Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Effect of traditional Chinese medicine formula Sinisan on chronic restraint stress-induced nonalcoholic fatty liver disease: a rat study

Authors: Fafeng Cheng, Chongyang Ma, Xueqian Wang, Changming Zhai, Guoli Wang, Xiaolin Xu, Jie Mu, Changxiang Li, Zisong Wang, Xiaoyu Zhang, Wenchao Yue, Xin Du, Yajun Lian, Wenxiang Zhu, Xiangjun Yin, Zhen Wei, Wenjie Song, Qingguo Wang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Login to get access

Abstract

Background

Nonalcoholic fatty liver disease (NAFLD) represents one of the most common forms of liver disease worldwide, and it is always regarded as a consequence of a sedentary, food-abundant lifestyle, sitting for an extended time, and a low physical activity level, which often coincide with chronic and long-lasting psychological stress. A Chinese medicine Sinisan (SNS) may be a potential formula for treating this kind of disease.

Methods

In this study, a long-term chronic restraint stress protocol was used to investigate the mechanism underlying stress-induced NALFD. To investigate the effect of SNS treatment on stress-induced NAFLD, we measured the liver and serum values of total cholesterol (TC), triglyceride (TG), liver free fatty acids (FFA), low-density lipoprotein, superoxide dismutase, tumor necrosis factor-α, malondialdehyde, interleukin (IL)-6, and serum values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase. Results are shown as a mean ± standard deviation. Significant differences between the groups were evaluated using the Student t-test. For multiple comparisons, one-way analysis of variance (ANOVA) was used. If the results of ANOVA indicated significant differences, post hoc analysis was performed with the Tukey test or Dunnett test, and p < 0.05 was considered statistically significant.

Results

Long-term chronic stress led to steatosis and non-alcoholic steatohepatitis. Additionally, SNS treatment significantly increased body weight gain (p < 0.01) and sucrose preference (p < 0.001), and it reduced the liver values of TC, TG, and FFA (p < 0.05). SNS also reduced the serum values of AST and ALT (p < 0.001), and the liver value of IL-6 (p < 0.01).

