Arctiin attenuates lipid accumulation, inflammation and oxidative stress in nonalcoholic fatty liver disease through inhibiting MAPK pathway

Main Article Content

Lin Li
Ying Zhang
Fangxi Xiao
Zhigang Wang
Ju Liu


arctiin, nonalcoholic fatty liver disease, lipid accumulation, inflammation, oxidative stress


Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that predominantly affects the adult population. It was reported that arctiin improves functioning of the liver through multiple pathways, but the exact molecular mechanism is not clear yet. First, a mouse obesity model was successfully constructed, and hematoxylin and eosin staining and enzyme-linked-immunosorbent serologic assay (ELISA) were used to assess the levels of alanine aminotransferase and aspartate aminotransferase, respectively, in liver tissue damage. Then lipid accumulation in liver tissues was detected by immunohistochemistry (IHC) staining, and detection kits were used to determine the levels of triglycerides and total cholesterol in serum. Western blotting was used to detect the expression of adipose synthesis proteins, sterol regulatory element-binding protein-1, stearoyl-CoA desaturase-1 and fatty acid synthase, in liver tissues. Further, the levels of glutathione peroxidase, malondialdehyde, superoxide dismutase, catalase and reactive oxygen species as well as that of interleukin 2 (IL-2), IL-1β, IL-6 and tumor necrosis factor-α, and the expression of p-P65 and P65, in liver tissues were measured by ELISA and IHC, respectively. Finally, the protein expression levels of extracellular signal-regulated kinase (ERK), phospho-ERK, Jun N-terminal kinase, phospho-JNK, p38 and phospho-p38 in liver tissues were examined by WB. The results showed that relative to normal diet, mice on high-fat diet had increased body weight as well as fat content in liver tissues, increased liver tissue damage, decreased oxidative stress capacity and enhanced inflammatory response, while arctiin changed these adverse effects and inhibited mitogen-activated protein kinase (MAPK) pathway. Arctiin exerts hepatoprotective effects by inhibiting MAPK pathway and improving lipid accumulation, inflammatory response and oxidative stress.

Abstract 252 | PDF Downloads 305 HTML Downloads 78 XML Downloads 5


Chalasani, N., Younossi, Z., Lavine, J.E., Diehl, A.M., Brunt, E.M., Cusi, K., Charlton, M. and Sanyal, A.J., 2012. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 55: 2005–2023. 10.1002/hep.25762

Cohen, J.C., Horton, J.D. and Hobbs, H.H., 2011. Human fatty liver disease: old questions and new insights. Science 332: 1519–1523. 10.1126/science.1204265

Golec, T. Č., Kavalar, R., Goričan, I. and Strnad, M., 2021. Sudden cardiac death in excited delirium, and how to prevent it. Signa Vitae NA: 1–6. Corpus ID: 244055126. 10.22514/sv.2021.222

Herbert, D., Franz, S., Popkova, Y., Anderegg, U., Schiller, J., Schwede, K., Lorz, A., Simon, J.C. and Saalbach, A., 2018. High-fat diet exacerbates early psoriatic skin inflammation independent of obesity: saturated fatty acids as key players. Journal of Investigative Dermatology 138: 1999–2009. 10.1016/j.jid.2018.03.1522

Jais, A. and Brüning, J.C., 2017. Hypothalamic inflammation in obesity and metabolic disease. Journal of Clinical Investigation 127: 24–32. 10.1172/jci88878

Keshvari, M., Rahmati, M., Mirnasouri, R. and Chehelcheraghi, F., 2020. Effects of endurance exercise and Urtica dioica on the functional, histological and molecular aspects of the-hippocampus in STZ-Induced diabetic rats. Journal of Ethno-pharmacology 256: 112801. 10.1016/j.jep.2020.112801

Kothari, V., Luo, Y., Tornabene, T., O'Neill, A.M., Greene, M.W., Geetha, T. and Babu, J.R., 2017. High fat diet induces brain insulin resistance and cognitive impairment in mice. Biochimica et Biophysica Acta–Molecular Basis of Disease 1863: 499–508. 10.1016/j.bbadis.2016.10.006

Landecho, M.F., Tuero, C., Valentí, V., Bilbao, I., de la Higuera, M. and Frühbeck, G., 2019. Relevance of leptin and other adipokines in obesity-associated cardiovascular risk. Nutrients 11(11): 2664. 10.3390/nu11112664

Lee, S., Shin, S., Kim, H., Han, S., Kim, K., Kwon, J., et al., 2011. Anti-inflammatory function of arctiin by inhibiting COX-2 expression via NF-κB pathways. Journal of Inflammation (London) 8: 16. 10.1186/1476-9255-8-16

Li, C.X., Gao, J.G., Wan, X.Y., Chen, Y., Xu, C.F., Feng, Z.M., et al., 2019. Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways. World Journal of Gastroenterology 25: 5120–5133. 10.3748/wjg.v25.i34.5120

Li, J., Yuan, Y.P., Xu, S.C., Zhang, N., Xu, C.R., Wan, C.X., et al., 2017. Arctiin protects against cardiac hypertrophy through inhibiting MAPKs and AKT signaling pathways. Journal of Pharmacological Sciences 135: 97–104. 10.1016/j.jphs.2017.05.012

