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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.
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RATIONALE: Gout in the spine and adnexa is rare in clinical practice and can also be easily misdiagnosed, we reported a patient with nerve root compression due to lumbar gout stones in the lumbar spinal canal. PATIENT CONCERNS: A 51-year-old male was admitted to the hospital with lumbar pain with numbness in the left lower limb for more than 6 months. The physical examination showed that tenderness and percussion pain were present at L4-S1 spinous process. Straight leg raise test: 50° on the left side were positive. Laboratory tests showed that the sUA was 669 µmol/L, MRI of the lumbar spine showed that cystic T1WI low signal and T2WI mixed high signal shadows were seen in the spinal canal at the level of L4-L5. DIAGNOSES: Combining with lab examinations, imaging examinations, and histopathological results, the patient was diagnosed with lumbar spinal canal tophi. INTERVENTIONS: After active improvement of all examinations, the patient underwent surgical treatment with decompression and internal fixation of the L4-L5 segment. OUTCOMES: After surgery, the patient's symptoms improved and muscle strength returned to normal. Among the 95 previously reported patients with lumbar gout, the ratio of men to women was 2.96:1, and the peak age group of incidence was 56 to 65 years. The onset of the disease was mainly in a single segment of the lumbar spine, with 34.41% of all cases occurring at the L4-L5 level. 61.05% of the patients had a history of gout attacks or hyperuricemia, and the most frequently involved site was the foot and ankle, followed by the wrist. Sixty-seven patients underwent surgical treatment, and 22 chose conservative treatment, with overall satisfactory results. LESSONS SUBSECTIONS: The incidence of lumbar gout is low and relatively rare in the clinic and pathological biopsy is still the gold standard. Vertebral plate incision and decompression are often selected for surgical treatment, and whether to perform fusion should be comprehensively considered for the destruction of vertebral bone by gout and the reasonable selection of the extent of surgical resection. Whether choosing surgical treatment or conservative therapy, the control of uric acid levels should be emphasized.