Study on the mechanism of action of Saposhnikovia divaricata and its key phytochemical on rheumatoid arthritis based on network pharmacology and bioinformatics.

ETHNOPHARMACOLOGICAL RELEVANCE: Saposhnikovia divaricata (Turcz.) Schischk (SD; called "fangfeng" in China) has been widely used in the clinical treatment of rheumatoid arthritis (RA) and has shown well therapeutic effects, but the specific mechanisms of action of its bioactive phytochemicals remain unclear. AIM OF THE STUDY: This study aimed to investigate the molecular biological mechanism of SD in treating RA through a pharmacology-based strategy. The SD-specific core ingredient Prangenidin was screened for further in-depth study. MATERIALS AND METHODS: The bioactive phytochemicals of SD and potential targets for the treatment of RA were screened by network pharmacology, and phytochemicals-related parameters such as pharmacology, and toxicology were evaluated. The protein interaction network was established to screen the core targets, and the correlation between the core targets and RA was further validated by bioinformatics strategy. Finally, molecular docking of core components and corresponding targets was performed. The in vitro experiments were performed to elucidate the regulation of Prangenidin on MH7A cells and on the PI3K/AKT pathway, and the in vivo therapeutic effect of Prangenidin was validated in collagen-induced arthritis (CIA) mice. RESULTS: A total of 18 bioactive phytochemicals and 66 potential target genes intersecting with the screened RA disease target genes were identified from SD. Finally, core ingredients such as wogonin, beta-sitosterol, 5-O-Methylvisamminol, and prangenidin and core targets such as PTGS2, RELA, and AKT1 were obtained. The underlying mechanism of SD in treating RA might be achieved by regulating pathways such as PI3K/AKT, IL-17 pathway, apoptosis, and multiple biological processes to exert anti-inflammatory and immunomodulatory effects. Molecular docking confirmed that all core ingredients and key targets had great docking activity. Prangenidin inhibited viability, migration, and invasion, and induced apoptosis in MH7A cells. Prangenidin also reduced the production of IL-1ß, IL-6, IL-8, MMP-1, and MMP-3. Molecular analysis showed that Prangenidin exerts its regulatory effect on MH7A cells by inhibiting PI3K/AKT pathway. Treatment with Prangenidin ameliorated synovial inflammation in the joints of mice with CIA. CONCLUSION: Our findings provide insights into the therapeutic effects of SD on RA, successfully predicting the effective ingredients and potential targets, which could suggest a novel theoretical basis for further exploration of its molecular mechanisms. It also revealed that Prangenidin inhibited viability, migration, invasion, cytokine, and MMPs expression, and induced apoptosis in RA FLSs via the PI3K/AKT pathway.

[Robot-assisted PVP for the treatment of osteoporotic fractures of the upper thoracic vertebra].

OBJECTIVE: To investigate the clinical effect of "Tianji" orthopedic robot-assisted percutaneous vertebro plasty(PVP) surgery in the treatment of upper thoracic osteoporotic fracture. METHODS: A retrospective analysis was performed on 32 patients with upper thoracic osteoporotic fracture who underwent PVP surgery in Shenzhen Hospital of Traditional Chinese Medicine from August 2016 to June 2022. There were 8 males and 24 females, ranging in age from 58 to 90 years old, with a mean of (67.75±12.27) years old. Fifteen patients were treated with robot-assisted PVP surgery (robot group), including 3 males and 12 females, with an average age of (68.5±10.3) years. Fracture location:1 case of T2 fracture, 1 case of T3 fracture, 3 cases of T4 fracture, 3 cases of T5 fracture, and 7 cases of T6 fracture. The follow-up period ranged from 1.0 to 3.0 months, with a mean of (1.6±0.7) months. Seventeen patients underwent routine PVP surgery (conventional group), including 5 males and 12 females, with an average age of (66.8±11.6) years old. Fracture location:1 case of T1 fracture, 5 cases of T4 fracture, 2 cases of T5 fracture and 9 cases of T6 fracture. The follow-up period ranged from 0.5 to 4.0 months, with a mean of (1.5±0.6) months. Preoperative and postoperative visual analogue scale(VAS) and Oswestry disability index(ODI) scores were compared between the two groups, and the number of punctures, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage, and intraoperative radiation dose were compared between the two groups. RESULTS: Number of punctures times, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage and intraoperative radiation dose in the robot group were all significantly better than those in the conventional group(P<0.05). VAS of 2.03±0.05 and ODI of (22.16±4.03) % in the robot group were significantly better than those of the robot group before surgery, which were (8.67±0.25) score and (79.40±7.72)%(t=100.869, P<0.001;t=25.456, P<0.001). VAS of 2.17±0.13 and ODI of (23.88±6.15)% in the conventional group were significantly better than those before surgery, which were (8.73±0.18) score and (80.01±7.59)%(t=121.816, P<0.001;t=23.691, P<0.001). There was no significant difference in VAS and ODI between the two groups after operation (t=-3.917, P=0.476;t=-0.922, P=0.364). CONCLUSION: Robot-assisted PVP in the treatment of upper thoracic osteoporotic fractures can further improve surgical safety, reduce bone cement leakage, and achieve satisfactory clinical efficacy.

