Dissection of the molecular targets and signaling pathways of Guzhi Zengsheng Zhitongwan based on the analysis of serum proteomics

Abstract

Background: Guzhi Zengsheng Zhitongwan (GZZSZTW) is an effective formula of traditional Chinese herbal medicine and has been widely applied in the treatment of joint diseases for many years. The aim of this study was to dissect the molecular targets and signaling pathways of Guzhi Zengsheng Zhitongwan based on the analysis of serum proteomics. Methods: The Chinese herbs of GZZSZTW were immersed in 5 l distilled water and boiled with reflux extraction method. The extract was filtered, concentrated and freeze-dried. The chemical profile of GZZSZTW extract was determined by high-performance lipid chromatography (HPLC). The 7-week old Sprague-Dawley (SD) rats in GZZSZTW groups were received oral administration at doses of 0.8, 1.05, and 1.3 g/kg per day and the rats in blank group were fed with drinking water. Serum samples were collected from the jugular veins. Primary chondrocyte viability was evaluated by CCK-8 assay. A full spectrum of the molecular targets and signaling pathways of GZZSZTW were investigated by isobaric tags for relative and absolute quantitation (iTRAQ) analysis and a systematic bioinformatics analysis accompanied with parallel reaction monitoring (PRM) and siRNA validation. Results: GZZSZTW regulated a series of functional proteins and signaling pathways responsible for cartilage development, growth and repair. Functional classification analysis indicated that these proteins were mainly involved in the process of cell surface dynamics. Pathway analysis mapped these proteins into several signalling pathways involved in chondrogenesis, chondrocyte proliferation and differentiation, and cartilage repair, including hippo signaling pathway, cGMP-PKG signaling pathway, cell cycle and calcium signaling pathway. Protein-protein interaction analysis and siRNA knockdown assay identified an interaction network consisting of TGFB1,

Deciphering the potential pharmaceutical mechanism of Guzhi Zengsheng Zhitongwan on rat bone and kidney based on the “kidney governing bone” theory

“…The filtrate was freeze-dried by a Heto PowerDry LL3000 Freeze Dryer (Thermo, USA) and stored at − 80°C. Quality control was carried out by a high-performance lipid chromatography (HPLC) using a 2695 liquid chromatography system (Waters, USA) as previously described [6].…”

Empowering Cartilage Restructuring with Biodegradable Magnesium Doped-Silicon Based-Nanoplatforms: Sustained Delivery and Enhanced Differentiation Potential

“…[13][14][15] Additionally, Ica has been reported to have anti-inflammatory effects, which can inhibit the production of inflammatory mediators and the activation of inflammatory signaling pathways in addition to treating chondrodysplasia by promoting chondrocyte proliferation and differentiation, thereby attenuating the adverse effects of the inflammatory response on chondrogenesis. [16][17][18] However, sustained administration or high doses of Ica may inhibit chondrocyte proliferation and potentially pose unnecessary biosafety risks to a certain extent. 19 Therefore, there is an urgent need to design biodegradable nano-drug carriers with favorable drug availability and controllable release for effective delivery of Ica and other therapeutic agents in the treatment of these disorders.…”