Cyclo(-Gly-Pro) is a cyclic dipeptide with oral activity, and exhibits antinociceptive activity [1]. Cyclo(-Gly-Pro) inhibits the Escherichia coli tryptophan indole-lyase (TIL) with a Ki value of 17μM through a mixed-type mechanism, which can reduce indole production in bacterial cultures and human fecal samples [2]. Cyclo(-Gly-Pro) has been widely used to inhibit the growth of tumor cells, suppress chitinase and enhance the antibiotic production of microorganisms[3].
In vitro, Cyclo(-Gly-Pro) treatment for 1 hour significantly inhibited the production of TNF-α in RAW 264.7 macrophages induced by lipopolysaccharide (LPS), with an IC50 value of 4.5μg/ml[4].
In vivo, sixty minutes before subcutaneous injection of formalin, intraperitoneal injection of 10μmol/kg dose of Cyclo(-Gly-Pro) (dissolved in 0.9% NaCl) could alleviate the nociceptive behaviors and inflammatory responses in mice[5].
References:
[1] Liu S, Mohri S, Manabe Y, et al. Gly-Pro protects normal human dermal fibroblasts from UVA-induced damages via MAPK-NF-κB signaling pathway[J]. Journal of Photochemistry and Photobiology B: Biology, 2022, 237: 112601.
[2] Oikawa D, Nakayama T. Cyclo-glycylproline, a food-derived diketopiperazine, inhibits bacterial indole production: implications for diabetic nephropathy prevention[J]. Bioscience, Biotechnology, and Biochemistry, 2026, 90(1): 57-65.
[3] Hu L, Lin J, Qin F, et al. Exploring Sources, Biological Functions, and Potential Applications of the Ubiquitous Marine Cyclic Dipeptide: A Concise Review of Cyclic Glycine-Proline[J]. Marine Drugs, 2024, 22(6): 271.
[4] Khan R, Basha A, Goverdhanam R, et al. Attenuation of TNF-α secretion by L-proline-based cyclic dipeptides produced by culture broth of Pseudomonas aeruginosa[J]. Bioorganic & Medicinal Chemistry Letters, 2015, 25(24): 5756-5761.
[5] Ferro J N S, de Aquino F L T, de Brito R G, et al. Cyclo‐Gly‐Pro, a cyclic dipeptide, attenuates nociceptive behaviour and inflammatory response in mice[J]. Clinical and Experimental Pharmacology and Physiology, 2015, 42(12): 1287-1295.
Cyclo(-Gly-Pro)是一种具有口服活性的环状二肽，并表现出抗伤害感受活性[1]。Cyclo(-Gly-Pro)通过混合型机制抑制大肠杆菌色氨酸吲哚裂解酶，Ki值为17μM，可减少细菌培养物和人类粪便样本中吲哚的产生。Cyclo(-Gly-Pro)已被广泛用于抑制肿瘤细胞生长、抑制几丁质酶并增强微生物的抗生素产生[3]。
在体外，Cyclo(-Gly-Pro)处理脂多糖诱导的RAW 264.7巨噬细胞1小时，显著抑制了TNF-α的产生，IC50值为4.5μg/ml [4]。
在体内，在皮下注射福尔马林前60分钟，腹腔注射10μmol/kg剂量的Cyclo(-Gly-Pro)（溶于 0.9% NaCl），可减轻小鼠的伤害性行为和炎症反应[5]。