Treatment of degenerative lumbar scoliosis using transforaminal lumbar interbody fusion based on the concept of intervertebral correction.

PURPOSE: The study aimed to examine the outcomes of posterior approach transforaminal lumbar interbody fusion (TLIF) in the treatment of degenerative lumbar scoliosis (DLS) based on the concept of intervertebral correction. METHODS: A retrospective analysis was performed on 76 surgical patients (36 males and 40 females) who underwent posterior TLIF and internal fixation based on the concept of intervertebral correction in Shenzhen Traditional Chinese Medicine Hospital from February 2014 to March 2021.The operation duration, intraoperative blood loss, incision length, and complications were recorded. Clinical efficacy was evaluated preoperatively and postoperative time points through the visual analog scale (VAS) and the Oswestry disability index (ODI). The changes in the coronal scoliosis curve (Cobb angle), coronal balance distance (CBD), the sagittal vertical axis (SVA), lumbar lordosis (LL), and pelvic tilt angle (PT) were assessed perioperatively at the last follow-up. RESULTS: All patients successfully underwent the operation. The average operation duration was 243.81 ± 35.35 (220 - 350) min; the average intraoperative blood loss was 836.27 ± 50.28 (700 - 2500) mL; the average incision length was 8.30 ± 2.33 (8 - 15) cm. The total complication rate was 18.42% (14/76). The VAS score of low back pain, lower extremity pain, and ODI score of patients at the last follow-up was significantly improved compared with those before the operation (P < 0.05). At the last follow-up, the Cobb Angle, CBD, SVA, and PT of patients were significantly lower than those before the operation (P < 0.05), and LL was higher than those before the operation (P < 0.05). CONCLUSION: TLIF based on the concept of intervertebral correction for the treatment of DLS may provide favourable clinical outcomes.

Curcumol Alleviates the Inflammation of Nucleus Pulposus Cells via the PI3K/Akt/NF-κB Signaling Pathway and Delays Intervertebral Disk Degeneration.

BACKGROUND: Intervertebral disk degeneration (IVDD) is closely associated with inflammatory environments. Curcumol has been shown to alleviate inflammation in various disease models, but its effects on IVDD remain unclear. In this study, we sought to determine the mechanism of curcumol in tumor necrosis factor (TNF)-α-induced nucleus pulposus cells and a mouse IVDD model. METHODS: Nucleus pulposus cells were pretreated with curcumol and then exposed to TNF-α. Cell viability was analyzed using CCK-8, and the messenger ribonucleic acid and protein levels of inflammatory cytokines and PI3K/Akt/NF-κB-related signaling molecules were detected using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. The mouse IVDD model was established by puncturing the C6/7 level of the caudal spine, and then it was treated with curcumol after surgery. Alcian blue/orange G staining was performed to evaluate the severity of intervertebral disk damage, and immunohistochemistry was performed to detect the expression of TNF-α. Toxicologic effects of curcumol were measured by performing hematoxylin-eosin staining and enzyme-linked immunosorbent assay. RESULTS: Curcumol reduced IL-1ß, IL-6, and TNF-α production in NPCs, and the phosphorylation of proteins in the PI3K/Akt/NF-κB signaling pathway was also decreased. The PI3K/Akt/NF-κB-related signaling molecules decreased when TNF-α-induced NPCs were treated with a PI3K inhibitor; however, curcumol did not reverse these effects. In vivo, curcumol ameliorated the progression of IVDD at the early stage and did not exert toxicologic effects. CONCLUSIONS: These results suggest a potential therapeutic use of curcumol to alleviate inflammation via the PI3K/Akt/NF-κB signaling pathway and delay the progression of IVDD.