Paper Information

Journal:   RESEARCH IN PHARMACEUTICAL SCIENCES (RPS)   DECEMBER 2014 , Volume 9 , Number 6; Page(s) 431 To 443.
 
Paper:  IDENTIFICATION AND CHARACTERIZATION OF A COMPOUND FROM CUMINUM CYMINUM ESSENTIAL OIL WITH ANTIFIBRILATION AND CYTOTOXIC EFFECT
 
Author(s):  MORSHEDI D.*, SALMANI KESEJINI T., ALIAKBARI F., KARAMI OSBOO R., SHAKIBAEI M., TAYARANIAN MARVIAN A., KHALIFEH M., SOROOSH M.
 
* DEPARTMENT OF INDUSTRIAL AND ENVIRONMENTAL BIOTECHNOLOGY, NATIONAL INSTITUTE OF GENETIC ENGINEERING AND BIOTECHNOLOGY, TEHRAN, I.R. IRAN
 
Abstract: 

Amyloid pathology is associated with fibril aggregation of different proteins which results in the progressive damage of affected organs. It is strongly believed that specific small molecules interfere with fibrillation by interacting with the amyloidogenic proteins. We had previously reported the strong and long-term inhibition of fibrillation of hen egg white lysozyme (HEWL) by Cuminum cyminum oil. Herein, it was intended to rationally identify the active anti-amyloidogenic compounds of the oil. After fractionation, the highest inhibitory effect was observed in the toluene-ethyl acetate part of the oil. Gas chromatography-mass spectrometry (GC-MS) analysis of this fraction indicated that eight compounds were predominantly present in the fraction. Unexpectedly, two compounds including terpinolene and limonene, having very similar chemical structures, inhibited and induced fibrillation, respectively. PC12 cells (derived from a transplantable rat pheochromocytoma) were affected by HEWL fibrils, whereas the inhibited forms of fibrils in the presence of terpinolene led to higher levels of viability, as shown by 3- (4, 5-dimethylthiazol-2-yl) -2, 5- diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) and flow cytometry assays. Molecular local docking analysis suggested a site of interaction for terpinolene in the flexible cleft of the protein. This interaction site is close to tryptophan -62 and -63 and two other hydrophobic residues in the hot spot regions of the protein. Seemingly, these interactions interrupt protein self-assembly and therefore, fibril formation. Despite previously reported small anti-amyloid molecules which have aromatic flat rings, terpinolene ring is not flat. This functionally durable small molecule may aid us toward developing new anti-amyloidogenic compounds with extended activity.

 
Keyword(s): ANTI-FIBRILLATION COMPOUNDS, ESSENTIAL OIL FRACTIONATION, HEWL FIBRILLATION, IRANIAN CUMINUM CYMINUM, LOCAL DOCKING
 
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