Protective effects and mechanisms of total alkaloids of Rubus alceaefolius Poir on non‑alcoholic fatty liver disease in rats

Zheng,Haiyin; Zhao,Jinyan; Zheng,Yuqing; Wu,Juan; Liu,Yan; Peng,Jun; Hong,Zhenfeng

doi:10.3892/mmr.2014.2403

Protective effects and mechanisms of total alkaloids of Rubus alceaefolius Poir on non‑alcoholic fatty liver disease in rats

Authors:
- Haiyin Zheng
- Jinyan Zhao
- Yuqing Zheng
- Juan Wu
- Yan Liu
- Jun Peng
- Zhenfeng Hong
View Affiliations

Affiliations: College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China, Simulation Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
Published online on: July 21, 2014 https://doi.org/10.3892/mmr.2014.2403
Pages: 1758-1764

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The plant Rubus alceaefolius Poir is used as a hepatic protectant in Traditional Chinese Medicine. The aim of the present study was to confirm the protective effect of the total alkaloids of Rubus alceaefolius Poir (TARAP) on the liver and to evaluate the potential molecular mechanisms associated with adipocytokines underlying non‑alcoholic fatty liver disease (NAFLD) in rats. To generate the NAFLD model, Sprague‑Dawley rats were administered a high‑fat diet and following 12 weeks of model construction, rats were orally treated with a positive control drug and different doses of TARAP daily for 28 days. The rats were then sacrificed and the livers were collected to evaluate the liver index (LI) and observe histological changes by hematoxylin and eosin (H&E) staining. The secretion levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were examined by ELISA. Finally, the expression levels of leptin (LEP), resistin and adiponectin (APN) in liver tissues were determined by immunohistochemistry (IHC). The results demonstrated that, in the group treated with methionine and choline bitartrate tablets and in the groups treated with different doses of TARAP, there was a significant reduction in the LI (P<0.05 or P<0.01), a downregulation of the secretion levels of ALT and AST, reduced levels of LEP and resistin and an increased expression of APN in the liver of NAFLD rats compared with the model group. Furthermore, the effect of TARAP treatment of NAFLD rats was dose dependent. In conclusion, TARAP is a potential agent for downregulating LEP and resistin and upregulating APN expression in rats with NAFLD. Furthermore, TARAP may be a potential candidate for improving treatment responses in patients with NAFLD.

