Xianling Gubao Capsule Research Articles

Bencaosome [16:0 Lyso PA+XLGB28-sRNA] improves osteoporosis by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis in mice.

Osteoporosis (OP) is a systemic metabolic bone disease resulting in reduced bone strength and increased susceptibility to fractures, making it a significant public health and economic problem worldwide. The clinical use of anti-osteoporosis agents is limited because of their serious side effects or the high cost of long-term use. The Xianlinggubao (XLGB) formula is an effective traditional Chinese herbal medicine commonly used in orthopedics to treat osteoporosis; however, its mechanism of action remains unclear. In this study, we screened 40 small RNAs derived from XLGB capsules and found that XLGB28-sRNA targeting TNFSF11 exerted a significant anti-osteoporosis effect in vitro and in vivo by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis. Oral administration of bencaosome [16:0 Lyso PA+XLGB28-sRNA] effectively improved bone mineral density and reduced the damage to the bone microstructure in mice. These results suggest that XLGB28-sRNA may be a novel oligonucleotide drug that promotes osteogenesis and inhibits osteoclastogenesis in mice.

Targeting the PANoptosis signaling pathway for myocardial protection: therapeutic potential of Xian Ling Gu Bao capsule.

Introduction: Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The pathogenesis of MI is exceedingly intricate, with PANoptosis playing a pivotal role in its pathological process. Xian Ling Gu Bao capsule (XLGB) contains various active components, including flavonoids, terpenes, and phenylpropanoids, and exhibits a wide range of pharmacological activities. However, it remains unclear whether XLGB can protect the myocardium from damage after MI. This study aimed to investigate the impact of XLGB on isoprenaline (ISO)-induced MI in mice and its potential mechanisms. Methods: This study assessed the protective effects of XLGB against ISO-induced MI through techniques such as echocardiography, HE staining, Masson staining, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the potential mechanisms of XLGB's protective effects on MI were explored using bioinformatics, molecular docking, and molecular dynamics simulations. These mechanisms were further validated through immunofluorescence staining and Western blotting. Results: The results demonstrated that various doses of XLGB exhibited a significant reduction in myocardial injury induced by myocardial infarction. Intriguingly, higher dosages of XLGB displayed superior therapeutic efficacy compared to the positive control metoprolol. This protective effect is primarily achieved through the inhibition of oxidative stress and the inflammatory processes. Furthermore, we have elucidated that XLGB protected the myocardium from MI-induced damage by suppressing PANoptosis, with a critical role played by the NLRP3/Caspase3/RIP1 signaling pathway. Of particular note, the primary compounds of XLGB were found to directly interact with NLRP3/Caspase3/RIP1, a discovery further validated through molecular docking and molecular dynamics simulations. This suggests that NLRP3/Caspase3/RIP1 may be a therapeutic target for XLGB-induced myocardial protection. Conclusion: In summary, our findings reveal a novel property of XLGB: reverses myocardial damage following MI by inhibiting the NLRP3/Caspase3/RIP1-mediated PANoptosis pathway.

Efficacy of Xianling Gubao capsule vs. its combination therapy in the treatment of primary osteoporosis: A network meta-analysis of randomized controlled trials

