Acer truncatum seed oil has been used to treat normal aging mice, and found that the oil significantly improved the learning and memory ability. Proteomics revealed that acer truncatum seed oil administration changed many proteins expression involving in biological processes, including complement and coagulation cascades, inflammatory response pathway and innate immune response. brain-derived neurotrophic factor(BDNF)/tropomyosin receptor kinase B(TrkB) signaling pathway was also activated by acer truncatum seed oil treatment.

And acer truncatum seed oil administration increased the expression of postsynaptic related proteins including postsynaptic density protein 95(PSD95), glutamate receptor 1(GluA1), and NMDAR1, and decreased the mRNA level of inflammatory factors containing IL-1β, TNF-α, and IL-6. These findings suggest that acer truncatum seed oil holds a promise as a therapeutic food supplement for delaying aging with multiple mechanisms.

In the present study, we found that acer truncatum seed oil improved learning and memory of aging mice, with multiple mechanisms including activation of BDNF/TrkB signaling pathway, up-regulated postsynaptic related proteins expression, and down-regulated inflammatory factors mRNA level. The Venn diagram showed that acer truncatum seed oil treatment reversed the expression of forty-four proteins in the hippocampus of aging mice. Molecular Complex Detection(MCODE) analysis indicated the differentially expressed(DE) proteins in acer truncatum seed oil treated aging mice were related to complement and coagulation cascades, inflammatory response and innate immune response.

In addition, we found that 109 proteins were significantly up-regulated between the aging control mice and young control mice, while only 12 proteins were down-regulated. These aging-related proteins were primarily involved in synapse, oxidative stress, inflammation, mitochondria, and apoptosis process, etc.

Aging is a strong risk factor for multiple diseases including stroke, some aging-associated cancers, neurodegeneration, osteoarthritis, macular degeneration, and many other diseases. It remained a challenge to find effective drugs for the prevention and amelioration of aging.

Diet therapy is considered to be a promising approach to reverse or delay aging. Polyunsaturated acids such as DHA and omega-3, have been widely reported to improve learning and memory on animals, but marine organisms are the major source for DHA and Omega-3. The oil used in this study is derived from the plant seed of acer truncatum, which is easier to obtain in high quantity.

In addition to DHA and Omega-3, acer truncatum seed oil is also rich in linoleic acid, erucic acid, oleic acid, nervonic acids and VE, etc. Previous research showed that the inflammatory responses induced by palmitic acid treatment in the microglial cells were effectively reversed by linoleic acid. DHA diet in the Sprague-Dawley rats increased the expression level of BDNF, which acted on TrkB receptor signaling to attenuate learning disability in rats. Erucic acid improved the learning memory in the model of scopolamine-induced cognitive impairment mice by enhancing the protein level of p-ERK, p-CREB, and p-Akt in the hippocampus.

Age-related cognitive impairment and onset of (Alzheimer’s disease)AD were prevented by given oleic acid supplements in humans. Acer truncatum seed oil rich in nervonic acid treatment markedly improved learning and memory of mouse models, which could better improve by the addition of DHA and VE.

Additionally, antioxidant VE played an essential role in protecting cellular membrane-associated PUFAs from oxidative damage. Therefore, acer truncatum seed oil that has multiple effects, may be a better choice for anti-aging than DHA or Omega-3.

Furthermore, we found that the seed oil had no toxic effects on tissues. As expected, BDNF and TrkB was activated by acer truncatum seed oil treatment in aging mice. Moreover, postsynaptic proteins including PSD95, GluA1, and NMDAR1 were increased. The p-CREB was sensitive to the concentration of the BDNF, which regulated the transcription of specific target genes by BDNF. The level of p-CREB/CREB was significantly up-regulated by acer truncatum seed oil in the aging mouse. In general, CREB/BDNF pathway may underlie the acer truncatum seed oil elevated expression of synaptic proteins in the aging mice to alleviate cognitive impairment.

Aging and age-related diseases share basic mechanisms largely involving in the inflammation. Inflammation was also a prominent aging-associated change in intercellular communication. Indeed, inflammation had recently been proposed as one of the important symptoms of aging. By MCODE analysis, we found that these DE proteins by seed oil treated aging mice vs. aging control mice were involved in innate immune response, inflammatory response pathway and complement and coagulation cascades.

In addition, the gene expression levels of pro-inflammatory factors including IL-1β, IL-6, and TNF-α were rescued by acer truncatum seed oil administration. Thus, the oil may alleviate aging by decreasing the inflammation.

Although only 61 DE proteins were identified in the oil-treated aging mice, 44 up-regulated DE proteins in the aging control were markedly recovered to approximate levels of the young control. These DE proteins were associated with the biological process including cellular response to interferon-beta, vitamin transport, and response to nutrient, etc.

Meantime, PI3K-Akt signaling pathway involved in LAMC1, COL1A1, LAMA5, COL4A1, COL4A2, and FINC, were reversed by acer truncatum seed oil administration in the aging mice. Previous results explored that the PI3K-Akt pathway could regulate the replicative senescence of human vascular smooth muscle cells. Radix Astragali and Radix Astragali preparata exerted anti-aging function via network pharmacology and PI3K-Akt signaling pathway.

The activity of PI3K/Akt signaling influencing neuronal survival and synaptic plasticity was declined in the aging rats of brain. BDNF/TrkB signaling pathway performs a wide range of biological functions including inflammatory response and postsynaptic related proteins. The increased expression of C1q in the prefrontal cortex of adult offspring after maternal immune activation was prevented by activation of TrkB. Akt could also be activated by BDNF/TrkB.

Therefore, BDNF/TrkB signaling pathway may be a key factor for the improvement effects of acer truncatum seed oil. In the next step, we will use BDNF receptor inhibitor K252a to inactivate TrkB, and then investigate whether acer truncatum seed oil treatment still has the improved effects on aging mice.

Proteomics of the hippocampus also showed that there were 121 DE proteins in the aging mice, which mainly involved in synapse, mitochondria, oxidative stress, and apoptosis, etc. In addition, MCODE analysis revealed that the significant module identified from the PPI network including metabolism, cell migration, PI3K-Akt signaling pathway, mitophagy and complement activation, etc. These findings may become the basis for regulating protein expression levels to delay or reverse aging.

In conclusion, we discovered that acer truncatum seed oil improved cognitive deficits of aging mice by multiple pathways containing inflammation, synapse, BDNF/TrkB signaling, and PI3K-Akt signaling pathway. As a dietary supplement, acer truncatum seed oil, containing a variety of unsaturated fatty acids, β-Carotene and VE, would be a potential and effective choice for aging treatment.