Extract of <i>Siraitia grosvenorii</i> (Luo Han Guo) protects against hepatic fibrosis in mice on a choline-deficient, methionine-lowered, L-amino acid-defined, high-fat diet without trans fatty acids

Abstract

Nonalcoholic steatohepatitis (NASH) is an aggressive form of nonalcoholic fatty liver disease that presents with steatosis, inflammation, and fibrosis and can progress to cirrhosis and cancer. Thus, methods for controlling this lifestyle-related disease are urgently needed. An extract of Siraitia grosvenorii (Luo-Han-Guo) (luohanguo extract (LE)) is widely used as a sweetener; its major bioactive constituents, mogrosides, have shown anti-oxidative and anti-inflammatory properties, exerting multiple pharmacological effects in various disorders. In the present study, we investigated the effects of LE on NASH induced in mice fed a choline-deficient, methionine-lowered, L-amino acid-defined, high-fat diet without trans fatty acids (CDAA-HF-T(−)). Mice were fed with CDAA-HF-T(−) and drinking water containing LE at concentrations of 0%, 0.2%, 0.6%, and 2% for 28 weeks. Our results showed that LE was not toxic under the experimental conditions evaluated. In the liver of mice fed CDAA-HF-T(−), LE did not affect steatosis or early phase events from macrophage recruitment to hepatocyte death but inhibited late phase events, the progression of inflammation, and fibrosis (mechanisms independent of transforming growth factor-β signaling). Sweeteners with beneficial biological functions, such as LE, may be useful for controlling lifestyle-related diseases, such as NASH, and promoting human health.

A comprehensive review of Siraitia grosvenorii (Swingle) C. Jeffrey: chemical composition, pharmacology, toxicology, status of resources development, and applications

“…The majority of the phenotypic and mechanistic traits of human NASH are replicated in these models, including the rapid induction of fibrosis and the proliferation of lesions in the liver. SGEs prevent NASH in CDAA-HF-T (-) mice by inhibiting fibrosis without changing steatosis ( Suzuki-Kemuriyama et al, 2021 ). It is possible that SGEs prevent liver fibrosis by preventing the NF-κB pathway from being active ( Uno et al, 2023 ).…”

Effects of <i>Siraitia grosvenorii</i> extract on nonalcoholic steatohepatitis-like lesions in Sprague Dawley rats fed a choline-deficient, methionine-lowered, l-amino acid-defined diet

“…The SGE water samples were prepared five days a week. These concentrations were selected based on previous studies [13][14][15] . The no-observedadverse-effect level of SGE was ≥5% in Wistar Hannover rats 16 .…”

“…Reportedly, S. grosvenorii can prevent hepatic steatosis in a NAFLD mouse model fed a high-fat diet 11,12 . In NASH model mice fed a CDAA high-fat diet without trans fatty acids, S. grosvenorii could inhibit the progression of inflammation and fibrosis 13 . However, the mechanisms underlying these actions and their associated factors remain unclear.…”

Sanguisorba officinalis L. Ameliorates Hepatic Steatosis and Fibrosis by Modulating Oxidative Stress, Fatty Acid Oxidation, and Gut Microbiota in CDAHFD-Induced Mice

“…In addition, a cholinedeficient, L-amino-acid-defined, high-fat diet (CDAHFD) leads to liver fibrosis progression within a short period in a diet-induced NAFLD mouse model, which is potentially useful for mimicking human NAFLD [6,9]. Previous studies used CDAHFD to induce NAFLD and fibrosis and confirmed the efficacy of drugs and natural products [14,15].…”