ObjectiveThis study aimed to evaluate the efficacy of the Xianling Gubao (XLGB) capsule alone and its combination therapy in primary osteoporosis (POP). MethodsDatabases including PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and SinoMed were searched from their inception to January 16, 2024, for randomized controlled trials (RCTs) investigating the XLGB treatment for POP. A network meta-analysis (NMA) was performed to evaluate the efficacy and safety of multiple interventions in the treatment of POP. The Cochrane risk-of-bias tool was used to assess the quality of RCTs included in the meta-analysis. Software Stata (version 15.0) was used for statistical analysis. The surface under the cumulative ranking curve (SUCRA) method was used to present the findings from this NMA numerically and graphically by ranking multiple interventions. ResultsA total of 107 RCTs were included in the meta-analysis, involving 10,032 participants and 21 interventions. Meta-analysis showed that XLGB + calcium (Ca) + calcitonin (99.9 %) was the most desirable treatment option for improving clinical efficacy. XLGB + Ca + bisphosphonate (BP) was most effective for improving bone mineral density (BMD) at the lumbar spine, femoral neck BMD, and serum bone Gla protein (BGP). SUCRA values for improving these three outcome measures by XLGB + Ca + BP were 87.4 %, 77.2 %, and 84.3 %, respectively. XLGB + calcitonin was the optimal option in terms of safety evaluation and improving visual analogue scale (VAS), with the SUCRA values being 89.6 % and 94.9 %, respectively. ConclusionsThe XLGB combination therapy is a desirable option for treating POP as it can effectively improve the therapeutic effects, BMD, and serum BGP, as well as relieve pain in patients with POP.

A Combination Therapy of Methotrexate and Xianling Gubao Capsule for Female Patients with Moderate to Severe Active Rheumatoid Arthritis and its Impact on Ovarian Function

Rheumatoid arthritis is a common immune disease with early symptoms of joint swelling, morning stiffness, pain, and swelling. It could develop into a joint deformity as the disease progresses, resulting in the loss of normal joint function and seriously affecting the patient’s quality of life. Methotrexate is the “anchor drug” for rheumatoid arthritis treatment, which has an immunosuppressive effect and could effectively prevent the abnormal activation of B cells in vivo, inhibit the abnormal generation of cytokines, and relieve related symptoms. However, in some cases, methotrexate alone is not ideal and often needs to be combined with other drugs like xianlinggubao capsules. This study has provided an experimental basis for the combined efficacy of methotrexate and xianlinggubao capsules for female patients with moderate to severe rheumatoid arthritis and their impact on ovarian function.

Network Meta-analysis of Oral Chinese Patent Medicine in Treatment of Primary Osteoporosis

The efficacy of oral proprietary Chinese medicine in the prevention and treatment of primary osteoporosis was systematically evaluated through a network meta-analysis. The computer retrieved the four major Chinese databases of CNKI, VIP, Wang Fang, CBM in China and abroad, as well as the three English databases and Web of Science of Medline, EMbase and Cochrane Library. The search cycle was designed as the database was established until February 15, 2022, and screened randomized controlled trials of export taking proprietary Chinese medicine combined with conventional western medicine for the prevention and treatment of primary osteoporosis according to the system evaluation pre-formulated exclusion criteria. Literature screening and data extraction are completed by at least 2 clinical investigators alone. Bias assessment and mapping of included studies using the Revman software, using the Cochrane Bias Risk Assessment tool, using Stata 16. 0 Software for data acquisition and analysis. In the end, 19 RCTS were included, involving 8 kinds of oral proprietary Chinese medicines (You Gui Pills, Jin Tiange Capsules, Gu Shu Kang Granules, Qiang Bone Capsules, Gu Songbao Granules, Xianling Gu Bao Capsules, Hu Gu Capsules, Zuo Gui Pills). The results of the network meta-study are as follows: (1) in terms of improving clinical efficiency, conventional western medicine combined with Hu Gu Capsules has the best effect; (2) in terms of improving bone density, conventional western medicine combined with Xianling Gu Bao has the best effect. This network meta-analysis provides evidence for the efficacy of the above eight proprietary Chinese medicines in the treatment of patients with POP.

