UPLC-Q-TOF/MS Based Plasma Metabolomics for Identification of Paeonol’s Metabolic Target in Endometriosis

Abstract

Endometriosis is a common gynecological illness in women of reproductive age that significantly decreases life quality and fertility. Paeonol has been shown to play an important part in endometriosis treatments. Understanding the mechanism is critical for treating endometriosis. In this study, autologous transplantation combined with a 28 day ice water bath was used to create a rat model of endometriosis with cold clotting and blood stagnation. The levels of estradiol and progesterone in plasma were detected by ELISA, and the pathological changes of ectopic endometrial tissue were examined by H&E staining, which proved the efficacy of paeonol. For metabolomic analysis of plasma samples, UPLC-Q/TOF-MS was combined with multivariate statistical analysis to identify the influence of paeonol on small molecule metabolites relevant to endometriosis. Finally, the key targets were screened using a combination of network pharmacology and molecular docking approaches. The results showed that the pathological indexes of rats were improved and returned to normal levels after treatment with paeonol, which was the basis for confirming the efficacy of paeonol. Metabolomics results identified 13 potential biomarkers, and paeonol callbacks 7 of them, involving six metabolic pathways. Finally, four key genes were found for paeonol therapy of endometriosis, and the results of molecular docking revealed a significant interaction between paeonol and the four key genes. This study was successful in establishing a rat model of endometriosis with cold coagulation and blood stagnation. GCH1, RPL8, PKLR, and MAOA were the key targets of paeonol in the treatment of endometriosis. It is also demonstrated that metabolomic techniques give the potential and environment for comprehensively understanding drug onset processes.

Design, Synthesis, Docking Studies and Molecular Dynamics Simulation of New 1,3,5‐Triazine Derivatives as Anticancer Agents Selectively Targeting Pancreatic Adenocarcinoma (Capan‐1)

“…[5][6][7][8][9][10][11][12] The 1,3,5-triazine ring has proven to be a successful framework for developing novel anticancer agents. [13] Several 2,4,6-trisubstiuted 1,3,5-triazine derivatives have demonstrated remarkable antitumor activities [14][15][16][17][18][19][20][21][22][23][24][25][26] and serve as templates for several of clinically used drugs and drug candidates, e. g., tretamine (Figure 1, 1) [27] is a drug used in chemotherapy, hexamethylmelamine (altretamine, HMM) (Figure 1, 2) and its hydroxylated analogue are clinically utilized for treatment of epithelial ovarian carcinoma. [28] A recently developed metformin derivative (Figure 1, 3) has been documented for its capability to inhibit the growth and metastasis of triplenegative breast cancer cells.…”

Graphene-derived composites: a new Frontier in thermoelectric energy conversion

“…[15][16][17] Over the past decade, significant developments have been made in organic thermoelectric (OTE) materials with remarkable thermoelectric performance. 18,19 The OTE materials hold promise for various applications because of their unique properties, such as flexibility, cost-effectiveness, environmental friendliness, and tunable characteristics. 20,21 Because of flexibility and lightweightness, OTE materials are often suitable for wearable and flexible electronics and are likely to contribute significantly to the development of energy-efficient technologies and sustainable electronic devices.…”