Abstract

ZSWF, a traditional Chinese medicine and nutritional supplement for nourishing kidney, presents ameliorating cognitive deficits effect. However, its mechanism remains unclear. Imbalance of neural mitochondrial homeostasis is a pathogenesis of AD. Considering “tonify kidney and nourish encephala” in traditional Chinese medicine theory is consistent with “mitochondria provides energy for neuros to maintain brain activity”, we hypothesized whether ZSWF could improve cognitive ability by regulating neuronal mitochondrial homeostasis. In this study, we firstly confirmed that ZSWF could improve the cognitive function of SAMP8 mice, alleviate histopathological lesion and inhibit neuro apoptosis. Then the components of ZSWF in cerebrospinal fluid and hippocampus were identified to fish their potential targets, which further indicated ZSWF might regulate mitochondrial homeostasis. Experimentally, we verified that ZSWF could reverse the neuronal mitochondrial loss of SAMP8 mice by upregulating PINK1, Parkin and PGC-1α to simultaneously regulate mitophagy and mitochondrial biogenesis to maintain mitochondrial homeostasis.