:Cucurbitacin E

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Cucurbitacin E anti-inflammatory activities are proved in vivo and in vitro.{{Citation needed|reason=Evidence?|date=May 2017}} It is useful in the treatment of inflammation because of the inhibition of cyclooxygenase and reactive nitrogen species (RNS) but not reactive oxygen species (ROS).{{Citation needed|date=May 2017}}

Macrophages are responsible for the production of various cytokines, RNS and ROS, growth factors and chemokines as a response to activation signal such as chemical mediators, cytokines and lipopolysaccharide.{{Citation needed|date=May 2017}} Although these molecules have an important role, they can also have damaging effects, like some RNS.{{Citation needed|date=May 2017}} Cucurbitacin possesses dose-dependent anti-inflammatory activity related to its inhibition of nitric oxide (an RNS) production in macrophages without affecting the viability of these cells.{{Citation needed|date=May 2017}}

As cucurbitacin E doesn't affect normal human liver cells, it may have therapeutic potential and effective treatment for a variety of inflammation mediated diseases.{{Cite journal | last1 = Abdelwahab | first1 = S. I. | last2 = Hassan | first2 = L. E. A. | last3 = Sirat | first3 = H. M. | last4 = Yagi | first4 = S. M. A. | last5 = Koko | first5 = W. S. | last6 = Mohan | first6 = S. | last7 = Taha | first7 = M. M. E. | last8 = Ahmad | first8 = S. | last9 = Chuen | first9 = C. S. | last10 = Narrima | doi = 10.1016/j.fitote.2011.08.002 | first10 = P. | last11 = Rais | first11 = M. M. | last12 = Hadi | first12 = A. H. A. | title = Anti-inflammatory activities of cucurbitacin E isolated from Citrullus lanatus var. Citroides: Role of reactive nitrogen species and cyclooxygenase enzyme inhibition | journal = Fitoterapia | volume = 82 | issue = 8 | pages = 1190–1197 | year = 2011 | pmid = 21871542 }}

Cucurbitacin E glycoside has demonstrated antioxidant and free-radical scavenging properties. Its antioxidant and free-radical scavenging properties were measured by the ability of cucurbitacin glycoside combination (CGC), a combination of cucurbitacin B and E glycosides, to reduce ABTS cation to its original form and also the capacity to inhibit MDA formation originated in the oxidation of linoleic acid. Using electron paramagnetic resonance, it was confirmed that CGC had antioxidant properties because of its capacity for scavenging free radicals, such as: superoxide anion (O2-), hydroxyl radical (OH-) and singlet oxygen. Not all natural antioxidants have strong free-radical scavenging properties against multiple free-radicals.{{Cite journal | last1 = Tannin-Spitz | first1 = T. | last2 = Bergman | first2 = M. | last3 = Grossman | first3 = S. | doi = 10.1016/j.bbrc.2007.09.075 | title = Cucurbitacin glucosides: Antioxidant and free-radical scavenging activities | journal = Biochemical and Biophysical Research Communications | volume = 364 | issue = 1 | pages = 181–186 | year = 2007 | pmid = 17942079 }}

CGC is being investigated as a treatment for human diseases that are linked to oxidative or free-radical damage such as atherosclerosis, cancer, Alzheimer's disease and diabetes.{{Cite journal | last1 = Clancy | first1 = D. | last2 = Birdsall | first2 = J. | title = Flies, worms and the Free Radical Theory of ageing | doi = 10.1016/j.arr.2012.03.011 | journal = Ageing Research Reviews | year = 2012 | pmid = 22504404 | volume=12 | issue=1 | pages=404–12 | s2cid = 23139852 | url = https://zenodo.org/record/896014 }}

Cucurbitacin E is an inhibitor during the S to M phase in the cell mitosis. It causes a reduction of cell multiplication.{{Citation needed|date=May 2017}}

This triterpene can inhibit the phosphorylation of the cofilin protein, a family of actin-binding proteins that disassembles actin filaments.{{Cite journal | last1 = Drubin | first1 = D. G. | last2 = Lappalainen | first2 = P. | title = Cofilin promotes rapid actin filament turnover in vivo | journal = Nature

| volume = 388 | issue = 6637 | pages = 78–82 | doi = 10.1038/40418 | year = 1997 | pmid = 9214506 | bibcode = 1997Natur.388R..78L | s2cid = 205027806 | doi-access = free }}{{Cite journal | last1 = Nakashima | first1 = S. | last2 = Matsuda | first2 = H. | last3 = Kurume | first3 = A. | last4 = Oda | first4 = Y. | last5 = Nakamura | first5 = S. | last6 = Yamashita | first6 = M. | last7 = Yoshikawa | first7 = M. | doi = 10.1016/j.bmcl.2010.02.062 | title = Cucurbitacin E as a new inhibitor of cofilin phosphorylation in human leukemia U937 cells | journal = Bioorganic & Medicinal Chemistry Letters | volume = 20 | issue = 9 | pages = 2994–2997 | year = 2010 | pmid = 20347305}}

