Guidelines for the Diagnosis and Treatment of Rotator Cuff Tear with Integrated Traditional Chinese and Western Medicine.

Rotator cuff tear is one of the common diseases among middle-aged and elderly people, which has a great impact on patients' physical and mental health and quality of life. The integrative medicine based on traditional Chinese medicine has certain characteristics and advantages in the diagnosis and treatment of Rotator cuff tear. Chinese medicine, which mainly focus on plant-based natural products, has a relatively stable and reliable curative effect. It is of great significance to formulate the combined diagnosis and treatment plan for Rotator cuff tear based on evidence-based medicine, which can help to make the clinical diagnosis and treatment techniques of Chinese and Western medicine more scientific and standardized, and achieve better therapeutic effects. This guideline standardizes the diagnosis and treatment process of Rotator cuff tear from the aspects of range, terminology and definition, diagnosis, TCM syndrome differentiation, treatment, functional exercise, prevention and care, etc. It can better provide clinicians with diagnosis and treatment strategies and suggestions. This guideline adapts well to clinical practice and is both safe and effective.

Efficacy and safety of curcumin therapy for knee osteoarthritis: A Bayesian network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a polyphenolic compound extracted from turmeric (Curcuma longa L.), is widely used in traditional Chinese medicine to treat osteoarthritis and rheumatoid arthritis. Clinical and experimental studies show that curcuminoid formulations have considerable clinical application value in the treatment of knee osteoarthritis (KOA). AIM OF THE STUDY: To evaluate the efficacy and safety of curcumin, both alone and in combination with other drugs, in KOA treatment through a Bayesian network meta-analysis (NMA). METHODS: We searched PubMed, Embase and Cochrane Library for randomized controlled trials of curcumin for KOA treatment. The time range of the search was from the establishment of each database to April 26, 2023. The NMAs of outcome indicators were all performed using a random-effects model. NMAs were calculated and graphed in R using MetaInsight and Stata 140 software. Measurement data were represented by the mean difference (MD), while count data were represented by the odds ratio (OR); the 95% confidence interval (CI) of each effect size was also calculated. RESULTS: This study included 23 studies from 7 countries, including 2175 KOA patients and 6 interventions. The NMA results showed that compared with placebo, curcumin significantly reduced the visual analogue scale pain score (MD = -1.63, 95% CI: -2.91 to -0.45) and total WOMAC score (MD = -18.85, 95% CI: -29.53 to -8.76). Compared with placebo, curcumin (OR = 0.17, 95% CI: 0.08 to 0.36), curcumin + NSAIDs (OR = 0.01, 95% CI: 0.00 to 0.13) and NSAIDs (OR = 0.11, 95% CI: 0.02 to 0.47) reduced the use of rescue medication. Compared with NSAIDs, curcumin (OR = 0.51, 95% CI: 0.25 to 0.94) and curcumin + NSAIDs (OR = 0.23, 95% CI: 0.06 to 0.9) had a reduced incidence of adverse reactions. The surface under the cumulative ranking curve results indicated that curcumin monotherapy, curcumin + chondroprotective agents, and curcumin + NSAIDs have good clinical value in KOA treatment. CONCLUSIONS: Curcumin, either alone or in combination with other treatments, is considered to have good clinical efficacy and safety in KOA treatment. Drug combinations containing curcumin may have the dual effect of enhancing efficacy and reducing adverse reactions, but this possibility still needs to be confirmed by further clinical and basic research.

Guidelines for the diagnosis and treatment of knee osteoarthritis with integrative medicine based on traditional Chinese medicine.

Knee osteoarthritis (KOA) is a common geriatric disease in middle-aged and elderly people. Its main pathological characteristics are articular cartilage degeneration, changes in subchondral bone reactivity, osteophyte formation at joint edges, synovial disease, ligament relaxation or contracture, and joint capsular contracture. The prevalence rate of symptomatic KOA in middle-aged and elderly people in China is 8.1%, and this is increasing. The main clinical manifestations of this disease are pain and limited activity of the knee joint, which seriously affect the quality of life of patients and may cause disability, posing a huge burden on society and the economy. Although the pathogenesis of KOA is not clear, the treatment of KOA is diverse, and Chinese medicine, which mainly relies on plant-based natural products, has a relatively stable and reliable curative effect. This guideline aims to emphasize the evidence-based staging and stepped treatment of KOA and the therapeutic effect of integrative medicine based on traditional Chinese medicine on KOA. We make recommendations that include the adoption of manual therapy, acupuncture, external application of herbs, herbal plasters, exercise therapy, and other integrative medicine based on traditional Chinese medicine. Users of the above guidelines are most likely to include clinicians and health managers in healthcare settings.

