Mechanism and application in tissue engineering of the active ingredient of Drynariae Rhizoma promoting bone defect repair / 中国药房

Bone defect has always been a major clinical challenge because of its great difficulty and long period of treatment. Drynariae Rhizoma is a commonly used medicine in osteology and traumatology of traditional Chinese medicine， and its active ingredients（mainly flavonoids） facilitate osteoblast differentiation of bone marrow mesenchymal stem cells， osteoclast proliferation， vascular-osteogenic coupling， and inhibit osteoclast activity to promote bone mineralization， and repair and reconstruction of bone defect. As a good substitute for bone regeneration drugs， the active constituents of Drynariae Rhizoma can be loaded on scaffold materials of tissue engineering， which greatly improves the bioavailability of the drug. Meanwhile， the sustained-release microspheres also solve some problems such as sudden drug release from the scaffolds， and the composite scaffolds with active ingredient of Drynariae Rhizoma prepared by them have good ossification activity and osteoinduction， with precise bone repair effects， which meet the diverse performance requirements of bone grafts and have a promising clinical application prospect.

Total flavonoids of Drynariae Rhizoma regulates ER-p38 MAPK signaling pathway to improve scopolamine-induced learning and memory impairments in model mice / 中国中药杂志

This study intended to explore the effect and mechanism of total flavonoids of Drynariae Rhizoma in improving scopola-mine-induced learning and memory impairments in model mice. Ninety four-month-old Kunming(KM) mice were randomly divided into six groups. The ones in the model group and blank group were treated with intragastric administration of normal saline, while those in the medication groups separately received the total flavonoids of Drynariae Rhizoma, Kangnaoshuai Capsules, donepezil, as well as total flavonoids of Rhizoma Drynariae plus estrogen receptor(ER) blocker by gavage. The mouse model of learning and memory impairments was established via intraperitoneal injection of scopolamine. Following the measurement of mouse learning and memory abilities in Morris water maze test, the hippocampal ERβ expression was detected by immunohistochemistry, and the expression levels of ERβ and phosphorylated p38(p-p38) in the hippocampus and B-cell lymphoma 2(Bcl-2), Bcl-2-associated death promoter(Bad), and cysteinyl aspartate-specific protease-3(caspase-3) in the apoptotic system were assayed by Western blot. The contents of malondia-ldehyde(MDA), superoxide dismutase(SOD), and nitric oxide(NO) in the hippocampus were then determined using corresponding kits. Compared with the control group, the model group exhibited significantly prolonged incubation period, reduced frequency of cros-sing the platform, shortened residence time in the target quadrant, lowered ERβ, Bcl-2 and SOD activity in the hippocampus, and increased p-p38/p38, Bad, caspase-3, MDA, and NO. Compared with the model group, the total flavonoids of Rhizoma Drynariae increased the expression of ERβ and SOD in the hippocampus, down-regulated the expression of neuronal pro-apoptotic proteins, up-re-gulated the expression of anti-apoptotic proteins, and reduced p-p38/p38, MDA, and NO. The effects of total flavonoids of Drynariae Rhizoma on the above indexes were reversed by ER blocker. It has been proved that the total flavonoids of Drynariae Rhizoma obviously alleviate scopolamine-induced learning and memory impairments in mice, which may be achieved by regulating the neuronal apoptotic system and oxidative stress via the ER-p38 mitogen-activated protein kinase(ER-p38 MAPK) signaling pathway.

Research progress on chemical compositions and pharmacological action of Drynariae Rhizoma / 中国中药杂志

Drynariae Rhizoma is warm in nature and bitter in taste, mainly acting on liver and kidney systems. It is a common Chinese herbal medicine for the treatment of fracture and bone injury. The chemical compositions of Drynariae Rhizoma mainly include flavonoids, triterpenoids, phenylpropanoids and lignans. At present, modern pharmacological and clinical studies have shown that Drynariae Rhizoma has the effects of anti osteoporosis, promoting fracture healing, kidney protection, anti-inflammatory, promoting tooth growth, preventing and treating aminoglycoside ototoxicity and lowering blood lipid. In addition, the toxicity evaluation experiment of Drynariae Rhizoma has also shown that it has no obvious toxic and side effects. Naringin is a kind of dihydroflavone in Drynariae Rhizoma. Many studies have shown that naringin and other total flavonoids play an important role in anti-osteoporosis, promoting fracture healing, anti-inflammation, promoting tooth growth and lowering blood lipid. In this study, the research progresses on chemical consti-tuents and pharmacological activities of Drynariae Rhizoma in recent years were reviewed, and some mechanisms of action were summarized, to provide references for the further research and development of Drynariae Rhizoma.

