{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T20:17:58Z","timestamp":1772569078303,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["121859"],"award-info":[{"award-number":["121859"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is a spectrum of hepatic metabolic perturbations ranging from simple steatosis to steatohepatitis, cirrhosis and hepatocellular carcinoma. Currently, lifestyle modifications to reduce weight gain are considered the most effective means of preventing and treating the disease. The aim of the present study was to determine the therapeutic benefit of Sclerocarya birrea (Marula leaf extract, MLE) on hepatic steatosis. Obese db\/db mice were randomly stratified into the obese control, metformin (MET) or MLE-treated groups. Mice were treated daily for 29 days, at which point all mice were euthanized and liver samples were collected. Hematoxylin and eosin staining was used for histological assessment of the liver sections, while qRT-PCR and Western blot were used to determine hepatic mRNA and protein expression, respectively. Thereafter, the association between methylenetetrahydrofolate reductase (Mthfr a key enzyme in one-carbon metabolism and DNA-methylation-induced regulation of gene transcription) and lipogenic genes was evaluated using Pearson\u2019s correlation coefficient. Mice treated with MLE presented with significantly lower body and liver weights as compared with the obese control and MET-treated mice (p \u2264 0.05). Further, MLE treatment significantly inhibited hepatic steatosis as compared with the obese control and MET-treated mice (p \u2264 0.05). The reduced lipid accumulation was associated with low expression of fatty acid synthase (Cpt1; p \u2264 0.05) and an upregulation of the fatty acid oxidation gene, carnitine palmitoyltransferase (Cpt1; p \u2264 0.01), as compared with the obese control mice. Interestingly, MLE treatment improved the correlation between Mthfr and Cpt1 mRNA expression (r = 0.72, p \u2264 0.01). Taken together, the results suggest that Marula leaf extracts may inhibit hepatic steatosis by influencing the association between Mthfr and genes involved in hepatic lipid metabolism. Further studies are warranted to assess DNA methylation changes in lipid metabolism genes.<\/jats:p>","DOI":"10.3390\/ijerph19073782","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T14:55:35Z","timestamp":1647960935000},"page":"3782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Sclerocarya birrea (Marula) Extract Inhibits Hepatic Steatosis in db\/db Mice"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6499-3396","authenticated-orcid":false,"given":"Lawrence","family":"Mabasa","sequence":"first","affiliation":[{"name":"Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anri","family":"Kotze","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa"},{"name":"Centre for Cardiometabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1238-4673","authenticated-orcid":false,"given":"Samukelisiwe","family":"Shabalala","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa"},{"name":"Division of Medical Microbiology, Department of Pathology and Laboratory-Medicine, Faculty of Health Sciences, Walter Sisulu University, Mthatha 5117, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clare","family":"Kimani","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa"},{"name":"Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa"},{"name":"Institute of Primate Research, P.O. Box 24481, Karen, Nairobi 00502, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0144-6664","authenticated-orcid":false,"given":"Kwazi","family":"Gabuza","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6328-0789","authenticated-orcid":false,"given":"Rabia","family":"Johnson","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa"},{"name":"Centre for Cardiometabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nonhlakanipho F.","family":"Sangweni","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa"},{"name":"Centre for Cardiometabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6512-304X","authenticated-orcid":false,"given":"Vinesh","family":"Maharaj","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Pretoria, Pretoria 0001, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6821-2120","authenticated-orcid":false,"given":"Christo J. F.","family":"Muller","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa"},{"name":"Centre for Cardiometabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa"},{"name":"Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3880, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/hep.23280","article-title":"Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications","volume":"51","author":"Fabbrini","year":"2010","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22042","DOI":"10.1016\/j.cld.2015.10.001","article-title":"Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in the United States and the Rest of the World","volume":"20","author":"Sayiner","year":"2016","journal-title":"Clin. 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