Mechanisms of action and synergetic formulas of plant-based natural compounds from traditional Chinese medicine for managing osteoporosis: a literature review.

Osteoporosis (OP) is a systemic skeletal disease prevalent in older adults, characterized by substantial bone loss and deterioration of microstructure, resulting in heightened bone fragility and risk of fracture. Traditional Chinese Medicine (TCM) herbs have been widely employed in OP treatment owing to their advantages, such as good tolerance, low toxicity, high efficiency, and minimal adverse reactions. Increasing evidence also reveals that many plant-based compounds (or secondary metabolites) from these TCM formulas, such as resveratrol, naringin, and ginsenoside, have demonstrated beneficial effects in reducing the risk of OP. Nonetheless, the comprehensive roles of these natural products in OP have not been thoroughly clarified, impeding the development of synergistic formulas for optimal OP treatment. In this review, we sum up the pathological mechanisms of OP based on evidence from basic and clinical research; emphasis is placed on the in vitro and preclinical in vivo evidence-based anti-OP mechanisms of TCM formulas and their chemically active plant constituents, especially their effects on imbalanced bone homeostasis regulated by osteoblasts (responsible for bone formation), osteoclasts (responsible for bone resorption), bone marrow mesenchymal stem cells as well as bone microstructure, angiogenesis, and immune system. Furthermore, we prospectively discuss the combinatory ingredients from natural products from these TCM formulas. Our goal is to improve comprehension of the pharmacological mechanisms of TCM formulas and their chemically active constituents, which could inform the development of new strategies for managing OP.

Effects of resveratrol in an animal model of osteoporosis: a meta-analysis of preclinical evidence.

Background: Resveratrol is a natural polyphenol compound that is widely present in herbal medicines such as Reynoutria japonica Houtt., Veratrum nigrum L., and Catsiatora Linn and is used in traditional Chinese medicine to treat metabolic bone deseases. Animal experiments have shown that resveratrol may have a strong treatment effect against osteoporosis (OP). The purpose of this study was to explore the efficacy of resveratrol in treating OP animal models based on preclinical research data. Methods: This study was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases from inception to May 8, 2023, to identify animal experiments on the treatment of OP with resveratrol. The effect sizes of bone mineral density (BMD), parameters of micro-CT, serum calcium, phosphorus, alkaline phosphatase (ALP) and osteocalcin were expressed as the mean differences (MDs) and 95% confidence intervals (CIs). RevMan 5.4 software was used for data analysis. Results: This meta-analysis included a total of 15 animal experiments, including 438 OP rats. The meta-analysis results showed that compared with the control group, resveratrol (<10, 10-25, 40-50, ≥ 60 mg/kg/day) significantly increased femoral and lumbar bone mineral density (BMD) in OP rats (p < 0.05). Resveratrol (<10 mg/kg/day) significantly increased the BMD of the total body (MD = 0.01, 95% CI: 0.01 to 0.01, p < 0.001). In terms of improving the parameters related to micro-CT, resveratrol (40-50 mg/kg/day) can increase trabecular thickness and trabecular number and reduce trabecular spacing (p < 0.05). Compared with the control group, resveratrol can reduce the concentration of calcium and phosphorus in serum but has no significant effect on serum ALP and osteocalcin (p > 0.05). The results of subgroup analysis showed that resveratrol increased the whole-body BMD of SD rats (p = 0.002) but did not improve the whole-body BMD of 3-month-old rats (p = 0.17). Conclusion: Resveratrol can increase BMD in OP rat models, and its mechanism of action may be related to improving bone microstructure and regulating calcium and phosphorus metabolism. The clinical efficacy of resveratrol in the treatment of OP deserves further research.

Network pharmacology identifies fisetin as a treatment for osteoporosis that activates the Wnt/ß-catenin signaling pathway in BMSCs.

