Study on the mechanism of Shenling Baizhu powder on the pathogenesis of pregnancy complicated with non-alcoholic fatty liver, based on PI3K/AKT/mTOR signal pathway

Submitted: 19 June 2024
Accepted: 2 September 2024
Published: 17 September 2024
Abstract Views: 326
PDF: 111
HTML: 7
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

This study investigates the effectiveness of Shenlin Baizhu powder in managing non-alcoholic fatty liver disease (NAFLD) during pregnancy and its mechanism through the PI3K/AKT/mTOR signaling pathway. Eight healthy male and 24 female Sprague-Dawley rats were used. After acclimatization, 6 female rats were fed normal chow, and 18 female rats were fed high-fat chow to induce NAFLD. After 8 weeks, female rats were mated with males to create a pregnant NAFLD model. The rats were divided into four groups: normal feeding, high-fat diet with saline, high-fat diet with 1.6 g/kg Shenlin Baizhu powder, and high-fat diet with 4.8 g/kg Shenlin Baizhu powder. Maternal body weight, serum and liver levels of aspartate aminotransferase (AST), alanine transaminase (ALT), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), related inflammatory indexes interleukin-1 β (IL-1 β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. Liver tissue was examined using hematoxylin and oil red O staining, and protein expression related to the PI3K/AKT/mTOR pathway was assessed via Western blotting, immunohistochemistry and RT-PCR. Results showed significant weight gain and increases in ALT, AST, TG, TC, LDL-C, IL-1β, TNF-α, and IL-6, along with decreased HDL-C in NAFLD rats compared to controls. The high and low-dose Shenlin Baizhu powder groups exhibited improvements in body weight, liver histopathology, and reductions in serum TG, TC, LDL-C, ALT, AST, IL-1β, TNF-α, and IL-6, with increased HDL-C levels. Notably, the high-dose group showed greater efficacy in reducing hepatic fat accumulation, liver function markers, blood lipids, and inflammatory indexes, and decreased expression of hepatic PPARγ mRNA, SREBP1 mRNA, AKT mRNA, and related proteins. Shenlin Baizhu powder demonstrates potential in ameliorating high-fat diet-induced NAFLD in pregnant rats, likely through modulation of the PI3K/AKT/mTOR pathway, suggesting its therapeutic potential for gestational NAFLD.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology 2023;77:1797-835. DOI: https://doi.org/10.1097/HEP.0000000000000323
Younossi ZM, Stepanova M, Younossi Y, Golabi P, Mishra A, Rafiq N, et al. Epidemiology of chronic liver diseases in the USA in the past three decades. Gut 2020;69:564-8. DOI: https://doi.org/10.1136/gutjnl-2019-318813
Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology 2023;77:1335-47. DOI: https://doi.org/10.1097/HEP.0000000000000004
Zhou J, Zhou F, Wang W, Zhang XJ, Ji YX, Zhang P, et al. Epidemiological features of NAFLD from 1999 to 2018 in China. Hepatology 2020;71:1851-64. DOI: https://doi.org/10.1002/hep.31150
Agyapong G, Dashti F, Banini BA. Nonalcoholic liver disease: epidemiology, risk factors, natural history, and management strategies. Ann NY Acad Sci 2023;1526:16-29. DOI: https://doi.org/10.1111/nyas.15012
Simon TG, Roelstraete B, Khalili H, Hagstrom H, Ludvigsson JF. Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort. Gut 2021;70:1375-82. DOI: https://doi.org/10.1136/gutjnl-2020-322786
Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA 2015;313:2263-73. DOI: https://doi.org/10.1001/jama.2015.5370
Ilyas F, Ali H, Patel P, Sarfraz S, Basuli D, Giammarino A, et al. Increasing nonalcoholic fatty liver disease-related mortality rates in the United States from 1999 to 2022. Hepatol Commun 2023;7:e00207. DOI: https://doi.org/10.1097/HC9.0000000000000207
Herath RP, Siriwardana SR, Ekanayake CD, Abeysekara V, Kodithuwakku S, Herath HP. Non-alcoholic fatty liver disease and pregnancy complications among Sri Lankan women: A cross sectional analytical study. PLoS One 2019;14:e0215326. DOI: https://doi.org/10.1371/journal.pone.0215326
Sarkar M, Grab J, Dodge JL, Gunderson EP, Rubin J, Irani RA, et al. Non-alcoholic fatty liver disease in pregnancy is associated with adverse maternal and perinatal outcomes. J Hepatol 2020;73:516-22. DOI: https://doi.org/10.1016/j.jhep.2020.03.049
Kubihal S, Gupta Y, Shalimar, Kandasamy D, Goyal A, Kalaivani M, et al. Prevalence of non-alcoholic fatty liver disease and factors associated with it in Indian women with a history of gestational diabetes mellitus. J Diabetes Invest 2021;12:877-85. DOI: https://doi.org/10.1111/jdi.13411
Koralegedara IS, Warnasekara JN, Dayaratne KG, De Silva FN, Premadasa JK, Agampodi SB. Non-alcoholic fatty liver disease (NAFLD): a significant predictor of gestational diabetes mellitus (GDM) and early pregnancy miscarriages-prospective study in Rajarata Pregnancy Cohort (RaPCo). BMJ Open Gastroenter 2022;9:e000831. DOI: https://doi.org/10.1136/bmjgast-2021-000831
