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The current study aimed to explore the mechanism of Guizhi Shaoyao Zhimu Decoction in the treatment of gouty arthritis based on the combination of Vanquish Ultra High Performance Liquid Chromatography Q Exactive IV Pole-electrostatic field orbital trap high resolution mass spectrometer (UHPLC-Q-Orbitrap HRMS) and network pharmacology. Firstly, UHPLC-Q-Orbitrap HRMS was established and applied to separation and identification of the chemical components of GSZD. Then, using network pharmacology analysis to obtain the potential active components and candidate targets underlying the effect of GSZD on gouty arthritis (GA). Through targeted and untargeted analysis, a total of 79 components, including 3 chromones, 26 flavonoids, 10 alkaloids, 10 phenolic acids, 7 nucleosides and nucleobases, and 23 other components, were characterized from GSZD. 11 compounds were considered to potentially key active compounds against GA which may be via interacting with multiple inflammatory factors and multiple inflammatory pathways.

Background: Rheumatoid arthritis (RA) is a complex chronic inflammatory disease that is associated with the aberrant activation of fibroblast-like synoviocytes (FLS). The extract of Cinnamomi ramulus has been reported to exert alleviates pain, anti-tumor and anti-inflammatory effects. The present study was designed to investigate the effects of Cinnamomi ramulus on RA and explore the underlying mechanisms. Material/methods: TNF-α induced human synoviocyte MH7A cells was performed to evaluate the anti-proliferative and anti-migration effect of Cinnamomi ramulus. The anti-proliferative effect of Cinnamomi ramulus was determined by CCK-8 assay and colony formation assay. Apoptosis was measured by AnnexinV FITC/PI staining and flow cytometry. Cell cycle was evaluated by flow cytometry. The expressions of mitochondrial apoptosis and cell cycle-related molecules, including Bcl-2, Bax, C-Caspase-3, CDC2 and Cycylin B1 were determined by Western blotting. Furthermore, the migration and invasion abilities of MH7A cells were determined using scratch wound healing assay and transwell assay. mRNA expressions of (MMP)-1, -2, & -3, P53, P21 and Cyclin D were determined using qRT-PCR analysis. For qualitative analysis on its chemical components, an ultra-high performance liquid chromatography (UPLC) coupled with Q-Exactive MS (QE-MS) was established for rapid separation and structural identification of the constituents in Cinnamomi ramulus. The further computationally study on the relationships between the 9 compounds and the potential target proteins of RA were carried out with molecular docking strategy. Results: Our data demonstrate that Cinnamomi ramulus inhibited proliferation of MH7A cells, induced cell apoptosis, blocked the cell cycle in the G2/M phase and regulated the protein expression of Bcl-2, Bax, C-Caspase-3, CDCD2 and Cyclin B1. Moreover, Cinnamomi ramulus was proven to significantly inhabited migration and invasion of MH7A cells through inhibition of levels of matrix metalloproteinase (MMP)-1, -2, & -3.Cinnamomi ramulus reduced mRNA levels of CDK4 whereas increased the expression of P53, P21 and CyclinD, implying its regulation effects on apoptosis and cell cycle distribution in MH7A cells. The chromatographic profiling of the extract by UPLC-QE-MS/MS analysis showed 9 compounds are the main components. And the molecular docking strategy results showed that the compounds in Cinnamomi ramulus have good affinity with protein crystal, and benzyl cinnamate may be the main active component of Cinnamomi ramulus to induce cell apoptosis and cycle resistance. Conclusions: Cinnamomi ramulus exhibits anti-proliferative and anti-migration effects on MH7A rheumatoid arthritis-derived fibroblast-like synoviocytes through induction of apoptosis & cell arrest and suppression of matrix metalloproteinase.

Sinomenine, an important isoquinoline from Sinomenium acutum (Menispermaceae), is currently considered as a reliable drug for treating various malignant cancers including breast cancer, colon cancer, lung cancer, liver cancer, gastric cancer, osteosarcoma cervical cancer, and esophageal cancer. The pharmacological mechanisms are probably related to induction of apoptosis and cell cycle arrest. This paper was aimed at reviewing the anticancer potential of sinomenine, which is expected to be beneficial in developing this compound as a candidate drug for cancer therapy. Keywords: Sinomenine, Anticancer, Sinomenium acutum, Traditional Chinese Medicine

We have performed an analysis of a family with kidney-yang deficiency syndrome (KDS) in order to determine the structural genomic variations through a novel approach designated as “copy number variants” (CNVs). Twelve KDS subjects and three healthy spouses from this family were included in this study. Genomic DNA samples were genotyped utilizing an Affymetrix 100 K single nucleotide polymorphism array, and CNVs were identified by Copy Number Algorithm (CNAT4.0, Affymetrix). Our results demonstrate that 447 deleted and 476 duplicated CNVs are shared among KDS subjects within the family. The homologus ratio of deleted CNVs was as high as 99.78%. One-copy-duplicated CNVs display mid-range homology. For two copies of duplicated CNVs (CNV4), a markedly heterologous ratio was observed. Therefore, with the important exception of CNV4, our data shows that CNVs shared among KDS subjects display typical Mendelian inheritance. A total of 113 genes with established functions were identified from the CNV flanks; significantly enriched genes surrounding CNVs may contribute to certain adaptive benefit. These genes could be classified into categories including: binding and transporter, cell cycle, signal transduction, biogenesis, nerve development, metabolism regulation and immune response. They can also be included into three pathways, that is, signal transduction, metabolic processes and immunological networks. Particularly, the results reported here are consistent with the extensive impairments observed in KDS patients, involving the mass-energy-information-carrying network. In conclusion, this article provides the first set of CNVs from KDS patients that will facilitate our further understanding of the genetic basis of KDS and will allow novel strategies for a rational therapy of this disease.