[an error occurred while processing this directive]

Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (7): 814-820.doi: 10.3736/jcim20120713

• Original Experimental Research • Previous Articles     Next Articles

Effects of Chinese herbal medicine Guanxinkang on expression of PPARγ-LXRα-ABCA1 pathway in ApoE-knockout mice with atherosclerosis

Mei-jiao Mao1, Jun-ping Hu1, Cong Wang2, Yi-yi Zhang1, Ping Liu1()   

  1. 1. Science and Technology Agency, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
    2. Celluar Biology Laboratory, Seientific Research Center, Shanghai Public Health Clinical Center, Shanghai 201508, China
  • Received:2011-10-24 Accepted:2011-11-28 Online:2012-07-20 Published:2018-07-15
  • Contact: Ping Liu E-mail:liuping23@sina.com

RichHTML

2

PDF (PC)

77

Like

Objective: To observe the effects of Guanxinkang (GXK) decoction, a compound traditional Chinese herbal medicine, on expressions of peroxisome proliferator-activated receptor γ (PPARγ), liver X receptor α (LXRα) and ATP-binding cassette transporter A1 (ABCA1) in apolipoprotein E (ApoE)-knockout mice with atherosclerosis.
Methods: Fourteen 6-week-old C57BL/6 J mice were used as normal control group. Seventy 6-week-old ApoE-knockout mice receiving a high-cholesterol diet to induce atherosclerosis were randomly divided into untreated group, simvastatin group and low-dose (concentration of crude drugs at 0.864 g/mL), medium-dose (crude drugs at 1.728 g/mL) and high-dose (crude drugs at 3.456 g/mL) GXK groups. After treated with the drugs for eight weeks continuously, the livers and aortas of mice were separated. The expressions of PPARγ, LXRα and ABCA1 were measured by real-time quantitative polymerase chain reaction and Western blotting respectively.
Results: Compared with the normal control group, mRNAs and proteins of PPARγ, LXRα and ABCA1 over-expressed in the untreated group (P<0.05). After the treatment, GXK decoction and simvastatin decreased the expressions of PPARγ, LXRα and ABCA1 (P<0.05). High-dose GXK decoction had more marked effects than low- and medium-dose GXK and simvastatin.
Conclusion: The PPARγ-LXRα-ABCA1 pathway is involved in lipid regulation and inflammation activities. Over-expression of the genes has complicated effects on atherosclerosis in ApoE-knockout mice with high-cholesterol diet. GXK decoction has anti-inflammatory and anti-matrix metalloproteinase activities by regulating PPARγ, LXRα and ABCA1 interactions in the ApoE-knockout mice.

Key words: drugs, Chinese herbal, atherosclerosis, apolipoprotein E, ATP-binding cassette transporter A1, peroxisome proliferator-activated receptor γ, liver X receptor α, mice

Table 1

Reactive system of real-time fluorescent quantization PCR"

Content Volume (μL)
2×Toyobo Premix EX Taq 12.5
FCD 1
ddH2O 8.8
Primers 0.7
Template 2

Table 2

Relative expression levels of PPARγ, LXRα and ABCA1 mRNAs in livers of ApoE-knockout mice (x±s)"

Group n PPARγ mRNA LXRα mRNA ABCA1 mRNA
Normal control 8 1.02±0.18 1.02±0.16 1.05±0.32
Untreated 8 8.54±0.82** 3.63±1.35** 4.95±0.63**
Simvastatin 8 6.54±1.59*△ 1.89±0.69*△ 3.77±0.95*△
Low-dose GXK 8 8.19±1.83*▲▲□□■■ 3.14±0.68*▲▲□□■■ 4.82±1.27*▲▲□□■■
Medium-dose GXK 8 6.08±1.56*△ 1.98±0.38*△ 3.59±0.44*△
High-dose GXK 8 2.25±0.92△▲▲□□ 1.51±0.64△ 1.66±0.34△▲▲□□

Table 3

Relative expression levels of PPARγ, LXRα and ABCA1 mRNAs in aortas of ApoE-knockout mice (x±s)"

Group n PPARγ mRNA LXRα mRNA ABCA1 mRNA
Normal control 8 1.04±0.34 1.01±0.16 1.03±0.30
Untreated 8 7.88±1.21** 2.14±0.51** 4.50±1.00**
Simvastatin 8 6.07±1.65*△△ 1.36±0.38△△ 2.77±0.59*△△
Low-dose GXK 8 7.34±0.69*▲□■ 1.80±0.37*▲□■ 4.26±1.22*▲▲□■
Medium-dose GXK 8 5.68±0.71*△△ 1.43±0.31*△△ 2.65±0.80*△△
High-dose GXK 8 2.48±0.42*△△▲▲□□ 0.98±0.28△△▲□ 1.26±0.16△△▲▲□□

Figure 1

Expressions of PPARγ, LXRα and ABCA1 proteins in livers (A) and aortas (B) of ApoE-knockout mice H: High-dose GXK group; M: Medium-dose GXK group; L: Low-dose GXK group; N: Normal control group; C: Untreated group; S: Simvastatin group. PPARγ: peroxisome proliferator-activated receptor γ; LXRα: liver X receptor α; ABCA1: ATP-binding cassette transporter A1; GXK: Guanxinkang; GAPDH: glyceraldehyde-3-phosphate dehydrogenate."