BACKGROUND: Although fisetin may exist widely in many natural herbs, its anti-OP mechanism is still unclear. The aim of this study is to explore the molecular anti-osteoporosis (OP) mechanism of fisetin based on network pharmacology and cell experiments. METHODS: The target of fisetin was extracted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The targets of OP were obtained by DisGeNET, GeneCards and the Comparative Toxicogenomics Database, and the targets of fisetin in OP were screened by cross-analysis. The protein-protein interaction (PPI) network was constructed by STRING, and the core targets were obtained. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on common targets via the Database for Annotation, Visualization and Integrated Discovery. Finally, an in vitro cell experiment was used to verify the anti-OP effect and mechanism of fisetin. RESULTS: There are 44 targets of fisetin related to the treatment of OP. The PPI results suggest that CTNNB1, CCND1, TP53, JUN, and AKT1 are the core targets. A total of 259 biological process, 57 molecular function and 26 cell component terms were obtained from GO enrichment analysis. The results of KEGG pathway enrichment analysis suggested that fisetin treatment of OP may be related to the Wnt signaling pathway, estrogen signaling pathway, PI3K-Akt signaling pathway and other signaling pathways. In vitro cell experiments showed that fisetin significantly increased the expression levels of ALP, collagen I, osteopontin and RUNX2 in bone marrow mesenchymal stem cells (BMSCs) (p < 0.05). Fisetin also increased the gene expression levels of Wnt3 and ß-catenin (CTNNB1) in BMSCs, which indicates that fisetin can regulate the Wnt/ß-catenin signaling pathway and promote the osteogenic differentiation of BMSCs. CONCLUSIONS: Fisetin acts on multiple targets and pathways in the treatment of OP; mechanistically, it regulates the Wnt/ß-catenin signaling pathway, which promotes the osteogenic differentiation of BMSCs and maintains bone homeostasis. The results of this study provide a theoretical basis for further study on the complex anti-OP mechanism of fisetin.

Osteoporosis guidelines on TCM drug therapies: a systematic quality evaluation and content analysis.

Objective: The aims of this study were to evaluate the quality of osteoporosis guidelines on traditional Chinese medicine (TCM) drug therapies and to analyze the specific recommendations of these guidelines. Methods: We systematically collected guidelines, evaluated the quality of the guidelines using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool, and summarized the recommendations of TCM drug therapies using the Patient-Intervention-Comparator-Outcome (PICO) model as the analysis framework. Results and conclusions: A total of 20 guidelines were included. Overall quality evaluation results revealed that four guidelines were at level A, four at level B, and 12 at level C, whose quality needed to be improved in the domains of "stakeholder involvement", "rigor of development", "applicability" and "editorial independence". Stratified analysis suggested that the post-2020 guidelines were significantly better than those published before 2020 in the domains of "scope and purpose", "stakeholder involvement" and "editorial independence". Guidelines with evidence systems were significantly better than those without evidence systems in terms of "stakeholder involvement", "rigor of development", "clarity of presentation" and "applicability". The guidelines recommended TCM drug therapies for patients with osteopenia, osteoporosis and osteoporotic fracture. Recommended TCM drugs were mainly Chinese patent medicine alone or combined with Western medicine, with the outcome mainly focused on improving bone mineral density (BMD).

Effect of Rhizoma Drynariae on differential gene expression in ovariectomized rats with osteoporosis based on transcriptome sequencing.

Osteoporosis is increasingly becoming a serious problem affecting the quality of life of the older population. Several experimental studies have shown that Chinese medicine has a definite effect on improving osteoporosis. Based on transcriptome sequencing, we analyzed the differential gene expression and mechanism of the related signaling pathways. Fifteen rats were randomly divided into an experimental group, a model group, and a sham surgery group. The rat model for menopausal osteoporosis was established using an ovariectomy method. One week after modeling, the experimental group was administered(intragastric administration)8.1 g/kg of Rhizoma drynariae, whereas the model and sham groups received 0.9% saline solution twice daily for 12 weeks. Subsequently, the rats were sacrificed, and the left femur of each group was removed for computerized tomography testing, while right femurs were used for hematoxylin and eosin staining. High-throughput RNA sequencing and functional and pathway enrichment analyses were performed. Comparing the gene expression between the experimental and model groups, 149 differential genes were identified, of which 44 were downregulated and 105 were upregulated. The criteria for statistical significance were |log2 Fold Change| > 1 and P < 0.05. Gene ontology analysis showed that the differentially expressed genes were enriched in cell component terms such as cell part and outer cell membrane part, and the genes were associated with cell process, biological regulation, metabolic processes, DNA transcription, and catalytic activity. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways showed significantly enriched pathways associated with systemic lupus erythematosus, herpes simplex infection, circadian rhythm, vascular smooth muscle contraction, the AGE-RAGE signaling pathway in diabetic complications, and the TNF, Apelin, and Ras signaling pathways. Our results revealed that the Npas2, Dbp, Rt1, Arntl, Grem2, H2bc9, LOC501233, Pla2g2c, Hpgd, Pde6c, and Dner genes, and the circadian rhythm, lipid metabolism, inflammatory signaling pathway, and immune pathways may be the key targets and pathways for traditional Chinese medicine therapy of Rhizoma Drynariae in osteoporosis.

