Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (9): 998-1004.doi: 10.3736/jcim20110911

• Original Experimental Research • Previous Articles     Next Articles

Effects of Chinese herbal medicine Jiangzhi Granule on expressions of liver X receptor α and sterol regulatory element-binding protein-1c in a rat model of non-alcoholic fatty liver disease

Li-li Yang1, Miao Wang1,2, Tao Liu1, Hai-yan Song1, Dong-fei Li3, Pei-yong Zheng1, Ping Liu4, Guang Ji1()   

  1. 1. Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
    2. Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine,Shanghai 200032, China
    3. Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Shanghai 200125, China
    4. Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2011-04-13 Accepted:2011-05-09 Online:2011-09-20 Published:2011-09-15
  • Contact: Ji Guang

Objective: To study the effects of Jiangzhi Granule (JZG), a compound traditional Chinese herbal medicine, in regulating liver X receptor α (LXRα) and sterol regulatory element-binding protein-1c (SREBP-1c) expressions in a rat model of non-alcoholic fatty liver disease (NAFLD).

Methods: Forty specific pathogen-free Wistar male rats were randomly divided into normal group, untreated group, pioglitazone (PIO) group and JZG group. All rats were fed with high-fat diet (88% normal chow plus 10% lard plus 2% cholesterol) for 4 weeks except for the normal group. After the NAFLD model was established, PIO and JZG were fed to rats in the corresponding groups respectively for another 4 weeks. At the end of the 8th week, liver steatosis level was observed under a light microscope with hematoxylin and eosin (HE) staining; serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and triacylglycerol (TAG) and free fatty acid (FFA) contents in liver tissues were measured. LXRα and SREBP-1c expressions in liver tissues were determined by real-time polymerase chain reaction and Western blot methods.

Results: Compared with the normal group, there were physiological changes for hepatic steatosis in liver tissues in the untreated group as observed by HE staining. JZG improved serum ALT and AST levels which were significantly increased in the untreated group. Both JZG and PIO improved FFA and TAG levels in liver tissues which were significantly increased in the untreated group. mRNA and protein levels of LXRα and SREBP-1c in the untreated group were higher than those in the normal group, while the treatment of JZG and PIO lowered their expressions.

Conclusion: JZG may regulate fatty acid metabolic disorder by decreasing the levels of LXRα and SREBP-1c.

Key words: fatty liver, antilipemic agents (TCD), drugs,Chinese herbal, liver X receptor a, sterol regulatory element-binding protein-1, rats

Table 1

Primer sequences and size of products"

Gene Primer and probe Size of product (bp)

Figure 1

Effects of Jiangzhi Granule on pathological changes of rat liver observed by light microscopy with hematoxylin and eosin staining (×200) A: Normal group; B: Untreated group; C: Pioglitazone group; D: Jiangzhi Granule group."

Table 2

Effects of Jiangzhi Granule on serum ALT and AST levels in rats ($\overline{x}$±s, U/L)"

Group n ALT AST
Normal 10 46.11±5.78** 249.10±77.45*
Untreated 10 60.61±5.10 308.82±72.70
Pioglitazone 10 64.63±5.03 268.34±47.81
Jiangzhi Granule 8 55.09±3.93* 240.98±40.68*

Table 3

Effects of Jiangzhi Granule on TAG and FFA contents in liver tissues of rats ($\overline{x}$±s)"

Group n TAG (mg/g) FFA (μmol/g prot)
Normal 9 23.64±3.85** 84.09±21.47**
Untreated 9 118.50±9.72 172.94±37.02
Pioglitazone 9 68.21±8.09** 128.83±17.18*
Jiangzhi Granule 8 95.12±15.54* 125.76±51.92*

Table 4

Effects of Jiangzhi Granule on LXRα and SREBP-1c mRNA expressions in liver tissues of rats ($\overline{x}$±s)"

Group n LXRα mRNA SREBP-1c mRNA
Normal 3 0.34±0.12** 0.34±0.12**
Untreated 3 0.74±0.14 0.68±0.18
Pioglitazone 3 0.41±0.11* 0.36±0.06**
Jiangzhi Granule 3 0.44±0.15* 0.42±0.03*

