Sowjanya K, Girish C, Bammigatti C, Lakshmi NCP. Efficacy of Phyllanthus niruri on improving liver functions in patients with alcoholic hepatitis: A double-blind randomized controlled trial. Indian J Pharmacol. 2021;53(6):448.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tomah S, Hamdy O, Abuelmagd MM, Hassan AH, Alkhouri N, Al-Badri MR, Gardner H, Eldib AH, Eid EA. Prevalence of and risk factors for non-alcoholic fatty liver disease (NAFLD) and fibrosis among young adults in Egypt. BMJ Open Gastroenterol. 2021;8(1): e000780.

Article  PubMed  PubMed Central  Google Scholar 

Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–57.

Article  PubMed  Google Scholar 

Fouad Y, Waked I, Bollipo S, Gomaa A, Ajlouni Y, Attia D. What’s in a name? Renaming ‘NAFLD’to ‘MAFLD.’ Liver Int. 2020;40(6):1254–61.

Article  PubMed  Google Scholar 

Filipovic B, Lukic S, Mijac D, Marjanovic-Haljilji M, Vojnovic M, Bogdanovic J, Glisic T et al. The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease. Int J Mol Sci. 2021; 22(24): 13219.

Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84.

Article  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, Luketic VA, Shiffman ML, Clore JN. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 2001;120(5):1183–92.

Article  CAS  PubMed  Google Scholar 

McClain CJ, Mokshagundam SP, Barve SS, Song Z, Hill DB, Chen T, Deaciuc I. Mechanisms of non-alcoholic steatohepatitis. Alcohol. 2004;34(1):67–79.

Article  CAS  PubMed  Google Scholar 

Maulana R, Helms-Lorenz M, Irnidayanti Y, van de Grift W. Autonomous motivation in the Indonesian classroom: Relationship with teacher support through the lens of self-determination theory. The Asia-Pacific Education Res. 2016;25(3):441–51.

Article  Google Scholar 

Takahashi Y, Sugimoto K, Inui H, Fukusato T. Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol: WJG. 2015;21(13):3777.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Leoni S, Tovoli F, Napoli L, Serio I, Ferri S, Bolondi L. Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis. World J Gastroenterol. 2018;24(30):3361.

Article  PubMed  PubMed Central  Google Scholar 

Tokushige K, Ikejima K, Ono M, Eguchi Y, Kamada Y, Itoh Y, Akuta N, et al. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020. J Gastroenterol. 2021;56(11):951–63.

Article  PubMed  PubMed Central  Google Scholar 

Pan SY, Pan S, Yu ZL, Ma DL, Chen SB, Fong WF, Han YF, Ko KM. New perspectives on innovative drug discovery: an overview. J Pharm Pharmaceutical Sci. 2010;13(3):450–71.

Article  Google Scholar 

Abenavoli L, Bellentani S. Milk thistle to treat non-alcoholic fatty liver disease: dream or reality? Expert Rev Gastroenterol Hepatol. 2013;7(8):677–9.

Article  CAS  PubMed  Google Scholar 

Hupa KL, Jaeckel E, Manns MP. Silymarin for Treatment of Nonalcoholic Steatohepatitis–A New Kid on the Block? Clin Gastroenterol Hepatol. 2017;15(12):1863–5.

Article  PubMed  Google Scholar 

Loguercio C, Andreone P, Brisc C, Cristina Brisc MC, Bugianesi E, Chiaramonte M, Cursaro C, et al. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Rad Biol Med. 2012;52(9):1658–65.

Article  CAS  PubMed  Google Scholar 

Trappoliere M, Caligiuri A, Schmid M, Bertolani C, Failli P, Vizzutti F, Novo E, et al. Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells. J Hepatol. 2009;50(6):1102–11.

Article  CAS  PubMed  Google Scholar 

Clichici S, Olteanu D, Filip A, Nagy A-L, Oros A, Mircea PA. Beneficial effects of silymarin after the discontinuation of CCl4-induced liver fibrosis. J Med Food. 2016;19(8):789–97.

Article  CAS  PubMed  Google Scholar 

Solhi H, Ghahremani R, Kazemifar AM, Yazdi ZH. Silymarin in treatment of non-alcoholic steatohepatitis: A randomized clinical trial. Caspian J Int Med. 2014;5(1):9.

Google Scholar 

Hashemi SJ, Eskandar H, Sardabi EH. A placebo-controlled trial of silymarin in patients with nonalcoholic fatty liver disease. 2009;9(4):265–70.

Zhong S, Fan Y, Yan Q, Fan X, Wu B, Han Y, Zhang Y, Chen Y, Zhang H and Niu J. The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease: A meta-analysis (PRISMA) of randomized control trials. Medicine. 2017;96(49):e9061.

