Luteolin loaded on zinc oxide nanoparticles ameliorates non-alcoholic fatty liver disease associated with insulin resistance in diabetic rats via regulation of PI3K/AKT/FoxO1 pathway

Abstract

Objective Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem with high prevalence and morbidity associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. Nano-formulation of luteolin with Zn oxide in the form of Lut/ZnO NPs may improve the anti-diabetic property of each alone and ameliorate the insulin resistance thus management of NAFLD. This study aimed to measure the efficiency of Lut/ZnO NPs against insulin resistance coupled with NAFLD and T2DM. Methods A diabetic rat model with NAFLD was induced by a high-fat diet and streptozotocin (30 mg/kg I.P). Serum diabetogenic markers levels, lipid profile, and activity of liver enzymes were measured beside liver oxidative stress markers. Moreover, the hepatic expressions of PI3K/AKT/FoxO1/SERBP1c as well as heme oxygenase-1 were measured beside the histopathological examination. Results Lut/ZnO NPs treatment effectively reduced hyperglycemia, hyperinsulinemia, and ameliorated insulin resistance. Additionally, Lut/ZnO NPs improved the hepatic functions, the antioxidant system, and reduced the oxidative stress markers. Furthermore, the lipid load in the liver, as well as the circulating TG and TC, was minified via the suppression of lipogenesis and gluconeogenesis. Moreover, Lut/ZnO NPs activated the PI3K/AKT signaling pathway, hence inactivating FoxO1, therefore enhancing the hepatic cells’ insulin sensitivity. Conclusion Lut/ZnO NPs have a hepatoprotective effect and may relieve the progression of NAFLD by alleviating insulin resistance, ameliorating the antioxidant status, and regulating the insulin signal pathway.

Effect of Codonopsis Radix and Polygonati Rhizoma on the regulation of the IRS1/PI3K/AKT signaling pathway in type 2 diabetic mice

“…Luteolin is a natural flavonoid with a variety of pharmacological activities ( 21 ). Luteolin inhibits the expression of TLR4 and JNK mRNA in pancreases of T2DM rats, and it improves IR and alleviates pancreatic inflammatory reactions in T2DM rats ( 22 ). Baicalein is a flavonoid found in traditional Chinese medicine, such as yellow essence and baicalensis, and it has various pharmacological effects.…”

Nano-scale drug delivery systems for luteolin: advancements and applications

“…Ahmed et al investigated the efficacy of Lu-loaded zinc oxide nanoparticles (Lut/ZnO NPs) for treating nonalcoholic fatty liver disease (NAFLD) associated with insulin resistance. 76 Their findings revealed that Lut/ZnO NPs enhanced insulin sensitivity in hepatic cells by activating the PI3K/AKT signaling pathway and inactivating FOXO1, resulting in significant hepatoprotective effects and effectively alleviating the progression of NAFLD. Additionally, Shi et al utilized a magnetic composite Fe 3 O 4 @ZIF-67 as a carrier for delivering Lu, exhibiting a maximum drug loading capacity of 308.07 μg mg −1 and excellent sustained release properties.…”

Human diet‐derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization

“…Additionally, reducing luteolin to the nanoscale with zinc oxide showed potential for treating and improving NAFLD by activating the PI3K/AKT signaling pathway, thereby deactivating FoxO1 and potentially improving insulin resistance (Ahmed et al, 2022). Overall, nanoscale delivery of polyphenols holds promise as an approach for liver diseases.…”

“…The outcomes indicated effective reversal of hepatic fibrosis attributed to curcumin's capability to interact with proteins involved in fibrosis (PDGFRB, TIMP‐1, TLR‐9, and TGF‐β) (Elzoheiry et al, 2022). Additionally, reducing luteolin to the nanoscale with zinc oxide showed potential for treating and improving NAFLD by activating the PI3K/AKT signaling pathway, thereby deactivating FoxO1 and potentially improving insulin resistance (Ahmed et al, 2022). Overall, nanoscale delivery of polyphenols holds promise as an approach for liver diseases.…”