Table 4

Relative expression levels of PPARγ、LXRα、ABCA1 proteins in livers of ApoE-knockout mice (x±s)"

Group n PPARγ protein LXRα protein ABCA1 protein
Normal control 8 0.33±0.05 0.38±0.06 1.49±0.08
Untreated 8 1.64±0.06* 1.37±0.32* 2.22±0.02*
Simvastatin 8 0.61±0.06*△ 1.10±0.06*△ 1.90±0.07*△
Low-dose GXK 8 1.01±0.03*△▲□■ 1.02±0.10*△□■ 1.21±0.25*△▲□■
Medium-dose GXK 8 0.49±0.01*△▲ 0.58±0.12△▲ 0.77±0.18*△▲
High-dose GXK 8 0.51±0.01*△▲ 0.76±0.22*△▲ 0.34±0.13*△▲□

Table 5

Relative expression levels of PPARγ, LXRα and ABCA1 proteins in aortas of ApoE-knockout mice (x±s)"

Group n PPARγ protein LXRα protein ABCA1 protein
Normal control 8 0.36±0.04 0.19±0.02 1.66±0.04
Untreated 8 2.99±0.24* 2.18±0.32* 2.62±0.22*
Simvastatin 8 1.25±0.19*△ 1.69±0.05*△ 1.06±0.15*△
Low-dose GXK 8 1.23±0.05*△□■ 1.38±0.07*△□■ 1.18±0.04*△□■
Medium-dose GXK 8 0.88±0.06*△▲ 1.16±0.23*△▲ 0.33±0.04*△▲
High-dose GXK 8 0.67±0.08*△▲ 0.80±0.19*△▲□ 0.15±0.01*△▲
[1] Soumian S, Albrecht C, Davies AH, Gibbs RG . ABCA1 and atherosclerosis[J]. Vasc Med, 2005,10(2):109-119
doi: 10.1191/1358863x05vm593ra
[2] Mao MJ, Hu JP, Chen FR, Zhang YY, Liu P . Effects of Chinese herbal medicine Guanxinkang on lipid metabolism and serum C-reactive protein, amyloid A protein, and fibrinogen in apolipoprotein E-knockout mice with atherosclerosis[J]. J Chin Integr Med, 2011,9(3):306-312
毛美娇, 胡俊萍, 陈富荣, 章怡祎, 刘萍 . 冠心康对载脂蛋白E基因敲除动脉粥样硬化小鼠血脂及炎性标志物的影响[J]. 中西医结合学报, 2011,9(3):306-312
[3] Hanriot D, Bello G, Ropars A, Seguin-Devaux C, Poitevin G, Grosjean S, Latger-Cannard V, Devaux Y, Zannad F, Regnault V, Lacolley P, Mertes PM, Hess K, Longrois D . C-reactive protein induces pro- and anti-inflammatory effects, including activation of the liver X receptor alpha, on human monocytes[J]. Thromb Haemost, 2008,99(3):558-569
doi: 10.1160/TH07-06-0410
[4] Filep JG . Perplexity of monocyte responses to C-reactive protein(CRP)[J]. Thromb Haemost, 2008,99(3):461-462
doi: 10.1160/TH08-02-0072 pmid: 18327390
[5] Lawn RM, Wade DP, Couse TL, Wilcox JN . Localization of human ATP-binding cassette transporter 1(ABC1) in normal and atherosclerotic tissues[J]. Arterioscler Thromb Vasc Biol, 2001,21(3):378-385
doi: 10.1161/01.ATV.21.3.378
[6] Reddy ST, Hama S, Ng C, Grijalva V, Navab M, Fogelman AM . ATP-binding cassette transporter 1 participates in LDL oxidation by artery wall cells[J]. Arterioscler Thromb Vasc Biol, 2002,22(11):1877-1883
doi: 10.1161/01.ATV.0000035700.82829.2A pmid: 12426219
[7] Joyce CW, Amar MJ, Lambert G, Vaisman BL, Paigen B, Najib-Fruchart J, Hoyt RF Jr, Neufeld ED, Remaley AT, Fredrickson DS, Brewer HB Jr, Santamarina-Fojo S . The ATP binding cassette transporter A1(ABCA1) modulates the development of aotric atherosclerosis in C57BL/6 and apoE-knockout mice[J]. Proc Natl Acad Sci U S A, 2002,99(1):407-412
doi: 10.1073/pnas.012587699
[8] Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, Mangelsdorf DJ . Regulation of mouse sterol regulatory element-binding protein-1c gene(SREBP-1c) by oxysterol receptors, LXRα and LXRβ[J]. Genes Dev, 2000,14(22):2819-2830
doi: 10.1101/gad.844900
[9] Zhou J, Febbraio M, Wada T, Zhai Y, Kuruba R, He J, Lee JH, Khadem S, Ren S, Li S, Silverstein RL, Xie W . Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARγ in promoting steatosis[J]. Gastroenterology, 2008,134(2):556-567
doi: 10.1053/j.gastro.2007.11.037
[10] Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM . PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL[J]. Cell, 1998,93(2):241-252
doi: 10.1016/S0092-8674(00)81575-5