Efficacy of Duhuo Jisheng Decoction for Treating Cold-Dampness Obstruction Syndrome-Type Knee Osteoarthritis: A Pooled Analysis.

Aim: The aim of this study is to provide evidence of the effect of Duhuo Jisheng decoction (DHJSD) on knee osteoarthritis (KOA) of the cold-dampness obstruction syndrome type. Methods: We searched PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the Wanfang database, and the China Biology Medicine for randomized controlled trials (RCTs) evaluating DHJSD or DHJSD combined with other conventional therapies (DHJSD group) compared to conventional therapy (control group) for cold-dampness obstruction syndrome-type KOA. We calculated the pooled odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) using fixed- or random-effects models. Results: Eleven RCTs, with a total of 895 patients, were included. The results showed that DHJSD could significantly improve the effective rate (OR = 3.13, 95%CI = 2.07 to 4.72, P < 0.001), reduce both the WOMAC (MD = -12.06, 95%CI = -16.34 to -7.79, P < 0.001) and VAS (MD = -1.02, 95%CI = -1.54 to -0.50, P = 0.0001) scores, and reduce the serum IL-6 (MD = -0.80, 95%CI = -0.90 to -0.69, P < 0.001) and TNF-α (MD = -2.49, 95%CI = -2.77 to -2.21, P < 0.001) levels during the treatment of cold-dampness obstruction syndrome-type KOA. The subgroup analysis showed that compared with glucosamine sulfate (GS) alone, DHJSD combined with GS significantly improved the effective rate (OR = 2.59, 95%CI = 1.19 to 5.65, P = 0.02) and reduced the WOMAC (MD = -13.83, 95%CI = -16.14 to -11.51, P < 0.001) and VAS (MD = -0.91, 95%CI = -1.27 to -0.55, P < 0.001) scores. DHJSD + warm-needle acupuncture (WA) lowered the VAS score more than WA alone. There was no significant difference in the decrease in serum IL-1ß between the DHJSD and control groups. Conclusion: This study shows that DHJSD can improve the clinical efficacy and reduce the VAS and WOMAC scores in the treatment of cold-dampness obstruction syndrome-type KOA. Compared with GS or WA alone, the combined application of DHJSD with GS or WA could better reduce both the VAS and WOMAC scores.

An ALBI- and Ascites-Based Model to Predict Survival for BCLC Stage B Hepatocellular Carcinoma.

Background: We aimed to develop a predictive model constituted with the ALBI grade, the ascites, and tumor burden related parameters in patients with BCLC stage B HCC. Methods: Patients diagnosed as the BCLC stage B HCC were collected from a retrospective database. Construction and validation of the predictive model were performed based on multivariate Cox regression analysis. Predictive accuracy, discrimination (c-index), and fitness performance (calibration curve) of the model were compared with the other eight models. The decision curve analysis (DCA) was used to evaluate the clinical utility. Results: A total of 1773 patients diagnosed as BCLC stage B HCC between 2007 and 2016 were included in the present study. The ALBI-AS grade, the AFP level, and the 8-and-14 grade were used for the development of a prognostic prediction model after multivariate analysis. The area under the receiver operator characteristic curve (AUROC) for overall survival at 1, 2, and 3 years predicted by the present model were 0.73, 0.69, and 0.67 in the training cohort. The concordance index (c-index) and the Aiken information criterion (AIC) were 0.68 and 6216.3, respectively. In the internal and external validation cohorts, the present model still revealed excellent predictive accuracy, discrimination, and fitness performance. Then the ALBI-AS based model was evaluated to be superior to other prognostic models with the highest AUROC, c-index, and lowest AIC values. Moreover, DCA also demonstrated that the present model was clinically beneficial. Conclusion: The ALBI-AS grade is a novel predictor of survival for patients with BCLC stage B HCC.