Table 4

Effects of Jiangzhi Granule on LXRα and SREBP-1c expressions in liver tissues of rats ($\overline{x}$±s)"

Group n LXRα SREBP-1c
Normal 3 0.38±0.12** 0.27±0.08**
Untreated 3 1.24±0.09 0.89±0.10
Pioglitazone 3 0.66±0.13** 0.43±0.15**
Jiangzhi Granule 3 0.57±0.16** 0.45±0.07**

Figure 2

Effects of Jiangzhi Granule on LXRα and SREBP-1c expressions in liver tissues of rats observed by Western blotting JZG: Jiangzhi Granule; PIO: pioglitazone; LXRα: liver X receptor α; SREBP-1c: sterol regulatory element-binding protein-1c; GAPDH: glyceraldehyde-3-phosphate dehydrogenase."

[1] Nakamuta M, Fujino T, Yada R, Yada M, Yasutake K, Yoshimoto T, Harada N, Higuchi N, Kato M, Kohjima M, Taketomi A, Maehara Y, Nakashima M, Kotoh K, Enjoji M . Impact of cholesterol metabolism and the LXRalpha-SREBP-1c pathway on nonalcoholic fatty liver disease[J]. Int J Mol Med, 2009,23(5):603-608
[2] Higuchi N, Kato M, Shundo Y, Tajiri H, Tanaka M, Yamashita N, Kohjima M, Kotoh K, Nakamuta M, Takayanagi R, Enjoji M . Liver X receptor in cooperation with SREBP-1c is a major lipid synjournal regulator in nonalcoholic fatty liver disease[J]. Hepatol Res, 2008,38(11):1122-1129
doi: 10.1111/hep.2008.38.issue-11
[3] Moya M , Gómez-Lechón MJ , Castell JV , Jover R.Enhanced steatosis by nuclear receptor ligands: a study in cultured human hepatocytes and hepatoma cells with a characterized nuclear receptor expression profile on nonalcoholic fatty liver disease[J]. Chem Biol Interact, 2010,184(3):376-387
doi: 10.1016/j.cbi.2010.01.008
[4] Zheng PY, Ma ZS, Liu T, Xing LJ, Ji G . Effect of Jiangzhi granulas on serum leptin and liver leptin receptor mRNA of nonalcoholic fatty liver disease rat[J]. Zhongguo Zhong Yi Yao Xin Xi Za Zhi, 2008,15(6):36-38
郑培永, 马赞颂, 柳涛, 邢练军, 季光 . 降脂颗粒对非酒精性脂肪肝模型大鼠血清瘦素及肝脏瘦素受体mRNA的影响[J]. 中国中医药信息杂志, 2008,15(6):36-38
[5] Zhang L, Liu T, Wang M, Xing LJ, Ji G, Zheng PY . Effect of Jiangzhi granula on leptin and leptin receptor of hypothalamus in rats with nonalcoholic liver disease[J]. Zhong Xi Yi Jie He Gan Bing Za Zhi, 2009,19(2):88-91
张莉, 柳涛, 王淼, 邢练军, 季光, 郑培永 . 降脂颗粒对非酒精性脂肪肝大鼠下丘脑瘦素及瘦素受体的影响[J]. 中西医结合肝病杂志, 2009,19(2):88-91
[6] 郑培永, 张莉, 柳涛, 王淼, 邢练军, 季光 . 下丘脑STAT3在非酒精性脂肪性肝病大鼠发病中的作用及降脂颗粒的干预[J]. 世界华人消化杂志, 2009,17(8):753-757
Zheng PY, Zhang L, Liu T, Wang M, Xing LJ, Ji G . Effect of Jiangzhi granule on STAT3 expression in hypothalamus of rats with nonalcoholic fatty liver disease[J]. Shi Jie Hua Ren Xiao Hua Za Zhi, 2009,17(8):753-757
[7] Xu ZJ, Fan JG, Wang GL, Ding XD, Tian LY, Zheng XY . Rat model of nonalcoholic steatohepatitis with fibrosis by a fat-rich diet[J]. Shi Jie Hua Ren Xiao Hua Za Zhi, 2002,10(4):392-396
徐正婕, 范建高, 王国良, 丁晓东, 田丽艳, 郑晓英 . 高脂饮食致大鼠非酒精性脂肪性肝炎肝纤维化模型[J]. 世界华人消化杂志, 2002,10(4):392-396
[8] Akbar DH , Kawther AH . Non-alcoholic fatty liver disease and metabolic syndrome: what we know and what we don’t know[J].Med Sci Monit, 2006, 12(1):RA23-RA26
pmid: 16369477
[9] Fan JG, Zeng MD. Fatty liver diseases[M]. Beijing: People's Medical Publishing House, 2005,118
范建高, 曾民德 . 脂肪性肝病[M]. 北京: 人民卫生出版社, 2005,118
[10] Angulo P, Lindor KD . Non-alcoholic fatty liver disease[J]. J Gastroenterol Hepatol, 2002,17(Suppl):S186-S190
doi: 10.1046/j.1440-1746.17.s1.10.x
[11] Kim JB, Wright HM, Wright M, Spiegelman BM . ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand[J]. Proc Natl Acad Sci U S A, 1998,95(8):4333-4337
doi: 10.1073/pnas.95.8.4333
[12] Osborne TF . Sterol regulatory element-binding proteins(SREBPs): key regulators of nutritional homeostasis and insulin action[J]. J Biol Chem, 2000,275(42):32379-32382
doi: 10.1074/jbc.R000017200
