Search Results (149)

Metabolic syndrome, a collective term for lipid and carbohydrate disorders in the organism, is the primary cause of type 2 diabetes mellitus development and its associated systemic side effects. The current approach for the medical treatment of this condition usually requires multiple medications, targeting multiple pathophysiological pathways. A promising drug class in that regard is the dual PPARα/γ agonists, which impact both lipid and carbohydrate metabolism, yet to this day the vast majority of them have not passed the clinical trials, due to potential toxicity risks. In the present study we synthesized and tested a series of monoterpene-substituted (S)-2-ethoxy-3-(4-(4-hydroxyphenethoxy)phenyl)propanoic acids as potentially effective and safe novel dual PPARα/γ agonists. In vitro studies showed that nearly all of the tested compounds were sufficiently active towards both PPARα and PPARγ. All compounds were tested in vivo, using C57BL/6 A^y/_a mice with T2DM symptoms, in order to evaluate their impact on carbohydrate and lipid metabolism. The most promising of them was found to be compound 5h, containing a cumin fragment, which showed pronounced hypoglycemic activity by boosting tissue insulin sensitivity and hypolipidemic effects manifested by reductions in fat tissue mass and blood triglyceride levels, while simultaneously displaying a relatively safe profile. Full article

Background: Chronic diseases are leading causes of morbidity and mortality worldwide and their prevalence is increasing due to aging and lifestyle factors. A central element in their pathophysiology is chronic low-grade inflammation, linking metabolic, cardiovascular, neurodegenerative, and proliferative disorders. In this context, Opuntia dillenii, a cactus species traditionally used in folk medicine, has attracted considerable scientific interest due to its promising nutraceutical potential. Methods: This systematic review was conducted through a PRISMA-guided literature search using PubMed, Scopus, and Web of Science, identifying 45 studies that analyze the phytochemical composition and biological activity of O. dillenii. Results: The compounds highlighted include betalains, polyphenols, flavonoids, and polysaccharides that exhibit potent anti-inflammatory and analgesic effects by modulating key inflammatory mediators. In addition, O. dillenii demonstrates antiproliferative activity, inducing apoptosis and inhibiting tumor growth in various in vivo models, suggesting a potential role in cancer prevention and as a complementary therapy. The cactus also exhibits antiatherogenic and hypotensive effects, as well as hypolipidemic and antidiabetic properties by improving lipid profiles, reducing serum cholesterol and triglycerides, and enhancing insulin sensitivity. Furthermore, its protective actions against tissue damage extend its therapeutic potential. Antimicrobial properties have also been reported, reinforcing its value as a functional food. Conclusions: Taken together, the evidence supports the use of O. dillenii as a versatile nutraceutical resource with a low toxicity profile, capable of contributing to the prevention and treatment of various chronic inflammatory and metabolic diseases. Nevertheless, human clinical trials are needed to validate these findings and explore their full therapeutic utility. Full article

Background/Objectives: Cardiovascular diseases remain the leading cause of mortality worldwide. According to the World Heart Federation, more than 500 million people were living with cardiovascular diseases in 2021. In this context, the use of medicinal plants has become increasingly widespread in populations as a preventive strategy against cardiovascular disorders. Foeniculum vulgare Mill., commonly known as fennel, is an aromatic and medicinal plant recognized for its beneficial properties in the treatment of various ailments, due to its richness in bioactive compounds. This review aims to summarize and analyze the cardiovascular activities of this plant, based on experimental evidence, and to provide an updated overview of its phytochemical composition and safety profile. Methods: A comprehensive literature search was conducted using databases including PubMed, Scopus, Web of Science, and Google Scholar, encompassing all publications available up to 2024. This search included research articles, reviews, mini-reviews, and clinical studies published in English. Exclusion criteria comprised publication types such as letters, conference abstracts, unpublished theses, and non-peer-reviewed reports. Studies were also excluded if they did not specifically address Foeniculum vulgare Mill. or its cardiovascular activities. All studies were screened according to predefined inclusion and exclusion criteria, and relevant data were systematically extracted and analyzed to synthesize current knowledge on the cardiovascular activities, mechanisms of action, phytochemical composition, safety, and potential drug interactions of Foeniculum vulgare Mill. Results: Numerous in vitro and in vivo studies have demonstrated that Foeniculum vulgare Mill. exhibits a wide range of activities beneficial for cardiovascular health. These include antihypertensive, cardioprotective, vasorelaxant, anti-inflammatory, antioxidant, diuretic, hypotensive, hypolipidemic, antiplatelet, and anticoagulant effects. Such pharmacological actions are largely attributed to its rich phytochemical composition, particularly its volatile oils (e.g., trans-anethole, fenchone), flavonoids (e.g., quercetin, kaempferol), and phenolic acids (e.g., p-coumaric acid, ferulic acid). Most studies report no significant signs of toxicity. Conclusions: Foeniculum vulgare Mill. emerges as a promising medicinal plant for the prevention and management of cardiovascular diseases, owing to its multifaceted beneficial effects and its favorable safety profile. However, potential interactions with cardiovascular drugs and the current limitations of existing studies highlight the need for further clinical research to fully establish its therapeutic potential. Full article