Evolving Roles of Natural Terpenoids From Traditional Chinese Medicine in the Treatment of Osteoporosis.

Osteoporosis (OP) is a systemic metabolic skeletal disease which can lead to reduction in bone mass and increased risk of bone fracture due to the microstructural degradation. Traditional Chinese medicine (TCM) has been applied in the prevention and treatment of osteoporosis for a long time. Terpenoids, a class of natural products that are rich in TCM, have been widely studied for their therapeutic efficacy on bone resorption, osteogenesis, and concomitant inflammation. Terpenoids can be classified in four categories by structures, monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids. In this review, we comprehensively summarize all the currently known TCM-derived terpenoids in the treatment of OP. In addition, we discuss the possible mechanistic-of-actions of all four category terpenoids in anti-OP and assess their therapeutic potential for OP treatment.

Network Pharmacological Study on Mechanism of the Therapeutic Effect of Modified Duhuo Jisheng Decoction in Osteoporosis.

Background: Modified Duhuo Jisheng Decoction (MDHJSD) is a traditional Chinese medicine prescription for the treatment of osteoporosis (OP), but its mechanism of action has not yet been clarified. This study aims to explore the mechanism of MDHJSD in OP through a combination of network pharmacology analysis and experimental verification. Methods: The active ingredients and corresponding targets of MDHJSD were acquired from the Traditional Chinese Medicine System Pharmacology (TCMSP) database. OP-related targets were acquired from databases, including Genecards, OMIM, Drugbank, CTD, and PGKB. The key compounds, core targets, major biological processes, and signaling pathways of MDHJSD that improve OP were identified by constructing and analysing the relevant networks. The binding affinities between key compounds and core targets were verified using AutoDock Vina software. A rat model of ovariectomized OP was used for the experimental verification. Results: A total of 100 chemical constituents, 277 targets, and 4734 OP-related targets of MDHJSD were obtained. Subsequently, five core components and eight core targets were identified in the analysis. Pathway enrichment analysis revealed that overlapping targets were significantly enriched in the tumour necrosis factor-alpha (TNF-α) signaling pathway, an inflammation signaling pathway, which contained six of the eight core targets, including TNF-α, interleukin 6 (IL-6), transcription factor AP-1, mitogen-activated protein kinase 3, RAC-alpha serine/threonine-protein kinase, and caspase-3 (CASP3). Molecular docking analysis revealed close binding of the six core targets of the TNF signaling pathway to the core components. The results of experimental study show that MDHJSD can protect bone loss, inhibit the inflammatory response, and downregulate the expression levels of TNF-α, IL-6, and CASP3 in ovariectomized rats. Conclusion: The mechanism of MDHJSD in the treatment of OP may be related to the regulation of the inflammatory response in the bone tissue.

