Mechanism of Yougui Pills in the treatment of knee osteoarthritis based on network pharmacology and molecular docking / 西安交通大学学报(医学版)

【Objective】 To explore the mechanism of Yougui Pills in the treatment of knee osteoarthritis （KOA） based on network pharmacology and molecular docking. 【Methods】 The active components of Yougui Pills were obtained by searching TCMSP database. With the active component targets predicted by TCMSP， SwissTargetPrediction and TargetNet， we searched TCMIP， CTD， DisGeNET and GeneCards databases for KOA related targets. By crossing the two sets of targets， we obtained therapeutic targets of Yougui Pills for KOA. FDA-approved drugs for KOA and their targets were searched in the DrugBank database， and the drug-target network was constructed by using Cytoscape. Then the protein-protein interaction （PPI） network was constructed by using STRING database. After Go and KEGG enrichment analyses， the network of “traditional Chinese Medicine-active components-key targets-significant pathways-biological process” was constructed. 【Results】 A total of 132 active components were obtained from the nine herbal medicines of Yougui Pills， corresponding to 490 targets， of which 76 were potential therapeutic targets. Of them 13 were the same as the targets of 5 Western medicines for KOA. We screened out 18 key targets by the PPI network. Go enrichment analysis revealed 1281 biological processes， 60 molecular functions， and 17 cellular components， which were mainly related to inflammation， infection and oxidative stress. KEGG enrichment analysis showed that 50 pathways were significantly enriched， including IL-17 signaling pathway and TNF signaling pathway， whose functions were mainly involved in immune system， signal transduction， endocrine system， cell growth and death and other biological processes. 【Conclusion】 With multiple compounds acting on multiple molecular targets， Yougui Pills can treat KOA through molecular mechanisms including inhibiting inflammation， reducing oxidative stress， and promoting cartilage cell proliferation.

The therapeutic effects of Yougui pill on knee osteoarthritis and the expression of Wnt signal pathway related factors in rats / 中国应用生理学杂志

OBJECTIVES@#To observe the effects of Yougui pill (Traditional Chinese Medicine) on the related factors of Wnt signal pathway of rats with knee osteoarthritis (KOA), and explore its protective mechanism.@*METHODS@#Sixty SPF SD rats were randomly divided into the sham-operative group, model group, glucosamine sulfate group, high-dose, middle-dose, low-dose of Yougui pill treated group (=10). KOA model was established by modified Hulth method for six weeks. The rats in the high, middle and low-dose of Yougui pill group were treated with Yougui pills at the doses of 20,10 and 5 g/kg respectively by gastrogavage once a day for 8 weeks, while equal volume of normal saline was given to those in the sham and model control group and an equal volume of glucosamine sulfate (1.7 g/kg·d) was given to those in glucosamine sulfate group for 8 weeks. The knee joint was removed after the last dose of drug. The pathological changes of cartilaginous tissues were observed under a microscope. The mRNA levels of Dickkopf homolog 1(DKK1), Wnt induced secreted protein 1(WISP1), Wnt1, low density lipoprotein receptor related protein 5(LRP5) and beta -catenin in rats cartilaginous tissues were analyzed by using RT-PCR method, and the protein contents of DKK1, WISP1, Wnt1, LRP5 and beta-catenin in cartilaginous tissues were detected by Western blot.@*RESULTS@#Compared with the sham group, the articular cartilage was severely damaged, the Mankin score was increased significantly (<0. 05), the mRNA and protein expression levels of DKK1 in cartilaginous tissue were markedly decreased(<0.05), while those of WISP, Wnt1, LRP5 and beta-catenin were increased significantly in model group(<0.05). Compared with model group, the articular cartilage lesions was light (<0.05), the Mankin Score was decreased significantly(<0.05), and the mRNA and protein levels of DKK1 in cartilaginous tissue were increased(<0.05), while those of WISP, Wnt1, LRP5 and beta-catenin were decreased in Yougui pill high-dose group and glucosamine sulfate group (<0.05).@*CONCLUSIONS@#Yougui pill has protective effects on the KOA by inhibiting the expressions of WISP, Wnt1, LRP5, beta-catenin and increasing the expression of DKK1 cytokine in the Wnt signaling pathway.

Imolantation of Quadrate Muscle Thigh with Bone Flap Combined with internal Fixation for Infracaput Fracture of Collum Femoris in the Youth / 广州中医药大学学报

Infracaput fracture of collum femoris in the youth is usually caused by tremendous violenceand characterized by obvious translocation and high ratio of ischemic necmeis of femoral head. Artificialfemoral head replacement or hip replacement is not suitable for the youth. Twenty-eight cases of suchfracture were treated with implantation of quadrate muscle of thigh with bone flap combined with internalfixation by screw,and a follow-up Period of 8 ~ 36 months was carried on. The results showed that allcases resulted in a bony union and ischemic necrosis of femoral head did not occur.It is suggested thatthe opelation should be Performed as early as possible to restore the blood circulation of femoral head,and proper reduction and firm internal fixation guarantee the union of fracture,Quadrate muscle of thighwith bone flap has a rich blood supply and operation can be accomplished in the same incision of internalfixation,so that the injury is iess and the successful rate is high.

Effect of Yougui Pill on Cerebral Gene Chip of Mice with Kidney-yang Asthenia Induced by Excessive Physical and Sexual Activity / 中医杂志

Objective To study the functional mechanism of Yougui Pill(Right Restoring Pill)through its effect on cerebral gene of mice models with kidney-yang asthenia caused by excessive physical and sexual activity.Methods There were 10,15,10 male mice in the control,model and treatment groups respectively.The control and model groups were treated with 0.5ml permouse perday distilled water by gavage while the treatment group was given 0.5ml permouse perday suspension of Yougui Pill.In the model and treatment groups,the ratio of male and female was 1∶6,feeding in the same cage,and the males were swimming everyday for 30~40 minutes,4 weeks in succession,to induce the kidney-yang asthenia.The 36K mouse cerebral gene chips were used to measure the brain genes of mice of 3 groups.The intensity ratio of fluorescence signals ≥2 and ≤0.5 were used as the scale to screen out the remarkably different genes.Results In the model and control groups,totally 186 gene with different expressions were screened out,including the 150 up-regulated genes and 36 down-regulated genes.In the treatment and model groups,155 gene with different expressions were screened out,including the up-regulated 64 genes and 91 down-regulated genes.There were 32 genes up-regulated in the model and control groups but down-regulated in the treatment and model groups,mainly involving the inflammation perimmunity and neurotransmissions persignal transduction genes.There were 12 genes down-regulated in the model and control groups but up-regulated in the treatment and model group,mainly involving the hormone related genes of melanin and orphan nuclear receptor.Conclusion Yougui Pill may make the notably down-regulated genes of melanin markedly up-regulated in mice models of kidney-yang asthenia,improving the effect of hormone related orphan nuclear receptor and promoting the cellular proliferation.