Résumé
Along with the development of economy and society, type 2 diabetic mellitus (T2DM) has become one of the most common diseases at the global level. As one of the complications of T2DM, diabetic neuropathic pain (DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion (DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents (I(Na)). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2DM and its various complications including DNP effectively. The present study demonstrates that the I(Na) of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin.
Sujets)
Animaux , Rats , Curcumine , Pharmacologie , Diabète expérimental , Diabète de type 2 , Neuropathies diabétiques , Traitement médicamenteux , Ganglions sensitifs des nerfs spinaux , Biologie cellulaire , Métabolisme , Névralgie , Traitement médicamenteux , Neurones , Métabolisme , Sodium , Canaux sodiques voltage-dépendants , PhysiologieRésumé
Objective: To study the anti-complementary anthraquinones from Polygonum cuspidatum and their action targets. Methods: The anti-complementary activity-directed isolation was carried out with the hemolysis test as guide. All isolates were evaluated for their in vitro anti-complementary activities. The action targets of the main bioactive constituents were also examined using complement-depleted sera. Results: Ten anthraquinones and three other compounds were isolated from the EtOAc fraction of P. cuspidatum extract, including physcion (1), chrysophanol (2), questin (3), emodin-8-O-β-D-glucoside (4), emodin (5), rhein (6), fallacinol (7), citreorosein (8), xanthorin (9), isorhodoptilometrin (10), 2, 5-dimethyl-7-hydroxychromone (11), 7-hydroxy-4-methoxy-5-methylcoumarin (12), and 5, 7-dihydroxy-1-isobenzofuranone (13). Compounds 9 and 10 were isolated from the the plants of Polygonaceae for the first time, and compound 9 was the alizarin-type anthraquinone first obtained from P. cuspidatum. Compounds 3-9 showed the anti-complementary activity in different degrees, and compound 7 exhibited the most significant activity against the classical and alternative pathway [CH50 = (6 ± 2) μg/mL, AP50 = (50 ± 5) μg/mL]. The study on the preliminary mechanism revealed that compound 4 interacted with C1q, C2, and C9 in complement activation cascade, while compound 7 acted on C1q, C2, C4, and C9. Conclusion: The anthraquinones are main anti-complementary constituents in P. cuspidatum; and fallacinol (7) is a potential complement inhibitor with strong activity and definite targets, which should be further studied in future.
Résumé
<p><b>OBJECTIVE</b>To identify new genes required for neurosecretory control of aging in C. elegans.</p><p><b>METHODS</b>In view of the importance of nervous system in aging regulation, we performed the screen for genes involved in the aging regulation from genetic loci encoding synaptic proteins by lifespan assay and accumulation of lipofuscin autofluorescence. We further investigated the dauer formation phenotypes of their corresponding mutants and whether they were possibly up-regulated by the insulin-like signaling pathway.</p><p><b>RESULTS</b>The genetic loci of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4, nrx-1, unc-13, sbt-1 and unc-64 might be involved in the aging control. In addition, functions of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4 and nrx-1 in regulating aging may be opposite to those of unc-13, sbt-1 and unc-64. The intestinal autofluorescence assay further indicated that the identified long-lived and short-lived mutants were actually due to the suppressed or accelerated aging. Among the identified genes, syd-2, hlb-1, mkk-4, scd-2, snb-1, ric-4 and unc-64 were also involved in the control of dauer formation. Moreover, daf-2 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, ric-4, sbt-1, rpm-1, unc-10, dlk-1 and unc-13. The daf-16 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, sbt-1, rpm-1, unc-10, dlk-1 and unc-13.</p><p><b>CONCLUSION</b>These data suggest the possibly important status of the synaptic transmission to the animal's life-span control machinery, as well as the dauer formation control.</p>