Sclerocarya birrea (Marula) Extract Inhibits Hepatic Steatosis in db/db Mice

Lawrence Mabasa, Anri Kotze, Samukelisiwe Shabalala, Clare Kimani, Kwazi Gabuza, Rabia Johnson, Nonhlakanipho F. Sangweni, Vinesh Maharaj and Christo J. F. Muller
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Lawrence Mabasa: Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa
Anri Kotze: Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa
Samukelisiwe Shabalala: Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa
Clare Kimani: Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa
Kwazi Gabuza: Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa
Rabia Johnson: Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa
Nonhlakanipho F. Sangweni: Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa
Vinesh Maharaj: Department of Chemistry, University of Pretoria, Pretoria 0001, South Africa
Christo J. F. Muller: Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa

IJERPH, 2022, vol. 19, issue 7, 1-15

Abstract: 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’s 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 ≤ 0.05). Further, MLE treatment significantly inhibited hepatic steatosis as compared with the obese control and MET-treated mice ( p ≤ 0.05). The reduced lipid accumulation was associated with low expression of fatty acid synthase ( Cpt1 ; p ≤ 0.05) and an upregulation of the fatty acid oxidation gene, carnitine palmitoyltransferase ( Cpt1 ; p ≤ 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 ≤ 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.

Keywords: Marula leaf extract; non-alcoholic fatty liver disease; DNA methylation; methylenetetrahydrofolate reductase; ?-oxidation (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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