Diabetic muscular atrophy is a complication of diabetes mellitus that can decrease quality of life. Its complex mechanisms include alterations in proteolytic pathways, oxidative stress, and intracellular lipid accumulation. NADPH oxidase enzymes (NOX) play a key role in the production of ROS, contributing to oxidative damage and insulin resistance. Apocynin, a NOX inhibitor, has antioxidant and anti-inflammatory effects, suggesting its therapeutic potential in various diabetic complications. This study evaluated the impact of apocynin on the mechanisms of muscle atrophy in slow- and fast-twitch muscles of diabetic rats. Diabetes was induced in male Wistar rats by intraperitoneal injection of a single dose of streptozotocin (60 mg/kg). Apocynin treatment (3 mg/kg/day) was administered for 8 weeks. Fasting blood glucose levels, lipid profile, and weight gain were measured. Both slow-twitch (soleus) and fast-twitch (extensor digitorum longus, EDL) skeletal muscles were weighed and used to assess triglycerides (TG) content, histological analysis, lipid peroxidation levels, and gene expression evaluated by qRT-PCR. Apocynin reduced blood glucose levels, improved body weight, and exhibited hypolipidemic effects. It significantly increased muscle weight in EDL and soleus, especially in EDL muscle, lowering triglycerides, lipid peroxidation, and increasing fiber size. Additionally, it decreased mRNA expression levels of MuRF-1, atrogin-1, myostatin and p47phox mRNA and upregulated PGC-1α and follistatin mRNA. Apocynin exerted a myoprotective effect by mitigating muscle atrophy in diabetic rats. Its effects were differentially mediated on TG accumulation and muscle fiber size, reducing oxidative stress, atrogene expression, and positively regulating PGC-1α. Full article

The advancement of modern lifestyles has precipitated excessive consumption of energy-dense foods, driving the escalating global burden of lipid metabolism dysregulation-related pathologies—including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disorders—which collectively pose a formidable challenge to global public health systems. The almond hull, as a by-product of almond processing, is rich in polyphenolic compounds with demonstrated antioxidant, anti-inflammatory, and lipid-lowering potential, though its precise hypo-lipidemic mechanisms remain elusive. In this study, polyphenols were extracted from almond hulls using 50% ethanol with ultrasound-assisted extraction, followed by preliminary purification via solvent partitioning. The ethyl acetate fraction was analyzed by liquid chromatography–mass spectrometry (LC-MS). Network pharmacology and molecular docking were employed to investigate the interactions between key bioactive constituents (e.g., quercetin, baicalein, and kaempferol) and targets in lipid metabolism-related pathways. Molecular dynamics (MD) simulations further evaluated the stability of the lowest-energy complexes. Results revealed that the ethyl acetate fraction exhibited potent pancreatic lipase inhibitory activity (IC50 = 204.2 µg/mL). At 0.1 mg/mL after 24 h treatment, it significantly reduced free fatty acids (FFAs)-induced intracellular triglyceride accumulation (p < 0.01) and enhanced cellular antioxidant capacity. Network pharmacology and in vitro studies suggest almond hull extract modulates PI3K-AKT signaling and improves insulin resistance, demonstrating lipid-lowering effects. These findings support its potential in functional foods and pharmaceuticals, though further in vivo validation and mechanistic investigations are required. Full article

