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Journal of Chinese Integrative Medicine ›› 2010, Vol. 8 ›› Issue (5): 453-457.doi: 10.3736/jcim20100509

• Original Experimental Research • Previous Articles     Next Articles

Effects of Fufang Jiangzhi No.3 on cholesterol-bile acid metabolism in rabbits with hypercholesterolemia

 Qi-qi Maoa, Xu Suna, Dong-ni Qiua, Xiao-dong Fub, Yi Liua, Wen-jian Wangb   

  1. a Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai 200040, China
    b Department of Traditional Chinese Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
  • Received:2010-01-08 Accepted:2010-03-25 Online:2010-05-20 Published:2010-05-15
  • Contact: Xu Sun E-mail:sxzyys@163.com

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Objective

To investigate the effects of Fufang Jiangzhi No. 3, a compound traditional Chinese herbal medicine, on cholesterol-bile acid metabolism in rabbits with hypercholesterolemia and to explore the mechanism.
Methods

Twenty-four male New Zealand white rabbits were randomly assigned into normal control group, untreated group and Fufang Jiangzhi No. 3 group, with 8 rabbits in each group. Rabbits in the untreated group and Fufang Jiangzhi No. 3 group were fed high cholesterol diet to induce hypercholesterolemia. After 4-week treatment, serum total cholesterol and bile acid contents were assessed. Activity of cholesterol 7α-hydroxylase (CYP7A1) in liver tissues was measured by enzyme-linked immunosorbent assay. The expressions of CYP7A1, bile salt export pump (BSEP) and small heterodimer partner (SHP) mRNAs in liver tissues were observed by real-time fluorescent quantitative polymerase chain reaction.
Results

Compared with the normal control group, serum total cholesterol and bile acid contents in the untreated group were increased (P<0.01). Activity of CYP7A1 and expression of CYP7A1 mRNA were decreased and expressions of BSEP and SHP mRNAs were increased in liver tissues in the untreated group as compared with the normal control group (P<0.01). Serum total cholesterol level, and expressions of BSEP and SHP mRNAs in the Fufang Jiangzhi No. 3 group were lower than those in the untreated group (P<0.01). The CYP7A1 activity and expression of CYP7A1 mRNA in the Fufang Jiangzhi No. 3 group were increased as compared with the untreated group (P<0.01), however, there was no significant difference in bile acid between the Fufang Jiangzhi No. 3 group and the untreated group.
Conclusion

Fufang Jiangzhi No. 3 can up-regulate the expression of CYP7A1 mRNA, raise the activity of CYP7A1, and inhibit the expressions of BSEP and SHP mRNAs to regulate the metabolism of total cholesterol in rabbits.

Key words: Bile acid, Cholesterol, Chinese medical formula, Farnesoid X receptor, Cholesterol 7-alpha- hydroxylase, Bile salt export pump, Small heterodimer partner receptor, Rabbits

Table 1

Forward and reverse primers used for real-time fluorescent quantitative PCR"

Gene Primer Length of product (bp)
SHP Forward: 5,-TGGCCC A AG AC ATGGTG AC-3, Reverse ： 5 ^GCTCCTCCAGCAGGATCTTCT-3r 115
BSEP Forward: 5'-CAACGCATTGCTATTGCTCG-3’ Reverse: 5,-GTTCTGGATGGTGGACAAACG-3, 130
CYP7A1 Forward: 5AGG AG A AGGCG A ATGGGTGC-3, Reverse: 5,-GC AC AGCCC AG AT ATGG A ATC-3, 151
GAPDH Forward: 5 '-CCG AGGGCCC ACT A A AGG-3 ’ Reverse: 5,-GCTGTTGAAGTCACAGGAGA-3, 166

Table 2

Levels of serum total cholesterol and bile acid in different groups (x±s)"

Group n Total cholesterol (mmol/L) Bile acid (jumol/L)
Normal control 8 4. 51±0. 45 7. 45±1.33
Untreated 8 23. 14±3. 21* * 13. 95±1. 86〃
Compound No. 3 8 16.21±2.14**AA 13.31±1.27* *

Table 3

Concentration of CYP7A1 and expression of CYP7A1 mRNA in different groups (x±s)"

Group Concentration of n , CYP7A1 mRNA
CYP7A1 (pg/mL)
Normal control 8 0. 80±0. 22 1. 97±1. 50
Untreated 8 0. 44±0. 16** 0. 70±0. 27〃
Compound No. 3 8 0. 81±0. 21AA 3. 87±1. 68**aa

Table 4

Expressions of BSEP and SHP mRNAs in different groups (x±s)"

Group n SHP mRNA BSEP mRNA
Normal control 8 9. 83±2. 50 7. 33±2. 44
Untreated 8 85. 44±6. 79〃 16. 40±3. 01〃
Compound No. 3 8 20. 73±4. 9. 64±1. 63**AA
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