Bridging the Gap: Exploring the Preclinical Potential of Pereskia grandifolia in Metabolic‐Associated Fatty Liver Disease

Abstract

Metabolic-associated fatty liver disease (MAFLD) is a complex condition characterized by steatosis and metabolic disturbances. Risk factors such as diabetes, cigarette smoking, and dyslipidaemia contribute to its development and progression. Effective and safe therapies for MAFLD are urgently needed. Pereskia grandifolia has shown potential as an alternative treatment, but its effectiveness against liver disease remains unexplored. This research aims to determine the hepatoprotective properties of P. grandifolia using a model of MAFLD. The study was carried out through various phases to assess the safety and efficacy of the ethanol-soluble fraction of P. grandifolia. Initially, an in vitro assay was performed to assess cell viability. This was followed by an acute toxicity test conducted in rats to determine the safety profile of the extract. Subsequently, the anti-inflammatory properties of P. grandifolia were examined in macrophages. For the MAFLD study, diabetic Wistar rats were made diabetic and exposed to a high fat diet and cigarette smoke, for 4 weeks. During the last 2 weeks, the rats were orally given either the vehicle (negative control group; C-), P. grandifolia (30, 100, and 300 mg/kg), or insulin in addition to simvastatin. A basal group of rats not exposed to these risk factors was also assessed. Blood samples were collected to measure cholesterol, triglycerides, glucose, ALT, and AST levels. Liver was assessed for lipid and oxidative markers, and liver histopathology was examined. P. grandifolia showed no signs of toxicity. It demonstrated anti-inflammatory effects by inhibiting phagocytosis and macrophage spreading. The MAFLD model induced liver abnormalities, including increased AST, ALT, disrupted lipid profile, oxidative stress, and significant hepatic damage. However, P. grandifolia effectively reversed these changes, highlighting its potential as a therapeutic agent. These findings emphasize the significance of P. grandifolia in mitigating hepatic consequences associated with various risk factors.

Exploring the Potential Hepatoprotective Properties of Cactus (Cactaceae) in Liver Health and Disease Management: A Brief Review

“…The rats then received oral doses of the P. grandifolia extract (30, 100 and 300 mg/kg) or insulin in the final 2 weeks, in addition to simvastatin. The results demonstrated that the extracts reversed the increase in AST and ALT enzymes, as well as the changes in the lipid profile, oxidative stress, and liver damage caused by MAFLD [34].…”

“…These rats received extracts at doses of 30, 100, and 300 mg/kg for 3 weeks. It was reported that there were no significant changes in behavior, body weight, eating patterns, injuries, or abnormalities in organs including the liver and biochemical parameters in the blood, indicating that the plant did not cause immediate adverse effects in the rats [34]. Another study evaluated the acute toxicity of a dry ethanolic extract of Ora-pro-nobis (Pereskia aculeata), which was administered to female Wistar rats at doses of 1250 mg, 2500 mg, and 5000 mg/kg.…”

“…The extract showed anti-inflammatory activity, promoted by the inhibition of the phagocytosis process and dissemination of cellular macrophages. The extract also showed anticarcinogenic activity, demonstrated by the significant cytotoxic effect of P. grandifolia on HUH7 hepatocellular carcinoma cells, demonstrating the absence of toxicity and selective inhibition of hepatic cancer cells, inhibiting their growth and viability [34]. Table 2 summarizes the characteristics of in vitro studies and the main mechanisms and effects promoted by cacti on liver diseases.…”