Mechanism of Xianlinggubao Capsule Regulating RANKL / RANK / OPG Signaling Pathway and Inhibiting Aseptic Loosening of Artificial Joint

Mechanism of Xianlinggubao Capsule Regulating RANKL / RANK / OPG Signaling Pathway and Inhibiting Aseptic Loosening of Artificial Joint

Efficacy and mechanism of low glycoside from Epimedii Folium flavonoids on retinoic acid-induced osteoporosis in rats

In this study, the secondary osteoporosis model was induced by oral administration of retinoic acid for two weeks in SD male rats. The efficacy and mechanism of LG on secondary osteoporosis in rats were explored through the bone morphogenetic protein 2(BMP-2)/Runt-related transcription factor 2(Runx2)/Osterix signaling pathway. With Xianling Gubao Capsules(XLGB) as the positive control, three dose groups of low glycoside from Epimedii Folium flavonoids(LG), i.e., low-dose group(LG-L), medium-dose group(LG-M), and high-dose group(LG-H), were set up. After modeling, the rats in each group were treated correspondingly by gavage for eight weeks. The action target of LG in the treatment of secondary osteoporosis in rats was analyzed by measuring the body weight and the organ indexes of rats including heart index and testis index. The efficacy of LG was characterized by the pathological changes of the femur, the microstructural parameters of the trabecular bone, and the biomechanical properties of femoral tissues in rats. The mechanism of LG was explored by measuring the relevant biochemical indexes and the changes in BMP-2, Runx2, and Osterix content in rats with secondary osteoporosis. The results showed that the action target of LG in the treatment of secondary osteoporosis in rats was the testis. LG can improve the bone loss of the femur, increase the number and thickness of the trabecular bone, reduce the porosity and separation of the trabecular bone, potentiate the resistance of bone to deformation and destruction, up-regulate the serum content of Ca, P, aminoterminal propeptide of type Ⅰ procollagen(PINP), and osteocalcin(OC), promote bone matrix calcification and the expression of BMP-2, Runx2, and Osterix proteins, and accelerate bone formation, thereby reducing the risk of fractures, and ultimately exerting anti-secondary osteoporosis efficacy.

Bioinformatics analysis combined with experimental validation to explore the mechanism of XianLing GuBao capsule against osteoarthritis

Ethnopharmacological relevanceXianLing GuBao Capsule (XLGB) is often used to treat osteoarthritis (OA), osteoporosis, fractures, and other musculoskeleton disorders. However, the molecular mechanism of XLGB for treating OA is still unclear. Aim of the studyThis study set out to uncover the molecular mechanism underlying the treatment of osteoarthritis with XLGB. Materials and methodsDisease genes were obtained from CTD, DisGeNET, and GeneCards databases, and XLGB drug targets were obtained from ETCM and target genes predicted by XLGB metabolic components reported in the literature. Then we used the Venn diagram viewer to extract disease and drug intersection genes as potential therapeutic genes for Protein-protein interaction (PPI), GO terminology, and KEGG pathway analysis. Subsequently, we performed qRT-PCR, Western blot and histological analysis to validate the therapeutic effect of XLGB against OA and its molecular mechanism. ResultsA total of 1039 OA genes and 949 XLGB target genes were collected, and finally 188 potential therapeutic target genes were obtained. PPI network analysis indicated that the main target genes for XLGB to treat OA include Akt1, Mapk3, Il-6, Il-1β, Ptgs2, Mmp9, etc. The results of KEGG and GO enrichment analysis suggested that XLGB may treat OA by anti-inflammatory and reducing extracellular matrix degradation. In vitro, XLGB down-regulated the expressions of Mmp3, Mmp9, Mmp12, Mmp13, Cox-2, Il-6, increased the expression of Collagen II and Sox9. Mechanistically, XLGB inhibits the activation of PI3K/AKT/NF-κB and MAPK pathways. Moreover, the results of animal experiments indicated that XLGB reduced cartilage destruction, bone resorption, and synovitis in osteoarthritic rats. ConclusionsXLGB has a protective effect against OA by suppressing PI3K/AKT/NF-κB and MAPK signaling. Our study provides a theoretical basis for XLGB in the treatment of osteoarthritis.

