Examorelin (Hexarelin) (Synonyms: Examorelin, H-2-Me-WAWFK, His-2-Me-Trp-Ala-Trp-Phe-Lys-NH2, His-(D)-Mrp-Ala-Trp-(D)-Phe-Lys-NH2)

Examorelin, a synthetic growth hormone-releasing peptide, has been proven to possess cardioprotective actions through its binding to the growth hormone secretagogue receptor (GHSR) 1a and the non-GHSR receptor CD36.

Cultured MIN6 cells are incubated with serum-free medium (SFM) (control), 1 μM Examorelin (Hex), 1 mM Streptozotocin (STZ) alone or STZ followed by Examorelin for 6 hours. The viability of MIN6 is significantly affected by different treatments of the cells (F(3, 36)=5.244,P<0.01) . MIN6 cells treated with STZ followed by Examorelin receive a great increase in the cell viability (105.3% of control, P<0.01) as compared with those treated with STZ alone[2].

Examorelin (Hexarelin) treatment improves cardiac systolic function, decreases malondialdehyde production, and increases the number of surviving cardiomyocytes. The beneficial effects of Examorelin treatment are slightly superior to those of equimolar ghrelin treatment. Examorelin also induces down-regulation of IL-1β expression and up-regulation of IL-1Ra expression in I/R myocardium, which could be neutralized by the GHSR antagonist (D-Lys3)-GHRP-6. Examorelin protects in vivo cardiomyocytes from I/R injury partly by modification of the IL-1 signaling pathway through the activation of cardiac GHSR1a receptors[1]. The effect of Examorelin (100 μg/kg) in STZ-induced diabetic rats is examined. STZ-injection dramatically increased blood glucose levels in rats whereas Examorelin (Hex) treatment diminished the effect of STZ. Plasma insulin levels of rats are measured under both fasting and fed conditions respectively. Different treatment exerted significant effects on fasting insulin level (F(3, 28)=7.472, P<0.01) . The Examorelin alone increases the plasma insulin (P<0.05) whereas the STZ dramatically decreases it (P<0.001). STZ+Examorelin -treated rats show an increased insulin level (P<0.001). Similar to fasting insulin level, fed insulin level (Ftreatment (3, 28)=61.89, P<0.001) are significantly increased in Examorelin-treated rats (P<0.001) and reduced in STZ-treated rats. Furthermore, the Examorelin also ameliorates STZ-induced decrease in fed plasma insulin level[2].

[1]. Huang J, et al. The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From in vivo Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway. Int Heart J. 2017 Apr 6;58(2):257-263. [2]. Zhao Y, et al. Hexarelin Protects Rodent Pancreatic β-Cells Function from Cytotoxic Effects of Streptozotocin Involving Mitochondrial Signalling Pathways In Vivo and In Vitro. PLoS One. 2016 Feb 26;11(2):e0149730.