Abstract
This study aimed to investigate the hepatoprotective effects of lyophilized powder of goji ferment (LPGF) against acetaminophen (APAP)-induced hepatic damage in Hep3B cells and in mice. Eleven strains of lactic acid bacteria (LAB) were selected and their hepatoprotection against APAP-induced cellular damage in Hep3B cell line was evaluated. Four strains of LAB, including BCRC11652 (Leuconostoc mesenteroides subsp. mesenteroides), BCRC14619 (Lactobacillus gasseri), KODA-1 (Pediococcus acidilactici), and KODA-2 (Limosilactobacillus fermentum), have hepatoprotective potential against APAP in vitro. Goji significantly stimulated the growth of individual and combined strains of LAB and the optimal fermented condition was the treatment of goji at 10% (w/w) for 24 h. The prepared lyophilized powder of goji ferment (LPGF) containing fifteen combinations of LAB strains was used to explore their hepatoprotection in vitro. LPGF containing all combinations of LAB strains, except for KODA-2, significantly restored APAP-reduced cell viability and improved APAP-increased cellular levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In mice model, LPGF containing BCRC11652, BCRC14619, and KODA-2 was chosen to evaluate its hepatoprotection against APAP-induced liver injury. LPGF at diverse doses have a tendency but no significant improvement on APAP-reduced body weight gain and liver weight. LPGF significantly decreased APAP-increased serum ALT and AST levels in a dose-dependent manner. At the end of experiment, LPGF significantly and dose-dependently reversed APAP-reduced activities of GSH and antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase in hepatic tissue. Overall, LPGF was demonstrated to exhibit hepatoprotection against APAP-induced liver injury in vitro and in vivo.
Similar content being viewed by others
Availability of Data and Materials
The authors declare that all data and materials support published claims and comply with field standards.
References
Gloor Y, Schvartz D, F. Samer C (2019) Old problem, new solutions: biomarker discovery for acetaminophen liver toxicity. Expert Opin Drug Metab Toxicol 15:659–669. https://doi.org/10.1080/17425255.2019.1642323
Akakpo JY, Ramachandran A, Jaeschke H (2020) Novel strategies for the treatment of acetaminophen hepatotoxicity. Expert Opin Drug Metab Toxicol 16:1039–1050. https://doi.org/10.1080/17425255.2020.1817896
Chao X, Wang H, Jaeschke H, Ding WX (2018) Role and mechanisms of autophagy in acetaminophen-induced liver injury. Liver Int 38:1363–1374. https://doi.org/10.1111/liv.13866
Herndon CM, Dankenbring DM (2014) Patient perception and knowledge of acetaminophen in a large family medicine service. J Pain Palliat Care Pharmacother 28:109–116. https://doi.org/10.3109/15360288.2014.908993
Altyar A, Kordi L, Skrepnek G (2015) Clinical and economic characteristics of emergency department visits due to acetaminophen toxicity in the USA. BMJ Open 5:e007368. https://doi.org/10.1136/bmjopen-2014-007368
Nourjah P, Ahmad SR, Karwoski C, Willy M (2006) Estimates of acetaminophen (Paracetomal)-associated overdoses in the United States. Pharmacoepidemiol Drug Saf 15:398–405. https://doi.org/10.1002/pds.1191
Manthripragada AD, Zhou EH, Budnitz DS, Lovegrove MC, Willy ME (2011) Characterization of acetaminophen overdose-related emergency department visits and hospitalizations in the United States. Pharmacoepidemiol Drug Saf 20:819–826. https://doi.org/10.1002/pds.2090
Budnitz DS, Lovegrove MC, Crosby AE (2011) Emergency department visits for overdoses of acetaminophen-containing products. Am J Prev Med 40:585–592. https://doi.org/10.1016/j.amepre.2011.02.026
Yu Y, Wu Y, Yan HZ, Xia ZR, Wen W, Liu DY, Wan LH (2021) Rosmarinic acid ameliorates acetaminophen-induced acute liver injury in mice via RACK1/TNF-α mediated antioxidant effect. Pharm Biol 59:1286–1293. https://doi.org/10.1080/13880209.2021.1974059
