Humanin (HN) is a novel 24-amino acid mitochondrial-derived peptide that has demonstrated diverse cytoprotective effects, including an emerging role in diabetes. The purpose of this study was to examine the pharmacokinetics of humanin analogues, which show great potential as therapeutic agents (HNG and the non-IGFBP-3 binding, HNGF6A). 11-week-old male IGFBP-3(-/-) and wild type (WT) mice were divided into 3 groups: WT mice treated with HNG, WT mice treated with HNGF6A, and IGFBP-3(-/-) mice treated with HNG. Plasma was obtained from mice following ip injection with HN analogues, and HN levels were measured with ELISA. WT mice treated with HNGF6A and IGFBP-3(-/-) mice treated with HNG displayed a longer half-life of HN compared with WT mice treated with HNG. Following HNG injection, both IGF-1 and IGFBP-3 levels decreased over time. Adult male Sprague Dawley rats were also ip injected with HNG, and HN levels were measured in various tissues (plasma, liver, heart, and brain) by ELISA. The half-life of HN was found to be longer in rats compared with mice. In rats, HN levels were found to be highest in plasma, present in liver, and undetectable in brain or heart. The current study provides evidence of HN and IGFBP-3 association in the circulation and suggests that native HN may modulate the distribution of IGF-1 and IGFBP-3. The results also demonstrate varying kinetic profiles of HN analogues and interspecies variation in rodents. Sustainable levels of circulating HN measured in plasma underline the potential value of HN analogues as a new therapeutic intervention in the treatment of diabetes.
This publication used a rat HN analogue (018-27) from Phoenix Pharmaceuticals.
Chin YP, Keni J, Wan J, et al. Pharmacokinetics and tissue distribution of humanin and its analogues in male rodents. Endocrinology. 2013;154(10):3739-44.
Humanin (HN), a 24-residue peptide, was identified as a novel neuroprotective factor and shows anti-cell death activity against a wide spectrum of Alzheimer's disease (AD)-related cytotoxicities, including exposure to amyloid beta (Abeta), in vitro. We previously demonstrated that the injection of S14G-HN, a highly potent HN derivative, into brain ameliorated memory loss in an Abeta-injection mouse model. To fully understand HN's functions under AD-associated pathological conditions, we examined the effect of S14G-HN on triple transgenic mice harboring APP(swe), tau(P310L), and PS-1(M146V) that show the age-dependent development of multiple pathologies relating to AD. After 3 months of intranasal treatment, behavioral analyses showed that S14G-HN ameliorated cognitive impairment in male mice. Moreover, ELISA and immunohistochemical analyses showed that Abeta levels in brains were markedly lower in S14G-HN-treated male and female mice than in vehicle control mice. We also found the expression level of neprilysin, an Abeta degrading enzyme, in the outer molecular layer of hippocampal formation was increased in S14G-HN-treated mouse brains. NEP activity was also elevated by S14G-HN treatment in vitro. These findings suggest that decreased Abeta level in these mice is at least partly attributed to S14G-HN-induced increase of neprilysin level. Although HN was identified as an anti-neuronal death factor, these results indicate that HN may also have a therapeutic effect on amyloid accumulation in AD.
Although Polygala tenuifolia WILLD (PT) was classically mentioned as an anti-dementia drug in Chinese and Japanese traditional medicine, basic research showed only enhancement of the cholinergic function. In Alzheimer's disease, neuritic atrophy and synaptic loss occur prior to neuronal death event, and may be the first trigger of the memory impairment. Therefore, we studied effects of Polygala tenuifolia WILLD (PT) on Abeta(25-35)-induced neuronal damage using rat cortical neurons for characterization of activities of PT under Abeta-induced neuronal damage. Treatment with the water extract of PT enhanced axonal length dose-dependently after Abeta(25-35)-induced axonal atrophy. However, dendritic atrophy and synaptic loss induced by Abeta(25-35) were not recovered by treatment with PT extract. In contrast, Abeta(25-35)-induced cell damage was completely inhibited by PT extract. By characterization of PT effects on neuronal morphological plasticity and cell damage, usefulness as well as an insufficiency of PT as an anti-dementia drug was clarified.
This publication used a humanin peptide (018-30) from Phoenix Pharmaceuticals.
|018-26||Humanin, Nuclear-encoded / HN (N) (Human)||100 µg||$50|
|018-25||Humanin, Mitochondria-encoded / HN (M) (Human)||100 µg||$140|
|H-018-25||Humanin, Mitochondria-encoded / HN (M) (Human) - Antibody||50 µl||$482|
|B-018-25||Humanin, Mitochondria-encoded / HN (M) (Human) - Biotin Labeled||20 µg||$214|
|B-G-018-25||Humanin, Mitochondria-encoded / HN (M) (Human) - Biotin Labeled Purified IgG||100 µl||$536|
|FC3-G-018-25||Humanin, Mitochondria-encoded / HN (M) (Human) - Cy3 Labeled Purified IgG||100 µl||$589|
|FG-018-25A||Humanin, Mitochondria-encoded / HN (M) (Human) - FAM Labeled||1 nmol||$214|
|FG-G-018-25A||Humanin, Mitochondria-encoded / HN (M) (Human) - FAM Labeled Purified IgG||100 µl||$536|
|T-G-018-25||Humanin, Mitochondria-encoded / HN (M) (Human) - I-125 Labeled Purified IgG||10 µCi||$912|