Cell senescence is intensively related to aging and neurodegenerative diseases. This study aimed to explore the effect and targets of Astragaloside IV against amyloid-beta-induced astrocyte senescence. Oligomerized amyloid-beta was prepared to culture with human astrocytes. The effects of Astragaloside IV were assessed based on SA-β-gal staining analysis, senescence markers (p53, p16INK4, and p21WAF1), neurotrophic growth factor levels (qRT-PCR), and cell proliferation (CCK-8 kit). The targets for Astragaloside IV were predicted, and hsp90aa1 protein was verified using molecular docking. After hsp90aa1 overexpression, the effects of Astragaloside IV on amyloid-beta-induced astrocytes were assessed. Treatment of human amyloid-beta-induced astrocytes with Astragaloside IV can decrease the percentage of SA-β-gal positive cells, downregulate the p53, p16INK4, and p21WAF1 levels, and increase the levels of neurotrophic growth factors (IGF-1 and NGF mRNA) and cell proliferation. Based on target prediction, hsp90aa1 was found to be a potential target of Astragaloside IV. Moreover, cellular experiments demonstrated that exogenously enhanced expression of hsp90aa1 overexpression suppressed the protective effect of Astragaloside IV on amyloid-beta-induced human astrocytes. The results presented here demonstrate that Astragaloside IV could confront amyloid-beta-induced astrocyte senescence via hsp90aa1, possibly opening new therapeutic avenues.
- MeSH
- amyloidní beta-protein * metabolismus MeSH
- astrocyty * účinky léků metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- nervový růstový faktor farmakologie MeSH
- proliferace buněk * účinky léků MeSH
- proteiny tepelného šoku HSP90 metabolismus MeSH
- saponiny * farmakologie MeSH
- simulace molekulového dockingu MeSH
- stárnutí buněk * účinky léků MeSH
- triterpeny * farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- diuretika farmakologie klasifikace škodlivé účinky terapeutické užití MeSH
- edém diagnóza etiologie farmakoterapie klasifikace MeSH
- flavonoidy farmakologie klasifikace terapeutické užití MeSH
- lidé MeSH
- lymfedém * diagnóza etiologie farmakoterapie MeSH
- lymfoscintigrafie metody MeSH
- proteasy farmakologie klasifikace terapeutické užití MeSH
- saponiny farmakologie klasifikace terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Macranthoside B (MB) is a triterpenoid saponin extracted from Lonicera macranthoides, a traditional Chinese medicine. In the current study, we investigated the anticancer potential of MB in various cancer cells and elucidated its underlying mechanisms. MB exposure inhibited cell proliferation, induced mitochondrial membrane potential (MMP) loss, increased sub-G1 accumulation, and resulted in cleavage of caspase-3 and PARP, which are reflective of apoptosis. In HeLa cells, MB induced down-regulation of SOD2 and GPx1, phosphorylation of Akt and PDK1, and thus promoted ROS-mediated apoptosis. This was further supported by the protection of sub-G1 accumulation, MMP loss, cleavage of caspase-3 and PARP in the presence of N-acetylcysteine (NAC). Additionally, MB induced cell death via down-regulation of ubiquitin-like with PHD and ringfinger domains 1 (UHRF1) and Bcl-xL. Taken together, this study provides a new insight into the apoptosis- inducing potential of MB, and its molecular mechanisms are associated with an increase in oxidative stress and inhibition of the PDK1/Akt pathway.
- MeSH
- adenokarcinom * MeSH
- apoptóza MeSH
- HeLa buňky MeSH
- kaspasa 3 metabolismus MeSH
- lidé MeSH
- membránový potenciál mitochondrií MeSH
- nádorové buněčné linie MeSH
- PARP inhibitory farmakologie MeSH
- proteiny vázající zesilovač transkripce CCAAT metabolismus farmakologie MeSH
- protoonkogenní proteiny c-akt metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- saponiny * farmakologie MeSH
- ubikvitinligasy metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Background: The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods: Participants (ZOE-50: ≥50; ZOE-70: ≥70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing ≥2 of 4 activation markers assessed (CD42+) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results: After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD42+ T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained ≥5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions: Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination. Clinical Trials Registration: NCT01165177; NCT01165229.
- MeSH
- adjuvancia imunologická farmakologie MeSH
- buněčná imunita imunologie MeSH
- CD4-pozitivní T-lymfocyty MeSH
- herpes zoster imunologie MeSH
- humorální imunita imunologie MeSH
- imunogenicita vakcíny imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipid A analogy a deriváty farmakologie MeSH
- proteiny virového obalu imunologie MeSH
- protilátky virové imunologie MeSH
- saponiny farmakologie MeSH
- senioři MeSH
- subjednotkové vakcíny imunologie MeSH
- vakcína proti pásovému oparu imunologie MeSH
- vakcinace metody MeSH
- virus varicella zoster imunologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
A practical synthesis of 28a-homo-28a-selenolupane triterpenes and the corresponding selenosaponins containing d-mannose, l-arabinose, l-rhamnose, and d-idose moieties is described. Selenium containing triterpenes were obtained from the readily available 3-O-allyl-homobetulin mesylate by nucleophilic substitution with the selenocyanate ion which upon reduction of the -SeCN group afforded the free selenol. Glycosylation using classical Schmidt donors gave 1,2-trans selenosaponins as the main product as well as minute amounts of 1,2-cis isomers. This is one of the very few examples of the synthesis of selenoglycosides by direct glycosylation of free selenols. The studied selenol showed high resistance to air oxidation resulting in good stability during the synthesis of selenolupane derivatives. Cytotoxic activities of new homoselenolupane derivatives were also evaluated in vitro and revealed that some triterpenes exhibited an interesting profile against human cancer cell lines.
- Klíčová slova
- astragalan I, II, cykloastragenol, astragalosidy I-VIII, Astragalus mongholicus Bunge, Astragalus propinquus Schisch., huangqí (čín.), Astragali radix (Jap XI, ChinP IX),
- MeSH
- Astragalus propinquus * anatomie a histologie chemie MeSH
- autoimunitní nemoci MeSH
- dítě MeSH
- kořeny rostlin MeSH
- laktace MeSH
- lékové interakce MeSH
- lidé MeSH
- polysacharidy * aplikace a dávkování farmakologie chemie kontraindikace terapeutické užití MeSH
- preklinické hodnocení léčiv MeSH
- saponiny * aplikace a dávkování farmakologie chemie izolace a purifikace kontraindikace terapeutické užití MeSH
- těhotenství MeSH
- terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- těhotenství MeSH
- zvířata MeSH
- MeSH
- časná diagnóza MeSH
- chronická nemoc farmakoterapie terapie MeSH
- diagnostické techniky kardiovaskulární klasifikace využití MeSH
- diferenciální diagnóza MeSH
- dolní končetina chirurgie patofyziologie patologie MeSH
- farmakoterapie metody MeSH
- flavonoidy aplikace a dávkování farmakologie terapeutické užití MeSH
- kompresivní punčochy využití MeSH
- lidé MeSH
- nemoci cév diagnóza klasifikace terapie MeSH
- saponiny aplikace a dávkování farmakologie terapeutické užití MeSH
- stupeň závažnosti nemoci MeSH
- varixy diagnóza prevence a kontrola terapie MeSH
- životní styl MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
