1. Gly-Pro protects normal human dermal fibroblasts from UVA-induced damages via MAPK-NF-κB signaling pathway
Shuyu Liu, Shinsuke Mohri, Yuki Manabe, Akika Ejima, Kenji Sato, Tatsuya Sugawara J Photochem Photobiol B. 2022 Dec;237:112601. doi: 10.1016/j.jphotobiol.2022.112601. Epub 2022 Nov 18.
Photoaging is characterized by skin dysfunction and wrinkle formation predominantly caused by chronic exposure to ultraviolet (UV) irradiation. Collagen peptides are well-recognized as nutritional supplements for enhancing skin health. Gly-Pro, a dipeptide found in collagen as a major repetitive sequence, is considered a prospect collagen peptide derivative that displays anti-photoaging potential. Herein, we evaluated the photoprotective effects of Gly-Pro in normal human dermal fibroblasts (NHDFs). Pretreatment by Gly-Pro at a concentration of 0.1 μM inhibited UVA-driven generation of reactive oxygen species (ROS) in NHDFs and attenuated UVA-induced changes in mRNA expression and activation of proteins of the MAPK-NF-κB signaling pathway. Meanwhile, Pro-Gly and cyclo(-Gly-Pro), two dipeptides that are structurally similar to Gly-Pro, depicted less anti-photoaging effects against UVA irradiation. Collectively, our data suggests that Gly-Pro has potential as a novel ingredient in nutricosmetic products for skincare and anti-photoaging.
2. Cyclo-Gly-Pro, a cyclic dipeptide, attenuates nociceptive behaviour and inflammatory response in mice
Jamylle Nunes de Souza Ferro, et al. Clin Exp Pharmacol Physiol. 2015 Dec;42(12):1287-95. doi: 10.1111/1440-1681.12480.
The present study aimed to investigate the antinociceptive and anti-inflammatory effects of the cyclic dipeptide cyclo-Gly-Pro (CGP) in mice. Antinociceptive activity was assessed by employing different pain models, such as formalin test, acetic acid-induced writhing, hot plate test, and carrageenan-induced hyperalgesia, in mice. The number of c-Fos-immunoreactive cells in the periaqueductal gray (PAG) was evaluated in CGP-treated mice. Anti-inflammatory activity was evaluated using paw oedema induced by carrageenan, compound 48/80, serotonin, and prostaglandin E2 (PGE2) and analyzed by plethysmometry. Quantitation of myeloperoxidase (MPO) in the paw was carried out to analyze the presence of neutrophils in the tissue. Intraperitoneal injection of CGP produced a significant inhibition in both neurogenic and inflammatory phases of formalin-induced pain. The antinociceptive effect of CGP, evaluated in the acetic acid-induced writhing test, was detected for up to 6 h after treatment. Further, in the hot plate test, antinociceptive behaviour was evoked by CGP, and this response was inhibited by naloxone. Animals treated with CGP did not present changes in motor performance. In CGP-treated mice there was an increase in the number of c-Fos-positive neurons in the periaqueductal gray. In another set of experiments, CGP attenuated the hyperalgesic response induced by carrageenan. Furthermore, CGP also reduced the carrageenan-increased MPO activity in paws. In addition, CGP also reduced the paw oedema evoked by compound 48/80, serotonin, and PGE2 . Taken together, these results may support a possible therapeutic application of the cyclic dipeptide cyclo-Gly-Pro toward alleviating nociception and damage caused by inflammation conditions.
3. Restoration of Cyclo-Gly-Pro-induced salivary hyposecretion and submandibular composition by naloxone in mice
Igor Santana Melo, et al. PLoS One. 2020 Mar 10;15(3):e0229761. doi: 10.1371/journal.pone.0229761. eCollection 2020.
Cyclo-Gly-Pro (CGP) attenuates nociception, however its effects on salivary glands remain unclear. In this study, we investigated the acute effects of CGP on salivary flow and composition, and on the submandibular gland composition, compared with morphine. Besides, we characterized the effects of naloxone (a non-selective opioid receptor antagonist) on CGP- and morphine-induced salivary and glandular alterations in mice. After that, in silico analyses were performed to predict the interaction between CGP and opioid receptors. Morphine and CGP significantly reduced salivary flow and total protein concentration of saliva and naloxone restored them to the physiological levels. Morphine and CGP also reduced several infrared vibrational modes (Amide I, 1687-1594cm-1; Amide II, 1594-1494cm-1; CH2/CH3, 1488-1433cm-1; C = O, 1432-1365cm-1; PO2 asymmetric, 1290-1185cm-1; PO2 symmetric, 1135-999cm-1) and naloxone reverted these alterations. The in silico docking analysis demonstrated the interaction of polar contacts between the CGP and opioid receptor Cys219 residue. Altogether, we showed that salivary hypofunction and glandular changes elicited by CGP may occur through opioid receptor suggesting that the blockage of opioid receptors in superior cervical and submandibular ganglions may be a possible strategy to restore salivary secretion while maintaining antinociceptive action due its effects on the central nervous system.