Miah, P., Mohona, S.B.S., Rahman, M.M., Subhan, N., Khan, F., Hossain, H., Sharker, S.M. and Alam, M.A., 2021. Supple-mentation of cumin seed powder prevents oxidative stress, hyperlipidemia and non-alcoholic fatty liver in high fat diet fed rats. Biomedicine & Pharmacotherapy 141: 111908. 10.1016/j.biopha.2021.111908

Min, B., Lee, H., Song, J.H., Han, M.J. and Chung, J., 2014. Arctiin inhibits adipogenesis in 3T3-L1 cells and decreases adiposity and body weight in mice fed a high-fat diet. Nutrition Research and Practice 8: 655–661. 10.4162/nrp.2014.8.6.655

Musso, G., Gambino, R., Tabibian, J.H., Ekstedt, M., Kechagias, S., Hamaguchi, M., et al., 2014. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Medicine 11: e1001680. 10.1371/journal.pmed.1001680

Najafi, M., Nazari, Z., Shamsi, R., Nikpayam, O., Bahrami, A., Hekmatdoost, A. and Hejazi, E., 2020. Dietary patterns and risk of cervical cancer: a case-control study. European Journal of Gynaecological Oncology 41: 943–948. 10.31083/j.ejgo.2020.06.2149

Negi, C.K., Babica, P., Bajard, L., Bienertova-Vasku, J. and Tarantino, G., 2022. Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease. Metabolism 126: 154925. 10.1016/j.metabol.2021.154925

Piché, M.E., Tchernof, A. and Després, J. P., 2020. Obesity Phenotypes, Diabetes, and Cardiovascular Diseases. Circ Res 126: 1477–1500. 10.1161/circresaha.120.316101

Rahmati, M., Keshvari, M., Mirnasouri, R. and Chehelcheraghi, F., 2021. Exercise and Urtica dioica extract ameliorate hippocampal insulin signaling, oxidative stress, neuroinflammation, and cognitive function in STZ-induced diabetic rats. Biomedicine & Pharmacotherapy 139: 111577. 10.1016/j.biopha.2021.111577

Rahmati, M., Keshvari, M., Xie, W., Yang, G., Jin, H., Li, H., Chehelcheraghi, F. and Li, Y., 2022. Resistance training and Urtica dioica increase neurotrophin levels and improve cognitive function by increasing age in the hippocampus of rats. Biomedicine & Pharmacotherapy 153: 113306. 10.1016/j.biopha.2022.113306

Song, K., Guo, C.-R., Li, C.-L. and Ding, N., 2021. Comparison of clinical characteristics in acute pancreatitis with and without diabetes mellitus: a retrospective study. Signa Vitae 17: 181–187. 10.22514/sv.2020.16.0113

Tarantino, G., Balsano, C., Santini, S.J., Brienza, G., Clemente, I., Cosimini, B. and Sinatti, G., 2021. It is high time physicians thought of natural products for alleviating NAFLD. Is there sufficient evidence to use them? International Journal of Molecular Sciences 22: 13424. 10.3390/ijms222413424

Wu, T., Liu, Q., Li, Y., Li, H., Chen, L., Yang, X., et al., 2021a. Feeding-induced hepatokine, Manf, ameliorates diet-induced obesity by promoting adipose browning via p38 MAPK pathway. Journal of Expeimental Medicine 218(6): e20201203. 10.1084/jem.20201203

Wu, Y., Sun, H., Yi, R., Tan, F. and Zhao, X., 2021b. Anti-obesity effect of Liupao tea extract by modulating lipid metabolism and oxidative stress in high-fat-diet-induced obese mice. Journal of Food Science 86: 215–227. 10.1111/1750-3841.15551

Wu, J.G., Wu, J.Z., Sun, L.N., Han, T., Du, J., Ye, Q., Zhang, H. and Zhang, Y.G., 2009. Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats. Phytomedicine 16: 1033–1041. 10.1016/j.phymed.2009.04.005

Xu, X., Zeng, X.Y., Cui, Y.X., Li, Y.B., Cheng, J.H., Zhao, X.D., Xu, G.H., Ma, J., Piao, H.N., Jin, X. and Piao, L.X., 2020. Antidepressive effect of arctiin by attenuating neuroinflammation via HMGB1/TLR4-and TNF-α/TNFR1-mediated NF-κB activation. ACS Chemical Neuroscience 11: 2214–2230. 10.1021/acschemneuro.0c00120

Younossi, Z.M., Koenig, A.B., Abdelatif, D., Fazel, Y., Henry, L. and Wymer, M., 2016. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 64: 73–84. 10.1002/hep.28431

Yu, J.-H., Lin, Y.-L., Ji, Z.-H., Chen, Y.-Z. and Li, Y., 2021. Malignant struma ovarii: a case report and literature review. European Journal of Gynaecological Oncology 42: 244–249. 10.31083/j.ejgo.2021.02.5198

Zhou, B., Weng, G., Huang, Z., Liu, T. and Dai, F., 2018. Arctiin prevents LPS-induced acute lung injury via inhibition of PI3K/AKT signaling pathway in mice. Inflammation 41: 2129–2135. 10.1007/s10753-018-0856-x

Zhou, Y., Xia, L., Yao, W., Han, J. and Wang, G., 2020. Arctiin antagonizes triptolide-induced hepatotoxicity via activation of Nrf2 pathway. BioMed Research International 2020: 2508952. 10.1155/2020/2508952