Conclusions

This study’s results demonstrate that psychological stress may be a significant risk factor of NAFLD. Furthermore, the traditional Chinese medicine formula SNS may have some beneficial effect in antagonizing psychological stress and stress-related NAFLD.
Literature
1.
2.
Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, Mccullough AJ, Natale S, Forlani G, Melchionda N. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 2001;50(8):1844–50.CrossRefPubMed
3.
Younossi ZM, Otgonsuren M, Henry L, Venkatesan C, Mishra A, Erario M, Hunt S. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology. 2015;62(6):1723–30.CrossRefPubMed
4.
Ratziu V, Bellentani S, Cortez-Pinto H, Day C, Marchesini G. A position statement on NAFLD/NASH based on the EASL 2009 special conference ☆. J Hepatol. 2010;53(2):372–84.CrossRefPubMed
5.
Masarone M, Federico A, Abenavoli L, Loguercio C, Persico M. Non alcoholic fatty liver: epidemiology and natural history. Rev Recent Clin Trials. 2014;9(3):126–33.CrossRefPubMed
6.
Wong WS, Wong LH, Tse CH, Chan LY. Prevalence of the TM6SF2 variant and non-alcoholic fatty liver disease in Chinese. J Hepatol. 2014;61(3):708–9.CrossRefPubMed
7.
Farrell GC, Wong VW, Chitturi S. NAFLD in Asia--as common and important as in the West. Nat Rev Gastroenterol Hepatol. 2013;10(5):307–18.CrossRefPubMed
8.
Day CP, James OFW. Steatohepatitis: a tale of two “hits”? Gastroenterology. 1998;114(4):842–45.
9.
Periasamy S, Chien SP, Chang PC, Hsu DZ, Liu MY. Sesame oil mitigates nutritional steatohepatitis via attenuation of oxidative stress and inflammation: a tale of two-hit hypothesis ☆ ☆☆. J. Nutr. Biochem. 2014;25(2):232–40.CrossRefPubMed
10.
Liver EAftSot, Diabetes EAftSo. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Obesity facts. 2016;9(2):65–90.CrossRef
11.
Ryu S, Chang Y, Jung H-S, Yun KE, Kwon M-J, Choi Y, Kim C-W, Cho J, Suh B-S, Cho YK. Relationship of sitting time and physical activity with non-alcoholic fatty liver disease. J Hepatol. 2015;63(5):1229–37.CrossRefPubMed
12.
Zelber-Sagi S, Godos J, Salomone F. Lifestyle changes for the treatment of nonalcoholic fatty liver disease: a review of observational studies and intervention trials. Ther Adv Gastroenterol. 2016;9(3):392–407.CrossRef
13.
Landmann R, Müller F, Perini C, Wesp M, Erne P, Bühler F. Changes of immunoregulatory cells induced by psychological and physical stress: relationship to plasma catecholamines. Clin Exp Immunol. 1984;58(1):127.PubMedPubMedCentral
14.
Cohen S, Janicki-Deverts D, Miller GE. Psychological stress and disease. JAMA. 2007;298(14):1685–7.CrossRefPubMed
15.
Liu YZ, Chen JK, Zhang Y, Wang X, Jiang CL. Chronic stress directly induces steatohepatitis while decreases visceral fat mass in mice. BMC Gastroenterol. 2014;14(1):7075–8.
16.
Tsigos C, Chrousos GP. Chronic stress at work and the metabolic syndrome: prospective study. BMJ. 2006;332(7540):521–5.CrossRef
17.
Conti R, Caprioli A, Coccurello R. Psychosocial stress affects energy balance in mice: Modulation by social status. Psychoneuroendocrinology. 2006;31(5):623–33.CrossRefPubMed
18.
Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, Vanni E, Villanova N, Melchionda N. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37(4):917–23.CrossRefPubMed
19.
Serikov VS, Lyashev YD. Effects of Melatonin on Stress-Induced Changes in the Liver of Rats with Different Resistance to Stress. Bull. Exp. Biol. Med. 2015;159(3):1–4.CrossRef
20.
Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A. 2004;101(49):17312–5.CrossRefPubMedPubMedCentral
21.
Han Y, Lin M, Wang X, Guo K, Wang S, Sun M, Wang J, Han X, Fu T, Hu Y. Basis of aggravated hepatic lipid metabolism by chronic stress in high-fat diet-fed rat. Endocrine. 2015;48(2):483–92.CrossRefPubMed
22.
Sun Y, Chen T, Xu Q. Si-Ni-San, a traditional Chinese prescription, and its drug-pairs suppress contact sensitivity in mice via inhibition of the activity of metalloproteinases and adhesion of T lymphocytes. J Pharm Pharmacol. 2003;55(6):839–46.CrossRefPubMed
23.
Tsai CC, Kao CT, Hsu CT, Lin CC, Lin JG. Evaluation of four prescriptions of traditional Chinese medicine: Syh-Mo-Yiin, Guizhi-Fuling-Wan, Shieh-Qing-Wan and Syh-Nih-Sann on experimental acute liver damage in rats. J Ethnopharmacol. 1997;55(3):213–22.CrossRefPubMed
