GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Potentiation of ghrelin signaling attenuates cancer anorexia-cachexia and prolongs survival.
Fujitsuka. N N; Asakawa. A A; Uezono. Y Y; Minami. K K; Yamaguchi. T T; Niijima. A A; Yada. T T; Maejima. Y Y; Sedbazar. U U; Sakai. T T; Hattori. T T; Kase. Y Y; Inui. A A
Key Findings
- Tumor‑bearing rats have low ghrelin levels and become resistant to its effects.
- Blocking the ghrelin receptor with (D‑Lys3)‑GHRP‑6 worsens anorexia and shortens survival.
- The herbal formula rikkunshito improves appetite, gut motility, muscle wasting, anxiety, and survival, and its effect is blocked by a ghrelin antagonist.
- Components of rikkunshito (hesperidin and atractylodin) boost ghrelin secretion and signaling.
Practical Outcomes
- For enthusiasts, using ghrelin secretagogues (e.g., GHRP‑6) could help increase hunger and preserve lean mass, especially during calorie restriction or illness. However, the survival advantage is only shown in cancer models, so expectations should be modest. Exploring safe herbal supplements like rikkunshito or its active ingredients may offer a gentler way to enhance ghrelin signaling, but more human data are needed.
Summary
The study shows that in cancer‑related wasting, the body’s ghrelin (hunger hormone) system is weakened, and boosting ghrelin signaling can improve appetite, gut function, muscle loss, and even extend survival in animal models. Blocking ghrelin makes things worse, while a Japanese herbal mix (rikkunshito) that enhances ghrelin helps. For non‑cancer biohackers, the take‑away is that ghrelin‑boosting agents like GHRP‑6 might aid appetite and muscle maintenance, but the survival benefits seen are specific to disease states.
Abstract
Cancer anorexia-cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut-brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia-cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia-cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia-cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia-cachexia.
Study Information
pubmed
2011
2011-07-26T00:00:00.000Z
10.1038/tp.2011.25
128
57