[Effects of Guben Zenggu Decoction on Bone Metabolism and Bone Microstructure in Ovariectomized Rats].

OBJECTIVE: To test the effects of Guben Zenggu Decoction on bone metabolism and bone microstructure in ovariectomized rats for the purpose of preventing and treating postmenopausal osteoporosis. METHODS: Osteoporosis rat models were established by ovariectomy. The model rats were randomly divided into control, estradiol valerate treatment, and Guben Zenggu Decoction treatment groups with high, medium and low dosages. After 12 weeks of treatments, 10 rats from each group were randomly selected for cardiac blood sampling after abdominal anesthesia. The serum levels of estradiol (E2), osteocalcin (BGP), carboxyterminal of type Ⅰ procollagen (PICP), collagen type Ⅰ pyridine crosslinking peptide (ICTP) and acid tartaric acid phosphatase-5b (TRAP-5b) were determined by ELISA. Bone histomorphometric analysis was performed on the right femoral specimen of rats using micro-CT imaging. RESULTS: The models rats had lower levels of E2, bone alkaline phosphatase (BALP) and relative bone volume fraction (BV/TV), trabecular thickness (Tb.Th), number of trabeculae (Tb.N) and connectivity density (Conn.D), and higher levels of BGP, ICTP, PICP, TRAP-5b and degree of trabecular separation (Tb.Sp), structural model index (SMI) than their normal counterparts (P < 0.05). Estradiol valerate and Guben Zenggu Decoction treatments increased the levels of E2, BALP, BV/TV, Tb.Th, Tb.N, and Conn.D significantly (P < 0.05). Higher doses of Guben Zenggu Decoction resulted in higher changes (P < 0.05). CONCLUSION: Guben Zenggu Decoction can improve bone metabolism and bone micro-structure in ovariectomized rats, thus playing a preventive and therapeutic role in postmenopausal osteoporosis.

[Effect of Guben Zenggu Decoction on Expressions of Serum BALP and CaM, CaMKâ ¡ mRNA in NEI Network of Ovariectomized Rats].

OBJECTIVE: To observe the effect of Guben Zenggu Decoction on the expressions of calmodulin (CaM) and calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) mRNA in the hypothalamus, pituitary, spleen, adrenal gland and femur in ovariectomized rats. To explore the mechanism of Guben Zenggu Decoction regulating and controlling osteoporosis through neuro-endocrine-immune (NEI) network. METHODS: The osteoporosis model was established by ovariectomy and randomly divided into model control group, Estradiol valerate group, Guben Zenggu Decoction high, medium and low concentration group. Selected the same age rats as the blank control group, after intervention, 10 rats were randomly selected at the time of 4th, 8th, 12th and 16th weeks from each group, After the success of the model and the successful intervention of Guben Zenggu Decoction for 4, 8, 12 and 16 weeks, the blood were taken from the heart, the serum bone alkaline phosphatase (BALP) levels was measured by the enzyme-linked immunosorbent assay (ELISA), and the thalamus, pituitary, spleen, adrenal, femoral tissue of rats were collected to detected the expressions of CaM and CaMKⅡ mRNA by using real-time fluorescence quantitative polymerase chain reaction (RT-PCR). RESULTS: At different time points (4 weeks, 8 weeks, 12 weeks, 16 weeks), the expressions of serum BALP and CaM and CaMKⅡ mRNA in NEI network in model group were significantly different from those in blank control group ( P<0.05). Compared with the model control group, serum BALP concentration and CaM mRNA expression in hypothalamus and pituitary tissue were significantly increased in estradiol valerate and Guben Zenggu Decoction groups ( P<0.05). However, the expression of CaM mRNA in adrenal gland, spleen and femur and the expression of CaMKⅡ mRNA in hypothalamus, pituitary, adrenal gland, spleen and femur were significantly decreased ( P<0.05); compared with estradiol valerate group, the effect of Guben Zenggu Decoction on the expressions of CaM mRNA and CaMKⅡ mRNA in femoral and adrenal tissues was significantly different ( P<0.05). CONCLUSION: Guben Zenggu Decoction can increase the serum concentration of BALP, regulate the expression of CaM mRNA and CaMKⅡ mRNA in hypothalamus, pituitary, adrenal gland, spleen and femur, thus play a role in prevention and treatment of osteoporosis by regulating NEI network.

[Effects of Huoxue Dingxuan Capsule Glare on Vertebral Artery Blood Flow,Plasma PAI and t-PA in CSA Rat Models.]

OBJECTIVES: To determine the effects of Huoxue Dingxuan Capsule on vertebral artery blood flow,plasma plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in rats with cervical spondylosis of vertebral artery type (CSA). METHODS: Ninety healthy male Wistar rats were equally and randomly divided into control,model and treatment groups.The rats in the model and treatment groups were subject to composite modeling manufacturing CSA.The treatment group was given six-week interventions with Huoxue Dingxuan capsule 4 weeks after the modeling.Vertebral artery blood flow,plasma PAI,and t-PA contents were detected before modeling,prior to the interventions,and post interventions. RESULTS: Before the interventions,the rats in the model and treatment groups had significantly lower blood flow of vertebral artery than the controls (P<0.05).The model rats also had increased serum PAI and t-PA contents (P<0.01).After the interventions,significantly higher vertebral blood flow was found in the treatment group compared with the controls (P<0.05).After the interventions,increased serum PAI and t-PA contents were observed in the rats in the model group (P<0.01);whereas,decreased serum PAI and t-PA contents were observed in the rats in the treatment group (P<0.01).The treatment group had lower levels of serum PAI and t-PA contents than the model group (P<0.01). CONCLUSIONS: Huoxue Dingxuan Capsule glare can improve the blood flow of vertebral artery and reduce serum PAI and t-PA contents.