Chen C, Liu X, Qi S, C P Dias A, Yan J, Zhang X (2020) Hepatoprotective effect of Phellinus linteus mycelia polysaccharide (PL-N1) against acetaminophen-induced liver injury in mouse. Int J Biol Macromol 154:1276–1284. https://doi.org/10.1016/j.ijbiomac.2019.11.002
Sakeran MI, Zidan N, Rehman H, Aziz AT, Saggu S (2014) Abrogation by Trifolium alexandrinum root extract on hepatotoxicity induced by acetaminophen in rats. Redox Rep 19:26–33. https://doi.org/10.1179/1351000213Y.0000000068
Skenderidis P, Mitsagga C, Lampakis D, Petrotos K, Giavasis I (2019) The effect of encapsulated powder of goji berry (Lycium barbarum) on growth and survival of probiotic bacteria. Microorganisms 8:57. https://doi.org/10.3390/microorganisms8010057
Tian X, Liang T, Liu Y, Ding G, Zhang F, Ma Z (2019) Extraction, structural characterization, and biological functions of Lycium barbarum polysaccharides: a review. Biomolecules 9:389. https://doi.org/10.3390/biom9090389
Ahn M, Park JS, Chae S, Kim S, Moon C, Hyun JW, Shin T (2014) Hepatoprotective effects of Lycium chinense Miller fruit and its constituent betaine in CCl4-induced hepatic damage in rats. Acta Histochem 116:1104–1112. https://doi.org/10.1016/j.acthis.2014.05.004
Inbaraj BS, Lu H, Kao TH, Chen BH (2010) Simultaneous determination of phenolic acids and flavonoids in Lycium barbarum Linnaeus by HPLC-DAD-ESI-MS. J Pharm Biomed Anal 51:549–556. https://doi.org/10.1016/j.jpba.2009.09.006
Inbaraj BS, Lu H, Hung CF, Wu WB, Lin CL, Chen BH (2008) Determination of carotenoids and their esters in fruits of Lycium barbarum Linnaeus by HPLC-DAD-APCI-MS. J Pharm Biomed Anal 47:812–818. https://doi.org/10.1016/j.jpba.2008.04.001
Gündüz E, Dursun R, Zengin Y, İçer M, Durgun HM, Kanıcı A, Kaplan İ, Alabalık U, Gürbüz H, Güloğlu C (2015) Lycium barbarum extract provides effective protection against paracetamol-induced acute hepatotoxicity in rats. Int J Clin Exp Med 8:7898–7905. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509291/pdf/ijcem0008-7898.pdf. Accessed 25 Feb 2022
Kechagia M, Basoulis D, Konstantopoulou S, Dimitriadi D, Gyftopoulou K, Skarmoutsou N, Fakiri EM (2013) Health benefits of probiotics: a review. ISRN Nutr 2013:481651. https://doi.org/10.5402/2013/481651
Li L, Wang L, Fan W, Jiang Y, Zhang C, Li J, Peng W, Wu C (2020) The application of fermentation technology in traditional Chinese medicine: a review. Am J Chin Med 48:899–921. https://doi.org/10.1142/S0192415X20500433
Manov I, Hirsh M, Iancu TC (2002) Acetaminophen hepatotoxicity and mechanisms of its protection by N-acetylcysteine: a study of Hep3B cells. Exp Toxicol Pathol 53:489–500. https://doi.org/10.1078/0940-2993-00215
Chuang CH, Tsai CC, Lin ES, Huang CS, Lin YY, Lan CC, Huang CC (2016) Heat-killed Lactobacillus salivarius and Lactobacillus johnsonii reduce liver injury induced by alcohol in vitro and in vivo. Molecules 21:1456. https://doi.org/10.3390/molecules21111456
Lee JY, Kim H, Jeong Y, Kang CH (2021) Lactic acid bacteria exert a hepatoprotective effect against ethanol-induced liver injury in HepG2 cells. Microorganisms 9:1844. https://doi.org/10.3390/microorganisms9091844
Gan Y, Tong J, Zhou X, Long X, Pan Y, Liu W, Zhao X (2021) Hepatoprotective effect of Lactobacillus plantarum HFY09 on ethanol-induced liver injury in mice. Front Nutr 8:684588. https://doi.org/10.3389/fnut.2021.684588
Jantararussamee C, Rodniem S, Taweechotipatr M, Showpittapornchai U, Pradidarcheep W (2021) Hepatoprotective effect of probiotic lactic acid bacteria on thioacetamide-induced liver fibrosis in rats. Probiotics Antimicrob Proteins 13:40–50. https://doi.org/10.1007/s12602-020-09663-6
Nam Y, Kim JH, Konkit M, Kim W (2019) Hepatoprotective effects of Lactococcus chungangensis CAU 1447 in alcoholic liver disease. J Dairy Sci 102:10737–10747. https://doi.org/10.3168/jds.2019-16891
Xu RH, Xiu L, Zhang YL, Du RP, Wang X (2019) Probiotic and hepatoprotective activity of lactobacillus isolated from Mongolian camel milk products. Benef Microbes 10:699–710. https://doi.org/10.3920/BM2018.0131