Effective Components and Mechanisms of Drynariae Rhizoma Anti-osteoporosis Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To predict the target of active components of Drynariae Rhizoma by the network pharmacology, map related targets of osteoporosis (OP), and analyze key nodes of interaction topologically, so as to comprehensively explore the pharmacological mechanism of anti-op of osteoclasts. Method:Firstly, the main active components of Drynariae Rhizoma were screened out from TCMSP based on the pharmacokinetic characteristics, and the related targets were predicted by Pubchem and Swiss Target Prediction database according to the Two-dimensional/Three-dimensional(2D/3D)structural similarity. Then, through Online Mendelian Inheritance in Man (OMIM) and Pubmed text, known OP therapeutic targets were mined, based on putative targets, String database was imported to build Drynariae Rhizoma treatment target OP interaction network diagram. With the help of CytoNCA software, the interaction key nodes were topologically identified according to relevant node parameters, and then imported into String database to build the protein interaction network graph. Finally, biological functions and metabolic pathways of key nodes were analyzed through DAVID database. Result:Sixteen active components of Drynariae Rhizoma were screened out, and 118 related targets were predicted according to the target prediction technique. Totally 316 known therapeutic targets for OP were retrieved. The protein interaction network was constructed according to the String network database. A total of 97 key nodes were screened via CytoNCA topology. The enrichment analysis showed that Drynariae Rhizoma may play an anti-osteoporosis role by regulating stem cells, osteoblasts, osteoclasts and immune cells through multiple signaling pathways in aspects of proliferation, differentiation, immunity and oxidative stress. Conclusion:Studies based on network pharmacology have shown that Drynariae Rhizoma may play an anti-op role through direct or indirect targets and multiple major signaling pathways and affect the proliferation and differentiation of multiple types of cells, in order to provid a scientific basis for explaining the material basis and mechanism of Drynariae Rhizoma's anti-osteoporosis effect.

Investigation of the Mechanism of Osteoporosis Treated by Drynariae rhizoma Based on Network Pharmacology / 中国药房

OBJECTIVE： To investigate the mechanism of Drynariae rhizoma in the treatment of osteoporosis （OP）. METHODS： The active compounds and targets of D. rhizoma were obtained by using Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM database）. The targets of relevant compounds were also obtained by GeneCards database， and targets of D. rhizoma were obtained by the combination of the two. The disease targets corresponding to OP were obtained by using TTD， DrugBank， OMIM， GAD， PharmGKB and CTD database. The D. rhizoma-OP disease intersection targets were obtained after intersecting with the target of D. rhizoma. PPI network was constructed by STRING online database， analyzed by using Cytoscape 3.6.1 software to obtain key targets and showed by network visualization. Gene ontology（GO） analysis of drug-disease intersection target were conducted by DAVID online tools. KEGG pathway enrichment analysis was conducted by KOBAS online tools to screen the significant enrichment pathway （P＜0.05）. The key genes were screened by MCC algorithm. RESULTS： There were 7 active compounds of D. rhizoma 136 intersection targets of D. rhizoma-OP disease. GO analysis results showed that the biological function of intersection target mainly included chemical reaction， steroid metabolic process as well as cellular response to chemical stimulus and so on； cell composition mainly included extracellular space， extracellular area and cytoplasm；molecular functions included heme binding， tetrapyrrole binding and monooxygenase activity， etc. KEGG pathway enrichment showed that above targets were mainly related to bone metabolism， endocrinology， inflammation， tumor， apoptosis， etc. Thirty key genes （such as ALB， AKT1， JUN， etc.， P≤1.96×10－9） were screened by MCC algorithm. CONCLUSIONS： The mechanism of action of D. rhizoma in the treatment of OP is in multi-target and multi-system manner. In addition to influencing the related pathways of bone metabolism， it can also affect various metabolic pathways in vivo.

