Ghrelin: A Promising Therapeutic Peptide Facing Significant Delivery Hurdles

Ghrelin is a fascinating peptide hormone primarily synthesized in the stomach, renowned for its role as the body's only known circulating orexigenic (appetite-stimulating) hormone. Beyond regulating energy balance and stimulating growth hormone release, ghrelin exerts diverse physiological effects, including cardioprotection, neuroprotection, and modulation of gastrointestinal motility and inflammation. Despite its broad therapeutic potential, the clinical translation of ghrelin is significantly hampered by its inherent instability and poor pharmacokinetic properties. This comprehensive review aims to synthesize the current understanding of ghrelin's multifaceted physiopharmacological actions, evaluate its therapeutic advantages and disadvantages, and critically assess the challenges associated with its pharmaceutical delivery.

The review highlights ghrelin's potent orexigenic effects, making it a strong candidate for treating cachexia (severe muscle wasting) associated with conditions like cancer, AIDS, and chronic heart failure. It details ghrelin's significant cardioprotective properties, including its ability to improve cardiac function, reduce inflammation, and mitigate cardiac remodeling in models of heart failure. Furthermore, the paper discusses ghrelin's neuroprotective effects, suggesting potential benefits in neurodegenerative diseases by reducing neuronal apoptosis and improving cognitive function. The authors noted that ghrelin's actions are primarily mediated through the growth hormone secretagogue receptor 1a (GHSR-1a). The authors emphasize that despite ghrelin's broad therapeutic promise, its short plasma half-life (often measured in minutes) and poor oral bioavailability (typically <1%) represent the most significant barriers to its clinical development and widespread use, necessitating parenteral administration or advanced delivery technologies.