Total saponins extracted from Dioscorea collettii (TSD), extracts of the Chinese herb Dioscorea, are thought to exhibit therapeutic benefit in gouty arthritis. However, its exact mechanism remains unclear. The current study aimed to elucidate the underlying mechanisms by investigating the effects of TSD on the inflammation induced by monosodium urate (MSU) crystals in THP‑1 macrophages. The viability of THP‑1 macrophages was examined using the MTT assay and the levels of inflammatory cytokines, including interleukin (IL)‑1β, IL‑18 and tumor necrosis factor (TNF)‑α, released by the cells were quantitatively measured using ELISA kits. The results revealed that the protein level of cluster of differentiation 11b increased in THP‑1 cells treated with 100 ng/ml phorbol ester, suggesting that monocytic THP‑1 cells were successfully differentiated into macrophages. TSD decreased the levels of inflammatory cytokines, including TNF‑α, IL‑18 and IL‑1β, secreted by THP‑1 macrophages. As the release of IL‑1β and IL‑18 is dependent on the NLR family pyrin domain containing 3 (NALP3) inflammasome and caspase‑1, the current study investigated the effect of TSD on the aforementioned proteins. The results revealed that TSD decreased the protein levels of NALP3 and apoptosis‑associated speck‑like, which serve important roles in the assembly of the NALP3 inflammasome. Furthermore, NALP3 inflammasome‑related proteins were also decreased by TSD in rotenone induced THP‑1 macrophages, TSD inhibited the activation of caspase‑1 and rotenone‑induced NALP3 inflammasome activation in THP‑1 macrophages. The results obtained in the current study revealed that TSD attenuated MSU crystal‑induced inflammation by inhibiting rotenone‑induced activation of the NALP3 inflammasome and caspase‑1, suggesting that these two proteins may be novel targets for the treatment of gouty arthritis.

Background. Rhizomes from Dioscorea collettii are extensively used in traditional medicine for the treatment of arthritic diseases, particularly gouty arthritis (GA). This study aims to investigate whether the total saponin of Dioscorea collettii (TSD) can attenuate monosodium urate (MSU) crystal-induced inflammatory effects by suppressing the activation of the TLR4/NF-κB signaling pathway in vivo and in vitro. Methods. Seventy-two male Wistar rats and THP-1 cells were used in this study. Pathological examination was used to examine the ankle joints of rats. The expression levels of TLR4, NF-κB, MyD88, and IL-1β were detected by qRT-PCR, Western blotting, or immunofluorescence. Results. Compared with those in the normal group, the ankle joints of rats in the model group exhibited significant swelling, synovial tissue hyperplasia, inflammatory cell infiltration, and increased expression of IL-1β protein. The joint swelling degree of rats in the TSD high- and medium-dose groups and the colchicine group was significantly decreased, and the histopathology was obviously improved. TSD and colchicine reduced the levels of IL-1β and TNF-α in synovial fluid. They also decreased the mRNA expression of TLR4, NF-κB, and IL-1β in rat joint synovial tissue and the protein expression of TLR4, MyD88, and NF-κB. NF-κB protein expression in both the cytoplasm and nuclei of THP-1 cells showed the opposite trend. Furthermore, immunofluorescence showed that TSD reduced the nuclear translocation of NF-κBp65 in the model group. Conclusion. TSD exhibits an anti-inflammatory effect in the MSU-induced inflammation model, and the mechanism may be to reduce the production of cytokines by inhibiting the activation of the TLR4/NF-κB signaling pathway.

Increased arterial stiffness is highly prevalent in patients with hypertension and is associated with cardiovascular (CV) risk. Increased white blood cell (WBC) counts may also be an independent risk factor for arterial stiffness and CV events. The aim of the study was to investigate the relationship between differential WBC counts and brachial-ankle pulse wave velocity (baPWV) in hypertensive adults. A total of 14 390 participants were included in the final analysis. A multivariate linear regression model was applied for the correlation analysis of WBC count and baPWV. Higher WBC counts were associated with a greater baPWV: adjusted β = 10 (95% CI, 8-13, P < .001). The same significant association was also found when WBC count was assessed as categories or quartiles. In addition, the effect of differential WBC subtypes, including neutrophil count and lymphocyte count on baPWV, showed the similar results. These findings showed that baPWV has positive associations with differential WBC counts in hypertensive adults.

Morellic acid (MA), a typical compound found in Garcinia plants, is known for its anticancer properties. In present study, we isolated MA from resin of Garcinia hanburyi Hook. f. using preparative chromatography. We have successfully prepared MA-loaded nanostructured lipid carriers (MA-NLCs) and refined the production process via orthogonal testing. Optimization of the preparation process resulted in an average particle size of 165.50±1.70 nm with a PDI of 0.19±0.01. The EE% and DL% of MA-NLCs were 78.17±0.34% and 7.25±0.38%, respectively. The zeta potential of MA-NLCs was -21.85±0.67 mV. Comparatively, MA-NLCs showed a greater area under the curve (AUC) and an extended half-life (t1/2) than free MA. Pharmacokinetics analysis revealed that the AUC_0-t increased from 4.91±0.65 μg/mL∙min (free MA) to 18.91±3.40 μg/mL∙min (MA-NLCs) and the t_1/2 value for MA-NLCs was 7.93-fold longer than that of free MA. In vitro cytotoxic assessments indicated that MA formulations curtailed the proliferation of cancer cells. In vivo, MA-NLCs significantly inhibited the tumor growth in tumor-bearing mouse model. Molecular mechanism studies revealed that up-regulation of apaf-1 and activation of caspase-3, caspase-9 and GSDME by MA-NLCs may trigger to apoptosis and pyroptosis in cancer cells. Consequently, our findings support the potential of NLCs as an effective MA delivery system for the clinical management of cancer.