The efficacy and safety of Jinwu Gutong capsule in the treatment of knee osteoarthritis: A meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jinwu Gutong (JWGT) capsule is a Chinese patent medicine that is widely used in the treatment of knee osteoarthritis (KOA) and osteoporosis in China and is considered to have the potential for good clinical efficacy. AIM OF THE STUDY: The purpose of this study was to systematically evaluate the clinical efficacy and safety of JWGT in the treatment of KOA. MATERIALS AND METHODS: We searched the China National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, PubMed, Embase and Cochrane Library databases to identify clinical trials that explore the use of JWGT only or JWGT combined with Western drugs (JWGT group) compared with the use of conventional Western drugs (Western drugs group) for the treatment of KOA. The clinical trials, that were retrieved from each database from the inception of the database to December 2021, were screened. We used the risk of bias assessment tool recommended by Cochrane to evaluate the quality of the included literature and RevMan 5.3 software for data analysis. RESULTS: A total of 17 clinical randomized controlled trials (RCTs) were included in this study, with a total of 1930 participants, including 1015 people in the experimental group and 915 people in the control group. The results of the meta-analysis showed that the JWGT group exhibited better efficacy than the Western drug group with respect to WOMAC score (WMD = -6.25, 95% CI = -8.09 to -4.41, P < 0.001), VAS score (WMD = -1.36, 95% CI = -2.17 to -0.55, P = 0.001), KSS score (WMD = 23.01, 95% CI = 21.42 to 24.59, P < 0.001), IL-6 (SMD = -3.30, 95% CI = -4.84 to -1.76, P < 0.001), TNF-α (SMD = -1.70, 95% CI = -2.02 to -1.38, P < 0.001). The effective rate (OR = 2.56, 95% CI = 1.83 to 3.57, P < 0.001) and incidence of adverse reactions was significantly lower in the JWGT group than in the control group (OR = 0.13, 95% CI = 0.07 to 0.21, P < 0.001). Subgroup analysis showed that JWGT + NSAIDs had more advantages in regard to efficacy (OR = 2.05, 95% CI = 1.35 to 3.12, P < 0.001), and reducing adverse reactions (OR = 0.10, 95% CI = 0.06 to 0.18, P < 0.001), VAS score (WMD = -1.00, 95% CI = -1.93 to -0.07, P = 0.04), KSS score (WMD = 17.39, 95% CI = 15.39 to 19.39, P < 0.001), WOMAC score (WMD = -2.84, 95% CI = -10.75 to 5.08, P < 0.001), IL-6 (SMD = -1.42, 95% CI = -2.08 to -0.75, P < 0.001) and TNF-α (SMD = -1.68, 95% CI = -1.93 to -1.43, P < 0.001) than NSAIDs alone. Compared with hyaluronic acid (HA) alone, JWGT + HA had better clinical efficacy (OR = 3.08, 95% CI = 1.48 to 6.40, P < 0.001). Compared with glucosamine (GS) alone, JWGT + GS significantly reduced the Lequesne index score (WMD = -0.53, 95% CI = -0.85 to -0.21, P = 0.001) and the serum TNF-α level (SMD = -1.68, 95% CI = -1.93 to -1.43, P < 0.001), but it had no significant advantage in reducing the serum IL-6 level (SMD = -4.53, 95% CI = -10.13 to 1.07, P = 0.11). CONCLUSION: JWGT is considered effective and safe in the treatment of KOA and is worthy of clinical application. In addition, the application of JWGT combined with NSAIDs, HA or GS can significantly improve the clinical efficacy of the latter agents in KOA treatment.

Mechanism and Experimental Verification of Luteolin for the Treatment of Osteoporosis Based on Network Pharmacology.

Purpose: To explore the molecular mechanism of luteolin in the treatment of osteoporosis (OP) by network pharmacological prediction and experimentation. Methods: The target proteins of luteolin were obtained with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). OP-related proteins were extracted from the Comparative Toxicogenomics Database (CTD) and GeneCards and DisGeNET databases. We imported the common protein targets of luteolin and OP into the STRING database to obtain the relationships between the targets. The common target proteins of luteolin and OP were assessed by KEGG and GO enrichment analyses with the DAVID database. Animal experiments were conducted to verify the effect of luteolin on bone mineral density in ovariectomised (OVX) rats. Finally, the effects of luteolin on key signalling pathways were verified by cell experiments in vitro. Results: Forty-four targets of luteolin involved in the treatment of OP, including key target proteins such as TP53, AKT1, HSP90AA1, JUN, RELA, CASP3, and MAPK1, were screened. KEGG enrichment analysis found that luteolin inhibits OP by regulating the PI3K-Akt, TNF, oestrogen and p53 signalling pathways. The results of animal experiments showed that bone mass in the low-dose luteolin group (Luteolin-L group, 10 mg/kg), high-dose luteolin group (Luteolin-H group, 50 mg/kg) and positive drug group was significantly higher than that in the OVX group (P<0.05). Western blot (WB) analysis showed that the protein expression levels of Collagen I, Osteopontin and RUNX2 in bone marrow mesenchymal stem cells (BMSCs) cultured with 0.5, 1 and 5 µM luteolin for 48 h were significantly higher than those in the dimethyl sulfoxide (DMSO) group (P<0.05). In vitro cell experiments showed that the p-PI3K/PI3K and p-Akt/Akt expression ratios in BMSCs cultured with 0.5, 1 and 5 µM luteolin for 48 h were also significantly higher than those in the DMSO group (P<0.05). Conclusions: Luteolin has multitarget and multichannel effects in the treatment of OP. Luteolin could reduce bone loss in OVX rats, which may be due to its ability to promote the osteogenic differentiation of BMSCs by regulating the activity of the PI3K-Akt signalling pathway.

