Ophiopogonin D ameliorates non‑alcoholic fatty liver disease in high‑fat diet‑induced obese mice by improving lipid metabolism, oxidative stress and inflammatory response

Huang,Xi; Ji,Qi; She,Chen-Yi; Cheng,Yi; Zhou,Jian-Rong; Wu,Qing-Ming

doi:10.3892/etm.2023.12116

Ophiopogonin D ameliorates non‑alcoholic fatty liver disease in high‑fat diet‑induced obese mice by improving lipid metabolism, oxidative stress and inflammatory response

Authors:
- Xi Huang
- Qi Ji
- Chen-Yi She
- Yi Cheng
- Jian-Rong Zhou
- Qing-Ming Wu
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Affiliations: Medical College, Wuhan University of Science and Technology, Wuhan, Hubei 430065, P.R. China, Department of Gastroenterology, General Hospital of Central Theater Command, Wuhan, Hubei 430064, P.R. China, Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510000, P.R. China
Published online on: July 13, 2023 https://doi.org/10.3892/etm.2023.12116
Article Number: 418
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lipid metabolic disorders, oxidative stress and inflammation in the liver are key steps in the progression of non‑alcoholic fatty liver disease (NAFLD). Ophiopogonin D (OP‑D), the main active ingredient of Ophiopogon japonicus, exhibits several pharmacological activities such as antioxidant and anti‑inflammatory activities. Therefore, the current study aimed to explore the role of OP‑D in NAFLD in a high‑fat diet (HFD)‑induced obesity mouse model. To investigate the effect of OP‑D on NAFLD in vivo, a NAFLD mouse model was established following feeding mice with HFD, then the mice were randomly treated with HFD or HFD + OP‑D for 4 weeks. Subsequently, primary mouse hepatocytes were isolated, and enzyme‑linked immunosorbent assay, reverse transcription‑quantitative PCR western blotting and immunofluorescence analysis were used for assessment to explore the direct effect of OP‑D in vitro. The results of the present study indicated that OP‑D could ameliorate NAFLD in HFD‑induced obese mice by regulating lipid metabolism and antioxidant and anti‑inflammatory responses. Additionally, OP‑D treatment decreased lipogenesis and inflammation levels in vitro, suggesting that the NF‑κB signaling pathway may be involved in the beneficial effects of OP‑D on NAFLD.