Platycladus orientalis, an evergreen tree belonging to the Cupressaceae family, has been traditionally used to treat various ailments, including fever, cough, diarrhea, diuresis, cold symptoms, and gastrointestinal disorders in folk medicine. As part of our ongoing investigation aimed at discovering bioactive natural products and elucidating their mechanisms of action from various natural sources, we investigated a methanol (MeOH) extract of P. orientalis leaves. This investigation led to the isolation and identification of a labdane-type diterpene, lambertianic acid (LA), via column chromatography and HPLC purification. The structure of LA was elucidated using LC/MS and NMR spectroscopic analyses, including HR-ESIMS, while its absolute configuration was confirmed through electronic circular dichroism (ECD) calculations. Recent studies have reported that labdane-type diterpenes exhibit diverse pharmacological activities, such as anticancer, anti-inflammatory, anti-obesity, and hypolipidemic effects. Notably, LA has been shown to modulate adipocyte metabolism via AMPK signaling; however, its role in skeletal muscle atrophy remains unexplored. Therefore, in this study, we investigated the effects of LA on dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. Treatment with LA at concentrations of 25 µM and 50 µM significantly rescued myotube diameter and reduced the expression of atrophy-related proteins, including MuRF-1 and atrogin-1/MAFbx, without compromising cell viability at these moderate concentrations. These findings suggest that LA derived from P. orientalis exerts protective effects against skeletal muscle atrophy, highlighting its potential as a promising natural therapeutic candidate for muscle-wasting disorders. Full article

In this study, figs were dried by hot air drying (HD), vacuum freeze-drying (FD), vacuum drying (VD) and far-infrared drying (FID). Four fig polysaccharides (FPs) were extracted from different dried figs, and the corresponding names were FPH, FPF, FPV and FPFI. The effects of different drying methods on the structural properties, rheological properties and biological activities of FPs were compared. The result shows that the extraction rate of polysaccharides after FD (2.49%) treatment was 58.60%, 50% and 28.35% higher than that of HD (1.57%), VD (1.66%) and FID (1.94%), respectively. Drying methods result in varying molar ratios of monosaccharides. FPFI has more stable gel properties. HD, VD and FID caused damage to the surface structure of the polysaccharides. FPF exhibited the highest uronic acid content (25.56%), along with relatively low apparent viscosity and molecular weight (1.45 × 10⁵ Da), which contributed to its superior antioxidant and lipid-lowering activities. Therefore, FD is a drying method to obtain fig polysaccharide with high antioxidant and hypolipidemic activity. The results provided a scientific basis for the drying process of fig polysaccharide and a reference for the development of potential hypolipidemic products of fig polysaccharide. Full article

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. Full article

In this work, the hypolipidemic and antioxidative capacity of FSGLR (S7) and GIEWA (S10) from miiuy croaker swim bladders was explored systematically in an oleic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model of HepG2 cells. Moreover, the hypolipidemic activity of S7 and S10 and their antioxidative abilities were preliminarily investigated in combination with molecular docking technology. The results indicated that S7 and S10 could decrease the amount of lipid accumulation and the content of triglycerides (TG) and total cholesterol (TC) in the OA-induced NAFLD cell model in a dose-dependent manner. In addition, S7 and S10 exhibited better bile salt binding, pancreatic lipase (PL) inhibition, and cholesterol esterase (CE) inhibition capacities. The hypolipidemic mechanisms of S7 and S10 were connected with the downregulation of the mRNA expression levels of adipogenic factors, including sterol-regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), sterol-regulatory element-binding protein (SREBP)-2, hydroxymethylglutaryl-CoA reductase (HMGR), and fatty acid synthase (FAS) (p < 0.01), and the upregulation of the mRNA expression of β-oxidation-related factors, including carnitine palmitoyltransferase 1 (CPT-1), acyl-CoA oxidase 1 (ACOX-1), and peroxisome proliferator-activated receptor α (PPARα). Moreover, FSGLR (S7) and GIEWA (S10) could significantly protect HepG2 cells against OA-induced oxidative damage, and their antioxidant mechanisms were related to the increased activity of intracellular antioxidant proteases (superoxide dismutase, SOD; glutathione peroxidase, GSH-PX; catalase, CAT) to remove excess reactive oxygen species (ROS) and decrease the production of malondialdehyde (MDA). The presented findings indicate that the hypolipidemic and antioxidant functions and mechanisms of S7 and S10 could make them potential hypolipidemic and antioxidant candidates for the treatment of NAFLD. Full article

