1.Treatment of Hyperuricemia and Gouty Arthritis by Buyang Huanwu Tongfeng Decoction via Inhibition of PPAR-γ/NF-κB/AGEs/RAGE Pathway Based on Network Pharmacology
Yue CAO ; Wanmei YAO ; Tao YANG ; Man YANG ; Ruimin JIA ; Rongrong LU ; Xue FENG ; Biwang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):182-192
ObjectiveThis paper aims to investigate the potential molecular biological mechanism of Buyang Huanwu Tongfeng decoction in treating hyperuricemia and gouty arthritis by network pharmacology and molecular docking technology and preliminarily verify the mechanism through animal experiments. MethodsThe active ingredients and targets in the Buyang Huanwu Tongfeng decoction were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and ETCM databases. The DisGeNET and GeneCards databases were utilized to acquire disease targets associated with hyperuricemia and gouty arthritis. These disease targets were then intersected with drug targets to identify key targets. The R language ClusterProfiler package and Python were employed for conducting gene ontology(GO) enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis. The regulatory network diagram of the drug-key target-function-pathway was visualized using Cytoscape 3.9.1 software, and the protein-protein interaction (PPI) network for key targets was depicted. Finally, the hub gene was determined through topological analysis. Auto Dock, PyMOL, and other software were used for molecular docking to explore the possible therapeutic mechanism of Buyang Huanwu Tongfeng decoction for hyperuricemia and gouty arthritis. In animal experiments, a composite rat model of hyperuricemia induced by intraperitoneal injection of oteracil potassium combined with gouty arthritis induced by the modified Coderre method was established. Through hematoxylin-eosin(HE) staining, uric acid test, enzyme linked immunosorbent assay(ELISA), Western blot, and real-time polymerase chain reaction(Real-time PCR), the molecular mechanism and key targets of Buyang Huanwu Tongfeng decoction for treating hyperuricemia and gouty arthritis were observed. ResultsAfter screening and removing duplicate values, 76 active ingredients and 15 key targets were finally obtained. GO enrichment analysis yielded that the treatment of hyperuricemia and gouty arthritis with Buyang Huanwu Tongfeng decoction was significantly associated with acute inflammatory response, astrocyte activation, regulation of interleukin (IL)-8 production, nuclear receptor activity, and binding of growth factor receptor. KEGG pathway enrichment analysis obtained that the key target genes were significantly associated with the IL-17 signaling pathway, advanced glycosylation end/receptor of advanced glycation endproducts(AGE/RAGE) signaling pathway, anti-inflammatory, and other pathways. PPI network indicated that albumin(ALB), peroxisome proliferator-activated receptor-γ (PPAR-γ), IL-6, IL-1β, and C-reactive protein(CRP) were the key protein targets. The molecular docking results showed that ALB had the strongest binding force with beta-carotene (β-carotene). Biochemical results showed that blood uric acid decreased in the Buyang Huanwu Tongfeng decoction groups. HE staining results showed that the low-dose (7.76 g·kg-1·d-1), medium-dose (15.53 g·kg-1·d-1), and high-dose (31.05 g·kg-1·d-1) groups of Buyang Huanwu Tongfeng decoction had different degrees of remission, and the remission of the high-dose group was the most obvious. Fibroblastic tissue hyperplasia in synovial joints accompanied with inflammatory cell infiltration, as well as inflammatory cell infiltration in renal tissue of the high-dose group was significantly reduced, followed by the medium-dose and low-dose groups, and the expression of ALB, PPAR-γ, IL-6, IL-1β, and CRP was down-regulated to different degrees. ConclusionBy regulating the targets such as ALB, PPAR-γ, IL-6, IL-1β, and CRP, inhibiting the PPAR-γ/nuclear transcription factor (NF)-κB pathway, and reducing AGEs/RAGE-mediated inflammation, Buyang Huanwu Tongfeng decoction exerts anti-inflammatory and analgesic effects and activates blood circulation and diuresis in the treatment of hyperuricemia and gouty arthritis.
2.Preoperative standing to prone spinal-pelvic sagittal parameter changes in old traumatic spinal fractures with kyphosis.
Wanmei YANG ; Xilong CUI ; Kangkang WANG ; Wei ZHANG ; Wen YIN ; Jishi JIANG ; Haiyang YU
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(5):596-600
OBJECTIVE:
To investigate the changes in spinal-pelvic sagittal parameters from preoperative standing to prone position in old traumatic spinal fractures with kyphosis.
METHODS:
The clinical data of 36 patients admitted between December 2016 and June 2021 for surgical treatment of old traumatic spinal fractures with kyphosis, including 7 males and 29 females, aged from 50 to 79 years (mean, 63.9 years), were retrospectively analyzed. Lesion segments included 2 cases of T 11, 12 cases of T 12, 2 cases of T 11, 12, 4 cases of T 12 and L 1, 12 cases of L 1, 2 cases of L 2, 1 case of L 2, 3, and 1 case of L 3. The disease duration ranged from 4 to 120 months, with an average of 19.6 months. Surgical procedures included Smith-Petersen osteotomy in 4 cases, Ponte osteotomy in 6 cases, pedicle subtraction osteotomy in 2 cases, and improved fourth level osteotomy in 18 cases; the remaining 6 cases were not osteotomized. The bone mineral density ranged from -3.0 to 0.5 T, with a mean of -1.62 T. The spinal-pelvic sagittal parameters from preoperative standing to prone positions were measured, including local kyphosis Cobb angle (LKCA), thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), and PI and LL mismatch (PI-LL). The kyphotic flexibility=(preoperative standing LKCA-preoperative prone LKCA)/preoperative standing LKCA×100%. Spinal-pelvic sagittal parameters were compared between standing position and prone position before operation, and Pearson correlation was used to judge the correlation between the parameters of standing position and prone position before operation.
RESULTS:
When the position changed from standing to prone, LKCA and TK decreased significantly ( P<0.05), while SS, LL, PT, and PI-LL had no significant difference ( P>0.05). Pearson correlation analysis showed that LL was significantly correlated with SS and PI-LL in both standing and prone positions ( P<0.05), and the correlation strength between LL and SS in prone position was higher than that in standing position. In the standing position, LKCA was significantly correlated with SS and PT ( P<0.05). However, when the position changed from standing to prone, the correlation between LKCA and SS and PT disappeared, while PT and PI-LL was positive correlation ( P<0.05). The kyphotic flexibility was 25.13%-78.79%, with an average of 33.85%.
CONCLUSION
For the patients of old traumatic spinal fractures with kyphosis, the preoperative LKCA and TK decrease significantly from standing position to prone position, and the correlation between spinal and pelvic parameters also changed, which should be taken into account in the formulation of preoperative surgical plan.
Male
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Female
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Humans
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Spinal Fractures/surgery*
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Standing Position
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Retrospective Studies
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Lumbar Vertebrae/surgery*
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Kyphosis/surgery*
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Lordosis/surgery*