A new strategy for choosing “Q-markers” via network pharmacology,application to the quality control of a Chinese medical preparation

Due to its chemical complexity, proper quality control for a Chinese medical preparation (CMP) has been a great challenge. Choosing the appropriate quality markers (Q-markers) for quality control of CMP is an important work. Best of all, the chosen Q-markers are the main chemical compounds from the herbals as well as the active constituents of this CMP. Only in this way the established quality control system can really achieve the purpose of controlling the quality of CMP and ensuring the safely and effectively use of CMP. To achieve the purpose, network pharmacology combined with the contents of chemical compounds in the CMP has been used in this research. We took an anti-arrhythmic CMP, Shenxian-Shengmai oral liquid (SSOL), as an example. Firstly, UPLC-QTOF-MS/MS method was used to analyze the main components of SSOL. A total of 64 compounds were unambiguously or tentatively identified and 32 of them were further validated by reference compounds. Secondly, the network was constructed based on the identified compounds to predict the effective compounds related to cardiac arrhythmias. Based on the existing database and the operation method of topology, a method of double network analysis (DNAA) was proposed, from which 10 important targets in the pathway of arrhythmia were screened out, and 26 compounds had good antiarrhythmic activity. Based on the prediction results of network pharmacology along with the contents of the compounds in this CMP, ten representative compounds were chosen as the Q-markers for the quality control of SSOL. We find that five of these ten compounds, including danshensu, rosmarinic acid, salvianolic acid A, epimedin A and icariin, have antiarrhythmic activity. Then, the UPLC-DAD method was established as the control method for SSOL.     

Chitosan-based zinc oxide nanoparticle for enhanced anticancer effect in cervical cancer: A physicochemical and biological perspective

In this study, chitosan-assembled zinc oxide nanoparticle (CZNP) was successfully prepared for evaluated for its anticancer efficacy against cervical cancer cells. The CZNP particles were nanosized and spherical in shape. The zinc oxide nanoparticle (ZNP) and CZNP showed significant cytotoxicity in cervical cancer cells in a concentration-dependent manner. Results showed that the enhanced cytotoxicity was mainly attributed to the reactive oxygen species (ROS) generation in the cancer cells. The apoptosis assay further revealed that apoptosis was the main reason behind the cell killing effect of the zinc oxide nanoparticles. The apoptosis was further confirmed by the nuclear chromatin assay. Live dead assay showed increased red fluorescent cell for CZNP treated cancer cells. Overall, metal oxide present in nanoparticulate dimensions will be advantageous in imparting the cytotoxicity to cervical cancer cell.     

Two new secoiridoid glucosides and a new lignan from the roots of <Emphasis Type="Italic">Ilex pubescens</Emphasis>

Two new secoiridoid glucosides, ilexpublignoside (1), pubzenoside (2), and a new lignan, ilexlignan B (3), along with seven known compounds (4–10) were isolated from the roots of Ilex pubescens for the first time. Their chemical structures were elucidated on the basis of extensive spectroscopic methods, including IR, UV, HR-ESI–MS, CD, NMR experiments, as well as comparison with the reported data.     

Protective effect of MOTILIPERM in varicocele-induced oxidative injury in rat testis by activating phosphorylated inositol requiring kinase 1α (p-IRE1α) and phosphorylated c-Jun N-terminal kinase (p-JNK) pathways

Context: MOTILIPERM was prepared as a mixture of extracts of three medicinal herbs [roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliaceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae)].

Objective: To investigate the role of reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress in a rat model of varicocele and the therapeutic efficacy of MOTILIPERM in this model.

Materials and methods: Sixty male rats were divided into five experimental groups: a normal control group (CTR?+?vehicle), a control group administered MOTILIPERM 200?mg/kg (CTR?+?M 200), a varicocele-induced control group (VC?+?vehicle) and two varicocele-induced groups administered MOTILIPERM 100 (VC?+?M 100) or 200 (VC?+?M 200) mg/kg for 4 weeks. Testis weights were recorded and serums were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathology, analyses of ER response protein expression levels and oxidative stress were assessed by measuring ROS, reactive nitrogen species (RNS), malondialdehyde (MDA) level and ratios of total glutathione (GSH)/oxidized GSH (GSSG).

Results: MOTILIPERM treatment of varicocele-induced groups significantly increased left testis weight, testosterone level, sperm motility, count and spermatogenic cell density. ER-response protein expression levels were dose-dependently decreased in VC?+?M 200 group compared with VC?+?vehicle group. MOTILIPERM treatment also decreased MDA and ROS/RNS level but increased GSH/GSSG ratio.

Discussion and conclusions: This study suggests that ROS-related ER stress may play a major role in varicocele-induced infertility and MOTILIPERM, a novel compound targeting ROS-based ER stress, may be therapeutically useful in treatment of varicocele, or as a supplement for the treatment of infertility.