Na Guo,Yong-Peng Zou,Hong-Kun Li,Ping Kou,Zhi-Ming Liu,Yu-Jie Fu
Conventional approaches for extraction and enrichment of phytochemicals from plant matrix have many drawbacks such as high organic solvent consumption, low extraction yields, time-consuming and large labor for the enrichment process. In the present study, ultrasound-assisted deep eutectic solvents extraction (UAE-DESs) was developed for extraction and determination of the linarin from Chrysanthemum indicum L. flower (CIF). And a feasible strategy was performed to separate and recover the linarin from denatured DESs using AB-8 macroporous resins as adsorbents. Under the optimal extraction conditions, the maximum linarin extraction yield reached 14.23 mg/g with liquid–solid ratio 32 mL/g, extraction power 340 w, extraction time 32 min and deep eutectic solvent of choline chloride-ethylene glycol with the molar ratio 1:2 and water content 30% (v/v) as a extraction system, which was 1.21 times higher than 80% ethanol extraction. After macroporous resins enrichment, the recovery efficiency of linarin reached 81.55%. In addition, the DESs could be regenerated for extraction process, and macroporous resins could be further used for enrichment process with desired performance. This study provided an effective and convenient extraction and recovery method for linarin determination from CIF which was also applicable to other natural plants.
Due to various factors, there is still a lack of effective neuroprotective agents for ischemic stroke in clinical practice. Neuroinflammation and neuronal apoptosis mediated by endoplasmic reticulum stress are some of the important pathological mechanisms in ischemic stroke. Linarin has been reported to have anti-inflammation, antioxidant, and anti-apoptotic effects in myocardial ischemia, osteoarthritis, and kidney disease. Whether it exerts neuroprotective functions in ischemic stroke has not been investigated. The results showed that linarin could reduce the infarct volume in cerebral ischemia animal models, improve the neurological function scores and suppress the expression of inflammatory factors mediating the NF-κB. Meanwhile, it could protect the neurons from OGD/R-induced-apoptosis, which was related to the PERK-eIF2α pathway. Our results suggested linarin could inhibit neuronal inflammation and apoptosis induced by endoplasmic reticulum stress. Furthermore, the neuroprotective effect of linarin may be related to the inhibition of AKR1B1. Our study offers new insight into protecting against ischemia-reperfusion injury by linarin treatment in stroke.
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.
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