Background: Hypertriglyceridemia has serious health risks such as cardiovascular disease, type 2 diabetes mellitus, nephropathy, and others. Fenofibrate is an effective hypolipidemic drug, but its benefits for ameliorating disorders associated with hypertriglyceridemia failed to be proven in clinical trials. Methods: To search for possible causes of this situation and possibilities of their favorable influence, we tested the effect of FF monotherapy and the combination of fenofibrate with silymarin on metabolic disorders in a unique model of hereditary hypertriglyceridemic rats (HHTg). Results: Fenofibrate treatment (100 mg/kg BW/day for four weeks) significantly decreased serum levels of triglyceride, (−77%) and free fatty acids (−29%), the hepatic accumulation of triglycerides, and the expression of genes encoding transcription factors involved in lipid metabolism (Srebf2, Nr1h4. Rxrα, and Slco1a1). In contrast, the hypertriglyceridemia-induced ectopic storage of lipids in muscles, the heart, and kidneys reduced glucose utilization in muscles and was not affected. In addition, fenofibrate reduced the activity of the antioxidant system, including Nrf2 expression (−35%) and increased lipoperoxidation in the liver and, to a lesser extent, in the kidneys and heart. Adding silymarin (micronized form, 600 mg/kg BW/day) to fenofibrate therapy increased the synthesis of glycogen in muscles, (+36%) and reduced hyperinsulinemia (−34%). In the liver, it increased the activity of the antioxidant system, including PON-1 activity and Nrf2 expression, and reduced the formation of lipoperoxides. The beneficial effect of combination therapy on the parameters of oxidative stress and lipoperoxidation was also observed, to a lesser extent, in the heart and kidneys. Conclusions: Our results suggest the potential beneficial use of the combination of FF with SLM in the treatment of hypertriglyceridemia-induced metabolic disorders. Full article

Background: Brassica nigra possesses a significant concentration of bioactive compounds and has been demonstrated to have a variety of pharmacological properties, although its sprout has not been extensively studied. Thus, the protective effects of Brassica nigra sprout hydroalcoholic extract (BNSE) on lipid homeostasis, hepatotoxicity, and nephrotoxicity in cyclophosphamide (CYP)-induced toxicity in rats were examined in this study. Methods: Four experimental rat groups (n = 8 for each group) were examined as follows: NR, normal rats that received normal saline by oral gavage daily; CYP, injected with a single dose of CYP at 250 mg kg⁻¹ intraperitoneally (i.p.) and did not receive any treatment, receiving only normal saline by oral gavage daily; CYP + BNSE250, injected with a single dose of CYP at 250 mg kg⁻¹ i.p. and treated with BNSE at 250 mg kg⁻¹ by oral gavage daily for three weeks; and CYP + BNSE500, injected with a single dose of CYP at 250 mg kg⁻¹ i.p. and treated with BNSE at 500 mg kg⁻¹ by oral gavage daily for three weeks. Results: The results indicated a significant increase (p < 0.05) in triglyceride (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-c), and very low-density lipoprotein cholesterol (VLDL-c) levels in CYP-induced toxicity rats. The administration of BNSE at 250 and 500 mg kg⁻¹ significantly (p < 0.05) attenuated TG, CHO, LDL-c, and VLDL-c at values comparable with the NR group. The most efficient treatment for improving the lipid profile and atherogenicity complication was BNSE at 500 mg kg⁻¹, performing even better than 250 mg kg⁻¹. Administrating BNSE at 250 or 500 mg kg⁻¹ improved the liver’s function in a dose-dependent manner. Comparing the lower dose of 250 mg kg⁻¹ of BNSE with 500 mg kg⁻¹ showed that administrating 250 mg kg⁻¹ attenuated alanine transaminase (ALT) by 28.92%, against 33.36% when 500 mg kg⁻¹ was given. A similar trend was observed in aspartate aminotransferase (AST), where 19.44% was recorded for BNSE at 250 mg kg⁻¹ and 34.93% for BNSE at 500 mg kg⁻¹. Higher efficiency was noticed for BNSE at 250 and 500 mg kg⁻¹ regarding alkaline phosphatase (ALP). An improvement of 38.73% for BNSE at 500 mg kg⁻¹ was shown. The best treatment was BNSE at 500 mg kg⁻¹, as it markedly improved liver function, such as total bilirubin (T.B.), in a dose-dependent manner. The administration of BNSE attenuated the total protein (T.P.), albumin, and globulin levels to be close to or higher than the typical values in NR rats. Conclusions: BNSE might be used for its promising hypolipidemic, hepatoprotective, and nephroprotective potential and to prevent diseases related to oxidative stress. Further research on its application in humans is highly recommended. Full article