[11] Hu Q, Zhang Y, Zhang XJ, Feng JB, Liu CX, Jiang H, Jiang GH, Wang R . PPARγ gene and protein expression in aortic plaque of different week-old knock-out mice and relationship with the composition of aortic plaque[J]. Zhongguo Bing Li Sheng Li Za Zhi, 2006,22(12):2289-2295
doi: 1000-4718
胡琴, 张运, 张宪军, 冯进波, 刘春喜, 姜虹, 蒋桂花, 王蓉 . PPARγ在不同周龄apoE-/-小鼠主动脉斑块表达及与斑块成分的相互关系[J]. 中国病理生理杂志, 2006,22(12):2289-2295
doi: 1000-4718
[12] Zhang YY, Liu P . The effects of Guanxinkang on aortic LXRα, ABCA1 gene expression in atherosclerosis rats[J]. Zhongguo Dong Mai Ying Hua Za Zhi, 2010,18(8):614-616
章怡祎, 刘萍 . 冠心康对动脉粥样硬化大鼠主动脉LXRα、ABCA1基因表达的影响[J]. 中国动脉硬化杂志, 2010,18(8):614-616
[1] Jian-sheng Li, Ya Li, Su-yun Li, Yuan-yuan Wang, Li Deng, Yan-ge Tian, Su-li Jiang , Ying Wang. Long-term effects of Tiaobu Feishen therapies on systemic and local inflammation responses in rats with stable chronic obstructive pulmonary disease. Journal of Chinese Integrative Medicine, 2012, 10(9): 1039-1048.
[2] Lu Yu, Shui-miao Lin, Ru-qian Zhou, Wei-jun Tang, Pin-xian Huang, Ying Dong, Jian Wang, Zhi-hua Yu, Jiu-lin Chen, Li Wei, San-li Xing, Hui-juan Cao, Hong-bin Zhao. Chinese herbal medicine for patients with mild to moderate Alzheimer disease based on syndrome differentiation: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(7): 766-776.
[3] Ling Xu, Qiao-ling Zhou, Jie Han, Dan-ying Zhang, Hui-juan Dong, Zai-long Cai, Chao-qin Yu, Dong-xia Zhai . Effects of Chinese herbal medicine Neiyi Recipe-medicated serum on angiopoiesis of endometriosis in the chick chorioallantoic membrane model. Journal of Chinese Integrative Medicine, 2012, 10(7): 800-806.
[4] Dong-mei Zhang, Li-xia Lou, Ai-ming Wu, Xi-ying Lü, Zhao-juan Hu, Yan-hong Zhang, Hong-fang Liu. Effects of Astragalus membranaceus and Potentilla discolor mixture on insulin resistance and its related mRNA expressions in KKAy mice with type 2 diabetes. Journal of Chinese Integrative Medicine, 2012, 10(7): 821-826.
[5] Lin Wang, Guan-liang Wang, Jia-han Liu, Di Li, De-zeng Zhu, Liang-neng Wu . Effects of ursolic acid in ameliorating insulin resistance in liver of KKAy mice via peroxisome proliferator-activated receptors α and γ. Journal of Chinese Integrative Medicine, 2012, 10(7): 793-799.
[6] Yi-tao Zhao , Xin-guang Zhang , Li Bai , Li-qing Li , Jian-er Yu . Effects of Chinese herbal medicine Pingchuan Formula on airway inflammation, interferon-γ and interleukin-4 in mice with asthma. Journal of Chinese Integrative Medicine, 2012, 10(7): 807-813.
[7] Shui-qiu Deng, Xue-nong Ouyang, Zong-yang Yu, Xi-hu Dai, Xi Chen, Fang-zheng Fang, Wen-wu Wang, Zhi-zhen Liu. Influence of Chinese herbal medicine Feitai Capsule on completion or delay of chemotherapy in patients with stage ⅢB/Ⅳ non-small-cell lung cancer: a Randomized controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(6): 635-640.
[8] Chuan Chen, Hui-ying Chi, Zhi-hua Yu, Jiu-lin Chen . Effects of Chinese herbal medicine Shoushen Granule on telomere length and telomerase activity of peripheral white blood cells and vascular cells in rats with atherosclerosis. Journal of Chinese Integrative Medicine, 2012, 10(6): 667-673.
[9] Hui Luo, Jian-ping Liu, Qing Li. Methodological issues and suggestions for improvement in randomized controlled trials of Chinese herbal medicine for recurrent miscarriage. Journal of Chinese Integrative Medicine, 2012, 10(6): 604-614.
[10] Daniel A. Weber, Janelle M. Wheat , Geoffrey M. Currie. Cancer stem cells and the impact of Chinese herbs, isolates and other complementary medical botanicals: A review. Journal of Chinese Integrative Medicine, 2012, 10(5): 493-503.
