Phytomedicine: Zishen Pills Relieve Diabetes-Related Cognitive Impairment

Background: Diabetic cognitive impairment (DCI) is prevalent in patients with diabetes, but its underlying mechanism is unclear and there are no better therapeutic drugs
.
Skeletal muscle is an important pathological organ of diabetes

.

Diabetic Cognitive Impairment (DCI) Diabetic Cognitive Impairment (DCI) Skeletal Muscle Skeletal Muscle Kynurenine (KYN) Kynurenine (KYN) KYNA KYNA KATs KATs PGC-1α-PPARα PGC-1α-PPARα PGC- 1α-KYN pathway PGC-1α-KYN pathway

In Chinese medicine, the main pathogenesis of DCI is "toxin damages the brain and collaterals " and " deficiency of kidney essence ", while " clearing heat and detoxifying " and " tonifying kidney and preserving essence " are the main treatment principles
.
Tongguan Pill (TGW) , also known as Zishen Pill (ZSW) or Zishen Tongguan Pill, is recorded in Li Dongyuan's "Orchid Secret Collection" in the Yuan Dynasty.

Toxin damages the brain and collaterals Toxin damages the brain collaterals and kidney essence Deficiency Kidney essence deficiency Clears heat and detoxification , clears heat and detoxifies the kidney, protects the essence , nourishes the kidney and protects the Jing Tongguan Pill (TGW) Clearance Pill (TGW) Zishen Pill (ZSW) Zishen Pill (ZSW) Enhanced Kidney- tonifying effect enhanced kidney-tonifying effect Zishen Wanfang (ZSWF) Zishen Wanfang (ZSWF)

Objective: From the perspective of peripheral skeletal muscle and brain communication, to explore the effect of ZSWF on the cognitive function of DCI mice and its mechanism, and to provide new strategies and prescriptions for clinical prevention and treatment of DCI
.

Effects of ZSWF on Cognitive Function of DCI Mice Effects of ZSWF on Cognitive Function of DCI Mice

Methods: DCI was induced by intraperitoneal injection of streptozotocin (STZ) combined with a high-fat diet , and ZSWF extracts of different doses were administered orally for 8 weeks, once a day
.
Cognitive function (water maze test) and skeletal muscle function ( grip test, muscle weight, HE-stained quadriceps cross section) were assessed, and synaptic plasticity was measured ( synaptophysin SYN, postsynaptic density protein PSD-95 expression in the hippocampus of DCI mice) and type 1 amino acid transporter (LAT1)

.

Intraperitoneal injection of streptozotocin (STZ) combined with high-fat diet Intraperitoneal injection of streptozotocin (STZ) combined with high-fat diet cognitive function cognitive function Its metabolites and metabolic enzymes KYN and its metabolites and metabolic enzymes PGC-1α PGC-1α PPARα PPARα

RESULTS: Compared with healthy mice, DCI mice exhibited cognitive decline and abnormal skeletal muscle function, as well as imbalance of KYN metabolism in brain, circulating blood, and skeletal muscle
.
Cognitive function, synaptic plasticity, and skeletal muscle function were significantly attenuated in DCI mice 8 weeks after ZSWF administration

.

Conclusion: The above results indicate that KYN metabolism disorder mediated by abnormal skeletal muscle PGC1α-PPARα signaling is one of the pathological mechanisms of DCI.
ZSWF can increase the expression of skeletal muscle KATs and maintain the stability of KYN metabolism by activating skeletal muscle PGC1α-PPARα signaling.
state, and ultimately improve synaptic plasticity and improve cognitive performance .
This provides some theoretical support for ZSWF clinical treatment of DCI .

Skeletal muscle PGC1α-PPARα signaling abnormal Skeletal muscle PGC1α-PPARα signaling abnormal KYN metabolic disorder KYN metabolic disorder

 

Source:

Source:

Yin Q, Zhang L, Han X, et al.
Zi Shen Wan Fang regulates kynurenine metabolism to alleviate diabetes-associated cognitive impairment via activating the skeletal muscle PGC1α-PPARα signaling [published online ahead of print, 2022 Feb 22].
Phytomedicine .

2022 ;99:154000.
doi:10.

Yin Q, Zhang L, Han X, et al.
Zi Shen Wan Fang regulates kynurenine metabolism to alleviate diabetes-associated cognitive impairment via activating the skeletal muscle PGC1α-PPARα signaling [published online ahead of print, 2022 Feb 22].
Phytomedicine .
2022 ;99:154000.
doi:10.
1016/j.
phymed.
2022.
154000 Phytomedicine commented here