Hexarelin · research summary

Hexarelin Modulation of MAPK and PI3K/Akt Pathways in Neuro-2A Cells Inhibits Hydrogen Peroxide-Induced Apoptotic Toxicity.

Pharmaceuticals (Basel, Switzerland) · 2021. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

In vitro study examining the effects of hexarelin on hydrogen peroxide-induced apoptosis in Neuro-2A cells.
“This study examined the inhibitory effects of hexarelin on hydrogen peroxide (H2O2)-induced apoptosis in Neuro-2A cells.”

Subjects

Neuro-2A cells (mouse neuroblastoma cell line).
“The neuroprotective and anti-apoptotic effects of hexarelin have not yet been assessed. Therefore, the primary aims of this study are to characterize the effects of hexarelin on H2O2-induced stress and to explore its neuroprotective mechanisms of action in a mouse neuroblastoma cell line (Neuro-2A cells), a well-established in vitro model, frequently used to study the neuroprotective activities of new drugs [24,25,26].”

Sample size

Experiments were performed in at least three independent experiments with varying replicates (e.g., n=21 for MTT, n=24 for Griess, n=18 for RT-PCR, n=3 for Western Blot).
“The assay was performed in at least three independent experiments (n = 21).”

Duration

24 hours of treatment.
“Neuro-2A cells were treated for 24 h with various concentrations of H2O2 or with the combination of H2O2 and hexarelin following which cell viability and nitrite (NO2−) release were measured.”

Reported findings

Hexarelin improved cell viability, reduced nitrite release, and restored normal cell morphology compared to H2O2 treatment alone.
“Our results indicate that hexarelin effectively antagonized H2O2-induced damage to Neuro-2A cells thereby (i) improving cell viability, (ii) reducing NO2− release and (iii) restoring normal morphologies.”
Hexarelin reduced mRNA levels of caspase-3, inhibited cleaved caspase-3 protein expression, and modulated BCL-2 family mRNA levels (reducing Bax and increasing Bcl-2).
“Hexarelin treatment also reduced mRNA levels of caspase-3 and its activation, and modulated mRNA levels of the BCL-2 family.”
Hexarelin inhibited MAPKs phosphorylation and increased p-Akt protein expression.
“Moreover, hexarelin inhibited MAPKs phosphorylation and increased p-Akt protein expression.”

Limitations stated by the authors

Further investigations are required to clarify the molecular mechanisms of action and whether effects are mediated by the ghrelin receptor.
“This study demonstrates that hexarelin is capable of protecting Neuro-2A cells from H2O2-caused cytotoxicity effects; however, further investigations are required to clarify hexarelin molecular mechanisms of action, and whether its effects are mediated by the ghrelin receptor (GHS-R1a).”

Source: PubMed 34066741 · DOI 10.3390/ph14050444 · all study summaries

Subjects

Neuro-2A cells (mouse neuroblastoma cell line).

“The neuroprotective and anti-apoptotic effects of hexarelin have not yet been assessed. Therefore, the primary aims of this study are to characterize the effects of hexarelin on H2O2-induced stress and to explore its neuroprotective mechanisms of action in a mouse neuroblastoma cell line (Neuro-2A cells), a well-established in vitro model, frequently used to study the neuroprotective activities of new drugs [24,25,26].”

Reported findings

Hexarelin improved cell viability, reduced nitrite release, and restored normal cell morphology compared to H2O2 treatment alone.

“Our results indicate that hexarelin effectively antagonized H2O2-induced damage to Neuro-2A cells thereby (i) improving cell viability, (ii) reducing NO2− release and (iii) restoring normal morphologies.”

Hexarelin reduced mRNA levels of caspase-3, inhibited cleaved caspase-3 protein expression, and modulated BCL-2 family mRNA levels (reducing Bax and increasing Bcl-2).

“Hexarelin treatment also reduced mRNA levels of caspase-3 and its activation, and modulated mRNA levels of the BCL-2 family.”

Hexarelin inhibited MAPKs phosphorylation and increased p-Akt protein expression.

“Moreover, hexarelin inhibited MAPKs phosphorylation and increased p-Akt protein expression.”

Limitations stated by the authors

Further investigations are required to clarify the molecular mechanisms of action and whether effects are mediated by the ghrelin receptor.

“This study demonstrates that hexarelin is capable of protecting Neuro-2A cells from H2O2-caused cytotoxicity effects; however, further investigations are required to clarify hexarelin molecular mechanisms of action, and whether its effects are mediated by the ghrelin receptor (GHS-R1a).”