Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (9): 921-927.doi: 10.3736/jcim20080909

• Original Experimental Research • Previous Articles     Next Articles

Effects of puerarin on expressions of leptin receptor mRNA, phosphoryla-ted Janus kinase 2/phosphorylated signal transducers and activators of transcription 3 proteins in the liver of rats with non-alcoholic fatty liver

Pei-yong Zheng1, Zan-song Ma1, Yong-qiang Hua1,2, Tao Liu1, Lian-jun Xing1, Guang Ji1()   

  1. 1. Institute of Digestive Diseases and Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
    2. Department of Traditional Chinese Medicine, Cancer Hospital, Fudan University, Shanghai 200032, China
  • Received:2008-01-11 Online:2008-09-20 Published:2008-09-15

Objective: To observe the effects of puerarin on the expressions of leptin receptor mRNA and phosphorylated Janus kinase 2 / phosphorylated signal transducers and activators of transcription 3 (P-JAK2/P-STAT3) proteins in the liver of rats with non-alcoholic fatty liver (NAFLD).
Methods: A rat model of NAFLD was successfully established by feeding high-fat diet. All SD rats were randomly divided into blank control group, untreated group, simvastatin-treated group and puerarin-treated group. After four-week treatment, the levels of hepatic triglyceride and total cholesterol were analyzed by using an automatic biochemical analyzer. The pathology of the liver tissue was observed by light microscopy. Serum leptin level was detected by enzyme-linked immunosorbent assay, and the expressions of leptin receptor mRNA and P-JAK2/P-STAT3 proteins in the liver of NAFLD rats were quantified by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis respectively.
Results: Puerarin significantly decreased the levels of hepatic triglyceride and total cholesterol in NAFLD rats. Fat degeneration and inflammatory reaction in liver tissues of NAFLD rats were ameliorated after puerarin treatment. The serum leptin level was increased and the expressions of leptin receptor mRNA and P-JAK2/P-STAT3 proteins were up-regulated in puerarin-treated group.
Conclusion: Puerarin can effectively attenuate liver lipid disorder and inflammation by improving the leptin resistance and enhancing the expressions of leptin receptor mRNA and P-JAK2/P-STAT3 proteins

Key words: puerarin, fatty liver, leptin, Janus kinase 2, activating transcription factor 3, rats

CLC Number: 

  • R575.5

Table 1

Liver index of rats in different groups (x±s)"

Group n Liver index
Blank control 8 2.54±0.23**
Untreated 10 4.20±0.20
Simvastatin-treated 12 3.87±0.43*
Puerarin-treated 12 3.58±0.29**

Table 2

Hepatic inflammation of NAFLD rats in different groups"

Group n Hepatic inflammation grade
0 1 2 3
Untreated 10 0 6 3 1
Simvastatin-treated* 12 3 7 2 0
Puerarin-treated** 12 0 4 8 0

Table 3

Hepatic steratosis of NAFLD rats in different groups"

Group n Hepatic inflammation grade
0 1 2 3
Untreated 10 0 1 6 3
Simvastatin-treated* 12 1 4 6 1
Puerarin-treated** 12 2 8 2 0

Figure 1

Liver characteristics of rats in different groups observed by light microscopy (HE staining, ×400) A: Blank control group; B: Untreated group; C: Simvastatin-treated group; D: Puerarin-treated group."

Table 4

Levels of hepatic TG, TC and serum leptin of rats in different groups (x±s)"

Group n TG (μmol/ml) TC (μmol/ml) Serum leptin (μg/L)
Blank control 8 0.11±0.04** 1.98±0.53** 131.10±17.24**
Untreated 10 0.77±0.10 9.19±1.03 317.22±39.27
Simvastatin-treated 12 0.67±0.12* 7.65±0.98** 213.56±19.96**
Puerarin-treated 12 0.43±0.12**△△ 6.69±2.43** 204.95±65.86**△△

Table 5

Expressions of LR mRNA and P-JAK/P-STAT3 proteins in the liver of rats in different groups (x±s)"

Group n LR mRNA expression P-JAK2 protein expression P-STAT3 protein expression
Blank control 3 3.13±0.04** 127.30±3.52** 105.20±2.52**
Untreated 3 0.93±0.04 86.74±1.63 79.06±0.69
Simvastatin-treated 3 1.50±0.05** 102.37±1.48* 83.15±1.01**
Puerarin-treated 3 2.78±0.04**△△ 124.34±3.42** 101.94±2.20**△△

Figure 2

Expression of LR mRNA in the liver of rats in different groups 1: Blank control group; 2: Untreated group; 3: Puerarin-treated group; 4: Simvastatin-treated group."

Figure 3

Expression of P-JAK2 protein in the liver of rats in different groups 1: Blank control group; 2: Untreated group; 3: Puerarin-treated group; 4: Simvastatin-treated group."

Figure 4

Expression of P-STAT3 protein in the liver of rats in different groups 1: Blank control group; 2: Untreated group; 3: Puerarin-treated group; 4: Simvastatin-treated group."