Network pharmacology study on Drynariae Rhizoma in treatment of osteoarthritis / 中草药

Objective: To investigate the potential molecular mechanism of Drynariae Rhizoma in the treatment of osteoarthritis based on network pharmacology and bioinformatics. Methods: The potential active constituents and targets of Drynariae Rhizoma were screened and predicted through the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). Using TTD and four other osteoarthritis related disease databases, combining the topological analysis, the specific target of Drynariae Rhizoma in the treatment of osteoarthritis was filtered. And the further possible molecular mechanism of Drynariae Rhizoma was analyzed through ClueGo method. Results: Seventy-one corresponding compounds of Drynariae Rhizoma were retrieved from TCMSP. According to the values of oral bioavailability (OB) and drug likeness (DL), 18 possible bioactive components were screened out, and 92 potential targets were obtained by using the related target prediction technique. A total of 168 known targets closely related to the development of osteoarthritis were retrieved from the disease-related databases. A total of 99 key genes were screened out through network topological analysis. The ClueGo analysis showed that the action mode of Drynariae Rhizoma in treating osteoarthritis was mainly working on 31 signaling pathways related to cell cycle, inflammation, infection and cancer etc. Conclusion: Drynariae Rhizoma has the characteristics of multisystem, multiple targets, and multicomponent in the treatment of osteoarthritis. Through analysis, the possible mechanism includes not only directly acting on proliferation, apoptosis, differentiation of cells related to bone reconstruction and regulation of the balance of bone metabolism, but also affecting and interfering the bone and cartilage microenvironment through regulating immunity, inflammation, and other systems, which is consistent with the current mechanism of osteoarthritis treatment.

Study on mechanism of Drynariae Rhizoma in treating osteoporosis with integrative pharmacology perspective / 中国中药杂志

Drynariae Rhizoma has great significance in the clinical practice of osteoporosis treatment. Based on the perspective of integrative pharmacology, the study explored the mechanism of action of Drynariae Rhizoma in the treatment of osteoporosis. Six active components in Drynariae Rhizoma were obtained, mainly including glycosides and sterols. Taking the median of 2 times of "node connectivity" as the card value, the core node of the Chinese medicine target disease gene interaction network was selected. Based on this, three topological structural eigenvalues, such as "node connectivity" "node tightness" and "node connectivity" were calculated, thereby screening out four core targets of Drynariae Rhizoma treatment for osteoporosis, including thyroid parathyroid hormone 1 receptor (PTH1R), parathyroid hormone 2 receptor (PTH2R), calcitonin receptor gene (CALCR), and SPTBN1 gene (SPTBN1). Based on the gene ontology database GO and KEGG pathway database, the molecular function, intracellular localization, and biological reactions and pathways of proteins encoded by drug target genes were determined. Combined with enrichment calculation, it is predicted that osteoporosis may play a role in biosynthetic processes, such as circulatory system, nervous system, energy metabolism, prolactin signal pathway, GnRH signaling pathway, neurotrophic factor signaling pathway and other pathway. The conclusion of this study is certain with the existing research results, and the new target and new pathway could also be used as a theoretical basis for the further verification of osteoporosis.

Influence of superfine grinding on physicochemical properties of Drynariae Rhizoma / 中草药

Objective: Comparing the powder characteristics and dissolution rate between common powder and micropowder of Drynariae Rhizoma to provide experimental evidence for the micropowder application and the control of paticle size. Methods: Particle size and distribution, hygroscopicity, and powder morphology of the powder characteristics and dissolution behavior were used to evaluate the impact of particle size on powder characteristics and dissolution of Drynariae Rhizoma powders. Results: There were significant differences between common powder and micropowder in powder characteristics and dissolution rate. In addition to the micropowder III, the dissolution rates and the concentrations of naringin in micropowders were higher than those in the common powder of Drynariae Rhizoma. Conclusion: An appropriate degree of micronization is helpful for the dissolution of the active components in Drynariae Rhizoma and the application of micronization technology to Drynariae Rhizoma is feasible. The particle diameter (D90) of the micropowders should be controlled in 61.4-23.5 μm.