Background/Objectives: In this paper, we created enteric delayed-release granules that load Dendrobine (DNL) directly into the intestinal flora of hyperlipidemic mice, based on the relationship between intestinal flora and hyperlipidemia. Methods: We then used pharmacodynamics and 16 Sr RNA high-throughput sequencing to examine the hypolipidemic effects and mechanism of these granules. Solvent evaporation was used to create the DNL, which was then characterized using FT–IR, XRD, SEM, and DSC. A high-fat diet was used to create the mouse model of hyperlipidemia in C57BL/6J mice. Dendrobine, various dosages of DNL, TMAO, and the combination of TMAO and DNL were subsequently gavaged on the mice. The makeup of the intestinal flora in the mouse colon was analyzed using 16S rRNA sequencing, and the effectiveness and mechanism of DNL in controlling the intestinal flora for the treatment of hyperlipidemia in mice were investigated. Results/Conclusions: The findings showed that DNL could effectively improve the dysbiosis brought on by hyperlipidemia by significantly lowering the mice’s body weight and blood lipid level (p < 0.05), while also regulating the function of their intestinal flora, increasing the abundance of Actinobacteria (p < 0.05) and Thick-walled bacterium (p < 0.05), and decreasing the abundance of Desulfovibrio (p < 0.05) and Mycobacterium anisopliae (p < 0.05) in the intestinal flora of mice, inhibiting the growth of intestinal harmful microorganisms, providing space for the reproduction of beneficial bacteria, and thus maintaining the stability of the intestinal flora’s structure. Full article

Flammulina velutipes is an edible mushroom widely cultivated in China. As a by-product of Flammulina velutipes, the roots are rich in high-quality dietary fiber (DF). In order to obtain high-quality soluble dietary fiber (SDF), steam explosion (SE) is used as an effective modification method to improve the extraction rate and avoid the loss of active substances. Mounting evidence shows that SDF alleviates lipid metabolism disorders. However, it is not well understood how the influence of SDF with SE pretreatment could benefit lipid metabolism. In this study, we extracted a soluble dietary fiber from Flammulina velutipes root with an SE treatment, named SE-SDF, using enzymatic assisted extraction. The physicochemical and structural properties of the SE-SDF were investigated, and its hypolipidemic effects were also analyzed using oleic-acid-induced HepG2 cells. In addition, the anti-obesity and hypolipidemic effects of SE-SDF were investigated using a high-fat diet (HFD) mouse model. The results indicate that SE treatment (1.0 MPa, 105 s) increased the SDF content to 8.73 ± 0.23%. The SE-SDF was primarily composed of glucose, galactose, and mannose. In HFD-fed mice, SE-SDF significantly reduced weight gain and improved lipid profiles, while restoring liver function and reducing injury. This work provides an effective method for the processing of fungi waste and adds to its economic value. In future studies, the structural characteristics and the anti-obesity and gut microbiota regulation mechanisms of SE-SDF will be explored in depth, supporting its high-value utilization in healthcare products. Full article