Chinese Proprietary Medicine Xianling Gubao Capsule for Osteoporosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

ObjectiveTo assess the benefit and harm of Chinese medicine Xianling Gubao (XLGB) capsule compared to conventional medication or placebo to inform clinical practice.MethodsWe included randomized controlled trials (RCTs) with Jadad score ≥3 of XLGB capsule compared to pharmaceutical medication, placebo, or no treatment for primary osteoporosis. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database (Sino-Med) from their inception till November 13th, 2021. Study selection and data extraction were done by two authors independently. The methodological quality of the RCTs was assessed using Cochrane’s risk of bias tool. The effect size was presented as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI).ResultsOur searches identified 2292 records and after exclusions, eight trials involving 846 participants were included. There was no statistically significant difference between conventional medications with or without XLGB on new fracture (RR: 0.50, 95% CI: [0.13, 1.87]). Quality of life by SF-36 questionnaire of XLGB plus calcium carbonate, vitamin D3, and calcitriol was improved than that of without XLGB (MD: 6.72 scores, 95% CI: [2.82, 10.62]). XLGB increased bone mineral density similarly as calcium carbonate plus vitamin D3 (MD: 0.21, 95% CI: [-0.16, 0.58]) or as alendronate sodium, calcium carbonate plus vitamin D3 (MD: 0.00, 95% CI: [-0.10, 0.10]), but it had no additional effect as an add-on treatment to conventional medications (MD: 0.13, 95% CI: [-0.12, 0.37]). XLGB relieved pain via visual analog scale more effectively when combined with medications (MD: -1.55 score, 95% CI: [-2.47, -0.63]). XLGB as monotherapy did not increase adverse events (RR: 0.63, 95% CI: [0.28, 1.41]), or as an add-on treatment (RR: 0.25, 95% CI: [0.03, 2.16]).ConclusionThis systematic review shows that XLGB capsule appears to be safe and has a beneficial effect on the quality of life and pain relief when used alone or in combination with conventional medications in osteoporosis patients. Further large, rigorous trials are warranted to test its long-term benefit.

Network Meta-analysis of efficacy and safety of Chinese patent medicines in treatment of ankylosing spondylitis

To evaluate the efficacy and safety of Chinese patent medicines in the treatment of ankylosing spondylitis(AS) by frequency network Meta-analysis. Randomized controlled trials(RCTs)of Chinese patent medicines for AS were retrieved from CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library databases from the time of database establishment to January 2021. The quality of the included RCTs was evaluated according to the Cochrane bias risk standard, and the data was analyzed by RevMan 5.3 and Stata/MP 15.1. A total of 12 kinds of Chinese patent medicines in 55 RCTs were included. According to Meta-analysis, in term of the effectiveness, the top three optimal medication regimens were Biqi Capsules, Yishen Juanbi Pills and Yaobitong Capsules combined with western medicine. The top three interventions to reduce the erythrocyte sedimentation rate(ESR)were Yishen Juanbi Pills, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. The top three interventions to reduce the C-reactive protein(CRP)were Biqi Capsules, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. In terms of the safety, top three optimal medication regimens were Total Glucosides of Paeony Capsules, Yishen Juanbi Pills, and Wangbi Tablets combined with western medicine. This network Meta-analysis suggests that Chinese patent medicines combined with conventional western medicine can effectively improve the joint pain symptoms of AS patients and reduce the acute inflammatory indicators, with high safety. However, the literature included in this study is generally of low methodological quality, and the conclusion needs to be verified by high-quality research.

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

ObjectiveThe 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.MethodsWe 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.ResultsThis 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.ConclusionsThe 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.

Uncovering Hidden Mechanisms of Different Prescriptions Treatment for Osteoporosis via Novel Bioinformatics Model and Experiment Validation.

