The application of Cortex Mori (CM) in the treatment of diabetes mellitus (DM) has been extensively documented in traditional medicine. In recent years, the chemical composition of CM has been gradually unraveled, and its therapeutic mechanism in treating DM, diabetic nephropathy, diabetic cardiomyopathy, and other related conditions has been highlighted in successive reports. However, there is no systematic study on the treatment of DM based on the chemical composition of CM. This study was conducted to systematically explore the hypoglycemic activity mechanism of CM based on its chemical composition. The material basis of Cortex Mori extract (CME) was investigated through qualitative analyses based on liquid chromatography-mass spectrometry (LC-MS). The possible acting mechanism was simulated using network pharmacology and validated in streptozotocin (STZ) + high fat diet (HFD)-induced diabetic rats and glucosamine-induced IR-HepG2 model with the assistance of molecular docking techniques. A total of 39 compounds were identified in CME by the LC-MS-based qualitative analysis. In diabetic rats, it was demonstrated that CME significantly ameliorated insulin resistance, blood lipid levels, and liver injury. The network pharmacology analysis predicted five major targets, including AKT1, PI3K, FoxO1, Gsk-3β, and PPARγ. Additionally, three key compounds (resveratrol, protocatechuic acid, and kaempferol) were selected based on their predicted contributions. The experimental results revealed that CME, resveratrol, protocatechuic acid, and kaempferol could promote the expression of AKT1, PI3K, and PPARγ, while inhibiting the expression of FoxO1 and Gsk-3β. The molecular docking results indicated a strong binding affinity between resveratrol/kaempferol and their respective targets. CME contains a substantial amount of prenylated flavonoids, which may be the focal point of research on the efficacy of CM in the treatment of DM. Besides, CME is effective in controlling blood glucose and insulin resistance, improving lipid levels, and mitigating liver injury in patients with DM. Relevant mechanisms may be associated with the activation of the PI3K/Akt pathway, the inhibition of the expression of FoxO1 and Gsk-3β, and the enhancement of PPARγ activity. This study represents the first report on the role of CME in the treatment of DM through regulating PPARγ, FoxO1, and Gsk-3β.

Mulberry leaves contain polysaccharides, phenols, alkaloids, and other active ingredients which have medicinal and edible value. In this study, fermented mulberry leaf powder was prepared by solid-state fermentation using Pediococcus pentosaceus JC30. The effects of the fermentation on the phytochemical, flavor characteristics, phenolics, and antioxidant activity of mulberry leaves were studied. The results showed that the content of γ-aminobutyric acid in fermented mulberry leaf powder (FMLP) increased by 6.73-fold and the content of phytic acid decreased by 11.16%. Ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) analysis showed that the fermentation of Pediococcus pentosaceus JC30 altered the phenolic composition of mulberry leaves, increasing the total free phenolic content by 88.43%. In particular, the contents of free phenols such as leucocyanidin, myricetin, and quercetin increased significantly and were positively correlated with antioxidant capacity. The fermentation of Pediococcus pentosaceus JC30 significantly enhanced the scavenging ability of DPPH free radicals, hydroxyl radicals, and the total reducing ability of mulberry leaves. Gas chromatography ion mobility spectrometry (GC-IMS) analysis showed that FMLP has an intense fruity and floral aroma, while having less grassy and earthy odor. The fermentation improved the phytochemical, flavor, and nutritional value of mulberry leaves, which provides more possibilities for the development of mulberry leaf products outside the sericulture industry.

Rhodiola crenulate is the edible medicinal herbal medicine widely used for altitude sickness in China. Interestingly, our previous work has found that Rhodiola crenulate extract (RCE) could significantly improve the pathology associated with Dextran sulfate sodium (DSS)-induced colitis. Thus, the current research aims to reveal the pharmacodynamic material basis of RCE, as well as its mechanism against colitis. The chemical characterization of RCE was performed by UHPLC-HR-MS, through which a total of 88 constituents were identified. Meanwhile, our results also found 29 constituents absorbed into blood and 8 metabolized absorbable compounds. The decreased flavonoids prototype and the elevated sulfated products of phenols were observed under pathophysiological conditions of colitis. The metabolomics study revealed that colitis caused the alternation of fatty acid metabolism, steroid hormone biosynthesis and bile acid metabolism. Correspondingly, RCE could prevent colitis by improving fatty acid metabolism and secondary bile acid metabolism.