Ghrelin as a candidate molecule in translational pharmacology: Physiopharmacological actions, therapeutic pros and...

Ghrelin is a peptide hormone consisting of 28 amino acids, characterized by octanoylation, and is primarily secreted by gastric X/A-like cells and is recognized as the sole circulating orexigenic hormone. Ghrelin, via its receptor growth hormone secretagogue receptor 1a, modulates key biological functions such as appetite, growth hormone release, glucose regulation, gastrointestinal motility, cardiovascular activity, immune, and stress reactivity. The characteristics of O-octanoyl substitution at Ser3 are not only crucial for receptor activation, but this alteration also makes it susceptible to enzymatic breakdown and therefore leads to a short plasma half-life, bridging both therapeutic possibilities and pharmacological constraints. This review summarizes the structural features of ghrelin, its receptor biology, and its significant physiological and pharmacological actions, particularly its differential effects on the hypothalamic pituitary adrenal axis and stress behaviors. We also discussed the hurdles associated with ghrelin-based treatments, and, therefore, briefly mentioned new delivery methods that could potentially address issues with pharmacokinetics and targeting constraints. There are numerous potential clinical applications, including metabolic disorders, gastrointestinal disease, neurodegeneration, chronic pain, psychiatric disorders, and wasting syndromes. The limitations, such as metabolic adverse effects, receptor desensitization, differential effects, and safety considerations, were critically evaluated. In translational pharmacology, ghrelin is a potential but challenging target that requires careful integration of physiopharmacological knowledge with prudent treatment design.