Osteoporosis (OP) is a systemic disease susceptible to fracture due to the decline of bone mineral density and bone mass, the destruction of bone tissue microstructure, and increased bone fragility. At present, the treatments of OP mainly include bisphosphonates, hormone therapy, and RANKL antibody therapy. However, these treatments have observable side effects and cannot fundamentally improve bone metabolism. Currently, the prescription of herbal medicine and their derived proprietary Chinese medicines are playing increasingly important roles in the treatment of OP due to their significant curative effects and few side effects. Among these prescriptions, Gushukang Granules (GSK), Xianling Gubao Capsules (XLGB), and Er-xian Decoction (EXD) are widely employed at the clinic on therapy of OP, which also is in line with the compatibility principle of “different treatments for the same disease” in herbal medicine. However, at present, the functional interpretation of “different treatments for the same disease” in herbal medicine still lacks systematic quantitative research, especially on the detection of key component groups and mechanisms. To solve this problem, we designed a new bioinformatics model based on random walk, optimized programming, and information gain to analyze the components and targets to figure out the Functional Response Motifs (FRMs) of different prescriptions for the therapy of OP. The distribution of high relevance score, the number of reported evidence, and coverage of enriched pathways were performed to verify the precision and reliability of FRMs. At the same time, the information gain and target influence of each component was calculated, and the key component groups in all FRMs of each prescription were screened to speculate the potential action mode of different prescriptions on the same disease. Results show that the relevance score and the number of reported evidence of high reliable genes in FRMs were higher than those of the pathogenic genes of OP. Furthermore, the gene enrichment pathways in FRMs could cover 79.6, 81, and 79.5% of the gene enrichment pathways in the component-target (C-T) network. Functional pathway enrichment analysis showed that GSK, XLGB, and EXD all treat OP through osteoclast differentiation (hsa04380), calcium signaling pathway (hsa04020), MAPK signaling pathway (hsa04010), and PI3K-Akt signaling pathway (hsa04151). Combined with experiments, the key component groups and the mechanism of “different treatments for the same disease” in the three prescriptions and proprietary Chinese medicines were verified. This study provides methodological references for the optimization and mechanism speculation of Chinese medicine prescriptions and proprietary Chinese medicines.

Chinese herbal medicine Xianling Gubao capsule for knee osteoarthritis: A protocol for systematic review and meta-analysis.

Background:Knee osteoarthritis (KOA) is the most prevalent degenerative joint disease among populations over 60 years old, and is the most common cause of musculoskeletal pain and disability worldwide. Xianling Gubao capsule (XLGBC), a Chinese patent medicine, is widely used for treatment of osteoporosis. Meanwhile, according to the theory of homotherapy for heteropathy, XLGBC is increasingly applied in the clinical practice of KOA. However, no systematic review has found that XLGBC is as effective in treatment of KOA as it is in treatment of osteoporosis. Therefore, we will conduct a systematic review of XLGBC in KOA treatments.Methods:All randomized controlled trials assessing the validity of XLGBC therapy for KOA will be retrieved from the following seven databases, including the Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wan Fang Database, and Chinese Scientific Journal Database. The primary outcome measures are the visual analogue scale pain score, and a comprehensive evaluation including the Western Ontario and McMaster Universities Arthritis Index scores, Lysholm scores, and Bristol scores. And the secondary outcome measures include cure rate and adverse events. The procedure such as retrieval and selection of literature, data extraction, evaluation of risk of bias, and assessment of reporting bias will be executed by 2 reviewers independently. The data synthesis for meta-analysis will be conducted by Review Manager 5.4 software.Results:A high-quality evidence of XLGBC for the treatment of KOA will be generated from the aspects of safety and efficacy.Conclusion:This systematic review will provide evidence to help us confirm the clinical efficacy of XLGBC in the treatment of KOA.OSF Registration number:Registration DOI 10.17605/OSF.IO/QD5SY.

