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. 2017 Sep;14(3):1961-1966.
doi: 10.3892/etm.2017.4732. Epub 2017 Jul 9.

Effect of the herbal formulation Shen-Zhi-Ling on an APP/PS1 mouse model of Alzheimer's disease by modulating the biliverdin reductase/heme oxygenase 1 system

Sanli Xing  1 , Dingzhu Shen  1 , Chuan Chen  1 , Beiling Wu  1 , Huiying Chi  1
Affiliations

Effect of the herbal formulation Shen-Zhi-Ling on an APP/PS1 mouse model of Alzheimer's disease by modulating the biliverdin reductase/heme oxygenase 1 system

Sanli Xing et al. Exp Ther Med. 2017 Sep.

Abstract

Shen-Zhi-Ling (SZL) oral liquid is a traditional Chinese medicine formula that is mainly used for the clinical treatment of mild to moderate Alzheimer's disease (AD). The aim of the present study was to investigate the effects and underlying mechanisms of SZL treatment on AD. APP/PS1 transgenic mice were utilized to evaluate the effect of SZL treatment (0.5 g/20 g/day). Morris water maze and Thioflavin S staining analyses were used to evaluate the cognitive impairment and β-amyloid plaques, respectively, while quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein expression levels of heme oxygenase 1 (HO-1) and biliverdin reductase (BVR). Furthermore, immunofluorescence staining was used to measure the BVR and HO-1 protein levels in the hippocampus. The findings of the current study demonstrated that SZL treatment was able to ameliorate the impairment of memory and reduce the accumulation of amyloid plaques, and its ameliorating effects may be attributed to the modulation of the HO-1/BVR system in the hippocampus. These results indicate that SZL may be a possible complementary and alternative therapy to delay the development of AD.

Keywords: Alzheimer's disease; Shen-Zhi-Ling oral liquid; biliverdin reductase; heme oxygenase 1.

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Figures

Figure 1.
Figure 1.
APP/PS1 mice exhibit decreased performance in the Morris water maze task, which is improved by SZL treatment. (A) Escape latency (time required to find the hidden platform) was determined in 5-day trial study. (B) Time spent in the target quadrant and (C) the number of platform crosses were determined on day 6 (probe trial; total time of the trial, 70 sec). Data are expressed the mean + standard error (n=10). *P<0.05 and **P<0.01 vs. C57BL/6 group; #P<0.05 vs. APP/PS1 group. SZL, Shen-Zhi-Ling.
Figure 2.
Figure 2.
Histological examples of Thioflavin S staining in the hippocampus and SZL treatment can reduce the number of amyloid plaques. SZL, Shen-Zhi-Ling.
Figure 3.
Figure 3.
Effects of SZL treatment on mRNA expression levels of (A) BVR and (B) HO-1 in the hippocampus of mice after 12 weeks of treatment, determined by reverse transcription-quantitative polymerase chain reaction. Values are demonstrated as the mean + standard error. *P<0.05 and **P<0.01 vs. C57BL/6 group; #P<0.05 and ##P<0.01 vs. APP/PS1 group. SZL, Shen-Zhi-Ling; BVR, biliverdin reductase; HO-1, heme oxygenase 1.
Figure 4.
Figure 4.
Western blot analyses of BVR and HO-1 levels in the hippocampus homogenates from 9-month-old mice. *P<0.05 and **P<0.01 vs. C57BL/6 group; #P<0.05 vs. APP/PS1 group. SZL, Shen-Zhi-Ling; BVR, biliverdin reductase; HO-1, heme oxygenase 1.
Figure 5.
Figure 5.
Effect of SZL treatment on the expression of (A) BVR and (B) HO-1, detected by immunofluorescence staining. Representative photomicrograph was shown. SZL, Shen-Zhi-Ling; BVR, biliverdin reductase; HO-1, heme oxygenase 1.
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