[1] Zeng MD . Fatty liver[J]. Zhonghua Xiao Hua Za Zhi, 1999,19(2):120-122
曾民德 . 脂肪肝[J]. 中华消化杂志, 1999,19(2):120-122
[2] Qing F, Pan JQ, Xiao LY , et al. Effect of puerarin on insulin sensitivity and blood glucose and lipids levels in insulin-resisting hypertension rats[J]. Zhong Yi Yan Jiu, 2006,19(3):14-17
doi: 10.3969/j.issn.1001-6910.2006.03.006
庆方, 潘竞锵, 肖柳英 , 等. 葛根素对胰岛素抵抗-高血压大鼠胰岛素敏感性的增强作用和降糖降脂作用[J]. 中医研究, 2006,19(3):14-17
doi: 10.3969/j.issn.1001-6910.2006.03.006
[3] Zhong L, Fan JG, Wang GL , et al. The establishment of nonalcohlic steatohepatitis(NASH) animal model[J]. Shi Yan Dong Wu Ke Xue Yu Guan Li, 2000,17(2):16-20
钟岚, 范建高, 王国良 , 等. 肥胖、高脂血症性脂肪性肝炎模型的建立[J]. 实验动物科学与管理, 2000,17(2):16-20
[4] Yan LP, Chen SH, Chen WM , et al. Regulatory effect of puerarin on lipid profile in hypercholesterolemic rats[J]. Zhongguo Lin Chuang Yao Li Xue Yu Zhi Liao Xue, 2006,11(5):574-577
doi: 10.3969/j.issn.1009-2501.2006.05.022
闫莉萍, 陈舜宏, 陈伟民 , 等. 葛根素对膳食诱导的高胆固醇血症大鼠的血脂调节作用[J]. 中国临床药理学与治疗学, 2006,11(5):574-577
doi: 10.3969/j.issn.1009-2501.2006.05.022
[5] Diehl AM, Goodman Z, Ishak KG . Alcohollike liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury[J]. Gastroenterology, 1988,95(4):1056-1062
doi: 10.1016/0016-5085(88)90183-7
[6] Knodell RG, Ishak KG, Black WC , et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis[J]. Hepatology, 1981,1(5):431-435
doi: 10.1002/(ISSN)1527-3350
[7] Wang TL, Liu X, Zhou YP , et al. A semiquantitative scoring system or assessment of hepatic inflammation and fibrosis in chronic hepatitis[J]. Zhonghua Gan Zang Bing Za Zhi, 1998,6(4):195-197
doi: 10.3760/j.issn:1007-3418.1998.04.002
王泰龄, 刘霞, 周元平 , 等. 慢性肝炎炎症活动度及纤维化程度计分方案[J]. 中华肝脏病杂志, 1998,6(4):195-197
doi: 10.3760/j.issn:1007-3418.1998.04.002
[8] Chitturi S, Abeygunasekera S, Farrell GC , et al. NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome[J]. Hepatology, 2002,35(2):373-379
doi: 10.1053/jhep.2002.30692
[9] He SL, Li JC, Qin XQ. Clinical physiology[M]. Beijing: Science Press,2001: 9
贺石林, 李俊成, 秦晓群 . 临床生理学[M]. 北京: 科学出版社,2001: 9
[10] Saxena NK, Ikeda K, Rockey DC , et al. Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice[J]. Hepatology, 2002,35(4):762-771
doi: 10.1053/jhep.2002.32029
[11] Rizk NM, Stammsen D, Preibisch G , et al. Leptin and tumor necrosis factor-alpha induce the tyrosine phosphorylation of signal transducer and activator of transcription proteins in the hypothalamus of normal rats in vivo[J]. Endocrinology, 2001,142(7):3027-3032
doi: 10.1210/endo.142.7.8225
[12] Larsson H, Elmståhl S, Berglund G , et al.Evidence for leptin regulation of food intake in humans[J]. J Clin Endocrinol Metab, 1998,83(12):4382-4385
doi: 10.1210/jcem.83.12.5342 pmid: 9851781
[13] Flynn MC, Plata-Salamán CR .Leptin(OB protein) and meal size[J]. Nutrition, 1999,15(6):508-509
doi: 10.1016/S0899-9007(99)00108-2
[14] Cohen P, Miyazaki M, Socci ND , et al. Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss[J]. Science, 2002,297(5579):240-243
doi: 10.1126/science.1071527 pmid: 12114623
[15] Petersen KF, Oral EA, Dufour S , et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy[J]. J Clin Invest, 2002,109(10):1345-1350
doi: 10.1172/JCI15001 pmid: 150981
[16] Tobe K, Suzuki R, Aoyama M , et al. Increased expression of the sterol regulatory element-binding protein-1 gene in insulin receptor substrate-2/mouse liver[J]. Biol Chem, 2001,276(42):38337-38340
doi: 10.1074/jbc.C100160200
[17] Tobe K, Ogura J, Tsuka M , et al. Relationship between serum leptin and fatty liver in Japnese male adolescent university students[J]. Am J Gastroenterol, 1999,94(11):3328-3335
doi: 10.1111/ajg.1999.94.issue-11
[18] Chitturi S, Farrell G, Frost L , et al. Serum leptin in NASH correlates with hepatic steatosis but not fibrosis: a manifestation of lipotoxicity[J]. Hepatology, 2002,36(2):403-409
doi: 10.1053/jhep.2002.34738
[19] Campillo B, Sherman E, Richardet JP , et al. Serum leptin levels in alcoholic liver cirrhosis: relationship with gender, nutritional status, liver function and energy metabolism[J]. Eur J Clin Nutr, 2001,55(1):980-988
doi: 10.1038/sj.ejcn.1601255
