Insulin resistance (IR) is a central pathophysiological process underlying numerous chronic metabolic disorders, including type 2 diabetes and obesity. Lycii Cortex, a widely used traditional Chinese herb, has demonstrated potential benefits in preventing and managing diabetes and IR. Whereas, the specific bioactive compounds responsible for these protective effects and their underlying mechanisms of action remain elusive. This study aimed to identify the bioactive components within Lycii Cortex that contribute to its anti-diabetic effects and to elucidate the molecular mechanisms underlying its beneficial actions on insulin resistance. Network pharmacology and molecular docking analyses were employed to identify the potential active compounds in Lycii Cortex and their corresponding target proteins. An in vitro model of IR was established using palmitic acid (PA)-treated HepG2 cells. Cell viability was assessed using the CCK-8 assay, while glucose uptake was evaluated by 2-NBDG staining and extracellular glucose measurement. To validate the in vitro findings, an in vivo model of obesity-induced IR was established using high-fat diet (HFD)-fed mice. The network pharmacology analysis preliminarily identified 13 candidate chemicals and 10 hub LyC and IR-related genes (LIRRGs). Molecular docking analysis demonstrates that Linarin as the potential active component exhibits the greatest potential to target c-FOS for preventing obesity-induced IR. Enrichment analysis suggested that Linarin-targeted pathways are correlated with inflammation. In vitro experimental validation demonstrated that Linarin was capable of protecting against PA-induced IR in HepG2 cells evidenced by improving glucose uptake ability and reducing extracellular glucose content. Additionally, we found that Linarin ablated PA-induced increase in the expression of c-FOS and inflammatory cytokines. Furthermore, in PA-treated cells, silencing c-FOS markedly improved glucose consumption, and reduced inflammation and Arginase 2 (ARG2) expression. Similarly, as exposure to PA, silencing ARG2 also ameliorated glucose uptake and inflammation, while not affecting c-FOS expression. In vivo experiments further showed that Linarin administration remarkably improved glucose tolerance and insulin sensitivity, and reduced the fat mass and body weight in HFD-induced obese mice. In this study, Linarin has been identified as the bioactive compound of Lycii Cortex to ameliorate obesity-related IR and inflammation through the c-FOS/ARG2 signaling cascade. These findings underscore the therapeutic potential of Linarin and provide valuable insights into developing novel intervention strategies for type 2 diabetes therapy.
To research the optimization of ultrasonic-assisted extraction of total flavonoids from Cortex Lycii and its biological activities. Box-Behnken design experiment was used to optimize the extraction process, and AB-8 macroporous resin was used for purification. Its biological activities were studied by the inhibition rate of α -glucosidase and α - amylase and the scavenging rate of DPPH and ABTS. The optimal extraction parameters of total flavonoids from Cortex Lycii were as follows: the extraction temperature was 63 ℃, the ethanol volume fraction was 71%, the solid–liquid ratio was 28 mL/g, the extraction time was 61 min. Under this optimal condition, the yield of total flavonoids was 1.674 mg/g, which was consistent with the predicted value of 1.637 mg/g, and was 5.85 times higher than that of the traditional water extraction method. The inhibitory rate (IC 50 ) of total flavonoids extract from Cortex Lycii on α -glucosidase was 3 μg/mL and on α -amylase was 5 μg/mL. The scavenging rate (IC 50 ) of DPPH radical was 0.648 mg/mL and the scavenging rate (IC 50 ) of ABTS radical IC 50 was 0.012 mg/mL. The optimized extraction process with response surface design was reliable, which could be used for the extraction of total flavonoids from Cortex Lycii . It has strong hypoglycemic and antioxidant activities and has a good prospect for future utilization and development.
危险品化学品经营许可证（带存储）