The therapeutic mechanism of Compound Lurong Jiangu Capsule for the treatment of cadmium-induced osteoporosis: network pharmacology and experimental verification.

Background: Among bone diseases, osteoporosis-like skeleton, such as trabecular thinning, fracture and so on, is the main pathological change of cadmium-induced osteoporosis(Cd-OP), accompanied by brittle bone and increased fracture rate. However, the mechanism underlying cadmium-induced osteoporosis has remained elusive. Compound Lurong Jiangu Capsule (CLJC) is an experienced formula for the treatment of bone diseases, which has the effect of tonifying kidney and strengthening bones, promoting blood circulation and relieving pain. Objective: Network pharmacology and molecular docking technology combined with experiments were used to investigate the potential mechanism of CLJC in treating Cd-OP. Method: The active compounds and corresponding targets of each herb in CLJC were searched in the TCMSP and BATMAN-TCM databases. The DisGeNet, OMIM, and GeneCards databases searched for Cd-OP targets. The relationship between both of them was visualized by establishing an herb-compound-target network using Cytoscape 3.9.1 software. Gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed after determining the intersection of the targets from CLJC and Cd-OP. What's more, molecular docking was performed to validate the results. All of them were aim to obtain hud signaling pathways for further study. Finally, BAX, BCL-2, and CASPASE-3 were screened and selected for further experiments, which included bone imaging and reconstruction analysis (Micro-CT), hematoxylin-eosin Staining (HE), and western blot (WB). Results: 106 common targets from CLJC and Cd-OP targets were identified. KEGG pathway analysis suggested that multiple signaling pathways, such as the pathways in cancer, may play roles in treatment. Verification of the molecular docking was successful. Here we showed that Cd-OP displayed Tb.Th and Tb.N significantly reduced and even broke, irregular proliferation of bone cortex, uneven and loose trabecular bone arrangement, changed in apoptosis-related proteins, such as significant upregulation of CASPASE-3, BAX protein and significant downregulation of BCL-2 protein in vivo, while CLJC rescued these phenotypes. Conclusion: This study revealed that CLJC can reduce the expression of apoptosis-related proteins, and multiple components and multiple targets inhibit Cd-OP through apoptosis signaling pathway.

The prevalence of osteoporosis in China, a community based cohort study of osteoporosis.

Background: Osteoporosis has already been a growing health concern worldwide. The influence of living area, lifestyle, socioeconomic, and medical conditions on the occurrence of osteoporosis in the middle-aged and elderly people in China has not been fully addressed. Methods: The study was a multicenter cross-sectional study on the middle-aged and elderly permanent residents, which gathered information of 22,081 residents from June 2015 to August 2021 in seven representative regions of China. The bone mineral density of lumbar vertebrae and hip were determined using the dual-energy X-ray absorptiometry densitometer instruments. Serum levels of bone metabolism markers were also measured. Information about education, smoking, and chronic diseases were also collected through face-to-face interviews. Age-standardized prevalence and 95% confidence intervals (CIs) of osteopenia and osteoporosis by various criteria were estimated by subgroups and overall based on the data of China 2010 census. The relationships between the osteoporosis or osteopenia and sociodemographic variables or other factors were examined using univariate linear models and multivariable multinomial logit analyses. Results: After screening, 19,848 participants (90%) were enrolled for the final analysis. The age-standardized prevalence of osteoporosis was estimated to be 33.49%(95%CI, 32.80-34.18%) in the middle-aged and elderly Chinese permanent residents, for men and women was 20.73% (95% CI, 19.58-21.87%) and 38.05% (95% CI, 37.22-38.89%), respectively. The serum concentrations of bone metabolic markers, and calcium and phosphorus metabolism were influenced by age, body mass index (BMI), gender, education level, regions, and bone mass status. Women, aged 60 or above, BMI lower than 18.5 kg/m2, low education level including middle school, primary school and no formal education as well as current regular smoking, a history of fracture were all significantly associated with a higher risk of osteoporosis and osteopenia in the middle-aged and elderly people. Conclusions: This study revealed dramatic regional differences in osteoporosis prevalence in China, and female, aged 60 or older, low BMI, low education level, current regular smoking, and a history of fracture were associated with a high risk of osteoporosis. More prevention and treatment resources should be invested into particular population exposed to these risk factors.

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.

[Protective effect of velvet antler polypeptide (VAP) on rats with the spinal cord injury].

OBJECTIVE: To investigate the protective effect of antler polypeptide on the rats with spinal cord injury (SCI). METHODS: The model rats were treated with different doses of antler polypeptide, and its effect on motor function, ethology and pathological changes of spinal cord of the rats observed. RESULTS: Seven days after treatment with different doses of antler polypeptide, rat's motor activity was recovered in some extent. Significant difference (P < 0.001)was found between the antler polypeptide treatment group and operation group. The effect could be enhanced by increase of the doses. We observerd the effect on the pathological change of spinal cord in rat, and found the tissue edema and inflammatory infiltration were relieved after treatment with different doses of antler polypeptide, especially in the dose of 15 mg antler polypeptide. CONCLUSION: Antler polypeptide can promote the motor function recovery in SCI rats, and its action is dose-dependent.