Network Pharmacological Analysis and Animal Experimental Study on Osteoporosis Treatment with GuBen-ZengGu Granules.

Aim: We explored the molecular pathway and material basis of GuBen-ZengGu granules (GBZGG) in treating osteoporosis using network pharmacology and animal experiments. Methods: The effective active components and potential targets of GBZGG were obtained from the TCMSP database and BATMAN-TCM database. Disease-related genes were obtained from GeneCard, NCBI, and DisGeNET. Next, a protein interaction network was established using the STRING database, and core genes were screened using the MCODE module. Cytoscape 3.8.0 was used to construct the network of component-disease-pathway-target, and KEGG pathway enrichment analyses were performed using the clusterProfiler R package to predict the mechanism of GBZGG in treating osteoporosis. An osteoporosis rat model was established by ovarian excision (OVX), and the partial results of network pharmacology were experimentally verified. Results: Pharmacodynamic results showed that GBZGG increased bone mineral density (BMD) and significantly improved the indexes of femur microstructure in model rats. The network pharmacology results showed that quercetin, luteolin, stigmasterol, angelicin, kaempferol, bakuchiol, bakuchiol, 7-O-methylisomucronulatum, isorhamnetin, formononetin, and beta-sitosterol are the major components of GBZGG, with MAPK1, AKT1, JUN, HSP90AA1, RELA, MAPK14, ESR1, RXRA, FOS, MAPK8, NCOA1, MYC, and IL-6 as its core targets for treating osteoporosis. Biological effects could be exerted by regulating the signaling pathways of fluid shear stress and the signaling pathways of atherosclerosis, advanced glycation end products (AGE-RAGE) of diabetic complications, prostate cancer, interleukin (IL-17), tumor necrosis factor (TNF), hepatitis B, mitogen-activated protein kinase (MAPK), etc. The results of animal experiments showed that GBZGG could reduce the serum levels of IL-6 and TNF-α, increase the expression of bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor 2 (RUNX2) protein, and inhibit the activity of extracellular-regulated protein kinases (ERK1/2) and phosphorylation ERK1/2 (p-ERK1/2) protein. Conclusion: GBZGG reduces the expression of ERK1/2 and p-ERK1/2 proteins and mRNAs through the inhibitory effects on IL-6 and TNF-α and negatively regulates the MAPK/ERK signaling pathway. The osteoporosis model showed that it effectively improved the loss of bone mass and destruction of bone microstructure in rats and maintained a positive balance for bone metabolism.

Comparative clinical outcomes of different therapies for traumatic meniscal tears in adults: A protocol for systematic review and network meta-analysis.

BACKGROUND: Meniscus tears are usually classified as degenerative or traumatic tears according to their pathogenesis. At present, traumatic meniscal tears are generally believed to have high healing potential. In recent years, multiple treatments have been described for traumatic meniscal tears, such as the inside-out technique, outside-in technique, all-inside technique, biological augmentation of meniscal repair, meniscectomy, and non-surgical treatment. However, the functional recovery of the knee joint and healing of the meniscus after treatment are quite different from the results reported in the literature, which requires more reliable evidence-based medical findings. This study will evaluate evidence from multiple types of research comparing different therapies for traumatic meniscal tears in adults. METHODS: We will search the EMBASE, Cochrane Library (the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials [CENTRAL], Cochrane Methodology Register), PubMed, Web of Science (Science and Social Science Citation Index), China Knowledge Network, CBM, Wanfang data, and VIP electronic databases from their inception to August 10, 2021, with no language restrictions. We will also manually search Baidu and Google Scholar to identify randomized controlled studies, non-randomized controlled studies, and cohort studies on the treatment of traumatic meniscal tears. Two researchers will independently screen the literature, extract the data, and evaluate the quality of the studies. Software programs, including Microsoft Access, Excel, Stata (Version 15), WinBUGS (Version 1.4.3), and ADDIS (Version 1.16.8), were used to analyze and manipulate the data. RESULTS: In this study, the main outcomes were physical function and healing rate, based on the Western Ontario and McMaster Universities Osteoarthritis Index, Lysholm Knee Scoring Scale, Knee Injury and Osteoarthritis Outcome Score, Functional Recovery Scale, and clinical healing rate. The secondary indexes included total cost, cost-effectiveness ratio, incremental cost-effectiveness ratio, Tegner activity scale score, visual analogue scale, numerical rating scale, and meniscal tear complications. CONCLUSIONS: This systematic review will provide reliable evidence-based findings for the clinical application of different therapies for traumatic meniscal tears in adults.