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Abstract

Regulation Effects of XPJY Decoction on Antioxidative and Mitochondrial Functions in Intracerebral and Extra Brain Tissue of CUMS Rats

Author(s): Yang Li, Qingjie Yuan, Yao Yu, Zhonghui Zhao, Rongjuan Guo

Background and objectives

The treatment of somatic symptoms of depression is a medical problem nowadays. More and more evidences show that oxidative stress and mitochondrial dysfunction may be an important pathogenesis of depression and are closely related to somatic symptoms. Currently, studies on oxidative stress and mitochondrial function are mostly concentrated in the brain, with less attention paid to peripheral tissues, and classical SSRIs are not direct antioxidants in treatment. XingPiJieYu (XPJY) Decoction is one of the most widely used clinical formulas of traditional Chinese medicine. Our study aims to exploring whether it has antioxidative and mitochondrial effects on intracerebral and extra brain tissue.

Materials and Methods

The rat model of depression was established by CUMS (chronic unpredictable mild stress, CUMS) for 6 weeks. They were randomly divided into six groups: control group, CUMS group, CUMS+XPJY (3.6g/kg/d, 7.2g/kg/d, 14.4g/kg/d) groups, CUMS+ sertraline (4.5mg/kg/d) group. We used sucrose preference test and forced swimming test to verify the success of the depression model. The contents of CK and SDH in orbital blood were measured weekly as well as the following assay index were measured on 14th day and 42th day, including MDA, ATP and mtDNA in hippocampus, prefrontal cortex, liver, small intestine and gastrocnemius muscle.

Results

At the 14th day, the sucrose preference ratio was decreased. Besides, the immobility time prolonged at the 42nd day. CUMS increased MDA content in hippocampus, prefrontal cortex and gastrocnemius muscle, but decreased mtDNA content in prefrontal cortex at the 14th day; CUMS decreased serum SDH level at the 35th day, but elevated serum CK level at the 42nd day; CUMS increased MDA content in hippocampus, prefrontal cortex, liver and gastrocnemius muscle, while decreased ATP and mtDNA content in hippocampus, prefrontal cortex, liver, small intestine and gastrocnemius muscle at the 42nd day. XPJY decoction at 14.4g/kg, the efficacy trend of which was better than the other drug groups, could prevent the depressive behavior caused by CUMS, reduce the serum CK content and the MDA content of the tissues mentioned above, and increase serum SDH content as well as ATP, mtDNA content in tissues.

Conclusion

CUMS could induce oxidative stress and mitochondrial dysfunction in hippocampus, PFC, liver, small intestine and gastrocnemius muscle in rats. Early application of sertraline can effectively prevent mtDNA damage in hippocampus, PFC and liver, but its regulation on MDA and ATP is not obvious. However, XPJY decoction plays an significant role in antioxidation by means of improving mitochondrial function, eliminating inflammation and increasing 5-HT content. This research provides an important theoretical basis for the clinical application of XPJY.


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