The major anthocyanin of Lycium ruthenicum Murr. relieves cognitive deficits, oxidative stress, neuroinflammation, and hippocampal metabolome alterations in aging rats

Abstract

• Pn3G5G is the most abundant anthocyanin in LRF. • Long term administration of Pn3G5G improved cognitive impairment of aging rats. • Pn3G5G reduced hippocampal pathologic changes, oxidative stress, and inflammation. • Pn3G5G effectively restored the abnormal hippocampal metabolites in aging rats. Lycium ruthenicum Murr. fruit (LRF) is a functional food that abundant in anthocyanins. In this study, the neuroprotection of the major anthocyanin in LRF, namely petunidin-3,5-O-diglucosides (Pn3G5G), was investigated in D-galactose-induced aging rats. Our results showed that administration of Pn3G5G by oral gavage (100 mg/kg·bw) for 7 weeks did not influence the body weight and motor function of rats. More importantly, Pn3G5G could relieve cognitive deficits, mitigate cortical and hippocampal neuron loss, reduce the levels of aging-related markers (AGEs and MDA), increase the ratio of GSH/GSSG, and suppress neuroinflammation in the hippocampus. LC-MS-based metabolomics revealed that Pn3G5G could restore the altered hippocampal metabolic profile. In total, 39 differential metabolites and 47 pathways were involved. Particularly, Pn3G5G corrected amino acid metabolic problems by restoring the levels of L-cystine, L-histidine, L-serine, S-sulfo-L-cysteine, L-asparagine, glutathione (reduced form), L-saccharopine, N-acetyl-L-leucine, 5-oxoproline (pyroglutamic acid), 3-N-methyl-L-histidine and N-methyl-L-glutamate to protect neurons from oxidative stress and inflammatory damage. Besides, Pn3G5G also regulate ABC transporters, protein digestion and absorption, and biosynthesis of cofactors to prevent abnormal energy metabolism of neurons. In conclusion, Pn3G5G likely enhance antioxidant and anti-inflammatory defenses, as well as maintain normal function of hippocampus through influencing these metabolic pathways, thereby alleviating cognitive impairment in aging rats.