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1	Kumar S, Duan Q, Wu R, Harris EN and Su Q: Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis. Adv Drug Deliv Rev. 176(113869)2021.PubMed/NCBI View Article : Google Scholar
2	Liebe R, Esposito I, Bock HH, Vom Dahl S, Stindt J, Baumann U, Luedde T and Keitel V: Diagnosis and management of secondary causes of steatohepatitis. J Hepatol. 74:1455–1471. 2021.PubMed/NCBI View Article : Google Scholar
3	Safari Z and Gérard P: The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD). Cell Mol Life Sci. 76:1541–1558. 2019.PubMed/NCBI View Article : Google Scholar
4	Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM and Sanyal AJ: The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 67:328–357. 2018.PubMed/NCBI View Article : Google Scholar
5	Lan T, Hu Y, Hu F, Li H, Chen Y, Zhang J, Yu Y, Jiang S, Weng Q, Tian S, et al: Hepatocyte glutathione S-transferase mu 2 prevents non-alcoholic steatohepatitis by suppressing ASK1 signaling. J Hepatol. 76:407–419. 2022.PubMed/NCBI View Article : Google Scholar
6	Rohm TV, Meier DT, Olefsky JM and Donath MY: Inflammation in obesity, diabetes, and related disorders. Immunity. 55:31–55. 2022.PubMed/NCBI View Article : Google Scholar
7	Khan RS, Bril F, Cusi K and Newsome PN: Modulation of insulin resistance in nonalcoholic fatty liver disease. Hepatology. 70:711–724. 2019.PubMed/NCBI View Article : Google Scholar
8	Katsiki N, Mikhailidis DP and Mantzoros CS: Non-alcoholic fatty liver disease and dyslipidemia: An update. Metabolism. 65:1109–1123. 2016.PubMed/NCBI View Article : Google Scholar
9	Farzanegi P, Dana A, Ebrahimpoor Z, Asadi M and Azarbayjani MA: Mechanisms of beneficial effects of exercise training on non-alcoholic fatty liver disease (NAFLD): Roles of oxidative stress and inflammation. Eur J Sport Sci. 19:994–1003. 2019.PubMed/NCBI View Article : Google Scholar
10	Mohammed S, Nicklas EH, Thadathil N, Selvarani R, Royce GH, Kinter M, Richardson A and Deepa SS: Role of necroptosis in chronic hepatic inflammation and fibrosis in a mouse model of increased oxidative stress. Free Radic Biol Med. 164:315–328. 2021.PubMed/NCBI View Article : Google Scholar
11	Huang X, Wang Y, Zhang Z, Wang Y, Chen X, Wang Y and Gao Y: Ophiopogonin D and EETs ameliorate Ang II-induced inflammatory responses via activating PPARα in HUVECs. Biochem Biophys Res Commun. 490:123–133. 2017.PubMed/NCBI View Article : Google Scholar
12	Kou J, Tian Y, Tang Y, Yan J and Yu B: Antithrombotic activities of aqueous extract from Radix Ophiopogon japonicus and its two constituents. Biol Pharm Bull. 29:1267–1270. 2006.PubMed/NCBI View Article : Google Scholar
13	Kou J, Sun Y, Lin Y, Cheng Z, Zheng W, Yu B and Xu Q: Anti-inflammatory activities of aqueous extract from Radix Ophiopogon japonicus and its two constituents. Biol Pharm Bull. 28:1234–1238. 2005.PubMed/NCBI View Article : Google Scholar
14	Qiao Y, Jiao H, Wang F and Niu H: Ophiopogonin D of Ophiopogon japonicus ameliorates renal function by suppressing oxidative stress and inflammatory response in streptozotocin-induced diabetic nephropathy rats. Braz J Med Biol Res. 53(e9628)2020.PubMed/NCBI View Article : Google Scholar
15	Li W, Ji L, Tian J, Tang W, Shan X, Zhao P, Chen H, Zhang C, Xu M, Lu R and Guo W: Ophiopogonin D alleviates diabetic myocardial injuries by regulating mitochondrial dynamics. J Ethnopharmacol. 271(113853)2021.PubMed/NCBI View Article : Google Scholar
16	Qin Y, Dong H, Sun J, Zhang Y, Li J, Zhang T, Chen G, Wang S, Song S, Wang W, et al: Evaluation of MTBH, a novel hesperetin derivative, on the activity of hepatic cytochrome P450 isoform in vitro and in vivo using a cocktail method by HPLC-MS/MS. Xenobiotica. 51:1389–1399. 2021.PubMed/NCBI View Article : Google Scholar
17	Ma L, Wei S, Yang B, Ma W, Wu X, Ji H, Sui H and Chen J: Chrysosplenetin inhibits artemisinin efflux in P-gp-over-expressing Caco-2 cells and reverses P-gp/MDR1 mRNA up-regulated expression induced by artemisinin in mouse small intestine. Pharm Biol. 55:374–380. 2017.PubMed/NCBI View Article : Google Scholar
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
19	Donaldson JG: Immunofluorescence staining. Curr Protoc Cell Biol. Chapter 4(Unit 4.3)2001.PubMed/NCBI View Article : Google Scholar
20	Zandani G, Anavi-Cohen S, Yudelevich T, Nyska A, Dudai N, Madar Z and Gorelick J: Chiliadenus iphionoides Reduces body weight and improves parameters related to hepatic lipid and glucose metabolism in a high-fat-diet-induced mice model of NAFLD. Nutrients. 14(4552)2022.PubMed/NCBI View Article : Google Scholar
21	Wu YK, Ren ZN, Zhu SL, Wu YZ, Wang G, Zhang H, Chen W, He Z, Ye XL and Zhai QX: Sulforaphane ameliorates non-alcoholic fatty liver disease in mice by promoting FGF21/FGFR1 signaling pathway. Acta Pharmacol Sin. 43:1473–1483. 2022.PubMed/NCBI View Article : Google Scholar
22	Arroyave-Ospina JC, Wu Z, Geng Y and Moshage H: Role of oxidative stress in the pathogenesis of non-alcoholic fatty liver disease: Implications for prevention and therapy. Antioxidants (Basel). 10(174)2021.PubMed/NCBI View Article : Google Scholar