Mechanism of Xianling Gubao Capsule in the Treatment of Steroid Induced Osteonecrosis of Femoral Head

This study aimed to obtain the main active components of Xianling Gubao capsule and identify their pharmacological characteristics and mechanism of action in treatment of steroid-induced femoral head necrosis. The chemical constituents and direct targets of Xianling Gubao capsule were obtained by the system pharmacology platform of traditional Chinese medicine. GeneCards database and gene expression omnibus database were used to obtain pathogenic genes related to steroid-induced femoral head necrosis. Through Venn diagram software, the intersection of direct drug targets and disease-related genes was obtained to obtain the potential drug targets of Xianling Gubao capsule. In the Cytoscape 3.7.1 software, the drug component-target and protein-protein interaction networks were visualized and analyzed by network analyze plugin and molecular complex detection plugin, the degree values of nodes were analyzed to screen the core genes. Finally, the database for annotation, visualization and integrated discovery database was used for gene enrichment analysis. We obtained 76 chemical components of Xianling Gubao, 583 pathogenic related genes of steroid-induced femoral head necrosis and 38 potential drug targets of Xianling Gubao capsule for the treatment of steroid-induced femoral head necrosis. A drug componenttargets network with 1001 nodes and 3661 edges, a protein-protein interaction network with 31 nodes and 67 edges were constructed. 15 core genes were obtained by network topology analysis and enrichment analysis of potential drug targets showed that they were mainly concentrated in chemokine signaling pathway. Finally, 5 optimal drug targets of Xianling Gubao capsule for steroid-induced femoral head necrosis were obtained, respectively. Xianling Gubao capsule can prevent or treat steroid-induced femoral head necrosis by promoting the reconstruction of new capillaries after necrosis, improving intravascular coagulation, accelerating the formation of callus and regulating the differentiation and direction of bone marrow stem cells.

Clinical practice guideline for postmenopausal osteoporosis with traditional Chinese medicine

The editorial group of the clinical practice guideline for postmenopausal osteoporosis(PMOP) with traditional Chinese medicine(TCM)(hereinafter referred to as "guideline") is composed of experts specialized in TCM orthopedics, TCM gynecology, clinical epidemiology, etc. The guideline was formulated through registration, collection and selection of clinical issues/outcome indicators, evidence retrieval and screening, preparation of systematic reviews, evaluation of evidence quality, formation of recommendations, drafting, and peer review. The syndromes and treatment of PMOP are elaborated in detail. Specifically, Liuwei Dihuang Pills and Zuogui Pills are recommended for PMOP with Yin deficiency in the liver and kidney, Qing'e Pills for PMOP with kidney deficiency and blood stasis, Yougui Pills and Jingui Shenqi Pills for PMOP with Yang deficiency in the spleen and kidney, and Er'xian Decoction for PMOP with Yin and Yang deficiency in the kidney. In addition, Duhuo Jisheng Decoction can be used to relieve pain. The commonly used Chinese patent medicines include Xianling Gubao Capsules, Qianggu Capsules, Jintiange Capsules, Gushukang Capsules, Hugu Capsules, Jinwu Gutong Capsules, and Guyuling Capsules. Acupuncture and moxibustion are also effective approaches for PMOP. The rehabilitation and daily management were carried out by exercise therapies such as Baduanjin(eight-section brocade), Wuqinxi(five-animal exercises), and Taijiquan(Tai Chi), Chinese medicine diet, health education, and fall prevention. The promotion and application of this guideline will facilitate the implementation of TCM prevention and treatment of PMOP, ensure the quality of life of PMOP patients, provide effective and safe TCM treatment measures for PMOP, and reduce the risk of fracture complications.

Xianling Gubao Capsule Prevents Cadmium-Induced Kidney Injury.

