'',2''R'',2a''R'',3a''S'',3b''R'',5a''R'',7''S'',9a''S'',9b''S'',11a''R'')-7-Hydroxy-9a,11a-dimethyl-1-(2-oxo-2''H''-pyran-5-yl)hexadecahydronaphthoindenooxiran-2-yl acetate |
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| OtherNames=Cinobufagin |
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|Section1={{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| CASNo_Ref = {{cascite|correct|??}} |
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| CASNo=470-37-1 |
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| CASNo=470-37-1 |
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| PubChem= 10103 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| SMILES= CC(=O)O1(C2(CCC3C(241O4)CC5C3(CC(C5)O)C)C)C6=CC(=O)OC=C6 |
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| UNII = T9PSN4R8IR |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 250785 |
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| ChEBI = 80805 |
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| KEGG = C16931 |
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| EINECS = 636-927-8 |
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| PubChem = 11969542 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 10142947 |
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| SMILES = O=C\1O\C=C(/C=C/1)46(C)CC3(CC2C(O)CC23C)65O54OC(=O)C |
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| InChI = 1/C26H34O6/c1-14(27)31-22-21(15-4-7-20(29)30-13-15)25(3)11-9-18-19(26(25)23(22)32-26)6-5-16-12-17(28)8-10-24(16,18)2/h4,7,13,16-19,21-23,28H,5-6,8-12H2,1-3H3/t16-,17+,18+,19-,21+,22-,23-,24+,25-,26-/m1/s1 |
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| InChIKey = SCULJPGYOQQXTK-OLRINKBEBZ |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C26H34O6/c1-14(27)31-22-21(15-4-7-20(29)30-13-15)25(3)11-9-18-19(26(25)23(22)32-26)6-5-16-12-17(28)8-10-24(16,18)2/h4,7,13,16-19,21-23,28H,5-6,8-12H2,1-3H3/t16-,17+,18+,19-,21+,22-,23-,24+,25-,26-/m1/s1 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = SCULJPGYOQQXTK-OLRINKBESA-N |
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|Section2={{Chembox Properties |
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|Section2={{Chembox Properties |
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| C=26 | H=34 | O=6 |
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| C=26 | H=34 | O=6 |
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|Section3={{Chembox Hazards |
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|Section3={{Chembox Hazards |
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| MainHazards=Toxic |
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| MainHazards=Toxic |
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| GHSPictograms = {{GHS06}} |
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| GHSSignalWord = Danger |
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| HPhrases = {{H-phrases|300|310|330}} |
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| PPhrases = {{P-phrases|260|262|264|270|271|280|284|301+310|302+350|304+340|310|320|321|322|330|361|363|403+233|405|501}} |
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'''Cinobufagin''' is a ] ] ] secreted by the Asiatic ] '']''. It has similar effects to ] and is used in ].<ref>Yang Z, Luo H, Wang H, Hou H. Preparative isolation of bufalin and cinobufagin from Chinese traditional medicine Chan Su. ''Journal of Chromatographic Science''. 2008 Jan;46(1):81-5. PMID 18218193</ref> |
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'''Cinobufagin''' is a ] ] ] secreted by the Asiatic ] '']''. It has similar effects to ] and is used in ].<ref>{{ cite journal |author1=Yang, Z. |author2=Luo, H. |author3=Wang, H. |author4=Hou H. | title = Preparative Isolation of Bufalin and Cinobufagin from Chinese Traditional Medicine ChanSu | journal = Journal of Chromatographic Science | year = 2008 | volume = 46 | issue = 1 | pages = 81–85 | doi = 10.1093/chromsci/46.1.81 | pmid = 18218193 | url = http://chromsci.oxfordjournals.org/content/46/1/81.full.pdf | doi-access = free }}</ref> |
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==Isolation and purification== |
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Cinobufagin, as well as other bufadienolides, can be isolated from the traditional Chinese medicine called ChanSu. ChanSu is made from a multitude of chemicals present in ] secretions. Resibufogenin can be eluted out with silica gel column ], using a 5:1 ratio of ] to ] for the ] in the mobile phase. Subsequently, cinobufagin and bufalin can be separated and purified using an ] column with a 72:28 ] to ] solvent. Yang et al. confirmed this method of isolation for cinobufagin with ].<ref>{{ cite journal |author1=Yang, Z. |author2=Luo, H. |author3=Wang, H. |author4=Hou H. | title = Preparative Isolation of Bufalin and Cinobufagin from Chinese Traditional Medicine ChanSu | journal = Journal of Chromatographic Science | year = 2008 | volume = 46 | issue = 1 | pages = 81–85 | doi = 10.1093/chromsci/46.1.81 | pmid = 18218193 | url = http://chromsci.oxfordjournals.org/content/46/1/81.full.pdf | doi-access = free }}</ref> |
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==Clinical significance== |
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Cinobufagin has been shown to have clinical applications in ] treatment as well as immunomodulatory and ] properties.{{Citation needed|date = March 2016}} |
