Ying Liu

Glabridin (GLD) is a flavonoid derived from licorice. This study aims to evaluate GLD's therapeutic potential in ameliorating type 2 diabetes mellitus (T2DM) and elucidate its underlying mechanisms of action. A T2DM model was established using male C57BL/6J mice fed a high‐fat, high‐glucose diet. GLD was administered via intraperitoneal injection at doses of 10, 20, and 30 mg/kg BW, with MET (200 mg/kg BW) as a positive control. Fasting blood glucose levels, glucose tolerance, insulin tolerance, pyruvate tolerance, and serum parameters were analyzed, along with key markers of glycogen synthesis, gluconeogenesis, lipid metabolism, mitochondrial function, and endoplasmic reticulum (ER) stress. GLD significantly lowered blood glucose levels in the diabetic mice. It suppressed gluconeogenesis by inhibiting PEPCK and G6P, while promoting glycogen synthesis by activating GCK and inhibiting GSK‐3β. Additionally, GLD enhanced insulin signaling by increasing IRS1 and IRS2 levels and promoting AKT phosphorylation, thereby improving insulin sensitivity. In lipid metabolism, GLD reduced hepatic steatosis and lipid accumulation by downregulating lipogenesis‐related genes ( SREBP1c , FAS , ACC1 , and SCD1 ) and upregulating lipolysis‐related genes ( PPARα and LCAD ). In energy metabolism, GLD increased mitochondrial membrane potential, reduced reactive oxygen species levels, and enhanced the expression of genes associated with mitophagy ( PINK1 and Parkin ) and mitochondrial biogenesis ( PGC‐1α , SIRT1 , and TFAM ). Moreover, GLD mitigated ER stress by decreasing GRP78 and CHOP levels, suppressing PERK phosphorylation, and inhibiting key stress response genes. GLD improves insulin sensitivity and exerts antidiabetic effects by ameliorating metabolic disorders, supporting its potential as a therapeutic agent for T2DM.

Type 2 diabetes mellitus (T2DM) is a persistent metabolic disorder marked by deficiencies in insulin secretion and/or function, affecting various tissues and organs and leading to numerous complications. Mitochondrial biogenesis, the process by which cells generate new mitochondria utilizing existing ones plays a crucial role in energy homeostasis, glucose metabolism, and lipid handling. Recent evidence suggests that promoting mitochondrial biogenesis can alleviate insulin resistance in the liver, adipose tissue, and skeletal muscle while improving pancreatic β-cell function. Moreover, enhanced mitochondrial biogenesis has been shown to ameliorate T2DM symptoms and may contribute to therapeutic effects for the treatment of diabetic nephropathy, cardiomyopathy, retinopathy, and neuropathy. This review summarizes the intricate connection between mitochondrial biogenesis and T2DM, highlighting the potential of novel therapeutic strategies targeting mitochondrial biogenesis for T2DM treatment and its associated complications. It also discusses several natural products that exhibit beneficial effects on T2DM by promoting mitochondrial biogenesis.

Type 2 diabetes mellitus (T2DM) is a severe, long‐term condition characterised by disruptions in glucolipid and energy metabolism. Autophagy, a fundamental cellular process, serves as a guardian of cellular health by recycling and renewing cellular components. To gain a comprehensive understanding of the vital role that autophagy plays in T2DM, we conducted an extensive search for high‐quality publications across databases such as Web of Science, PubMed, Google Scholar, and SciFinder and used keywords like ‘autophagy’, ‘insulin resistance’, and ‘type 2 diabetes mellitus’, both individually and in combinations. A large body of evidence underscores the significance of activating autophagy in alleviating T2DM symptoms. An enhanced autophagic activity, either by activating the adenosine monophosphate‐activated protein kinase and sirtuin‐1 signalling pathways or inhibiting the mechanistic target of rapamycin complex 1 signalling pathway, can effectively improve insulin resistance and balance glucolipid metabolism in key tissues like the hypothalamus, skeletal muscle, liver, and adipose tissue. Furthermore, autophagy can increase β‐cell mass and functionality in the pancreas. This review provides a narrative summary of autophagy regulation with an emphasis on the intricate connection between autophagy and T2DM symptoms. It also discusses the therapeutic potentials of natural products with autophagy activation properties for the treatment of T2DM conditions. Our findings suggest that autophagy activation represents an innovative approach of treating T2DM.

