YQBS Improves Cognitive Dysfunction in Diabetic Rats: Possible Association with Tyrosine and Tryptophan Metabolism

Yuzhao Liu; Jingru Cai; Yangang Wang; Xiangli Zhao; Yun Qiao; Chuan-Ju Liu

doi:10.2147/DMSO.S401863

YQBS Improves Cognitive Dysfunction in Diabetic Rats: Possible Association with Tyrosine and Tryptophan Metabolism

Diabetes Metab Syndr Obes. 2023 Mar 30:16:901-912. doi: 10.2147/DMSO.S401863. eCollection 2023.

Authors

Yuzhao Liu^#¹, Jingru Cai^#², Yangang Wang¹, Xiangli Zhao³, Yun Qiao⁴, Chuan-Ju Liu³

Affiliations

¹ Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
² Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China.
³ Department of Orthopaedic Surgery, New York University Grossman School of Medicine, New York, NY, USA.
⁴ Department of Traditional Chinese Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.

^# Contributed equally.

Abstract

Objective: This study is aimed to determine the metabolomic effects of the hybrid medicine formula Yi-Qi-Bu-Shen (YQBS) on the neurotransmitter aspects of cognitive impairment in diabetic rats.

Methods: In the current study, streptozotocin (STZ) was used to induce diabetic animal model in male Sprague Dawley (SD) rats. After successful establishment of diabetic SD rats' model, age-matched healthy SD rats and diabetic SD rats were treated with low and high doses of YQBS, and then tested for learning memory ability and analyzed for pathological changes. In addition, neurotransmitter metabolic changes in hippocampal subdivisions of rats from different treated groups were analyzed using liquid chromatography-mass spectrometry (LC-MS) technique.

Results: YQBS could significantly improve memory-cognitive impairment in diabetic rats as evidenced by the shortening of latency to target and the reduction of latency first entrance to target. Moreover, YQBS also improved the pathological alterations in the hippocampal region in the brains of diabetic rats. Metabolomic analysis showed that the expression of noradrenaline hydrochloride was down-regulated and the expressions of levodopa and 5-hydroxytryptophan were up-regulated in the hippocampal tissues of diabetic rats treated with YQBS.

Conclusion: These findings demonstrate that YQBS has protective effects against diabetic cognitive dysfunction, which might act through alteration in tyrosine and tryptophan metabolism.

Keywords: Yi-Qi-Bu-Shen; cognitive dysfunction; diabetes mellitus; hippocampus; metabolomics.

Grants and funding

This work is supported partly by the National Natural Science Foundation of China (grant no. 81173250), the Project of Qilu geriatrics traditional and western confluence school of Shandong Province, China (grant no.2022-93-10), and a research grant from Atreaon, Inc (Boston, MA, USA).