Han SY, Huh CS, Ahn YT, Lim KS, Baek YJ, Kim DH (2005) Hepatoprotective effect of lactic acid bacteria, inhibitors of beta-glucuronidase production against intestinal microflora. Arch Pharm Res 28:325–329. https://doi.org/10.1007/BF02977800
Zhou F, Jiang X, Wang T, Zhang B, Zhao H (2018) Lyciumbarbarum pPolysaccharide (LBP): a novel prebiotics candidate for Bifidobacterium and Lactobacillus. Front Microbiol 9:1034. https://doi.org/10.3389/fmicb.2018.01034
Lin FM, Chiu CH, Pan TM (2004) Fermentation of a milk-soymilk and Lycium chinense Miller mixture using a new isolate of Lactobacillus paracasei subsp. paracasei NTU101 and Bifidobacterium longum. J Ind Microbiol Biotechnol 31:559–564. https://doi.org/10.1007/s10295-004-0184-z
Prescott LF (1983) Paracetamol overdosage. Pharmacological considerations and clinical management. Drugs 25:290–314. https://doi.org/10.2165/00003495-198325030-00002
McGovern AJ, Vitkovitsky IV, Jones DL, Mullins ME (2015) Can AST/ALT ratio indicate recovery after acute paracetamol poisoning? Clin Toxicol (Phila) 53:164–167. https://doi.org/10.3109/15563650.2015.1006399
Dahlin DC, Miwa GT, Lu AY, Nelson SD (1984) N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. Proc Natl Acad Sci USA 81:1327–1331. https://doi.org/10.1073/pnas.81.5.1327
Albano E, Rundgren M, Harvison PJ, Nelson SD, Moldéus P (1985) Mechanisms of N-acetyl-p-benzoquinone imine cytotoxicity. Mol Pharmacol 28:306–311
Mitchell JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB (1973) Acetaminophen-induced hepatic necrosis. IV Protective role of glutathione. J Pharmacol Exp Ther 187:211–217
Klein-Schwartz W, Doyon S (2011) Intravenous acetylcysteine for the treatment of acetaminophen overdose. Expert Opin Pharmacother 12:119–130. https://doi.org/10.1517/14656566.2011.537261
Khodayar MJ, Kalantari H, Khorsandi L, Rashno M, Zeidooni L (2018) Betaine protects mice against acetaminophen hepatotoxicity possibly via mitochondrial complex II and glutathione availability. Biomed Pharmacother 103:1436–1445. https://doi.org/10.1016/j.biopha.2018.04.154
Jaeschke H, McGill MR, Ramachandran A (2012) Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity. Drug Metab Rev 44:88–106. https://doi.org/10.3109/03602532.2011.602688
Alipour M, Buonocore C, Omri A, Szabo M, Pucaj K, Suntres ZE (2013) Therapeutic effect of liposomal-N-acetylcysteine against acetaminophen-induced hepatotoxicity. J Drug Target 21:466–473. https://doi.org/10.3109/1061186X.2013.765443
Kim SK, Kim YC (2002) Attenuation of bacterial lipopolysaccharide-induced hepatotoxicity by betaine or taurine in rats. Food Chem Toxicol 40:545–549. https://doi.org/10.1016/s0278-6915(01)00102-8
Kim SK, Seo JM, Chae YR, Jung YS, Park JH, Kim YC (2009) Alleviation of dimethylnitrosamine-induced liver injury and fibrosis by betaine supplementation in rats. Chem Biol Interact 177:204–211. https://doi.org/10.1016/j.cbi.2008.09.021
Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22:659–661. https://doi.org/10.1096/fj.07-9574LSF
Funding
This research was supported by E10700007131-335 from the Small Business Innovation Research (SBIR), Ministry of Economic Affairs, Taiwan.
Author information
Authors and Affiliations
Contributions
Conceptualization, CH Chuang and CH Chen; Methodology, CM Yang, MY Chien, and LY Wang; Writing-original draft preparation, CM Yang, MY Chien, and LY Wang; Writing-review and editing, CH Chuang and CH Chen.
Corresponding authors
Ethics declarations
Ethics Approval and Consent to Participate
This study protocol was approved by the Animal Research Committee of HungKuang University, Taichung, Taiwan and the committee’s reference number was HK-P-10701.
Conflict of Interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Yang, CM., Chien, MY., Wang, LY. et al. Goji Ferment Ameliorated Acetaminophen-Induced Liver Injury in vitro and in vivo. Probiotics & Antimicro. Prot. 15, 1102–1112 (2023). https://doi.org/10.1007/s12602-022-09956-y
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12602-022-09956-y