Bhattacharjee R, Sil PC. The protein fraction of Phyllanthus niruri plays a protective role against acetaminophen induced hepatic disorder via its antioxidant properties. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2006;20(7):595–601.

Article  Google Scholar 

Chatterjee M, Sarkar K, Sil PC. Herbal (Phyllanthus niruri) protein isolate protects liver from nimesulide induced oxidative stress. Pathophysiology. 2006;13(2):95–102.

Article  PubMed  Google Scholar 

Venkateswaran PS, Millman I, Blumberg BS. Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies. Proceedings of the National Academy of Sciences. 1987;84(1):274–8.

Bagalkotkar G, Sagineedu SR, Saad MS, Stanslas J. Phytochemicals from Phyllanthus niruri Linn. and their pharmacological properties: a review. J Pharm Pharmacol. 2006;58(12):1559–70.

Article  CAS  PubMed  Google Scholar 

Bhattacharjee R, Sil PC. Protein isolate from the herb, Phyllanthus niruri L. (Euphorbiaceae), plays hepatoprotective role against carbon tetrachloride induced liver damage via its antioxidant properties. Food Chem Toxicol. 2007;45(5):817–26.

Article  CAS  PubMed  Google Scholar 

Manjrekar AP, Jisha V, Bag PP, Adhikary B, Pai MM, Hegde A, and Nandini M. Effect of Phyllanthus niruri Linn. treatment on liver, kidney and testes in CCl 4 induced hepatotoxic rats. 2008.

Obidike IC, Salawu OA, Ndukuba M, Okoli CO, Osunkwo UA. The anti-inflammatory and antinociceptive properties of the chloroform fraction from Phyllanthus niruri plant is mediated via the peripheral nervous system. J Diet Supplement. 2010;7(4):341–50.

Article  Google Scholar 

Hassan MR, Mustapha NR, Jaya F, Arjunan S, Ooi ET, Said RM, Menon J. et al. Efficacy and Safety of Phyllanthus Niruri in Non-alcoholic Steatohepatitis Treatment: Pilot Study from Malaysia. J Pharm Pract Commun Med. 2017;3(3):131–7.

Ezzat MI, Okba MM, Ahmed SH, El-Banna HA, Prince A, Mohamed SO, et al. In-depth hepatoprotective mechanistic study of Phyllanthus niruri: In vitro and in vivo studies and its chemical characterization. PLoS One. 2020;15(1): e0226185.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aida EMI, Ashraf ANB, Alaa B. Potential genotoxicity and histopathological alteration evaluation of Heptex®. Int J Pharm Pharm Sci. 2015;7(7):300–6.

CAS  Google Scholar 

Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. New England Journal of Medicine. 2010;362(18):1675–85.

Clinical trial to investigate the anti-oxidant activity of Heptex in patients with apparent risk factors of NASH. ClinicalTrials.gov Identifier: NCT05343780 [Internet]. (2022) [cited 2023 May 18]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT05343780

Ni X, Wang H. Silymarin attenuated hepatic steatosis through regulation of lipid metabolism and oxidative stress in a mouse model of nonalcoholic fatty liver disease (NAFLD). American journal of translational research. 2016;8(2):1073.

CAS  PubMed  PubMed Central  Google Scholar 

Anuragh S, Ilango K. Role of medicinal plants and their chemical constituents in ameliorating the cause for non-alcoholic fatty liver disorder—A review. Journal of Applied Pharmaceutical Science. 2022;12(6):043–55.

CAS  Google Scholar 

Newsome PN, Sasso M, Deeks JJ, Paredes A, Boursier J, Chan WK, et al. FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol. 2020;5(4):362–73.

Article  PubMed  PubMed Central  Google Scholar 

Woreta TA, Van Natta ML, Lazo M, Krishnan A, Neuschwander-Tetri BA, Loomba R, et al. Validation of the accuracy of the FASTTM score for detecting patients with at-risk nonalcoholic steatohepatitis (NASH) in a North American cohort and comparison to other non-invasive algorithms. PLoS One [Internet]. 2022;17(4 April):1–17. Available from: https://doi.org/10.1371/journal.pone.0266859

Navarro VJ, Belle SH, D’Amato M, Adfhal N, Brunt EM, Fried MW, K. Reddy R, Wahed AS, Harrison S and Silymarin in NASH and C Hepatitis (SyNCH) Study Group. Silymarin in non-cirrhotics with non-alcoholic steatohepatitis: A randomized, double-blind, placebo controlled trial. PLoS One. 2019; 14(9): e0221683.

Kheong CW, Mustapha NR, Mahadeva S. A randomized trial of silymarin for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2017;15(12):1940–9.

Article