24.
Liu CG, Wang XL, Du XW, Jiang DY, Geng NZ, Zhang SX, Zhou YY, Kuang HX. Metabolomic profiling for identification of potential biomarkers in the protective effects of modified Sinisan against liver injury in dimethylnitrosamine treated rats. Biol Pharm Bull. 2013;36(11):1700–7.CrossRefPubMed
25.
Jiang J, Zhou C, Xu Q. Alleviating effects of si-ni-san, a traditional Chinese prescription, on experimental liver injury and its mechanisms. Biol Pharm Bull. 2003;26(8):1089–94.CrossRefPubMed
26.
Lin KJ, Chen JC, Wei T, Lin CC, Lin JG, Tsai CC. Prophylactic effect of four prescriptions of traditional Chinese medicine on a-naphthylisothiocyanate and carbon tetrachloride induced toxicity in rats. Acta Pharmacol Sin. 2001;22(12):1159–67.PubMed
27.
Ninomiya F. Clinical Evaluation of Perspiration Reducing Effects of a Kampo Formula, Shigyaku-san, on Palmoplantar Hidrosis. Evid Based Complement Alternat Med. 2008;5(2):199–203.CrossRefPubMed
28.
Wang YT, Tan QR, Sun LL, Cao J, Dou KF, Xia B, Wang W. Possible therapeutic effect of a Traditional Chinese Medicine, Sinisan, on chronic restraint stress related disorders. Neurosci Lett. 2009;449(3):215–9.CrossRefPubMed
29.
Li Y, Sun Y, Ma X, Xue X, Zhang W, Wu Z, Ouyang Y, Chen J, Wang W, Guo S. Effects of Sini San used alone and in combination with fluoxetine on central and peripheral 5-HT levels in a rat model of depression. J Tradit Chin Med. 2013;33(5):674–81.CrossRefPubMed
30.
D-d F, Tang T, Lin X-p, Yang Z-y, Yang S, Z-a X, Wang Y, Zheng P, Wang Y, Zhang C-h. Nine traditional Chinese herbal formulas for the treatment of depression: an ethnopharmacology, phytochemistry, and pharmacology review. Neuropsychiatr Dis Treat. 2016;12:2387.CrossRef
31.
Luo HD, Lin LM, Qin-Hui T, Yao HL, Sun SW, Liao DF. Effect of Sini Powder on non-alcoholic fatty hepatocirrhosis induced by methionine-choline deficit diet. Drug Eval Res. 2014;37(3):231–34.
32.
Zhang L-J, Yang B, Yu B-P. Paeoniflorin protects against nonalcoholic fatty liver disease induced by a high-fat diet in mice. Biol Pharm Bull. 2015;38(7):1005.
33.
Wu X, Zhang L, Gurley E, Studer E, Shang J, Wang T, Wang C, Yan M, Jiang Z, Hylemon PB. Prevention of free fatty acid–induced hepatic lipotoxicity by 18β-glycyrrhetinic acid through lysosomal and mitochondrial pathways. Hepatology. 2008;47(6):1905–15.CrossRefPubMed
34.
Shan-Shan W, He-Jin Y, Huang J-W, Xue-Ping L, Ling-Fang P, Qing-Guo W. Traditional herbal formula Sini Powder extract produces antidepressant-like effects through stress-related mechanisms in rats. Chin J Nat Med. 2016;14(8):590–8.
35.
Bali A, Jaggi AS. Preclinical experimental stress studies: protocols, assessment and comparison. Eur J Pharmacol. 2015;746:282–92.CrossRefPubMed
36.
Boyko M, Kutz R, Grinshpun J, Zvenigorodsky V, Gruenbaum SE, Gruenbaum BF, Brotfain E, Shapira Y, Zlotnik A. Establishment of an animal model of depression contagion. Behav Brain Res. 2015;281:358–63.CrossRefPubMed
37.
Liu L, Zhou X, Zhang Y, Liu Y, Yang L, Pu J, Zhu D, Zhou C, Xie P. The identification of metabolic disturbances in the prefrontal cortex of the chronic restraint stress rat model of depression. Behav Brain Res. 2016;305:148–56.CrossRefPubMed
38.
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21.CrossRefPubMed
39.
Leamy AK, Egnatchik RA, Young JD. Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease. Prog Lipid Res. 2013;52(1):165–74.CrossRefPubMed
40.
Woods CP, Hazlehurst JM, Tomlinson JW. Glucocorticoids and non-alcoholic fatty liver disease. J Steroid Biochem Mol Biol. 2015;154:94–103.CrossRefPubMed
41.
Joo Ho Lee SF, Choi S-W. Epigenetic Mechanisms Underlying the Link between Non-Alcoholic Fatty Liver Diseases and Nutrition. Nutrients. 2014;6(8):3303–25.CrossRefPubMedPubMedCentral
42.
Hoek-van den Hil EF, Schothorst EM, Stelt I, Swarts HJ, Vliet M, Amolo T, Vervoort JJ, Venema D, Hollman PC, Rietjens IM. Direct comparison of metabolic health effects of the flavonoids quercetin, hesperetin, epicatechin, apigenin and anthocyanins in high-fat-diet-fed mice. Genes Nutr. 2015;10(4):1.CrossRef
43.
Czech B, Neumann ID, Muller M, Reber SO, Hellerbrand C. Effect of chronic psychosocial stress on nonalcoholic steatohepatitis in mice. Int J Clin Exp Pathol. 2013;6(8):1585–93.PubMedPubMedCentral