Cucurbitacin E shows cytotoxicity to:{{Cite journal | last1 = Chen | first1 = X. | last2 = Bao | first2 = J. | last3 = Guo | first3 = J. | last4 = Ding | first4 = Q. | last5 = Lu | first5 = J. | last6 = Huang | first6 = M. | last7 = Wang | first7 = Y. | doi = 10.1097/CAD.0b013e3283541384 | title = Biological activities and potential molecular targets of cucurbitacins | journal = Anti-Cancer Drugs | volume = 23 | issue = 8 | pages = 777–787 | year = 2012 | pmid = 22561419 | s2cid = 30016950 }}

• The colon cancer cell line HCT-116
• The lung cancer cell line NCI-H460
• The breast cancer cell lines MCF-7 and ZR-75-1
• The central nervous system tumor cell line SF-268
• The oral epidermoid carcinoma cell line KB
• The cervical cancer cell line HeLa
• The fibrosarcoma cell line HT1080
• The acute leukemia cell lines U937 and HL-60
• The prostate cancer cell lines PC, LNCaP and DU145
• The pancreatic cancer cell line Panc-1
• The ovarian cancer cell line S-2{{Dubious |Cell line "S-2" in chapter Cucurbitacin E#Cytotoxicity|reason=This probably means cell line ES-2|date=January 2018}}
• The bladder cancer cell line T24
• The hepatic carcinoma cell lines BEL-7402 and HepG2

Cucurbitacin can also inhibit VEGFR2-mediated Jak-STAT3 and MAPK signaling pathways. Anti-angiogenesis property of cucurbitacin E was demonstrated in vitro but also in vivo in a chick embryo chorioallantoic membrane and in a mouse corneal angiogenesis model.{{Citation needed|date=May 2017}}

In vitro, cucurbitacin E inhibits the adhesion of cancer cells in type I collagen.

In vitro, cucurbitacin E protects hepatocytes from CCl₄ (carbon tetrachloride), by reducing GPT, GOT, ALP, TP and TBIL serums.

Curcurbitacin E has insecticidal effects against the aphid Aphis craccivora.Torkey, H.M., Abou-Yousef, H.M., Abdel Azeiz, A.Z. and Hoda, E.A. Farid. Insecticidal Effect of Cucurbitacin E Glycoside Isolated from Citrullus colocynthis Against Aphis craccivora. Australian Journal of Basic and Applied Sciences 2009; 3(4): 4060-4066

• Angiogenesis
• Hepatocyte
• Glycoside
• JAK-STAT signaling pathway

{{reflist}}

• http://www.chemicalbook.com/ChemicalProductProperty_EN_CB3372306.htm
• https://web.archive.org/web/20120426084358/http://home.ncifcrf.gov/mtdp/Catalog/compounds/106399.html
• http://www.chemblink.com/products/18444-66-1.htm

• {{Cite journal | last1 = Attard | first1 = E. | last2 = Brincat | first2 = M. P. | last3 = Cuschieri | first3 = A. | doi = 10.1016/j.fitote.2005.02.007 | title = Immunomodulatory activity of cucurbitacin E isolated from Ecballium elaterium | journal = Fitoterapia | volume = 76 | issue = 5 | pages = 439–441 | year = 2005

| pmid = 15908139 }}

• {{Cite journal | last1 = Dong | first1 = Y. | last2 = Lu | first2 = B. | last3 = Zhang | first3 = X. | last4 = Zhang | first4 = J. | last5 = Lai | first5 = L. | last6 = Li | first6 = D. | last7 = Wu | first7 = Y. | last8 = Song | first8 = Y. | last9 = Luo | first9 = J. | last10 = Pang | doi = 10.1093/carcin/bgq167 | first10 = X. | last11 = Yi | first11 = Z. | last12 = Liu | first12 = M. | title = Cucurbitacin E, a tetracyclic triterpenes compound from Chinese medicine, inhibits tumor angiogenesis through VEGFR2-mediated Jak2-STAT3 signaling pathway | journal = Carcinogenesis | volume = 31 | issue = 12 | pages = 2097–2104

| year = 2010 | pmid = 20732905 | doi-access = free }}

• {{cite journal |url=http://www.romj.org/2012-0203 |last1=Navolokin|first1=NA |last2=Polukonova|first2=NV |last3=Maslyakova|first3=GN |last4=Bucharskaya|first4=AB |last5=Durnova|first5=NA |title=Effect of extracts of Gratiola officinalis and Zea mays on the tumor and the morphology of the internal organs of rats with transplanted liver cancer |journal=Russian Open Medical Journal |year=2012 |volume=1 |issue=2|page=0203|doi=10.15275/rusomj.2012.0203|doi-access=free}}

Category:Steroids