Investigating the mechanism of cornel iridoid glycosides on type 2 diabetes mellitus using serum and urine metabolites in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornel iridoid glycosides (CIG) are extracted from Corni fructus, a herbal medicine used in traditional Chinese medicine to treat diabetes. However, the antidiabetic effects of CIG and the underlying metabolic mechanisms require further exploration. AIM OF THE STUDY: This study aimed to assess the antidiabetic effects and metabolic mechanism of CIG by performing metabolomic analyses of serum and urine samples of rats. MATERIALS AND METHODS: A rat model of type 2 diabetes mellitus (T2DM) was established by administering a low dose of streptozotocin (30 mg/kg) intraperitoneally after 4 weeks of feeding a high-fat diet. The model was evaluated based on several parameters, including fasting blood glucose (FBG), random blood glucose (RBG), urine volume, liver index, body weight, histopathological sections, and serum biochemical parameters. Subsequently, serum and urine metabolomics were analyzed using ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS). Data were analyzed using unsupervised principal component analysis (PCA) and supervised orthogonal partial least squares discriminant analysis (OPLS-DA). Differential metabolites were examined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways to explore the underlying mechanisms. RESULTS: After 4 weeks of treatment with different doses of CIG, varying degrees of antidiabetic effects were observed, along with reduced liver and pancreatic injury, and improved oxidative stress levels. Compared with the T2DM group, 19 and 23 differential metabolites were detected in the serum and urine of the CIG treatment group, respectively. The key metabolites involved in pathway regulation include taurine, chenodeoxycholic acid, glycocholic acid, and L-tyrosine in the serum and glycine, hippuric acid, phenylacetylglycine, citric acid, and D-glucuronic acid in the urine, which are related to lipid, amino acid, energy, and carbohydrate metabolism. CONCLUSIONS: This study confirmed the antidiabetic effects of CIG and revealed that CIG effectively controlled metabolic disorders in T2DM rats. This seems to be meaningful for the clinical application of CIG, and can benefit further studies on CIG mechanism.

Six undescribed derivatives of stilbene isolated from Lindera reflexa Hemsl. and their anti-tumor and anti-inflammatory activities.

Six undescribed stilbene derivatives Reflexanbene DH (1-4, 6) and Reflexanbene J (5), as well as one known stilbene 3,5-dimethoxystilbene (7), were isolated from the dried roots of Lindera reflexa Hemsl. Their structures and absolute configurations were elucidated using spectroscopy and electronic circular dichroism (ECD) analysis. In cytotoxic assays, moderately inhibitory activities of Reflexanbene F (3) against MGC80-3 and A549 cell lines were observed, with IC50 values of 15.42 and 5.09 µM, respectively. The IC50 value of Reflexanbene E (2) on A549 cell lines was 19.78 µM. The isolated compounds were also tested for their inhibitory effect against LPS-induced NO and IL-6 production in RAW 264.7 cells. In particular, Reflexanbene J (5) and Reflexanbene H (6) showed significant inhibition of NO production in LPS-stimulated macrophage RAW 264.7 cells at the concentration of 20 µM. Furthermore, the expression of IL-6 protein in the LPS-induced RAW 264.7 cells can also be significantly inhibited by different concentrations (5, 10 and 20 µM, p < 0.05 or p < 0.01) of compounds 1-7.

Gastroprotective effect of an active ingredients group of Lindera reflexa Hemsl. On Ethanol-Induced gastric ulcers in Rats: Involvement of VEGFR2/ERK and TLR-2/Myd88 signaling pathway.

Lindera reflexa Hemsl. (LR) has been used for the treatment of gastrointestinal disorders. The present study was carried out to investigate the gastroprotective effect of an active ingredients group of Lindera reflexa Hemsl. (LRG) on ethanol-induced gastric ulcer in rats and its possible mechanisms. The ulcer area was measured, and samples of gastric tissue were taken for histochemical, pathological, and biochemical analyses. Pretreatment with LRG protected the gastric mucosa as seen by reduction the GUI and gastric juice volume, regulated gastric acid secretion. LRG counteracted the ethanol-induced oxidative stress by increasing the levels of depleted SOD and CAT as well as significantly attenuating the lipid peroxidation by reducing the levels of MDA and MPO. LRG also reduced release of inflammatory mediator TNF-α, increased the content of PGE2 and inhibited MTL secretion. Immunofluorescence and Western blot analyses confirmed that the co-localization of TLR-2 and MyD88 protein in the gastric mucosa of LRG-treated rats was significantly lower than that of rats with gastric ulcers. Furthermore, LRG also modulated the expression of Ki-67 antigens. LRG markedly increased the expression of phosphorylated form of extracellular signal-regulated kinaseVEGFR2, ERK1/2, AKT and p38, thereby protecting the gastric mucosa. These findings indicated that the gastroprotective effect of LRG is attributable to its antioxidant, anti-inflammatory, and antisecretory properties. In addition, LRG can ameliorate ethanol-induced gastric ulcers in rats by regulating the VEGFR2/ERK and TLR-2/MyD88 signaling pathways.