44.
Cudnoch-Jedrzejewska A, Gomolka R, Szczepanska-Sadowska E, Czarzasta K, Wrzesien R, Koperski L, Puchalska L, Wsol A. High-fat diet and chronic stress reduce central pressor and tachycardic effects of apelin in Sprague–Dawley rats. Clin Exp Pharmacol Physiol. 2015;42(1):52–62.CrossRefPubMed
45.
Tsochatzis EA, Papatheodoridis GV, Archimandritis AJ. Adipokines in nonalcoholic steatohepatitis: from pathogenesis to implications in diagnosis and therapy. Mediat Inflamm. 2009;2009
46.
Tarantino G, Finelli C. Pathogenesis of hepatic steatosis: the link between hypercortisolism and non-alcoholic fatty liver disease. World J Gastroenterol. 2013;19(40):6735–43.CrossRefPubMedPubMedCentral
47.
Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein AE. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol. 2008;103(6):1372–9.CrossRefPubMed
48.
Abenavoli L, Peta V. Role of adipokines and cytokines in non-alcoholic fatty liver disease. Rev Recent Clin Trials. 2014;9(3):134–40.CrossRefPubMed
49.
Kilic T, Parlakpinar H, Taslidere E, Yildiz S, Polat A, Vardi N, Colak C, Ermis H. Protective and therapeutic effect of apocynin on bleomycin-induced lung fibrosis in rats. Inflammation. 2015;38(3):1166–80.CrossRefPubMed
50.
Zaitone SA, Barakat BM, Bilasy SE, Fawzy MS, Abdelaziz EZ, Farag NE. Protective effect of boswellic acids versus pioglitazone in a rat model of diet-induced non-alcoholic fatty liver disease: influence on insulin resistance and energy expenditure. Naunyn Schmiedeberg's Arch Pharmacol. 2015;388(6):587–600.CrossRef
51.
Rotimi S, Ugwu E, Essien I, Adelani I, Rotimi O. Effects of Quercetin and α-Lipoic Acid on α-Cypermethrin-Induced Oxidative Stress in Rats. FASEB J. 2015;29(1 Supplement):612.612.
52.
53.
Cabello-Verrugio C, Ruiz-Ortega M, Mosqueira M, Simon F. Oxidative stress in disease and aging: mechanisms and therapies. Oxidative Med Cell Longev. 2016;2016
54.
Yang LN, Wen J, Sun Y, Liang JJ, Zheng WH, Zhang LL, Zhou YJ, Xiong ZL. Metabonomic study on the anti-liver injury effect of Si-Ni-San on rats by using UPLC-MS/MS. Acta Pharmaceutica Sinica 2014;49(3):368.
55.
Sun Y, Cai T-T, Shen Y, Zhou X-B, Chen T, Xu Q. Si-Ni-San, a traditional Chinese prescription, and its active ingredient glycyrrhizin ameliorate experimental colitis through regulating cytokine balance. Int Immunopharmacol. 2009;9(12):1437–43.CrossRefPubMed
56.
Willner P, Towell A, Sampson D, Sophokleous S, Muscat R. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology. 1987;93(3):358–64.CrossRefPubMed
Metadata
Title
Effect of traditional Chinese medicine formula Sinisan on chronic restraint stress-induced nonalcoholic fatty liver disease: a rat study
Authors
Fafeng Cheng
Chongyang Ma
Xueqian Wang
Changming Zhai
Guoli Wang
Xiaolin Xu
Jie Mu
Changxiang Li
Zisong Wang
Xiaoyu Zhang
Wenchao Yue
Xin Du
Yajun Lian
Wenxiang Zhu
Xiangjun Yin
Zhen Wei
Wenjie Song
Qingguo Wang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1707-2

Other articles of this Issue 1/2017

BMC Complementary Medicine and Therapies 1/2017 Go to the issue

Research article

MOK, a pharmacopuncture medicine, regulates thyroid dysfunction in L-thyroxin-induced hyperthyroidism in rats through the regulation of oxidation and the TRPV1 ion channel

Research article

An Overview of the Practitioner Research and Collaboration Initiative (PRACI): a practice-based research network for complementary medicine

Research article

An interpretive review of consensus statements on clinical guideline development and their application in the field of traditional and complementary medicine

Research article

Isolation and characterization of the compounds responsible for the antimutagenic activity of Combretum microphyllum (Combretaceae) leaf extracts

Research article

Effect of a herbal extract powder (YY-312) from Imperata cylindrica Beauvois, Citrus unshiu Markovich, and Evodia officinalis Dode on body fat mass in overweight adults: a 12-week, randomized, double-blind, placebo-controlled, parallel-group clinical trial

Research article

Litchi seed extract inhibits epidermal growth factor receptor signaling and growth of Two Non-small cell lung carcinoma cells