23	Zhang X, Shang X, Jin S, Ma Z, Wang H, Ao N, Yang J and Du J: Vitamin D ameliorates high-fat-diet-induced hepatic injury via inhibiting pyroptosis and alters gut microbiota in rats. Arch Biochem Biophys. 705(108894)2021.PubMed/NCBI View Article : Google Scholar
24	Wang Y, Huang X, Ma Z, Wang Y, Chen X and Gao Y: Ophiopogonin D alleviates cardiac hypertrophy in rat by upregulating CYP2J3 in vitro and suppressing inflammation in vivo. Biochem Biophys Res Commun. 503:1011–1019. 2018.PubMed/NCBI View Article : Google Scholar
25	De Gregorio E, Colell A, Morales A and Marí M: Relevance of SIRT1-NF-κB Axis as therapeutic target to ameliorate inflammation in liver disease. Int J Mol Sci. 21(3858)2020.PubMed/NCBI View Article : Google Scholar
26	Bansod S, Saifi MA and Godugu C: Molecular updates on berberine in liver diseases: Bench to bedside. Phytother Res. 35:5459–5476. 2021.PubMed/NCBI View Article : Google Scholar
27	Bagherniya M, Nobili V, Blesso CN and Sahebkar A: Medicinal plants and bioactive natural compounds in the treatment of non-alcoholic fatty liver disease: A clinical review. Pharmacol Res. 130:213–240. 2018.PubMed/NCBI View Article : Google Scholar
28	Wang Y, Li D, Song L and Ding H: Ophiopogonin D attenuates PM2.5-induced inflammation via suppressing the AMPK/NF-κB pathway in mouse pulmonary epithelial cells. Exp Ther Med. 20(139)2020.PubMed/NCBI View Article : Google Scholar
29	Qian J, Jiang F, Wang B, Yu Y, Zhang X, Yin Z and Liu C: Ophiopogonin D prevents H2O2-induced injury in primary human umbilical vein endothelial cells. J Ethnopharmacol. 128:438–445. 2010.PubMed/NCBI View Article : Google Scholar
30	Eslam M, Sanyal AJ and George J: International Consensus Panel. MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology. 158:1999–2014.e1. 2020.PubMed/NCBI View Article : Google Scholar
31	Godoy-Matos AF, Silva Júnior WS and Valerio CM: NAFLD as a continuum: From obesity to metabolic syndrome and diabetes. Diabetol Metab Syndr. 12(60)2020.PubMed/NCBI View Article : Google Scholar
32	Wasilewska N and Lebensztejn DM: Non-alcoholic fatty liver disease and lipotoxicity. Clin Exp Hepatol. 7:1–6. 2010.PubMed/NCBI View Article : Google Scholar
33	Fujii H and Kawada N: Japan Study Group of Nafld Jsg-Nafld. The role of insulin resistance and diabetes in nonalcoholic fatty liver disease. Int J Mol Sci. 21(3863)2020.PubMed/NCBI View Article : Google Scholar
34	Rhee EJ: Nonalcoholic fatty liver disease and diabetes: An epidemiological perspective. Endocrinol Metab (Seoul). 34:226–233. 2019.PubMed/NCBI View Article : Google Scholar
35	Ma Y, Lee G, Heo SY and Roh YS: Oxidative stress is a key modulator in the development of nonalcoholic fatty liver disease. Antioxidants (Basel). 11(91)2021.PubMed/NCBI View Article : Google Scholar
36	Li Q, Tan JX, He Y, Bai F, Li SW, Hou YW, Ji LS, Gao YT, Zhang X, Zhou ZH, et al: Atractylenolide III ameliorates non-alcoholic fatty liver disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway. Int J Biol Sci. 18:1594–1611. 2022.PubMed/NCBI View Article : Google Scholar
37	Irie M, Sohda T, Anan A, Fukunaga A, Takata K, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Shakado S and Sakisaka S: Reduced glutathione suppresses oxidative stress in nonalcoholic fatty liver disease. Euroasian J Hepatogastroenterol. 6:13–18. 2016.PubMed/NCBI View Article : Google Scholar
38	Polimeni L, Del Ben M, Baratta F, Perri L, Albanese F, Pastori D, Violi F and Angelico F: Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis. World J Hepatol. 7:1325–1336. 2015.PubMed/NCBI View Article : Google Scholar
39	Yang Y, Lu Y, Han F, Chang Y, Li X, Han Z, Xue M, Cheng Y, Sun B and Chen L: Saxagliptin regulates M1/M2 macrophage polarization via CaMKKβ/AMPK pathway to attenuate NAFLD. Biochem Biophys Res Commun. 503:1618–1624. 2018.PubMed/NCBI View Article : Google Scholar
40	Luo P, Qin C, Zhu L, Fang C, Zhang Y, Zhang H, Pei F, Tian S, Zhu XY, Gong J, et al: Ubiquitin-Specific Peptidase 10 (USP10) inhibits hepatic steatosis, insulin resistance, and inflammation through Sirt6. Hepatology. 68:1786–1803. 2018.PubMed/NCBI View Article : Google Scholar
41	Castoldi A, Naffah De Souza C, Câmara NO and Moraes-Vieira PM: The macrophage switch in obesity development. Front Immunol. 6(637)2015.PubMed/NCBI View Article : Google Scholar
42	Tang XL, Lin Y, Wang YG and Gao Y: Effects of ophiopogonin D on fatty acid metabolic enzymes in cardiomyocytes. Zhongguo Zhong Yao Za Zhi. 46:3672–3677. 2021.PubMed/NCBI View Article : Google Scholar : (In Chinese).
43	Wu FM, Yang HY, Yang RS, Li M, Bao XH and Zhou J: Study on Quality Evaluation of Ophiopogonis Radix in Sichuan. Zhong Yao Cai. 39:1803–1808. 2016.PubMed/NCBI(In Chinese).
44	Xu HH, Jiang ZH, Sun YT, Qiu LZ, Xu LL, Tang XL, Ma ZC and Gao Y: Differences in the hemolytic behavior of two isomers in ophiopogon japonicus in vitro and in vivo and their risk warnings. Oxid Med Cell Longev. 2020(8870656)2020.PubMed/NCBI View Article : Google Scholar