Background: This study investigates the hypolipidemic effects of a mixed extract of Salvia miltiorrhiza and Paeonia lactiflora (USCP119) in HFD-fed hamsters and in vitro cellular models. Methods: Over an 8-week period, HFD-fed hamsters were assigned to one of six groups: normal diet, HFD control, HFD with 50 mg/kg USCP119, HFD with 100 mg/kg USCP119, HFD with 50 mg/kg USCP119 twice daily (BID), and HFD with omega-3 fatty acids. Key outcomes assessed included body weight, serum triglycerides (TG), total cholesterol (TC), liver weight, hepatic TG levels, and epididymal fat. In cellular models, the impact of USCP119 on lipid accumulation and adipogenic markers was evaluated. Results: USCP119 treatment at 50 mg/kg BID resulted in the lowest weight gain (15.5%) and the most significant reductions in serum TG and hepatic TG levels compared to the HFD control. The 100 mg/kg dose also led to substantial reductions in serum TG and TC levels and notable decreases in low-density lipoprotein cholesterol. USCP119 at 50 mg/kg once daily reduced TG and TC levels but was less effective than the higher doses. In cellular models, USCP119 was non-toxic up to 400 µg/mL and effectively reduced lipid accumulation, modulated adipogenic markers, and enhanced AMPK signaling, improving lipid metabolism and insulin sensitivity. Conclusions: All USCP119 treatments demonstrated effectiveness in managing hyperlipidemia and related metabolic disorders, with variations in impact depending on the dosage. The ability of USCP119 to reduce fat accumulation, improve lipid profiles, and enhance insulin sensitivity highlights its potential as a valuable dietary supplement for addressing high-fat diet-induced hyperlipidemia and metabolic disturbances. Full article

This study aimed to examine the hepatic and anti-steatotic protective effects of methanolic extract from Carthamus tinctorius (safflower) flowers (SFFE), using a rat model of type 2 diabetes mellitus (T2DM), and to examine the molecular mechanisms underlying these effects. Adult male Wistar rats were used for this study. First, T2DM was induced in some rats by feeding them a high-fat diet (HFD) for 4 weeks, followed by a single dose of streptozotocin (STZ) (35 mg/kg, i.p.). Experimental groups included the following five groups (n = 8 in each): control, control + SFFE, T2DM, T2DM + SFFE, and T2DM + SFFE + brusatol (an Nrf2 inhibitor, 2 mg/kg, i.p.). SFFE was administered at a concentration of 300 mg/kg, and all experiments concluded after 8 weeks. Treatments with SFFE significantly reduced fasting blood glucose levels, free fatty acids (FFAs), cholesterol, triglycerides, and low-density lipoprotein cholesterol in both the control and T2DM rats, but they failed to reduce fasting insulin levels in these groups. SFFE treatments also improved the liver structure and reduced hepatocyte vacuolization and hepatic levels of triglycerides and cholesterol in T2DM rats, in addition to increasing the hepatic mRNA levels of keap1 and the cytoplasmic levels and nuclear activities of Nrf2 in both the control and T2DM rats. SFFE also stimulated the expression levels of PPARα and CPT-1 but reduced the malondialdehyde (MDA), mRNA levels of SREBP1, fatty acid synthase, and acetyl CoA carboxylase in both the control and T2DM rats; meanwhile, it reduced hepatic mRNA and the nuclear activities of NF-κB and increased levels of glutathione, superoxide dismutase, and heme oxygenase-1 in the livers of both groups of treated rats. Furthermore, SFFE suppressed the levels of caspase-3, Bax, tumor necrosis factor-α, and interleukin-6 in the T2DM rats. Treatment with brusatol prevented all of these effects of SFFE. In conclusion, SFFE suppresses liver damage and hepatic steatosis in T2DM through Nrf2-dependent hypoglycemic, antioxidant, anti-inflammatory, and hypolipidemic effects. Full article