Comparative Efficacy of Xianling Gubao Capsules in Improving Bone Mineral Density in Postmenopausal Osteoporosis: A Network Meta-Analysis.

OBJECTIVE: The clinical efficacy of Xianling Gubao capsule (XLGB) and its combination therapy in the treatment of postmenopausal osteoporosis (PMOP) was systematically evaluated by frequency-based network meta-analysis. METHODS: We searched the China National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, PubMed, Embase and Cochrane Library databases to identify clinical trials of XLGB for the treatment of PMOP from the establishment of each database to November 22, 2021. The quality of the included studies was evaluated by using the risk of bias assessment tool version 2.0 (Rob 2.0) recommended by Cochrane. Stata 14.0 was applied for statistical analysis of the data, and the surface under the cumulative ranking curve (SUCRA) was used to rank the intervention measures of each outcome index. RESULTS: This study included 22 clinical trials (including 19 RCTs and 3 non-RCTs) involving 12 drug therapies. According to the results of the network meta-analysis and SUCRA, the best three interventions for improving lumbar bone mineral density (BMD) are XLGB+BP+calcium (83.7%), XLGB+BP (68.5.7%) and XLGB+VD (67.1%). XLGB+calcium was the best combination regimen for improving femoral neck BMD and increasing bone Gla protein (BGP) and alkaline phosphatase (ALP) contents in serum. The SUCRA values of XLGB+calcium for improving the three outcome indicators were 68.0%, 59.5% and 82.1%, respectively. CONCLUSIONS: The results of this network meta-analysis show that combined application of XLGB can effectively improve BMD and serum BGP and ALP compared to calcium alone, VD or BP. In the future, multicenter, large-sample and double-blind clinical RCTs should be carried out to supplement and verify the results of this study.

Cinnamic Aldehyde, the main monomer component of Cinnamon, exhibits anti-inflammatory property in OA synovial fibroblasts via TLR4/MyD88 pathway.

Cinnamon is a wildly used traditional Chinese herbal medicine for osteoarthritis (OA) treatment, but the underlying mechanism remains ambiguous. The purpose of this study is to explore the mechanism of cinnamic aldehyde (CA), a bioactive substance extracted from Cinnamon, on synovial inflammation in OA. A total of 144 CA-OA co-targeted genes were identified by detect databases (PubChem, HIT, TCMSP, TTD, DrugBank and GeneCards). The results of GO enrichment analysis indicated that these co-targeted genes have participated in many biological processes including 'inflammatory response', 'cellular response to lipopolysaccharide', 'response to drug', 'immune response', 'lipopolysaccharide-mediated signalling pathway', etc. KEGG pathway analysis showed these co-targeted genes were mainly enriched in 'Toll-like receptor signalling pathway', 'TNF signalling pathway', 'NF-kappa B signalling pathway', etc. Molecular docking demonstrated that CA could successfully bind to TLR2 and TLR4. The results of in vitro experiments showed no potential toxicity of 10, 20 and 50 µM/L CA on human OA FLS, and CA can significantly inhibit the inflammation in LPS-induced human FLS. Further experimental mechanism evidence confirmed CA can inhibited the inflammation in LPS-induced human OA FLS via blocking the TLR4/MyD88 signalling pathway. Our results demonstrated that CA exhibited strong anti-inflammation effect in OA FLS through blocking the activation of TLR4/MyD88 signalling pathway, suggesting its potential as a hopeful candidate for the development of novel agents for the treatment of OA.

Efficacy of Chinese patent medicine for primary osteoporosis: A network meta-analysis.

