Peptide profiling of Internet‐obtained Cerebrolysin using high performance liquid chromatography – electrospray ionization ion trap and ultra high performance liquid chromatography – ion mobility – quadrupole time of flight mass spectrometry

Abstract

Cerebrolysin, a parenteral peptide preparation produced by controlled digestion of porcine brain proteins, is an approved nootropic medicine in some countries. However, it is also easily and globally available on the Internet. Nevertheless, until now, its exact chemical composition was unknown. Using high performance liquid chromatography (HPLC) coupled to ion trap and ultra high performance liquid chromatography (UHPLC) coupled to quadrupole-ion mobility-time-of-flight mass spectrometry (Q-IM-TOF MS), combined with UniProt pig protein database search and PEAKS de novo sequencing, we identified 638 unique peptides in an Internet-obtained Cerebrolysin sample. The main components in this sample originate from tubulin alpha- and beta-chain, actin, and myelin basic protein. No fragments of known neurotrophic factors like glial cell-derived neurotrophic factor (GDNF), neurotrophin nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) were found, suggesting that the activities reported in the literature are likely the result of new, hitherto unknown cryptic peptides with nootropic properties.

Cerebrolysin improves memory and ameliorates neuronal atrophy in spontaneously hypertensive, aged rats

“…In addition, a recent report (Gevaert et al, 2015) suggests that Cbl contained 639 peptides, whose main components are fragments of tubulin-alpha-and beta-chain, actin and myelin basic protein. Moreover, Gevaert et al (2015) failed to identify fragments of known nootropic proteins. However, several reports suggest that Cbl increases the levels of BDNF and NGF in several regions of the brain, including the hippocampus (Ahmed et al, 2014;Selianina and Karakulova, 2012;Ubhi et al, 2013).…”

Effect of cerebrolysin on remyelination processes in multiple sclerosis patients in stage of relapse regression

“…Мы предположили, что действие церебролизина обусловлено особенностями его состава. Так, по данным исследования группы авторов [12], установлено, что в церебролизине помимо аминокислот олигопептидный спектр представлен фрагментами тубулина, актина и основного белка миелина, что, по всей видимости, в совокупности необходимо для неспецифического трофического обеспечения регенерирующей миелиновой оболочки [13].…”

Identification of epidermal growth factor (EGF), in an unknown pharmaceutical preparation suspected to contain insulin like growth factor 1 (IGF‐1)

“…Reports originating from controlling agencies residing in Germany, the UK, Denmark, Norway, Italy, the USA, Australia, and Belgium show that monoclonal anti-cancer antibodies, insulins, growth hormones, human chorionic gonadotropin, Clostridium botulinum toxin type A, potential doping peptides, putative anti-obesity drugs, skin tanning peptides, neuropeptides and a putative anti-cancer polypeptide were identified in seized samples. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] The danger of these illegal polypeptides resides in the fact that these polypeptide products are not produced under controlled environment and therefore may contain the wrong ingredient, the wrong dosage, bacteria, viruses, heavy metals, etc., which could result in severe health issues. In some cases these illegal acts had a deadly outcome.…”