[20] Bartek J, Bartos J, Galuska J , et al. Expression of ob gene coding the production of the hormone leptin in hepatocytes of liver with steatosis[J]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2001,145(1):15-20
doi: 10.5507/bp.2001.003
[21] Koteish A, Diem AM . Animal models of steatosis[J]. Semin Liver Dis, 2001,21(1):89-104
doi: 10.1055/s-2001-12932
[22] Carpenter LR, Farruggella TJ, Symes A , et al. Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with ob receptor[J]. Proc Natl Acad Sci U S A, 1998,95(11):6061-6066
doi: 10.1073/pnas.95.11.6061
[23] Crouse JA, Elliott GE, Burgess TL , et al. Altered cell surface expression and signaling of leptin receptors containing the fatty mutation[J]. J Biol Chem, 1998,273(29):18365-18373
doi: 10.1074/jbc.273.29.18365 pmid: 9660803
[24] Guo QY, Gao Y, Cong L , et al. Effects of free fatty acids on gene and protein expression and tyrosine phosphorylation of leptin-receptor in rat hepatic cells[J]. Yi Xue Yan Jiu Sheng Xue Bao, 2003,16(9):659-662
doi: 10.3969/j.issn.1008-8199.2003.09.007
郭启煜, 高妍, 丛琳 , 等. 游离脂肪酸对大鼠肝细胞瘦素受体基因、蛋白表达及酪氨酸磷酸化的影响[J]. 医学研究生学报, 2003,16(9):659-662
doi: 10.3969/j.issn.1008-8199.2003.09.007
[25] Zhao CY, Li L, Li JM , et al. Change in the expression of leptin receptor in liver of rats with non-alcoholic fatty liver disease[J]. Zhongguo Zu Zhi Hua Xue Yu Xi Bao Hua Xue Za Zhi, 2005,14(6):613-617
doi: 10.3870/j.issn.1004-1850.2005.06.005
赵彩彦, 李丽, 李建梅 , 等. 非酒精性脂肪性肝病大鼠肝组织瘦素受体表达的变化[J]. 中国组织化学与细胞化学杂志, 2005,14(6):613-617
doi: 10.3870/j.issn.1004-1850.2005.06.005
[26] Guo F, Bakal K, Minokoshi Y , et al. Leptin signaling targets the thyrotropin-releasing hormone gene promoter in vivo[J]. Endocrinology, 2004,145(5):2221-2227
doi: 10.1210/en.2003-1312 pmid: 14764630
[1] 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.
[2] 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.
[3] 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.
[4] 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.
[5] 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.
[6] 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.
[7] 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.
[8] 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.
[9] 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.
[10] 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.
[11] 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.
[12] Qian Zhang, Xin-hua Xiao, Ming Li, Wen-hui Li, Miao Yu, Hua-bing Zhang, Fan Ping, Zhi-xin Wang, Jia Zheng ​. Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats. Journal of Integrative Medicine, 2014, 12(3): 162-170.
[13] Amir Rashidian​, Saeed Mehrzadi, Ali Reza Ghannadi, Parvin Mahzooni, Samira Sadr, Mohsen Minaiyan​. Protective effect of ginger volatile oil against acetic acid-induced colitis in rats: A light microscopic evaluation. Journal of Integrative Medicine, 2014, 12(2): 115-120.
[14] Dilpesh Jain​, Manish Kumar Bansal, Rahul Dalvi​, Aman Upganlawar​, Rahul Somani​. Protective effect of diosmin against diabetic neuropathy in experimental rats. Journal of Integrative Medicine, 2014, 12(1): 35-41.
[15] Manjusha Choudhary​, Vipin Kumar​, Surender Singh​. Gastric antisecretory and cytoprotective effects of hydroalcoholic extracts of Plumeria alba Linn. leaves in rats. Journal of Integrative Medicine, 2014, 12(1): 42-51.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 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
[2] 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
[3] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[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] Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[6] SUN Ming-yu, ZUO Jian, DUAN Ji-feng, HAN Jun, FAN Shi-ming, ZHANG Wei, ZHU Li-fang, YAO Ming-hui. Antitumor activities of kushen flavonoids in vivo and in vitro. Journal of Chinese Integrative Medicine, 2008, 6(1): 51-59
[7] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[8] 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
[9] 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
[10] Ning-qun Wang, Liang-duo Jiang, Zong-xing Li. Research progress in asthma-related quality of life. Journal of Chinese Integrative Medicine, 2008, 6(1): 93-97