Isolation and characterization of a hepatoprotective polysaccharide from Lonicera caerulea L. var. edulis Turcz. ex Herd. fruit against APAP-induced acute liver injury mice.

The structure and bioactivities of a novel polysaccharide from Lonicera caerulea L. var. edulis Turcz. ex Herd. fruit (THP-3) were investigated. The crude polysaccharides of Turcz. ex Herd. (THP) were extracted by hot water extraction. After purification, the chemical structure of polysaccharides was identified. Then, a mouse model of acute drug-induced liver injury was constructed using 4-acetamidophenol (APAP) and pretreated with THP. The number-average molecular weight of THP-3 was 48.89 kDa and the mass average molar mass was 97.87 kDa. THP-3 was mainly composed of arabinose (42.54 %), glucose (27.62 %), galacturonic acid and galactose (29.84 %). The main linkage types of THP-3 were 1-linked Araf, 1,4-linked Glcp, and 1,3,6-linked Galp. In addition, after THP treatment, serum Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and γ-glutamyl transpeptidase (γGT) in AILI mice were successfully down-regulated. The results showed that THP could prevent the characteristic morphological changes of hepatic lobular injury and lipid depletion caused by APAP, reduced the level of oxidative damage in mice, increased the expression of APAP-induced hypolipidemia and related inflammatory indicators, and improved the detoxification function of liver. In general, the newly extracted THP polysaccharide has a good liver protection effect and is an ideal natural medicine for the treatment of liver diseases.

Glucagon-like peptide-1 attenuates diabetes-associated osteoporosis in ZDF rat, possibly through the RAGE pathway.

BACKGROUND: Diabetes-associated osteoporosis are partly caused by accumulation of advanced glycation endproducts (AGEs). Glucagon-like peptide-1 (GLP-1) has been shown to regulate bone turnover. Here we explore whether GLP-1 receptor agonist (GLP1RA) can have a beneficial effect on bone in diabetes by ameliorating AGEs. METHODS: In the present study, we evaluated the effects of the GLP-1 receptor agonist liraglutide, insulin and dipeptidyl peptidase-4 inhibitor saxagliptin on Zucker diabetic fatty rats. Meanwhile, we observed the effect of GLP-1 on AGEs-mediated osteoblast proliferation and differentiation and the signal pathway. RESULTS: Liraglutide prevented the deterioration of trabecular microarchitecture and enhanced bone strength. Moreover, it increased serum Alpl, Ocn and P1NP levels and decreased serum CTX. In vitro we confirmed that GLP-1 could attenuate AGEs-mediated damage in osteogenic proliferation and differentiation. Besides, GLP-1 down-regulated the ROS that caused by AGEs and the mRNA and protein expression of Rage . CONCLUSIONS: Altogether, our findings suggest that GLP-1 receptor agonist promotes osteoblastogenesis and suppresses bone resorption on obese type 2 diabetic rats to a certain degree. The mechanism of these effects may be partly mediated by AGEs-RAGE-ROS pathway via the interaction with GLP-1 receptor.

Quercetin and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a reproductive endocrine disease, and results to opsomenorrhea or amenorrhea, hairy, acne, acanthosis, infertility, abortion. In the long term, PCOS may also increase the risk of endometrial cancer, diabetes, hypertension, dyslipidemia and other diseases. Till now there is no specific drug for PCOS due to the unclearness of the cause and pathogenesis, as current treatments for PCOS only target certain symptoms. Quercetin (QUR) is a flavonoid drug widely found in Chinese herbal medicines, fruits, leaves, vegetables, seeds and plants roots. Studies on other diseases have found that QUR has anti-oxidant, anti-inflammatory, anti-insulin resistance, anti-cancer and other effects. Some studies have shown that serum testosterone (T), luteinizing hormone (LH), the LH/follicule-stimulating hormone (FSH) ratio, fasting glucose, fasting insulin, HOMA-IR and lipid levels are reduced in PCOS patients with QUR treatment. However, the mechanisms of QUR in PCOS patients have not been completely elucidated. In this review, we retrospect the basic characteristics of QUR, and in vitro studies, animal experiments and clinical trials of QUR and plant extracts containing QUR in the treatment of PCOS. We also summarized the effects and mechanism of QUR in ovarian cells in vitro and PCOS model rats, the changes in relevant parameters after QUR administration in PCOS patients, and its potentially therapeutic applications.

Dapagliflozin Alleviates Hepatic Steatosis by Restoring Autophagy via the AMPK-mTOR Pathway.

As a newly approved oral hypoglycaemic agent, the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin, which is derived from the natural product phlorizin can effectively reduce blood glucose. Recent clinical studies have found that dapagliflozin alleviates non-alcoholic fatty liver disease (NAFLD), but the specific mechanism remains to be explored. This study aimed to investigate the underlying mechanism of dapagliflozin in alleviating hepatocyte steatosis in vitro and in vivo. We fed the spontaneous type 2 diabetes mellitus rats with high-fat diets and cultured human normal liver LO2 cells and human hepatocellular carcinoma HepG2 cells with palmitic acid (PA) to induce hepatocellular steatosis. Dapagliflozin attenuated hepatic lipid accumulation both in vitro and in vivo. In Zucker diabetic fatty (ZDF) rats, dapagliflozin reduced hepatic lipid accumulation via promoting phosphorylation of acetyl-CoA carboxylase 1 (ACC1), and upregulating lipid ß-oxidation enzyme acyl-CoA oxidase 1 (ACOX1). Furthermore, dapagliflozin increased the expression of the autophagy-related markers LC3B and Beclin1, in parallel with a drop in p62 level. Similar effects were observed in PA-stimulated LO2 cells and HepG2 cells. Dapagliflozin treatment could also significantly activated AMPK and reduced the phosphorylation of mTOR in ZDF rats and PA-stimulated LO2 cells and HepG2 cells. We demonstrated that dapagliflozin ameliorates hepatic steatosis by decreasing lipogenic enzyme, while inducing fatty acid oxidation enzyme and autophagy, which could be associated with AMPK activation. Moreover, our results indicate that dapagliflozin induces autophagy via the AMPK-mTOR pathway. These findings reveal a novel clinical application and functional mechanism of dapagliflozin in the treatment of NAFLD.