Riligustilide alleviates hepatic insulin resistance and gluconeogenesis in T2DM mice through multitarget actions

Abstract

Riligustilide (RG), one of the dimeric phthalides of Angelica sinensis and Ligusticum chuanxiong, was confirmed effective against many diseases. However, its effects on type 2 diabetes mellitus (T2DM) and the underlying molecular mechanisms have not been clearly elucidated yet. The current study was designed to investigate the hypoglycemic potential by which RG affects the pathogenesis of T2DM. Comprehensive insights into the effects and underlying molecular mechanisms of RG on attenuating aberrant metabolism of glucose were determined in high‐fat diet‐induced T2DM mice and insulin‐resistant (IR) HepG2 cells. In high‐fat diet‐induced C57BL/6J mice, RG administration significantly reduced hyperglycemia, decreased hyperinsulinemia, and ameliorated glucose intolerance. Mechanistically, RG activated PPARγ and insulin signaling pathway to improve insulin sensitivity, and increase glucose uptake as well as glycogenesis. In addition, RG also upregulated AMPK‐TORC2‐FoxO1 axis to attenuate gluconeogenesis in vivo and in vitro. According to the findings, RG may be a promising candidate for the treatment of T2DM.

Antidiabetic effect of sciadonic acid on type 2 diabetic mice through activating the PI3K-AKT signaling pathway and altering intestinal flora

“…GSK3β was reported to be significantly increased in patients with T2DM and was positively correlated with insulin resistance (26). In addition, PPARγ is a ligand-activated nuclear receptor, and activation of PPARγ improves insulin sensitivity (27). In summary, SA could activate the PI3K/AKT/GLUT2 protein pathway, regulate glucose metabolism gene expression, enhance insulin sensitivity, and improve insulin resistance.…”

Discovery, Preliminary Structure–Activity Relationship, and Evaluation of Oleanane-Type Saponins from Pulsatilla chinensis for the Treatment of Ulcerative Colitis

“…The method used was as previously described. 42 After fixing the colon tissue overnight with 4% formaldehyde, it was embedded in paraffin wax. Next, it was cut into 5 mm thick sections, deparaffinized, and rehydrated.…”

“…Western blotting was used to detect the expression levels of related proteins as reported in the literature. 42 The total protein was extracted from colon tissues (30−40 mg every sample). The following primary antibodies were used: anti-p-NF-κB p65, anti-claudin-2, anti-TNF-α, anti-NF-κB p65, and anti-GAPDH from Cell Signaling Technology (Beverly, MA) and anti-long MLCK and anti-p-MLC from Abcam (Cambridge, MA).…”

The Beneficial Effects of Two Polysaccharide Fractions from Sargassum fusiform against Diabetes Mellitus Accompanied by Dyslipidemia in Rats and Their Underlying Mechanisms

“…Gluconeogenesis is the process of transforming non-sugar substances such as glycerol, lactic acid and amino acids into glycogen or glucose [37]. When insulin resistance occurs, the dynamic balance of hepatic glucose production and glycogen synthesis is broken, and gluconeogenesis is increased, which further increases the blood glucose of patients [38]. Inhibiting the limiting velocity enzymes in gluconeogenesis expressions is an approach to reduce the occurrence of gluconeogenesis [39].…”