Cistanche deserticola has been found to exert protection against aging and age-related diseases, but mechanisms underlying its longevity effects remain largely unclear. Here, the multicellular model organism Caenorhabditis elegans was employed to identify lifespan extending and protective effects against β-amyloid (Aβ) induced toxicity by echinacoside (ECH), a phenylethanoid glycoside isolated from C. deserticola. Our results showed that ECH extends the mean lifespan of worms and increases their survival under oxidative stress. Levels of intracellular reactive oxygen species and fat accumulation were also significantly suppressed by ECH. Moreover, ECH-mediated lifespan extension was found to be dependent on mev-1, eat-2, daf-2, and daf-16, but not sir-2.1 or hsf-1 genes. Furthermore, ECH triggered DAF-16 nuclear localization and upregulated two of its downstream targets, sod-3 and hsp-16.2. In addition, ECH significantly improved the survival of CL4176 worms in response to proteotoxic stress induced by Aβ protein aggregation. Collectively, these findings suggested that reactive oxygen species scavenging, dietary restriction, and insulin/insulin-like growth factor signaling pathways could be partly involved in ECH-mediated lifespan extension. Thus, ECH may target multiple longevity mechanisms to extend lifespan and have a potency to prevent Alzheimer's disease progression.
SUMMARY The 2008 Wenchuan earthquake, which occurred on the eastern edge of the Tibetan Plateau, produced significant time-dependent post-seismic deformation in the northeastern Tibetan Plateau. To explore the spatio-temporal evolution of crustal deformation and its impact on nearby active faults due to the Wenchuan earthquake, we first solve the velocity fields, strain rates and slip rates of the major faults at different stages of the earthquake cycle, based on GPS observations spanning approximately 10 yr before and after the Wenchuan earthquake. The results show that: (a) during the late interseismic phase, the GPS velocity fields relative to the Sichuan basin and strain rates near the Longmenshan fault (the seismogenic fault of the Wenchuan earthquake) are insignificant in magnitude, and the geodetic slip rates of the major faults are in good agreement with geological investigations; (b) After the Wenchuan earthquake, post-seismic deformation on both flanks of the causative Longmenshan fault is asymmetrically distributed, with significant deformation distributed between the Longmenshan fault and the Longriba fault. The post-seismic deformation decreases with increasing distance away from the Longmenshan fault. Furthermore, geodetic slip rates for the major active faults at the early post-seismic stage differ significantly from those at the late interseismic stage; (c) The crustal deformation in the northeastern Tibetan Plateau is generally small during the late interseismic phase, but it increases significantly during the early post-seismic stage and begins to decrease again as it progresses to the second post-seismic stage. We speculate that this kinematic evolution of crustal deformation is ascribed to that the Longmenshan fault was in a locking state during the late interseismic period, whereas the Longmenshan fault is no longer locked after the Wenchuan earthquake, and thus the marked post-seismic deformation occurred in the epicentral and its surrounding area. Then, the post-seismic deformation becomes weaker with time lapse, and generally the crustal deformation begins to slowly recover to the pre-seismic level. Using a forward model, we test whether post-seismic deformation caused by viscoelastic relaxation of the lower crust 4 yr after the Wenchuan earthquake can explain the observed spatio-temporal pattern of the crustal deformation. We find that this mechanism can account for the evolutionary pattern of crustal motion in the Songpan-Ganzi block east of the Longriba fault in central-east Tibet and central-eastern and southern regions of the West Qinling-Songpan Tectonic Syntaxis in east Tibet 4 yr after the Wenchuan earthquake. Moreover, the post-seismic viscoelastic relaxation of the Wenchuan earthquake is the main cause of loading rate variations of primary faults in the early post-seismic stage in the northeastern Tibetan Plateau.
BackgroundOsteoclast excessive activation was closely related to bone diseases such as osteoporosis and rheumatoid arthritis. Sec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of divaricate Saposhnikovia, was reported to exhibit analgesic, anti-inflammatory and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis and bone resorption remained unclear.MethodsOsteoclast formation, bone resorption pit area formation and F-actin ring formation were examined by TRAP staining, modified Vonkonsa staining and immunofluorescence, respectively. RT-Realtime PCR assay and western blot analysis were performed. siRNA transfection was conducted to silence the expression of 5-LO in cells. LPS-induced bone-loss mice model was prepared and the left and right femurs were collected for Micro-CT and histomorphometric analysis, respectively.ResultsSOG markedly attenuated RANKL-induced osteoclastogenesis through decreasing TRAP activity, F-actin ring formation and bone resorption with reduction of mRNA levels of osteoclastogenesis marker genes such as TRAP, CTSK and DC-STAMP. Our results further indicated that SOG markedly reduced the induction of key transcription factors NFATc1 and c-Fos at both mRNA and protein levels during osteoclastogenesis. In addition, SOG treatment did not alter the transient phosphorylation of NF-κB p65 subunit and MAPKs (p38, ERK1/2 and JNK), AKT and GSK3β by RANKL. Interestingly, our results showed that SOG significantly inhibited the phosphorylation of AKT and GSK3β at middle-late stage of osteoclastogenesis, but did not alter calcineurin catalytic subunit PP2B-Aα expression. GSK3β inhibitor SB415286 could partly reverse inhibition of osteoclastogenesis by SOG. 5-LO knockdown at BMMs also markedly reduced RANKL-induced osteoclastogenesis. In consistent with in vitro results,SOG could significantly improve bone destruction in LPS-induced mice model.ConclusionsSOG attenuated formation and function of osteoclast through suppressing AKT-mediated GSK3β inactivation, and 5-LO catalytic activity. Moreover, SOG prevented LPS-induced bone loss in mice through inhibiting osteoclastogenesis. Taken together, this study provided the evidence that SOG may have a potential therapeutic effect on osteoclast-related bone lysis disease.
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