Mechanistic investigation of hepato-protective potential for cucurbitacins

Hajer M. Arjaibi, Mahmoud S. Ahmed, Fathi T. Halaweish

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Hepatocellular carcinoma is a major example for inflammatory-associated cancer. cucurbitacins are natural triterpenoids known for their potent anticancer and anti-inflammatory activities. Recent studies showed that cucurbitacins protect the HepG2 cell lines against carbon tetrachloride-induced toxicity, however the mechanism is unknown. A molecular docking study coupled with in vitro biological assays were conducted to test the hepatoprotective effect of cucurbitacin on the inhibition of potential inflammatory factors. The effect of cucurbitacins on the activation of NF-kB pathway was analyzed using in cell-based NF-kB immunoassay. Enzyme-linked immunosorbent assays revealed the potential of Cuc D and dihydro cucurbitacin D to prevent the production of tumor necrosis factor-alpha and interleukin-6 from HSC-T6 cells. Thus, Cuc D and dihydro cucurbitacin D could have hepatoprotective effects on the activated rat HSC-T6 cells due to inhibition of the production of tumor necrosis factor-alpha and interleukin-6 through NF-kB pathway. In-silico molecular modeling data revealed potential cucurbitacin analogs with higher binding affinity to the hydrophobic pocket of NF-kB and IKKβ compared to standard IKK inhibitor (PS-1145).

Original languageEnglish (US)
Pages (from-to)1567-1573
Number of pages7
JournalMedicinal Chemistry Research
Volume26
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

Fingerprint

Cucurbitacins
NF-kappa B
Interleukin-6
Assays
Tumor Necrosis Factor-alpha
Immunosorbents
Molecular modeling
Carbon Tetrachloride
Hep G2 Cells
Immunoassay
Biological Assay
Computer Simulation
Toxicity
Rats
Hepatocellular Carcinoma
Anti-Inflammatory Agents
Chemical activation
Enzyme-Linked Immunosorbent Assay
Cells
Cell Line

Keywords

  • Cucurbitacins
  • Hepatoprotection
  • HSC-T6
  • NF-kB
  • TNF-α

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Cite this

Mechanistic investigation of hepato-protective potential for cucurbitacins. / Arjaibi, Hajer M.; Ahmed, Mahmoud S.; Halaweish, Fathi T.

In: Medicinal Chemistry Research, Vol. 26, No. 7, 01.07.2017, p. 1567-1573.

Research output: Contribution to journalArticle

Arjaibi, Hajer M. ; Ahmed, Mahmoud S. ; Halaweish, Fathi T. / Mechanistic investigation of hepato-protective potential for cucurbitacins. In: Medicinal Chemistry Research. 2017 ; Vol. 26, No. 7. pp. 1567-1573.
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