[13] Chakravarty K, Leahy P, Becard D, Hakimi P, Foretz M, Ferre P, Foufelle F, Hanson RW . Sterol regulatory element-binding protein-1c mimics the negative effect of insulin on phosphoenolpyruvate carboxykinase(GTP) gene transcription[J]. J Biol Chem, 2001,276(37):34816-34823
doi: 10.1074/jbc.M103310200
[14] Foretz M, Guichard C, Ferré P, Foufelle F . Sterol regulatory element binding protein-1c is a major mediator of insulin action on the hepatic expression of glucokinase and lipogenesis-related genes[J]. Proc Natl Acad Sci U S A, 1999,96(26):12737-12742
doi: 10.1073/pnas.96.22.12737
[15] Shimano H . SREBPs: novel aspects of SREBPs in the regulation of lipid synjournal[J]. FEBS J, 2009,276(3):615
doi: 10.1111/j.1742-4658.2008.06805.x pmid: 19143829
[16] McPherson R, Gauthier A . Molecular regulation of SREBP function: the Insig-SCAP connection and isoform-specific modulation of lipid synjournal[J]. Biochem Cell Biol, 2004,82(1):201-211
doi: 10.1139/o03-090
[17] Zelcer N, Tontonoz P . Liver X receptors as integrators of metabolic and inflammatory signaling[J]. J Clin Invest, 2006,116(3):607-614
doi: 10.1172/JCI27883 pmid: 16511593
[18] Shulman AI, Mangelsdorf DJ . Retinoid x receptor heterodimers in the metabolic syndrome[J]. N Engl J Med, 2005,353(6):604-615
doi: 10.1056/NEJM200511103531921 pmid: 16282190
[19] Cha JY, Repa JJ . The liver X receptor(LXR) and hepatic lipogenesis. The carbohydrate-response element-binding protein is a target gene of LXR[J]. J Biol Chem, 2007,282(1):743-751
doi: 10.1074/jbc.M605023200
[20] 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 PPARgamma in promoting steatosis[J]. Gastroenterology, 2008,134(2):556-567
doi: 10.1053/j.gastro.2007.11.037
[21] Alberti S, Schuster G, Parini P, Feltkamp D, Diczfalusy U, Rudling M, Angelin B , Björkhem I , Pettersson S , Gustafsson JA .Hepatic cholesterol metabolism and resistance to dietary cholesterol in LXRbeta-deficient mice[J]. J Clin Invest, 2001,107(5):565-573
doi: 10.1172/JCI9794 pmid: 11238557
[22] Bobard A, Hainault I, Ferré P, Foufelle F, Bossard P . Differential regulation of sterol regulatory element-binding protein 1c transcriptional activity by insulin and liver X receptor during liver development[J]. J Biol Chem, 2005,280(1):199-206
doi: 10.1074/jbc.M406522200
[23] Liang G, Yang J, Horton JD, Hammer RE, Goldstein JL, Brown MS . Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c[J]. J Biol Chem, 2002,277(11):9520-9528
doi: 10.1074/jbc.M111421200
[24] Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Seminara G, Rapisarda F, Fatuzzo P, Buemi M, Nicocia G, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y . Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease[J]. J Am Soc Nephrol, 2002,13(1):134-141
[25] Larter CZ, Farrell GC . Insulin resistance, adiponectin, cytokines in NASH: Which is the best target to treat[J]. J Hepatol, 2006,44(2):253-261
doi: 10.1016/j.jhep.2005.11.030
[1] Meng-ya Shan, Ying Dai, Xiao-dan Ren, Jing Zheng, Ke-bin Zhang, Bin Chen, Jun Yan, Zi-hui Xu. Berberine mitigates nonalcoholic hepatic steatosis by downregulating SIRT1-FoxO1-SREBP2 pathway for cholesterol synthesis. Journal of Integrative Medicine, 2021, 19(6): 545-554.
[2] Mao-xing Pan, Chui-yang Zheng, Yuan-jun Deng, Kai-rui Tang, Huan Nie, Ji-qian Xie, Dong-dong Liu, Gui-fang Tu, Qin-he Yang, Yu-pei Zhang. Hepatic protective effects of Shenling Baizhu powder, a herbal compound, against inflammatory damage via TLR4/NLRP3 signalling pathway in rats with nonalcoholic fatty liver disease . Journal of Integrative Medicine, 2021, 19(5): 428-438.