[11] Surendra Kr. Sharma, Naveen Goyal. Protective effect of Heliotropium eichwaldi against cisplatin-induced nephrotoxicity in mice. Journal of Chinese Integrative Medicine, 2012, 10(5): 555-560.
[12] Qing-lan Wang, Yan-yan Tao , Li Shen , Hong-yan Cui , Cheng-hai Liu. Chinese herbal medicine Fuzheng Huayu recipe inhibits liver fibrosis by mediating the transforming growth factor-β1/Smads signaling pathway. Journal of Chinese Integrative Medicine, 2012, 10(5): 561-568.
[13] Jing Guo, Ju-yong Wang, Zhan Zheng, Qing Wang, Chang-sheng Dong . Effects of Chinese herbal medicine Feiyanning Decoction on the ratio of CD4+CD25+ regulatory T cells and expression of transcription factor Foxp3 in mice bearing Lewis lung carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(5): 584-590.
[14] Zhan gheng, Ju-yong Wang, Qing Wang, Ling Xu, Zhen-ye Xu. Effects of Chinese herbal medicine Feiyanning decoction on expressions of nucleosome conformation-regulating factors H3-K56, Rtt109, Asf1 and E2F1 in Lewis-bearing mice. Journal of Chinese Integrative Medicine, 2012, 10(4): 448-453.
[15] Mahmoudian Alireza, Rajaei Ziba, Haghir Hossein, Banihashemian Shahaboldin, Hami Javad. Effects of valerian consumption during pregnancy on cortical volume and the levels of zinc and copper in the brain tissue of mouse fetus. Journal of Chinese Integrative Medicine, 2012, 10(4): 424-429.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)". Journal of Chinese Integrative Medicine, 2008, 6(1): 15-21
[2] Yi-ting He, Qing-lin Zha, Jian-ping Yu, Yong Tan, Cheng Lu, Ai-ping Lv. Principal factor analysis of symptoms of rheumatoid arthritis and their correlations with efficacy of traditional Chinese medicine and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 32-36
[3] Jun Cai, Hua Wang, Sheng Zhou, Bin Wu, Hua-rong Song, Zheng-rong Xuan. Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2008, 6(1): 37-40
[4] Wei Zhang, Xiang-feng Lu, Xiao-mei Zhang, Jian-jun Wu, Liang-duo Jiang. A rat model of pulmonary fibrosis induced by infusing bleomycin quickly through tracheal intubation. Journal of Chinese Integrative Medicine, 2008, 6(1): 60-67
[5] A-gao Zhou, Yong Zhang, Gang Kui, De-Yun Kong, Hai-liang Ge, Qiu-hua Ren, Jia-rong Dong, Sheng Hong, Xu-ming Mao, Yin Wang, Hui-zheng Zhang, Shu-jun Wang. Influence of traditional Chinese compound recipes with different efficacy on body weight, tumor weight and immune function in H22 cancer-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 77-82
[6] Guo-hong Yuan, Xiao-jing Pang, He-chao Ma. Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 83-88
[7] Li Zhou, Hong-xing Zhang, Ling-guang Liu, Wen-jun Wan. Effect of electro-acupuncture at Fenglong (GV 16) on nitric oxide and endothelin in rats with hyperlipidemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 89-92
[8] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. Guiding principles of clinical research on mild cognitive impairment (protocol). Journal of Chinese Integrative Medicine, 2008, 6(1): 9-14
[9] Xin-jun Wang, Ling-ling Wang . A mechanism of endogenous opioid peptides for rapid onset of acupuncture effect in treatment of depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1014-1017
[10] Bo Wang , Wei Yan , Li-hui Hou, Xiao-ke Wu. Disorder of Tiangui (kidney essence) and reproductive dysfunction in patients with polycystic ovary syndrome. Journal of Chinese Integrative Medicine, 2010, 8(11): 1018-1022
[an error occurred while processing this directive]