BACKGROUND AND PURPOSE: Chinese patent medicines (CPMs) have gained increasing attention for the treatment of primary osteoporosis (POP), but there is a lack of high-quality evidence regarding their efficacy. We conducted a network meta-analysis that considered both direct and indirect comparisons to assess and rank the efficacy and safety of CPMs for POP. METHODS: Seven electronic databases were searched from their inception to May 2020. A random effects model was applied within a frequentist framework. RESULTS: Thirty-eight studies with 16 kinds of medicines (13 CPMs, 3 Western medicines) and 3,941 patients were included in this study. This study showed that Jintiange capsule was the most efficacious for increasing the L2-L4 average bone mineral density (BMD) and that Zuogui Wan was the most efficacious for increasing the femoral neck BMD. Compared with calcium, Gusongjiangu Wan (RR = 10.04, 95% CI 1.36-74.32, p = 0.008), Gushukang granules (RR = 12.63, 95% CI 2.02-78.99, p = 0.015) and Xianling Gubao capsule (RR = 6.06, 95% CI 1.38-26.65, p = 0.0003) had fewer adverse reactions. CONCLUSION: In the treatment of POP, Jintiange capsule and Zuogui Wan are effective CPMs for improving the BMD of the lumbar spine and femoral neck, respectively.

[Network Meta-analysis of oral Chinese patent medicine in treatment of knee osteoarthritis].

To evaluate the efficacy and safety of Chinese patent medicine in the treatment of knee osteoarthritis(KOA) with network Meta-analysis, and provide evidence-based medicine evidences for clinical practice. PubMed, Cochrane Library, EMbase, CNKI, Wanfang, VIP and CBM were used to search for clinical randomized controlled trials(RCTs) on Chinese patent medicines for treatment of knee osteoarthritis, with a time limit from the establishment of each database to March 2020. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included RCTs. The network Meta-analysis was performed by Stata 14.0 software. A total of 5 788 patients in 58 RCTs were included, involving 9 kinds of Chinese patent medicines. The results of the network Meta-analysis indicated that in terms of total effective rate, the top three optimal medication regimens were Jinwu Gutong Capsules + Amino Acid Glucose(AAG), Xianling Gubao + AAG and Biqi Capsules; the top three interventions to reduce the VAS score were Panlongqi Tablets > Xianling Gubao + AAG > Xianling Gubao + non steroidal anti-inflammatory drugs(NSAIDs); the top three interventions to reduce the total score of WOMAC were Jintiange Capsules+NSAIDs> Jinwu Gutong Capsules + AAG > Biqi Capsules + NSAIDs; the top three medication schemes with better curative effect to reduce Lequesnse index were Xianling Gubao + NSAIDs > Biqi Capsules + NSAIDs > Jintiange Capsules + NSAIDs; the top three interventions to reduce TNF-α level Xianling Gubao + AAG > Jintiange Capsules > Jintiange Capsules + AAG=Jinwu Gutong Capsules + AAG. In terms of safety, the top five interventions with the least adverse reactions were Biqi Capsules > Jinwu Gutong Capsules > Biqi Capsules + NSAIDs > Xianling Gubao + NSAIDs > Jintiange Capsules. The combined application of Chinese patent medicine and NSADIs or AAG can improve the clinical treatment effect and reduce adverse reactions in KOA patients.

Exploration of the Molecular Mechanism of Polygonati Rhizoma in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking.

Objective: To explore the effective components and mechanism of Polygonati Rhizoma (PR) in the treatment of osteoporosis (OP) based on network pharmacology and molecular docking methods. Methods: The effective components and predicted targets of PR were obtained through the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform (TCMSP) database. The disease database was used to screen the disease targets of OP. The obtained key targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database for protein-protein interaction (PPI) network analysis. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of key targets. Analysis and docking verification of chemical effective drug components and key targets were performed with IGEMDOCK software. Results: A total of 12 chemically active components, 84 drug target proteins and 84 common targets related to drugs and OP were obtained. Key targets such as JUN, TP53, AKT1, ESR1, MAPK14, AR and CASP3 were identified through PPI network analysis. The results of enrichment analysis showed that the potential core drug components regulate the HIF-1 signaling pathway, PI3K-Akt signaling pathway, estrogen signaling pathway and other pathways by intervening in biological processes such as cell proliferation and apoptosis and estrogen response regulation, with an anti-OP pharmacological role. The results of molecular docking showed that the key targets in the regulatory network have high binding activity to related active components. Conclusions: PR may regulate OP by regulating core target genes, such as JUN, TP53, AKT1, ESR1, AR and CASP3, and acting on multiple key pathways, such as the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and estrogen signaling pathway.