Xianling Gubao Capsule (XGC), a kind of capsule preparation of Chinese herbal officially approved for sale by the National Medical Products Administration (NMPA), has the effect of tonifying kidney and strengthening bones. Although the impact of XGC in treating bone diseases has been widely studied, the effect of XGC in kidney injury is unknown yet. The kidney injury model is established by intraperitoneal injection with cadmium chloride (CdCl2). Before model establishment, each XGC group was pregavaged with XGC for 10 d. After 10 d, CdCl2 was injected intraperitoneally into the model group and each XGC group, each XGC group continued to be gavaged with XGC for 4 weeks, and the control group was gavaged with equal doses of distilled water once daily. The level of serum urea nitrogen (BUN) and serum creatinine (Cr) is evaluated by kit. The effect of XGC on protecting kidney injury in mice with kidney injury is analyzed by histopathology (HE stain), immunohistochemistry (IHC), and real-time fluorescence quantitative PCR (RT-qPCR). The results show that CdCl2 significantly increases the level BUN and Cr in serum and results in remarkable pathological changes in the nephron, including tubule edema, congestion, and necrosis. While oral administration of XGC can significantly decrease BUN and Cr in serum and prevent and protect the kidney from the above injuries. In addition, the protein expression of p-mTOR was remarkably reduced, and the ratio of LC3II/LC3I protein and mRNA was significantly increased in mice with oral administration of XGC. Our findings suggest that XGC can prevent and protect kidney injury by improving the state of renal tubular hyperemia and necrosis and reduce the level of BUN and Cr in cadmium poisoning mice.

The Efficacy and Safety of Chinese Herbal Medicine Xianling Gubao Capsule Combined With Alendronate in the Treatment of Primary Osteoporosis: A Systematic Review and Meta-Analysis of 20 Randomized Controlled Trials.

Objective: Herein, we purposed to evaluate the efficacy along with the safety of Xianling Gubao capsule (XLGB) combined with alendronate (ALE) for primary osteoporosis (POP) from the current literature. Materials and Methods: We carried out a search for electronic literature in the PubMed, Chinese National Knowledge Infrastructure, EMBASE, Wanfang Web of Science, Chinese Biomedical Literature Database, Cochrane Library, as well as Chinese VIP databases targeting articles published from inception to December 2020. Only randomized controlled trials (RCTs) were enrolled into the study. Alkaline phosphatase (ALP), visual analogue scale (VAS), serum phosphorus (S-P), bone gla protein (BGP), serum calcium (S-Ca) and bone mineral density (BMD) were the primary outcome variable. The total clinical effective rate along with the adverse drug reaction (ADR) were the secondary outcome variables. The meta-analysis was conducted using RevMan 5.3 and STATA 12.0. GRADE pro3.6.1 software was used for the assessment of evidence quality. Results: Overall, 20 RCTs focusing on 1911 patients were enrolled into the study. Our meta-analysis demonstrated that XLGB combined with ALE remarkably increased BMD (p < 0.001), BGP (p < 0.001), S-Ca (p < 0.001), S-P (p < 0.001) and effective rate (p < 0.001) than ALE alone in patients with POP. Moreover, ALP (p < 0.001) and VAS (p < 0.001) were overtly by decreased XLGB. However, XLGB combined with ALE would not markedly increase the rate of ADR in contrast with ALE alone (p = 0.499). Conclusion: The results of our study demonstrated that XLGB is a potential candidate for OP treatment. We recommend that rigorous, as well as high-quality trials involving large samples sizes should be conducted to confirm our findings.

Network pharmacology combined with bioinformatics to investigate the mechanism of Xianlinggubao capsule in the treatment of osteoporosis