View Figures

View References

1	Fan JG and Farrell GC: Epidemiology of non-alcoholic fatty liver disease in China. J Hepatol. 50:204–210. 2009. View Article : Google Scholar : PubMed/NCBI
2	Everhart JE and Bambha KM: Fatty liver: think globally. Hepatology. 51:1491–1493. 2010. View Article : Google Scholar : PubMed/NCBI
3	Bruce KD and Byrne CD: The metabolic syndrome: common origins of a multifactorial disorder. Postgraduate Med J. 85:614–621. 2009. View Article : Google Scholar : PubMed/NCBI
4	Malaguarnera M, Di Rosa M, Nicoletti F and Malaguarnera L: Molecular mechanisms involved in NAFLD progression. J Mol Med (Berl). 87:679–695. 2009. View Article : Google Scholar : PubMed/NCBI
5	Adams LA, Angulo P and Lindor KD: Nonalcoholic fatty liver disease. CMAJ. 172:899–905. 2005. View Article : Google Scholar : PubMed/NCBI
6	Day CP and James OF: Steatohepatitis: a tale of two ‘hits’? Gastroenterology. 114:842–845. 1998.
7	Guzman G, Brunt EM, Petrovic LM, Chejfec G, Layden TJ and Cotler SJ: Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis? Arch Pathol Lab Med. 132:1761–1766. 2008.PubMed/NCBI
8	Yan E, Durazo F, Tong M and Hong K: Nonalcoholic fatty liver disease: pathogenesis, identification, progression and management. Nutr Rev. 65:376–384. 2007. View Article : Google Scholar : PubMed/NCBI
9	Kakuma T, Lee Y, Higa M, Wang ZW, Pan W, Shimomura I and Unger RH: Leptin, troglitazone and the expression of sterol regulatory element binding proteins in liver and pancreatic islets. Proc Natl Acad Sci USA. 97:8536–8541. 2000. View Article : Google Scholar : PubMed/NCBI
10	Matarese G, Moschos S and Mantzoros CS: Leptin in immunology. J Immunol. 174:3137–3142. 2005. View Article : Google Scholar : PubMed/NCBI
11	Murad A, Nath AK, Cha ST, Demir E, Flores-Riveros J and Sierra-Honigmann MR: Leptin is an autocrine/paracrine regulator of wound healing. FASEB J. 17:1895–1897. 2003.PubMed/NCBI
12	Mantzoros CS: The role of leptin in human obesity and disease: a review of current evidence. Ann Internal Med. 130:671–680. 1999. View Article : Google Scholar : PubMed/NCBI
13	Shklyaev S, Aslanidi G, Tennant M, et al: Sustained peripheral expression of transgeneadiponectin offsets the development of diet-induced obesity in rats. Proc Natl Acad Sci USA. 100:14217–14222. 2003. View Article : Google Scholar : PubMed/NCBI
14	Yalniz M, Bahcecioglu IH, Ataseven H, Ustundag B, Ilhan F, Poyrazoglu OK and Erensoy A: Serum adipokine and ghrelin levels in nonalcoholic steatohepatitis. Mediators Inflamm. 2006:342952006. View Article : Google Scholar : PubMed/NCBI
15	Li JX, Chen RH, Su DM and Li L: Advances in management of nonalcoholic fatty liver disease by Chinese medicine. World Chin J Digestol. 18:1443–1451. 2010.
16	Yao ZS and Yang WL: The Rubus medicinal plants in Jiangxi and suggestion of utilization. J Chin Med Mater. 18:551–554. 1995.
17	Xu PJ, Tan MX and Chen XM: New progress of the Rubupharmacological effects. Health Vocational Educ. 21:145–146. 2003.
18	Gan L, Wang B, Liang H, Zhao YY and Jiang FC: Chemical constituents from Rubus alceaefolius Poir. J Beijing Med Univ. 32:226–228. 2000.
19	Meng XJ, Liu B, Re ZCD, She GM and Jiang YY: Progress of chemical constituents and pharmacology of genus Rubus. Nat Prod Res Dev. 23:767–775. 2011.
20	Zheng HY, Zhao JY, Liu Y, Zheng YQ, Wu J and Hong ZF: Effect of total alkaloids of Rubus alceaefolius on oxidative stress in rats with non-alcoholic fatty liver disease. China J Chin Materia Medica. 36:2383–2387. 2011.
21	Zhao JY, Zheng YQ, Zheng HY, Zhong XY, Wu J and Hong ZF: Anti-oxidation of total alkaloids from Rubus alceaefolius Poir on nonalcoholic fatty liver. J Fujian Univ Traditional Chin Med. 21:15–17. 2011.
22	Zhao JY, Wu ZS, Chen W and Hong ZF: Study of protective effect of liver injury of total alkaloids from Rubus alceaefolius Poir from different part. Lishizhen Med Materia Medica Res. 21:2186–2188. 2010.
23	Hong ZF, Xu W, Li TJ, Zhou JH and Hu J: Determination of total alkaloids from the root of Rubus alceaefolius Poir. J Fujian Univ Traditional Chin Med. 18:28–30. 2008.
24	Soslow RA, Dannenberg AJ, Rush D, Woerner BM, Khan KN, Masferrer J and Koki AT: Cox-2 is expressed in human pulmonary, colonic and mammary tumors. Cancer. 89:2637–2645. 2000. View Article : Google Scholar : PubMed/NCBI
25	Matteoni C, Younossi ZM, Gramlich T, Boparai N, Liu YC and McCullough AJ: Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 116:1413–1419. 1999. View Article : Google Scholar : PubMed/NCBI
26	Lieber CS, Leo MA, Mak KM, Xu YQ, Cao Q, et al: Model of nonalcoholic steatohepatitis. Am J Clin Nutr. 79:502–509. 2004.PubMed/NCBI
27	Tilg H: Adipocytokines in nonalcoholic fatty liver disease: Key players regulating steatosis, inflammation and fibrosis. Curr Pharm Des. 16:1893–1895. 2010. View Article : Google Scholar : PubMed/NCBI
28	Heymsfield SB, Greenberg AS, Fujioka K, et al: Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA. 282:1568–1575. 1999. View Article : Google Scholar : PubMed/NCBI
29	Jarrar MH, Baranova A, Collantes R, Ranard B, Stepanova M, et al: Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 27:412–421. 2008. View Article : Google Scholar : PubMed/NCBI
30	Banerjee RR, Rangwala SM, Shapiro JS, et al: Regulation of fasted blood glucose by resistin. Science. 303:1195–1198. 2004. View Article : Google Scholar : PubMed/NCBI