Background/Objectives: Hyperlipidemia is a major contributor to metabolic complications and tissue damage, leading to conditions such as liver steatosis, atherosclerosis, and obesity. This study aimed to investigate the effects of aqueous artichoke bract extract (AE) on lipid metabolism, liver antioxidative defense, and liver steatosis in mice fed a high-fat, high-sucrose diet while elucidating the underlying mechanisms. Methods: An 8-week study used hyperlipidemic mice treated with AE at daily doses of 100 and 200 mg/kg bw, compared to fenofibrate. Plasma, liver, fecal, and biliary lipids, as well as blood glucose, were analyzed enzymatically. The liver antioxidative defense was assessed by measuring reduced glutathione, malondialdehyde (MDA), and antioxidant enzyme activities, while liver steatosis was evaluated through transaminase and alkaline phosphatase activities and histological monitoring of lipid droplets. Polyphenol profiling and quantification were performed using HPLC–DAD, and potential mechanisms were predicted by molecular docking and confirmed in HepG2 cells. Results: At 200 mg/kg, AE significantly improved plasma lipid profiles by reducing total cholesterol, triglycerides, and LDL–cholesterol while increasing HDL–cholesterol. It facilitated cholesterol reduction in the liver and its excretion, indicating activation of reverse cholesterol transport, which led to reduced body weight and liver steatosis. AE lowered MDA levels and enhanced antioxidant enzyme activities. AE was found to be safe (LD50 > 5000 mg/kg) and modulated gene expression in HepG2 cells. Conclusions: Based on our results, the artichoke bract extract could be considered a natural resource of bioactive compounds to treat hyperlipidemia and related cardiometabolic diseases.

Background/Objectives: Argania spinosa L. Skeels is a Moroccan endemic plant widely used by the local population as folk medicine. This study aimed to investigate the effects of Argan fruit pulp on lipid metabolism disorders and liver steatosis in hypercaloric diet-fed mice. Methods: Animals were treated with the Argan fruit pulp extract and its fractions for 12 weeks at 100 and 200 mg Kg⁻¹ BW daily. The analysis was conducted on lipid levels in plasma, liver, feces, and bile as well as on glycemia. The liver glutathione, malondialdehyde, and antioxidant enzyme activities were assessed. The hepatic steatosis was evaluated by measuring transaminases and alkaline phosphatase activities and examining histological sections. The polyphenol profiles were determined using HPLC-DAD. Possible underlying mechanisms in the hypolipidemic and hepatoprotective activities were predicted by molecular docking. Results: The crude extract and its aqueous fraction (rich in protocatechuic and gallic acids) significantly restored plasma lipids and glucose levels. Indeed, total cholesterol level (TCHO) was decreased in the liver but increased in bile and feces. The treatment also reduced body weight and liver and adipose tissue mass and prevented liver steatosis. The ethyl acetate fraction exhibited no effect on lipid metabolism but significantly prevented liver oxidative stress. The crude extract and its fractions appear to be nontoxic (LD50 > 5000 mg Kg⁻¹) in mice. The phenolic acids demonstrated strong binding affinity to key targets involved in regulating lipid homeostasis, including ABCA-1, LXR, CYP7A1, HMH-CoA reductase, and PCSK-9. However, the identified flavonoids exhibited high affinities to targets involved in oxidative stress defense (SOD, CAT, and CYP2E1). Conclusions: The Argan fruit pulp, particularly its polyphenols, could be a promising natural approach for preventing cardio-metabolic diseases by improving lipid metabolism and reducing liver oxidative stress.

Background: Loquat fruit is consumed for its flavorful taste and a rich array of health-promoting compounds like phenolics, flavonoids, and carotenoids. This study aimed at the biochemical characterization of fresh juice from the Moroccan Mkarkeb variety of loquat and evaluating its effects on lipid homeostasis and liver steatosis in hyperlipidemic mice. Methods: The biochemical characterization followed AOAC methods. In vivo study involved hyperlipidemic mice fed a high-fat, high-fructose diet for 6 weeks and treated with loquat juice at 3.5 and 7 mL kg⁻¹ or fenofibrate at 4 mg·kg⁻¹. The concentrations of lipids in plasma, liver, adipose tissue, feces, and bile and blood glucose levels were quantified. Liver steatosis was visually examined and confirmed histologically, and liver injury markers (AST, ALT, ALP, LDH, and TB) were measured. Liver oxidative stress was assessed by measuring MDA content and antioxidative enzyme activities. Results: Our findings indicate that fresh loquat juice is poor in fat and protein and contains moderate sugars with a low energy value (40.82 ± 0.25 kcal/100 g). It is also rich in minerals, vitamin C, phenolic acids, flavonoids, and carotenoids. The juice effectively restored lipid metabolism by enhancing reverse cholesterol transport and lowering LDL-cholesterol, triglycerides, and the atherogenic index. The studied juice decreases blood glucose and prevents weight gain and lipid accumulation in the liver and adipose tissue. The juice prevents lipotoxicity-induced liver injury, corrects toxicity markers, and improves the liver’s morphological and histological structures. It also reduces oxidative stress by lowering MDA and activating SOD and catalase. Conclusions: The juice holds high nutritional and medicinal value, potentially preventing lipid disorders and cardiovascular issues.

Introduction: The present study aimed to investigate the hypolipidemic and lipoprotein protective effects of a phenolic extract from sweet basil. Methods: The antihyperlipidemic activity was evaluated using Triton WR-1339 and a high-fat diet (HFD) induced hyperlipidemic mouse models. In the Triton model, plasma lipids were measured after 24h of treatment, whereas in ...

Background: Hyperlipidemia is a major risk factor for cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD), and is closely associated with oxidative stress. Opuntia ficus-indica (OFI) cladodes are recognized as a rich source of bioactive phytochemicals; however, the molecular mechanisms underlying their metabolic benefits remain incompletely understood. Objectives: This study aimed to comprehensively evaluate the hypolipidemic and hepatoprotective potential of a polyphenol-rich O. ficus-indica cladode extract (OCE) using an integrated approach combining in vivo evaluation, untargeted metabolomics (UHPLC-Orbitrap-MS/MS), molecular docking, and ADMET prediction. Methods: Hyperlipidemic mice fed a high-fat diet (HFD) were treated with OCE, while molecular docking was performed on ten major annotated phytochemicals against twelve key proteins involved in lipid metabolism and cholesterol homeostasis, including HMGCR, FAS, PPARα, PCSK9, and NPC1L1, using simvastatin as the reference compound. Results: OCE treatment significantly improved plasma and hepatic lipid profiles, improved glucose homeostasis, and markedly reduced hepatic malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. Histopathological analysis further supported a pronounced hepatoprotective effect, with a substantial reduction in hepatic steatosis. Untargeted metabolomics enabled the annotation of 102 metabolites, putatively identifying piscidic acid as the predominant phenolic constituent together with a diverse profile of flavonoids and phenolic acids. Molecular docking supported the potential contribution of these phytochemicals to the regulation of lipid metabolism through favorable interactions with multiple therapeutic targets, while ADMET prediction suggested an overall favorable pharmacokinetic and toxicity profile despite the lower intestinal permeability predicted for glycosylated derivatives. Conclusions: Overall, these findings support O. ficus-indica cladodes as a promising source of dietary bioactive compounds with potential applications in the nutritional management and prevention of hyperlipidemia and related cardiometabolic disorders.