ABSTRACT
Aim To predict and validate the mechanism of wenshen xuanbi tang(WSXBT) in treatment of osteoporosis (OP) based on network pharmacology, molecular docking techniques and in vivo experimental techniques. Methods Network pharmacology was used to screen the key ingredients and core targets of WSXBT for the treatment of osteoporosis. Metascape database was used for gene ontology (GO) biological process enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis of core targets. AutoDockTools 1. 5. 7 software was applied in molecular docking to simulate the binding activity of key active ingredients to core targets. To study the efficacy of WSXBT on rats with osteoporosis and to verify the related targets and pathways, rat models of osteoporosis were established by excising the bilateral ovaries of rats. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum OPG, PINP and RANKL content. Biomechanical tester was applied to test the biomechanics of rat femurs. Micro-CT was applied to detect the femoral bone density. Then, Western blot was employed to measure the protein expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt). Results A total of 156 active ingredients of WSXBT were screened, involving 229 potential targets, 23 core targets and 145 signaling pathways. The molecular docking results showed that five key ingredients, including quercetin, kaempferol, naringenin, isobavachin and licochalcone a, possessed good binding ability to the core targets of PIK3R1 and AKT1. The results of in vivo experiments showed that WSXBT could significantly increase bone density, improve bone tissue microstructure, enhance femur biomechanics and increase PINP expression and OPG/RANKL ratio in rats with osteoporosis. Results of WB showed that WSXBT significantly increased p-PI3K/PI3K and p-Akt/Akt ratios. Conclusions WSXBT could improve bone mineral density in postmenopausal osteoporotic rats through PI3K/ Akt signaling pathway and increasing OPG/RANKL ratio.
ABSTRACT
BACKGROUND: Osteonecrosis of femoral head is a difficult disease in orthopedics, and head-preserving surgery is adopted in the early stage, especially bone grafting, in which autogenous bone and allogenic bone are commonly used as bone graft materials. However, autogenous bone transplantation is traumatic and has limited source of donor bone. Although there are abundant sources of allogeneic bone, there are serious immunologic rejection and absorption risks. With the development of tissue engineering technology, osteonecrosis of femoral head treatment has entered a new mode. OBJECTIVE: To review the research status and new progress of tissue engineering technology in the treatment of osteonecrosis of femoral head. METHODS: PubMed database and CNKI database from 2000 to 2019 were searched by the first author. The key words were “osteonecrosis of femoral head, tissue engineering technology, mesenchymal stem cells, biomaterials, growth factor, bone grafting, hip preserving” in English and Chinese. Meta-analysis and repetitive articles were excluded. A total of 53 literatures related to tissue engineering techniques for the treatment of osteonecrosis of femoral head were included. RESULTS AND CONCLUSION: With the development of cytology and material science, great progress has been made in the treatment of osteonecrosis of femoral head with tissue engineering technology. It includes different kinds of gene-modified mesenchymal stem cells for repairing osteonecrosis, 3D printing and nanotechnology for scaffold materials, and the relationship between the expression of growth factor and osteonecrosis of femoral head. The ideal scaffold complex should be close to the biological characteristics of the organism itself. It can provide support for the necrotic area through effective biomechanical properties, thus reducing the pressure of necrotic area, promoting capillary repair and regeneration, and differentiation and proliferation of osteoblasts combined with cytokines, so as to complete the regeneration of new bone in necrotic area. However, most of these studies are still in the animal experimental stage. With the rapid development of nanotechnology, clinical medicine and tissue engineering, the full performance artificial manufacturing of bionic bone graft materials will be expected to be born, which will bring good news to hip patients.
ABSTRACT
Cinnamomi Ramulus and Cinnamomi Cortex are widely used to treat paralysis in traditional Chinese medicine (TCM). There are numerous and complicated relative records in ancient literatures. Doctors often use Cinnamomi Ramulus to dispel wind and cold, remove blood stasis and combine with warm-natured and heat-natured herbs to treat excess paralysis and early-stage paralysis. And Cinnamorni Cortex is used to warm and invigorate kidney Yang and combine with warm-benefiting herbs to treat deficiency paralysis and chronicle paralysis. However, modern pharmaceutical studies reported that their active substances are almost the same. The active substances in Cinnamomi Cortex are more than those in Cinnamomi Ramulus. The mechanisms of treating paralysis include:suppressing inflammation and regulating immunity by down-regulating nuclear factors(NF)-κB, mitogen activated protein kinase(MAPK), Janus kinase-signal transducers/activators of transcription(JAK/STAT) signaling pathways, regulating cell proliferation by inhibiting the proliferation of fibroblasts, osteoclasts and bone marrow mesenchymal stem cells and promoting the proliferation of osteoblast, resisting oxidation by scavenging oxygen free radicals, regulating pain by mediating TRPA1 and TRPV1,and enhancing substance metabolism and losing weight by regulating the secretion of intestinal hormones (Ghrelin, GLP-1) and improving insulin resistance. The main active ingredient Cinnamaldehyde is unstable in vivo and easily oxidized to cinnamic acid. The toxicity of the two medicines and their components are relatively low. This paper reviews and analyses relative records in ancient literatures, traditional Chinese medicine cognition of their effects in treating paralysis, the achievements and problems of chemical,pharmacological,pharmacokinetic and toxicological researches in recent years, with the aim to provide theoretical basis for further research and application.