Embelin protects against apoptosis and inflammation by regulating PI3K/Akt signaling in IL-1ß-stimulated human nucleus pulposus cells.

Embelin is a natural benzoquinone compound that displays a beneficial effect in various inflammatory-related diseases. However, the effect of embelin on degeneration of intervertebral disc (IDD), a chronic inflammatory disorder, has not been reported. This study was attempted to explore the therapeutic action of embelin on IDD in vitro. Network pharmacology analysis was performed for evaluating the link between embelin and IDD. The human nucleus pulposus cells (NPCs) were stimulated with IL-1ß to induce inflammation. Cell viability of NPCs was assessed by CCK-8 assay. Western blotting was conducted to detect the expression levels of PI3K, p-PI3K, Akt, p-Akt, cleaved caspase-3, caspase-3, Bax, Bcl-2, p65 and p-p65. Apoptotic deaths of NPCs were examined by TUNEL assay. The production of COX-2, IL-6, IL-8, and TNF-α was examined by ELISA. It can be seen that 16 overlapping genes were selected from 109 possible targets of embelin and 342 possible targets of IDD. KEGG pathway enrichment analysis showed that the PI3K/Akt signaling pathway was a close link between embelin and IDD. We found that embelin dose-dependently improved the cell viability in IL-1ß-stimulated NPCs. Embelin elevated the relative levels of p-PI3K/PI3K and p-Akt/Akt in IL-1ß-stimulated NPCs. IL-1ß induced a significant increase in apoptotic deaths of NPCs, which was attenuated by embelin treatment. IL-1ß-induced alternations in expression levels of apoptotic-related proteins including cleaved caspase-3, Bax and Bcl-2 were prevented by embelin treatment. Pretreatment with LY294002 (an inhibitor of PI3K) reversed the inhibitory effect of embelin on IL-1ß-induced apoptosis in NPCs. Embelin treatment caused inhibitory effects on the IL-1ß-stimulated production of COX-2, IL-6, IL-8, and TNF-α, which were abolished by LY294002 treatment. Furthermore, embelin treatment prevented IL-1ß-induced phosphorylation of p65 in NPCs, while LY294002 elevated the embelin-caused decrease in p-p65/p65 level. Overall, embelin protected human NPCs against IL-1ß-stimulated apoptosis and inflammation by regulating the PI3K/Akt signaling pathway. These findings provided new ideas for the clinical usage of embelin in the prevention and treatment of IDD.

Cyanidin attenuates the apoptosis of rat nucleus pulposus cells and the degeneration of intervertebral disc via the JAK2/STAT3 signal pathway in vitro and in vivo.

CONTEXT: Cyanidin has been shown to have therapeutic potential in osteoarthritis. However, it is unclear whether cyanidin prevents the progression of intervertebral disc degeneration (IVDD). OBJECTIVE: This study evaluates the effects of cyanidin on IVDD in vitro and in vivo. MATERIALS AND METHODS: Nucleus pulposus cells (NPCs) isolated from lumbar IVD of 4-week-old male Sprague-Dawley (SD) rats were exposed to 20 ng/mL IL-1ß, and then treated with different doses (0-120 µM) of cyanidin for 24 h. SD rats were classified into three groups (n = 8) and treated as follows: control (normal saline), IVDD (vehicle), IVDD + cyanidin (50 mg/kg). Cyanidin was administered intraperitoneally for 8 weeks. RESULTS: The IC50 of cyanidin for NPCs was 94.78 µM, and cyanidin had no toxicity at concentrations up to 500 mg/kg in SD rats. Cyanidin inhibited the apoptosis of NPCs induced by IL-1ß (12.73 ± 0.61% vs. 18.54 ± 0.60%), promoted collagen II (0.82-fold) and aggrecan (0.81-fold) expression, while reducing MMP-13 (1.02-fold) and ADAMTS-5 (1.40-fold) expression. Cyanidin increased the formation of autophagosomes in IL-1ß-induced NPCs, and promoted LC3II/LC3I (0.83-fold) and beclin-1 (0.85-fold) expression, which could be reversed by chloroquine. Cyanidin inhibited the phosphorylation of JAK2 (0.47-fold) and STAT3 (0.53-fold) in IL-1ß-induced NPCs. The effects of cyanidin could be enhanced by AG490. Furthermore, cyanidin mitigated disc degeneration in IVDD rats in vivo. DISCUSSION AND CONCLUSIONS: Cyanidin improved the function of NPCs in IVDD by regulating the JAK2/STAT3 pathway, which may provide a novel alternative strategy for IVDD. The mechanism of cyanidin improving IVDD still needs further work for in-depth investigation.

Percutaneous endoscopic lumbar discectomy compared with other surgeries for lumbar disc herniation: A meta-analysis.

OBJECTIVE: This meta-analysis was performed to investigate whether percutaneous endoscopic lumbar discectomy (PELD) had a superior effect than other surgeries in the treatment of patients with lumbar disc herniation (LDH). METHOD: We searched PubMed, Embase, and Web of Science through February 2018 to identify eligible studies that compared the effects and complications between PELD and other surgical interventions in LDH. The outcomes included success rate, recurrence rate, complication rate, operation time, hospital stay, blood loss, visual analog scale (VAS) score for back pain and leg pain, 12-item Short Form Health Survey (SF12) physical component score, mental component score, Japanese Orthopaedic Association Score, Oswestry Disability Index. A random-effects or fixed-effects model was used to pool the estimate, according to the heterogeneity among the included studies. RESULTS: Fourteen studies (involving 2,528 patients) were included in this meta-analysis. Compared with other surgeries, PELD had favorable clinical outcomes for LDH, including shorter operation time (weight mean difference, WMD=-18.14 minutes, 95%CI: -25.24, -11.05; P < .001) and hospital stay (WMD = -2.59 days, 95%CI: -3.87, -1.31; P < .001), less blood loss (WMD = -30.14 ml, 95%CI: -43.16, -17.13; P < .001), and improved SF12- mental component score (WMD = 2.28, 95%CI: 0.50, 4.06; P = .012)) and SF12- physical component score (WMD = 1.04, 95%CI: 0.37, 1.71; P = .02). However, it also was associated with a significantly higher rate of recurrent disc herniation (relative risk [RR] = 1.65, 95%CI: 1.08, 2.52; P = .021). There were no significant differences between the PELD group and other surgical group in terms of success rate (RR = 1.01, 95%CI: 0.97, 1.04; P = .733), complication rate (RR = 0.86, 95%CI: 0.63, 1.18; P = .361), Japanese Orthopaedic Association Score score (WMD = 0.19, 95%CI: -1.90, 2.27; P = .861), visual analog scale score for back pain (WMD = -0.17, 95%CI: -0.55, 0.21; P = .384) and leg pain (WMD = 0.00, 95%CI: -0.10, 0.10; P = .991), and Oswestry Disability Index score (WMD = -0.29, 95%CI: -1.00, 0.43; P = .434). CONCLUSION: PELD was associated with better effects and similar complications with other surgeries in LDH. However, it also resulted in a higher recurrence rate. Considering the potential limitations in the present study, further large-scale, well-performed randomized trials are needed to verify our findings.