[3] Bing-rong Li, Shi-yun Shao, Long Yuan, Ru Jia, Jian Sun, Qing Ji, Hua Sui, Li-hong Zhou, Yi Zhang, Hui Liu, Qi Li, Yan Wang, Bi-meng Zhang. Effects of mild moxibustion on intestinal microbiome and NLRP3 inflammasome in rats with 5-fluorouracil-induced intestinal mucositis. Journal of Integrative Medicine, 2021, 19(2): 144-157.
[4] Sitthichai Iamsaard, Supatcharee Arun, Jaturon Burawat, Supataechasit Yannasithinon, Saranya Tongpan, Sudtida Bunsueb, Natthapol Lapyuneyong, Pannawat Choowong-in, Nareelak Tangsrisakda, Chadaporn Chaimontri, Wannisa Sukhorum. Evaluation of antioxidant capacity and reproductive toxicity of aqueous extract of Thai Mucuna pruriens seeds. Journal of Integrative Medicine, 2020, 18(3): 265-273.
[5] Morufu Eyitayo Balogun, Elizabeth Enohnyaket Besong, Jacinta Nkechi Obimma, Ogochukwu Sophia Mbamalu, Fankou Serges Athanase Djobissie. Protective roles of Vigna subterranea (Bambara nut) in rats with aspirin-induced gastric mucosal injury. Journal of Integrative Medicine, 2018, 16(5): 342-349.
[6] Lucky Legbosi Nwidu, Raphael Ellis Teme. Hot aqueous leaf extract of Lasianthera africana (Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity. Journal of Integrative Medicine, 2018, 16(4): 263-272.
[7] Kylie Connolly, Douglas Jackson, Candice Pullen, Andrew Fenning. Alpha-adrenoceptor antagonism by Crassostrea gigas oyster extract inhibits noradrenaline-induced vascular contraction in Wistar rats. Journal of Integrative Medicine, 2015, 13(3): 194-200.
[8] Udhaya Lavinya Baskaran, Sherry Joseph Martin, Rasool Mahaboobkhan, Sabina Evan Prince. Protective role of Triphala, an Indian traditional herbal formulation, against the nephrotoxic effects of bromobenzene in Wistar albino rats. Journal of Integrative Medicine, 2015, 13(2): 115-121.
[9] Hussein O. B. Oloyede, Matthew C. Adaja, Taofeek O. Ajiboye, Musa O. Salawu. Anti-ulcerogenic activity of aqueous extract of Carica papaya seed on indomethacin-induced peptic ulcer in male albino rats. Journal of Integrative Medicine, 2015, 13(2): 105-114.
[10] Anirudha A. Lande, Shirishkumar D. Ambavade, Uma S. Swami, Prafulla P. Adkara Prashant D. Ambavade, Arun B. Waghamare. Saponins isolated from roots of Chlorophytum borivilianum reduce acute and chronic inflammation and histone deacetylase. Journal of Integrative Medicine, 2015, 13(1): 25-33.
[11] Elizabeth Abidemi Balogun, Sylvia Orume Malomo, Joseph Oluwatope Adebayo, Ahmed Adebayo Ishola, Ayodele Olufemi Soladoye, Lawrence Aderemi Olatunji, Olatunji Matthew Kolawole, Stephen Olubunmi Oguntoye, Abiola Samuel Babatunde, Oluwole Busayo Akinola . In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre. Journal of Integrative Medicine, 2014, 12(6): 504-511.
[12] Urmila Aswar, Mayuri Gurav, Ganesh More, Khaled Rashed, Manoj Aswar. Effect of aqueous extract of Solanum xanthocarpum Schrad. & Wendl. on postmenopausal syndrome in ovariectomized rats. Journal of Integrative Medicine, 2014, 12(5): 439-446.
[13] Xin-fang Zhang, Ji Zhu, Wen-ye Geng, Shu-jun Zhao, Chuan-wei Jiang, Sheng-rong Cai, Miao Cheng, Chuan-yun Zhou, Zi-bing Liu. Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease. Journal of Integrative Medicine, 2014, 12(5): 417-424.
[14] Benjamin Perry, Junzeng Zhang, Tarek Saleh, Yanwen Wang. Liuwei Dihuang, a traditional Chinese herbal formula, suppresses chronic inflammation and oxidative stress in obese rats. Journal of Integrative Medicine, 2014, 12(5): 447-454.
[15] Upendarrao Golla, Praveen Kumar Gajam, Solomon Sunder Bhimathati. Evaluation of diuretic and laxative activity of hydro-alcoholic extract of Desmostachya bipinnata (L.) Stapf in rats. Journal of Integrative Medicine, 2014, 12(4): 372-378.
Full text