Licochalcone A (LCA) is a bioactive chalcone compound identified in licorice. This study aimed to investigate the effects of LCA on glucolipid metabolism and energy homeostasis, as well as the underlying mechanisms. Blood glucose levels, oral glucose tolerance, serum parameters, and histopathology were examined in high‐fat‐high‐glucose diet (HFD)‐induced diabetic mice, with metformin as a positive control. Additionally, changes in key markers related to glucolipid metabolism and mitochondrial function were analyzed to comprehensively assess LCA's effects on metabolism. The results showed that LCA alleviated metabolic abnormalities in HFD‐induced diabetic mice, which were manifested by suppression of lipogenesis, promotion of lipolysis, reduction of hepatic steatosis, increase in hepatic glycogenesis, and decrease in gluconeogenesis. In addition, LCA restored energy homeostasis by promoting mitochondrial biogenesis, enhancing mitophagy, and reducing adenosine triphosphate production. Mechanistically, the metabolic benefits of LCA were associated with the downregulation of mammalian target of rapamycin complex 1 and activation of adenosine monophosphate‐activated protein kinase, the two central regulators of metabolism. This study demonstrates that LCA can alleviate abnormal glucolipid metabolism and restore energy balance in diet‐induced diabetic mice, highlighting its therapeutical potential for the treatment of diabetes.

INPLASY202360047 Protective effects and mechanism of Curcumin in animal models of acute lung injury: A preclinical systematic review and meta-analysis Keywords: Curcumin; ALI; ARDS; Animal Models. …

Glycyrrhiza uralensis Fisch. is prescribed as one of the original plants of licorice in Chinese Pharmacopoeia. This herbal medicine possesses numerous important pharmacological activities and has been used in clinic in China since ancient times. Glycyrrhizic acid (GA) is a triterpenoid compound isolated from G. uralensis and also one of the marker components for its quality control. Based on our pervious transcriptome study, three genes, the caffeic acid 3-O-methyltransferase gene (COMT), the β-carotene 3-hydroxylase gene (CRTZ), and the flavonoid 3'-monooxygenase gene (F3'H), were selected as our target genes due to a high correlation of their expression levels with GA biosynthesis. In this study, we investigated the regulatory effects of these genes on GA biosynthesis through gene editing and overexpression in G. uralensis hairy roots. We observed that neither knockout nor overexpression of any of the genes affects the viability of the transgenic hairy roots, indicating that these genes are not essential for survival of hairy roots. However, compared with the wild type and negative control hairy roots, GA contents were significantly lower in hairy roots overexpressing COMT, CRTZ, and F3'H, while higher in those knocking out the three genes. Our findings demonstrate that the three genes, COMT, CRTZ, and F3'H, all negatively regulate the GA biosynthesis.

The mechanistic target of rapamycin (mTOR) is a pivotal regulator of cell metabolism and growth. In the form of two different multi-protein complexes, mTORC1 and mTORC2, mTOR integrates cellular energy, nutrient and hormonal signals to regulate cellular metabolic homeostasis. In type 2 diabetes mellitus (T2DM), pathological conditions and end-organ complications can be attributed to aberrant mTOR. Substantial evidence suggests that two mTOR-mediated signaling schemes, mTORC1-p70S6 kinase 1 (S6K1) and mTORC2-protein kinase B (AKT), play a critical role in insulin sensitivity and that their dysfunction contributes to the development of T2DM. This review summarizes our current understanding of the role of mTOR signaling in T2DM and its associated complications, as well as the potential use of mTOR inhibitors in the treatment of T2DM.