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In human adrenocortical cells, cinobufagin inhibits the secretion of aldosterone and cortisol. Cinobufagin is able to inhibit the expression of the StAR protein as well as bind the transcription factor SF-1, which normally binds to the promoter for the StAR gene. This results in less StAR ] product and decreased levels of ] and ] synthesis. Cinobufagin first binds to a Ca<sup>2+</sup>/K<sup>+</sup> plasma membrane ], subsequently inducing the phosphorylation of ] (ERK). Phosphorylated ERK then blocks the SF-1 ] factor from binding to the ] region of the StAR ]. |
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Thus, cinobufagin plays important roles in regulation of ] synthesis and ]. It is speculated that cinobufagin may have therapeutic roles in treatment of ] and ].<ref>{{ cite journal |author1=Mei-Mei, Kau |author2=Jiing-Rong Wang |author3=Shiow-Chwen Tsai |author4=Ching-Han Yu |author5=Paulus S Wang | title = Inhibitory effect of bufalin and cinobufagin on steroidogenesis via the activation of ERK in human adrenocortical cells | journal = British Journal of Pharmacology | year = 2012 | volume = 165 | issue = 6 | pages = 1868–1876 | doi = 10.1111/j.1476-5381.2011.01671.x | pmid=21913902 | pmc=3372836}}</ref> |
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=== Immunology === |
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], cinobufagin can stimulate the proliferation of immune cells including splenocytes, ] ], ] and ]. Additionally cinobufagin can modulate levels of ] produced by immune cells. Exposure to cinobufagin increases levels of ] and ] while decreasing overall levels of ] and ].<ref>{{ cite journal |vauthors=Wang XL, Zhao GH, Zhang J, Shi QY, Guo WX, Tian XL, Qiu JZ, Yin LZ, Deng XM, Song Y | title = Immunomodulatory effects of cinobufagin isolated from Chan Su on activation and cytokines secretion of immunocyte in vitro. | journal = J Asian Nat Prod Res | year = 2011 | volume = 13 | issue = 5 | pages = 383–92 | doi = 10.1080/10286020.2011.565746 | pmid=21534035| s2cid = 205679985 }}</ref> |
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=== Analgesic properties === |
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Cinobufagin has been shown to increase pain threshold levels in mice to thermal and mechanical stimuli. It is thought to trigger increased synthesis of β-END and the up-regulation of the ] in mouse tumor tissue thereby leading to pain relief. β-END binds the ] to cause the ] effect.<ref>{{ cite journal |author1=Tao Chen |author2=Wei Hu |author3=Zhang J |author4=Haibo He |author5=Zipeng Gong |author6=Jing Wang |author7=Xueqin Yu |author8=Ting Ai |author9=Ling Zhan | title = A Study on the Mechanism of Cinobufagin in the Treatment of Paw Cancer Pain by Modulating Local β-Endorphin Expression In Vivo. | journal = Evidence-Based Complementary and Alternative Medicine | year = 2013 | volume = 2013 | pages = 1–9 | doi=10.1155/2013/851256|pmid=24187573 |pmc=3800629 |doi-access=free }}</ref> |
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=== Interaction with cancer cells and related biochemical pathways === |
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] can catabolize cinobufagin into five distinct metabolites, each of which has been shown to have cytotoxic effects to ] cancer cells.<ref>{{ cite journal |author1=Li Qiao |author2=Yu-zhi Zhou |author3=Zhang J |author4=Xiu-lan Qi |author5=Li-hong Lin |author6=Huan Chen |author7=Li-yan Pang |author8=Yue-hu Pei | title = Biotransformation of Cinobufagin by Cunninghamella elegans | journal = The Journal of Antibiotics | year = 2007 | volume = 60 | issue = 4 | pages = 261–264 | url = http://www.nature.com/ja/journal/v60/n4/pdf/ja200732a.pdf | doi=10.1038/ja.2007.32|pmid=17456977 |doi-access=free }}</ref> |
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Cinobufagin can induce ] arrest at the G2 and M phases as well as induce ] in ] cells. Potentially, cinobufagin could be used to stop proliferation of osteosarcoma cells as well as to induce ] them. At the protein level, cinobufagin treated osteosarcoma cells showed an increase in the Bax and cleaved-PARP apoptotic proteins, while inhibiting the ]β/] signaling pathway.<ref>{{ cite journal |vauthors=Yin JQ, Wen L, Wu LC, Gao ZH, Huang G, Wang J, Zou CY, Tan PX, Yong BC, Jia Q, Shen JN | title = The glycogen synthase kinase-3β/nuclear factor-kappa B pathway is involved in cinobufagin-induced apoptosis in cultured osteosarcoma cells.| journal = Toxicology Letters | year = 2013 | volume = 218 | issue = 2 | pages = 129–36 | doi = 10.1016/j.toxlet.2012.11.006 | pmid=23164673}}</ref> |
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With regards to the induction of ], cinobufagin has been shown to selectively bind K<sup>+</sup>/Na<sup>+</sup> ]s in ] ] cells to trigger a signaling cascade which leads to ] dependent pathways for ]. It is through the activation of ]s that Cinobufagin can cause ].<ref>{{ cite journal |author1=Akimova OA |author2=Bagrov AY |author3=Lopina OD |author4=Kamernitsky AV |author5=Tremblay J |author6=Hamet P |author7=Orlov SN | title = Cardiotonic steroids differentially affect intracellular Na+ and i/i-independent signaling in C7-MDCK cells. | journal = The Journal of Biological Chemistry | year = 2005 | volume = 280 | issue = 1 | pages = 832–839 | doi = 10.1074/jbc.M411011200 | pmid = 15494417 | doi-access = free }}</ref> |
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==References== |
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==References== |
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{{Toxins}} |
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{{Toxins}} |
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{{Cardiac glycosides}} |
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{{Cardiac glycosides}} |
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{{biochem-stub}} |
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