ACTH(4-7)-PGP mitigates colon atrophy and inflammation in restraint-stressed rats by reducing corticosterone

Chronic psychological stress significantly impacts gastrointestinal health, often leading to conditions like Irritable Bowel Syndrome (IBS) or exacerbating Inflammatory Bowel Disease (IBD). Restraint stress, a common animal model, induces systemic stress responses, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and subsequent release of corticosterone, which can compromise gut barrier function and promote inflammation. Current treatments often target symptoms, leaving a gap for interventions that address the underlying stress-induced gut pathology. ACTH(4-7)-PGP, a synthetic peptide fragment of ACTH, is known for its neuroprotective and adaptogenic properties, making it a candidate for mitigating stress-related physiological damage.

This study investigated the effects of ACTH(4-7)-PGP on the colon's morphofunctional state in Wistar male rats subjected to restraint stress. Rats received intraperitoneal (IP) injections of ACTH(4-7)-PGP at doses of 5, 50, 150, or 450 μg/kg 12-15 minutes before a restraint stress protocol. The control group underwent restraint stress without peptide administration. Researchers assessed the colon wall for signs of atrophy and inflammation, evaluated the functional activity and number of mast cells, and measured serum corticosterone levels using standard biochemical and histological methods.

In rats exposed to restraint stress, the large intestine exhibited clear signs of atrophy within the colon wall, indicative of tissue degradation. This was accompanied by a pronounced inflammatory reaction, suggesting immune activation and damage. Specifically, researchers noted significant alterations in the functional activity and overall number of mast cells, which are key mediators of inflammatory responses in the gut. These physiological changes correlated with systemic stress, as evidenced by an increased serum level of corticosterone, a primary stress hormone.

Administration of ACTH(4-7)-PGP demonstrated a notable protective effect against these stress-induced pathologies. The peptide consistently led to a decrease in the elevated corticosterone concentration, indicating a modulation of the hypothalamic-pituitary-adrenal (HPA) axis response to stress. Crucially, ACTH(4-7)-PGP alleviated the observed stress-induced pathomorphological changes in the colon, mitigating both the signs of atrophy and the inflammatory reaction. This intervention also promoted the adaptation of the intestinal wall to the severe stress conditions, suggesting a restoration of gut integrity and function. The positive effects were observed across the tested dose range, highlighting the peptide's potential to normalize stress-disrupted gut physiology.