BackgroundXianlinggubao capsule (XLGB), a traditional Chinese medicine (TCM) prescription, has been widely applied to treat osteoporosis (OP) in China. However, its active components and mechanism have not been fully elucidated. PurposeThis study aims to elucidate the active components of XLGB and its mechanism for the treatment of OP. MethodsNetwork pharmacology and bioinformatics are combined to elucidate the active components and mechanism of XLGB in the treatment of OP, including the acquisition of differentially expressed genes (DEGs) of OP, screening of active components and their targets of XLGB, construction of the drug-target-disease regulatory network, and analysis of the key subnetwork. Finally, these predicted results were validated by in vitro experiments and literature comparison. ResultsBy using bioinformatics, 2473 DEGs of OP were identified in the GEO datasets analysis (GSE35958). By using network analysis, 180 active compounds in the six herbs of XLGB and 61 OP-related targets were identified, which were significantly enriched in 118 signaling pathways and 108 GO terms. The in vitro studies showed that quercetin, luteolin, apigenin and ursolic acid, the active components of XLGB, could effectively promote the mineralization of MC3T3-E1 cells, and the combined application of ursolic acid and luteolin could significantly increase the mRNA and protein expression level of Runx2, OPN and Col l, and enhance the phosphorylation of p38 and JNK. ConclusionXLGB plays an anti-osteoporosis role in a multi-component, multi-target and multi-pathway manner. The combination of network pharmacology and bioinformatics provides a method for the study of TCM in the treatment of complex diseases.

Efficacy and safety of Xianling Gubao capsule in treating postmenopausal osteoporosis: A protocol for systematic review and meta-analysis.

Background:postmenopausal osteoporosis is a systemic metabolic skeletal disease associated with menopause-related estrogen withdrawal. postmenopausal osteoporosis is characterized by low bone mass, bone microstructure destruction, leading to increased bone brittleness and be prone to fracture, resulting in disability and death. At present, the commonly used drugs are estrogen, calcium, bone formation promoter and bone resorption inhibitor, and the side effects are obvious. In Traditional Chinese medicine, kidney-tonifying differentiating medicine is guided by the whole concept, Xianling Gubao capsule as the representative, the treatment of postmenopausal osteoporosis has certain therapeutic advantages, but lacks evidence-based medicine evidence. The purpose of this study is to systematically study the efficacy and safety of Xianling Gubao capsule in the treatment of postmenopausal osteoporosis.Methods:use computer to search English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (China Knowledge Network, Wanfang, Weipu, Chinese Biomedical Database), in addition manually search Baidu academic, Google academic, from the establishment of database to October 2020, for randomized controlled clinical study of postmenopausal osteoporosis in the Xianling Gubao capsule treatment. Two researchers independently did the data extraction and literature quality evaluation, using RevMan5.3 software to do meta-analysis of the included literature.Results:this study assessed the efficacy and safety of xianling gubao capsule in the treatment of postmenopausal osteoporosis by total effective rate, bone density after treatment, blood calcium level after treatment, blood phosphorus level after treatment, pain score, quality of life and so on.Conclusion:this study will provide reliable evidence-based evidence for the clinical application of Xianling Gubao capsule in the treatment of postmenopausal osteoporosis.OSF Registration number:DOI 10.17605/OSF.IO/TP394

Serum Pharmacochemistry Analysis Combined with Network Pharmacology Approach to Investigate the Antiosteoporosis Effect of Xianlinggubao Capsule in vivo

AbstractXianlinggubao capsule (XLGB) is a traditional Chinese medicine multi-component herbal prescription and has been widely used in osteoporosis (OP) treatment. However, the underlying anti-OP mechanisms of XLGB have not been fully studied. In this study, an ovariectomized rat model of OP was established. The OP rats were orally administrated with XLGB, and then the main absorbed components in serum sample were assessed based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Subsequently, the potential anti-OP markers in XLGB were screened based on a network pharmacology strategy. Molecular docking analysis was used for confirmation. LC-MS showed 22 absorbed components in the serum sample of OP rat with XLGB treatment. Network pharmacology and pathway analysis suggested 19 potential anti-OP markers in XLGB. According to molecular docking process, most of the potential markers displayed strong interactions with the 22 absorbed components mentioned above. Besides, an absorbed component–potential marker–pathway network was further established. In conclusion, our data suggested the possible mechanisms for XLGB in OP treatment, in which the “multicomponents, multitargets, and multipathways” participated. Our article provided possible direction for drug discovery in OP and could help for exploring novel application of XLGB in clinical setting.