Neuroprotective effects of ProBeptigen/CMI-168 on aging-induced cognitive decline and neuroinflammation in mice: a comparison with essence of chicken

Abstract

Neuroinflammation and cognitive decline are the key pathological features in aging that bring detrimental impacts upon quality of life. However, there is no effective anti-aging pharmacological therapy thus far. Dietary supplements in particular essence of chicken (EC) has been found to be an effective remedy for alleviating mental stress and improving memory. In addition, a novel hydrolyzed chicken extract, ProBeptigen/CMI-168 (PB), showed beneficial effects on cognitive ability. However, the antiaging effect and possible mechanism of PB and EC are still unknown. Here, we investigated the antiaging effects of PB and EC on hippocampus-related cognitive decline and neuroinflammation in aged mice. PB and EC were administered for 16 weeks in 10-month-old mice. Both PB and EC treatments ameliorated age-related deterioration of learning and memory, and attenuated oxidative stress and inflammation in the hippocampus. These results were associated with decreased inflammatory cytokine levels and increased neurotransmitter levels in the hippocampus. The overall effects of improving aging-induced cognitive decline were more robust in PB-treated mice, while EC was effective in decreasing oxidative stress and inflammation. Moreover, alterations in the diversity and composition of the gut microbiota in aged mice were also regulated by both PB and EC, which induced distinguished features in the gut microbiota and their related functions. This study showed that PB exerts neuroprotective effects in aged mice, the mechanism of which might be different from that of EC. Therefore, PB has a potential as dietary supplement for ameliorating cognitive dysfunction and neuroinflammation in elderly individuals.

Hydrolyzed Chicken Meat Extract Attenuates Neuroinflammation and Cognitive Impairment in Middle-Aged Mouse by Regulating M1/M2 Microglial Polarization

“…A novel extract from chicken meat, that is, hydrolyzed chicken extract (HCE) has undergone a proprietary bioprocessing technology and aqueous extraction as described previously. − HCE supplementation exhibited favorable neuroprotective effects in rodent studies, including improving learning ability, attenuating memory loss, and brain oxidative stress. , One recent clinical study found that HCE treatment improved stress-induced cognitive decline and alleviated inflammation in healthy middle-aged humans . In addition, our previous study suggested that HCE exerted impacts on ameliorating neuroinflammation, gliosis, oxidative stress, and cognitive decline in naturally aged mice compared with the traditional essence of chicken supplementation . However, the actual bioactive components (BCs) that contribute to the amelioration of neuropathology remains to be elucidated.…”

Hydrolyzed Chicken Extract (ProBeptigen®) on Cognitive Function in Healthy Middle-Aged People: A Randomized Double-Blind Trial

“…These results imply a potential anti-aging effect of ProBeptigen ® in alleviating cognitive deficits and promoting the antioxidant defense system [32]. In the most recent study using naturally aged mice, ProBeptigen ® ameliorated age-induced cognitive decline, reduced oxidative stress, and reduced neuroinflammation in the hippocampus and cortex [34]. A pilot clinical study [33] on 20 healthy subjects with six weeks of ProBeptigen ® (670 mg/day) consumption showed that ProBeptigen ® enhanced cognitive performances on Digit Span backwards, Letter-Number Sequencing, and the Rey Auditory Verbal Learning Test (RAVLT), in terms of working memory and episodic memory functions.…”

“…The declining levels of hs-CRP, an indicator of inflammation and cardiovascular risks, during and after ProBeptigen ® treatment is noteworthy. Chronic low-grade inflammation is a hallmark of aging, and a recent study [34] in naturally aged mice showed similarly that ProBeptigen ® exerted anti-neuroinflammatory effects and significantly diminished levels of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β), in the hippocampus and cortex, alongside antioxidant effects and improved learning and memory. It is suggested that the reduced levels of these cytokines could be explained by significantly decreased phosphorylation levels of nuclear factor-kB (NF-kB) p65 which may contribute to many age-related neuroinflammatory diseases if immunoreactivity is enhanced for NF-kB signaling [75].…”

“…This study purposefully included middle-aged subjects due to mechanisms of action of ProBeptigen ® beneficial in aging, and preclinical evidence of learning and memory efficacy in middle-aged or aged mice. Specifically, the antioxidant [32] and anti-inflammatory [34] mechanisms, reduction of mitochondrial DNA damage in the brain, and increased dopamine levels [32] are plausible mechanisms of action for improving cognitive function in middle-aged subjects. In this trial, the anti-inflammatory effects of ProBeptigen ® was confirmed in humans, as hs-CRP levels declined over time.…”

Dipeptide Extract Modulates the Oxi-Antioxidant Response to Intense Physical Exercise

“…One of recent clinical studies found that hydrolysed chicken extract treatment improved stress-induced cognitive decline and alleviated inflammation in healthy middle-aged humans [51]. Another available study by Ni et al [52] suggested that chicken meat extract ameliorated neuroinflammation, gliosis, oxidative stress and cognitive decline in naturally aged mice. Rezzani et al [2], in turn, demonstrated that a carnosine analogue improved oxidative stress, inflammation and cell metabolism, thereby becoming a greatly promising therapeutic molecule.…”