Luteolin mitigates tamoxifen-associated fatty liver and cognitive impairment in rats by modulating beta-catenin.

BACKGROUND AND AIM: Tamoxifen (TAM) therapy has been associated with fatty liver diseases. Recently, multiple reports have also shown that TAM is related to cognitive impairment in patients with breast cancer. Luteolin, a natural flavonoid, has been traditionally used to treat various inflammatory disorders, such as chronic liver diseases, cognitive impairments, and cancers. This study aimed to evaluate the potential protective effects of luteolin against the cognitive defects and liver steatosis induced by TAM in rats. EXPERIMENTAL APPROACH: The diseased group was subcutaneously (s.c) injected with TAM at a dose of 1 mg/kg daily for 7 days. The cotreated groups were given luteolin via oral gavage at a dose of 20 or 40 mg/kg concomitantly with s.c injection of TAM at a dose of 1 mg/kg for 7 days. All the groups were subjected to behavioral tests 24 h after the last TAM injection. Then, the rats were sacrificed 3 days after the last TAM injection. RESULTS: Luteolin cotreatment significantly alleviated the behavioral defects in rats with TAM-induced cognitive impairment. This finding was supported by the reversal of neurodegeneration in the cortex and in the hippocampal regions of the brain. Furthermore, luteolin attenuated hepatic steatosis and decreased the levels of serum aminotransferases and hypertriglyceridemia. As an anti-inflammatory agent, luteolin cotreatment similarly decreased the levels of hepatic inflammatory markers and increased the levels of hepatic ß-catenin in TAM-induced fatty liver. CONCLUSIONS: Luteolin improved the TAM-induced cognitive impairment and hepatic steatosis in rats by alleviating inflammation and modulating hepatic ß-catenin levels.

Obestatin can potentially differentiate Wharton's jelly mesenchymal stem cells into insulin-producing cells.

In vitro-generation of ß-cells from Wharton's jelly mesenchymal stem cells (WJ-MSCs) could provide a potential basis for diabetes mellitus cell therapy. However, the generation of functional insulin-producing cells (IPCs) from WJ-MSCs remains a challenge. Recently, obestatin, a gut hormone, was found to promote ß-cell generation from pancreatic precursor cells. Accordingly, we hypothesize that obestatin can induce the differentiation of WJ-MSCs into IPCs. Therefore, the purpose of the current study is to examine the ability of obestatin to generate IPCs in comparison to well-known extrinsic factors that are commonly used in IPCs differentiation protocols from MSCs, namely exendin-4 and glucagon-like peptide-1 (GLP-1). To achieve our aims, WJ-MSCs were isolated, cultured and characterized by immunophenotyping and adipocytes differentiation. Afterwards, WJ-MSCs were induced to differentiate into IPCs using two differentiation protocols incorporating either exendin-4, GLP-1 or obestatin. The pancreatic progenitor marker, nestin and ß-cell differentiation markers were assessed by qRT-PCR, while the functionality of the generated IPCs was assessed by glucose-stimulated insulin secretion (GSIS). Our results showed that WJ-MSCs exhibit all the characteristics of MSCs. Interestingly, using obestatin in both the short and long differentiation protocols managed to induce the expression of ß-cell markers, similar to exendin-4. In GSIS, IPCs generated using either GLP-1 or obestatin showed higher secretion of insulin as compared to those generated using exendin-4 under low-glucose conditions but failed to show a significant response to increased glucose. These results indicate obestatin can be considered as a novel potential factor to consider for generation of IPCs from WJ-MSCs.