Luteolin Protects Pancreatic β Cells against Apoptosis through Regulation of Autophagy and ROS Clearance

Abstract

Diabetes, which is mainly characterized by increased apoptosis and dysfunction of beta (β) cells, is a metabolic disease caused by impairment of pancreatic islet function. Previous studies have demonstrated that death-associated protein kinase-related apoptosis-inducing kinase-2 (Drak2) is involved in regulating β cell survival. Since natural products have multiple targets and often are multifunctional, making them promising compounds for the treatment of diabetes, we identified Drak2 inhibitors from a natural product library. Among the identified products, luteolin, a flavonoid, was found to be the most effective compound. In vitro, luteolin effectively alleviated palmitate (PA)-induced apoptosis of β cells and PA-induced impairment of primary islet function. In vivo, luteolin showed a tendency to lower blood glucose levels. It also alleviated STZ-induced apoptosis of β cells and metabolic disruption in mice. This function of luteolin partially relied on Drak2 inhibition. Furthermore, luteolin was also found to effectively relieve oxidative stress and promote autophagy in β cells, possibly improving β cell function and slowing the progression of diabetes. In conclusion, our findings show the promising effect of Drak2 inhibitors in relieving diabetes and offer a potential therapeutic target for the protection of β cells. We also reveal some of the underlying mechanisms of luteolin’s cytoprotective function.

The Medicinal Moroccan Plant Cladanthus arabicus as a Prominent Source of Sesquiterpenes Cladantholide and Sintenin

“…Extracts of C. arabicus are of interest to treat type 2 diabetes, owing to the presence of compounds like diosmetin and luteolin. This later flavonoid is well-known for its anti-inflammatory and antidiabetic properties [86,87]. But it is a common antioxidant compound found in many plants and is not specific to C. arabicus.…”

Demonstration of the impact of COVID-19 on metabolic associated fatty liver disease by bioinformatics and system biology approach

“…Luteolin is a tetrahydroxy flavone that can act as an antioxidant, an anti-inflammatory agent, and an immune system modulator. [ 66 ] A study found that Long-COVID syndrome symptoms, especially brain fog, can be mitigated by taking luteolin, [ 67 ] and Qi-Dong Xia et al found that Lianhua Qingwen capsule, a Chinese patent drug, has shown therapeutic effects in patients with COVID-19, while luteolin is one of its main active compounds. Moreover, luteolin can mitigate NASH, a stage of MAFLD, by targeting the pro-inflammatory IL-1 and IL-18 pathways.…”

Luteolin: A promising multifunctional natural flavonoid for human diseases

“…Molecular docking results showed that LUT had a strong binding affinity with DMrelated targets such as α-glucosidase (Yan et al, 2014) and key factors like ESR1, CAV1, VEGFA, TP53, CAT, AKT1, IL6, and IL1 (Luo et al, 2023). Han et al found that LUT had effects similar to deathrelated protein kinase-associated apoptosis-inducing kinase-2 (Drak2) inhibitors, inhibiting streptozotocin (STZ)-induced β cell apoptosis, promoting autophagy, improving β cell function, enhancing the metabolic function of ICR mice, and decelerating the progression of DM (Han, Lu, et al, 2023). Increased LUT intake has been shown to reduce all-cause mortality in patients with type 2 DM (T2DM), suggesting that LUT may positively affect the prognosis of T2DM through its anti-inflammatory properties (Zhang, Li, Shan, et al, 2023).…”