Gong XW, Xu YJ, Yang QH, Liang YJ, Zhang YP, Wang GL, et al. Effect of soothing Gan (liver) and invigorating Pi (spleen) recipes on TLR4-p38 MAPK pathway in Kupffer cells of non-alcoholic steatohepatitis rats. Chin J Integr Med 2019;25:216-24. DOI: https://doi.org/10.1007/s11655-018-2829-6
El JH, Eslick GD, Weltman M. Systematic review with meta-analysis: non-alcoholic fatty liver disease and the association with pregnancy outcomes. Clin Mol Hepatol 2022;28:52-66. DOI: https://doi.org/10.3350/cmh.2021.0205
Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell 2017;168:960-76. DOI: https://doi.org/10.1016/j.cell.2017.02.004
Wei X, Luo L, Chen J. Roles of mTOR signaling in tissue regeneration. Cells 2019;8:1075. DOI: https://doi.org/10.3390/cells8091075
Yao Z, Guo J, Du B, Hong L, Zhu Y, Feng X, et al. Effects of Shenling Baizhu powder on intestinal microflora metabolites and liver mitochondrial energy metabolism in nonalcoholic fatty liver mice. Front Microbiol 2023;14:1147067. DOI: https://doi.org/10.3389/fmicb.2023.1147067
Qiao B, Xiao N, Deng N, Tan Z. Shenling Baizhu powder attenuates lard diet in a fatigued state-induced diarrhea via targeting microbial metabolites short chain fatty acids-mediated lipid metabolism. 3 Biotech 2024;14:203. DOI: https://doi.org/10.1007/s13205-024-04045-z
Wu P, Wang Y, Ye Y, Yang X, Huang Y, Ye Y, et al. Liver biomarkers, lipid metabolites, and risk of gestational diabetes mellitus in a prospective study among Chinese pregnant women. BMC Med 2023;21:150. DOI: https://doi.org/10.1186/s12916-023-02818-6
Pan M, Deng Y, Qiu Y, Pi D, Zheng C, Liang Z, et al. Shenling Baizhu powder alleviates non-alcoholic fatty liver disease by modulating autophagy and energy metabolism in high-fat diet-induced rats. Phytomedicine 2024;130:155712. DOI: https://doi.org/10.1016/j.phymed.2024.155712
Prasomthong J, Limpeanchob N, Daodee S, Chonpathompikunlert P, Tunsophon S. Hibiscus sabdariffa extract improves hepatic steatosis, partially through IRS-1/Akt and Nrf2 signaling pathways in rats fed a high fat diet. Sci Rep 2022;12:7022. DOI: https://doi.org/10.1038/s41598-022-11027-9
Eslam M, Sanyal AJ, George J. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology 2020;158:1999-2014. DOI: https://doi.org/10.1053/j.gastro.2019.11.312
Heindel JJ, Blumberg B, Cave M, Machtinger R, Mantovani A, Mendez MA, et al. Metabolism disrupting chemicals and metabolic disorders. Reprod Toxicol 2017;68:3-33. DOI: https://doi.org/10.1016/j.reprotox.2016.10.001
Chen D, Wang Y, Yang J, Ou W, Lin G, Zeng Z, et al. Shenling Baizhu San ameliorates non-alcoholic fatty liver disease in mice by modulating gut microbiota and metabolites. Front Pharmacol 2024;15:1343755. DOI: https://doi.org/10.3389/fphar.2024.1343755
Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, et al. American Association of Clinical Endocrinology Clinical Practice Guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract 2022;28:528-62. DOI: https://doi.org/10.1016/j.eprac.2022.03.010
Arakawa Y, Miyazaki K, Yoshikawa M, Yamada S, Saito Y, Ikemoto T, et al. Value of the CRP-albumin ratio in patients with resectable pancreatic cancer. J Med Investig 2021;68:244-55. DOI: https://doi.org/10.2152/jmi.68.244
Cai SQ, Zhou SF, Zhou LF, Li YR, Zhou XY, Lyu FY. [Mechanism of Shenling Baizhu Powder on treatment of alcoholic liver disease by regulating TLR4/NLRP3 pathway].[Article in Chinese]. Zhongguo Zhong Yao Za Zhi 2024;49:1275-85.
Zhu W, Yan M, Cao H, Zhou J, Xu Z. Effects of Clostridium butyricum capsules combined with rosuvastatin on intestinal flora, lipid metabolism, liver function and inflammation in NAFLD patients. Cell Mol Biol 2022;68:64-9. DOI: https://doi.org/10.14715/cmb/2022.68.2.10
Fan N, Peng L, Xia Z, Zhang L, Song Z, Wang Y, et al. Triglycerides to high-density lipoprotein cholesterol ratio as a surrogate for nonalcoholic fatty liver disease: a cross-sectional study. Lipids Health Dis 2019;18:39. DOI: https://doi.org/10.1186/s12944-019-0986-7
Chyau CC, Wang HF, Zhang WJ, Chen CC, Huang SH, Chang CC, et al. Antrodan alleviates high-fat and high-fructose diet-induced fatty liver disease in C57BL/6 mice model via AMPK/Sirt1/SREBP-1c/PPARgamma pathway. Int J Mol Sci 2020;21:360. DOI: https://doi.org/10.3390/ijms21010360

Ethics Approval

all experiments and the protocol were approved by the Ethical Committee of 904 Hospital of the People’s Liberation Army joint Logistic Support Force

How to Cite

Le, Y., Wang, Z., Zhang, Q., Miao, L., Wang, X., & Han, G. (2024). Study on the mechanism of Shenling Baizhu powder on the pathogenesis of pregnancy complicated with non-alcoholic fatty liver, based on PI3K/AKT/mTOR signal pathway. European Journal of Histochemistry, 68(3). https://doi.org/10.4081/ejh.2024.4093

Similar Articles

<< < 1 2 3 4 5 6 7 8 9 10 > >> 

You may also start an advanced similarity search for this article.