[1] Wei-xiong Liang. Problems-solving strategies in clinical treatment guideline for traditional Chinese medicine and integrative medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 1-4
[2] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[3] Jun Hu, Jian-ping Liu. Non-invasive physical treatments for chronic/recurrent headache. Journal of Chinese Integrative Medicine, 2008, 6(1): 31
[4] Xue-mei Liu, Qi-fu Huang, Yun-ling Zhang, Jin-li Lou, Hong-sheng Liu, Hong Zheng. Effects of Tribulus terrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats. Journal of Chinese Integrative Medicine, 2008, 6(1): 45-50
[5] . Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication (Chinese version, part two). Journal of Chinese Integrative Medicine, 2010, 8(11): 1001-1005
[6] Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013
[7] Hong Liu , Guo-liang Zhang, Li Shen , Zhen Zeng, Bao-luo Zhou, Cheng-hai Liu, Guang Nie . Application and evaluation of a pseudotyped virus assay for screening herbs for anti-H5Nl avian influenza virus. Journal of Chinese Integrative Medicine, 2010, 8(11): 1036-1040
[8] Zhao-guo Li . A discussion of English translation of 1995 and 1997 Chinese National Standards of Traditional Chinese Medical Terminologies for Clinical Diagnosis and Treatment. Journal of Chinese Integrative Medicine, 2010, 8(11): 1090-1096
[9] Rui Jin, Bing Zhang. A complexity analysis of Chinese herbal property theory: the multiple formations of herbal property (Part 1). Journal of Chinese Integrative Medicine, 2012, 10(11): 1198-1205
[10] Hui-min Liu, Xian-bo Wang, Yu-juan Chang, Li-li Gu. Systematic review and meta-analysis of randomized controlled trials of integrative medicine therapy for treatment of chronic severe hepatitis. Journal of Chinese Integrative Medicine, 2012, 10(11): 1211-1228