ZiBuPiYin Recipe Protects db/db Mice from Diabetes-Associated Cognitive Decline through Improving Multiple Pathological Changes

Abstract

Multiple organ systems, including the brain, which undergoes changes that may increase the risk of cognitive decline, are adversely affected by diabetes mellitus (DM). Here, we demonstrate that type 2 diabetes mellitus (T2DM) db/db mice exhibited hippocampus-dependent memory impairment, which might associate with a reduction in dendritic spine density in the pyramidal neurons of brain, Aβ1-42 deposition in the prefrontal cortex (PFC) and hippocampus, and a decreased expression of neurostructural proteins including microtubule-associated protein (MAP2), a marker of dendrites, and postsynaptic density 95 (PSD95), a marker of excitatory synapses. To investigate the effects of the ZiBuPiYin recipe (ZBPYR), a traditional Chinese medicine recipe, on diabetes-related cognitive decline (DACD), db/db mice received daily administration of ZBPYR over an experimental period of 6 weeks. We then confirmed that ZBPYR rescued learning and memory performance impairments, reversed dendritic spine loss, reduced Aβ1-42 deposition and restored the expression levels of MAP2 and PSD95. The present study also revealed that ZBPYR strengthened brain leptin and insulin signaling and inhibited GSK3β overactivity, which may be the potential mechanism or underlying targets of ZBPYR. These findings conclude that ZBPYR prevents DACD, most likely by improving dendritic spine density and attenuating brain leptin and insulin signaling pathway injury. Our findings provide further evidence for the effects of ZBPYR on DACD.

Astragaloside IV Attenuates Podocyte Apoptosis Mediated by Endoplasmic Reticulum Stress through Upregulating Sarco/Endoplasmic Reticulum Ca2+-ATPase 2 Expression in Diabetic Nephropathy

“…After 8 weeks of treatment, mice were fasted for 6 h (8:00 AM to 2:00 PM), and the oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) experiments were performed as previously described (Chen et al, 2014b; Wang C. et al, 2014). Briefly, the animals were orally administered with glucose (2 g kg -1 body weight) or intraperitoneally administrated with insulin (0.75 U kg -1 body weight), and blood glucose levels were monitored over a 2 h period using Omron Glucometer.…”

Simultaneous determination of eight ginsenosides in Zibu Piyin Recipe using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UPLC-MS/MS)

“…Traditional Chinese medicine (TCM) plays an important role in clinical treatment by providing multicomponent, multi-pathway, and multi-target regulation with fewer side effects. 11 We also previously determined the content of volatile oils and polysaccharides in ZBPYR using gas chromatography/mass spectrometry (GC/MS) and sulfuric acid-anthrone colorimetry, respectively. [1][2][3] For example, Zibu Piyin Recipe (ZBPYR) is a TCM formula prescribed to treat amnesia.…”

Obesity, diabetes, and leptin resistance promote tau pathology in a mouse model of disease

“…One barrier that we encountered when using the Lepr db/db model is that these mice have a substantially decreased lifespan (approximately 15 to 16 months) and can develop severe complications associated with obesity and metabolic dysfunction. It is occasionally observed that db/db mice have deficits in the Morris water maze (Chen et al, 2014), these studies are mostly confined to younger animals (~3 months of age) than those used in the current study (~6 months). Although the precise reason for this discrepancy is beyond the scope of the current study, these deficits are typically quite small, and it is possible that they are transitory and can be compensated for as the mice mature.…”