Stroke and cerebral ischemia/reperfusion (IR) injury are severe conditions characterized by impaired blood flow to the brain, leading to tissue infarction and neurological impairments. Panax notoginseng saponins (PNS) have displayed various beneficial effects in alleviating cerebrovascular disorders. This study aimed to investigate the neuroprotective capacity of PNS in a rat model of middle cerebral artery occlusion (MCAO)-induced cerebral IR injury, focusing specifically on understanding the involvement of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in mediating this protective effect. Male Sprague-Dawley rats (n=45, weighing 250-280g and aged 12 weeks) were utilized in this experiment. Cerebral IR injury was induced by subjecting the rats to 30 minutes of MCAO followed by 24 hours of reperfusion. Prior to the surgery, PNS (120mg/kg) was administered once daily via gavage for 14 days. The evaluation measures included assessing cerebral infarct volume, neurological function using the Longa method, conducting histopathological analysis, examining the expression of SIRT1, Nrf2, and HO-1 genes and proteins, as well as measuring the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA). Pretreatment with PNS markedly decreased infarct volume, enhanced neurological function, and mitigated histopathological alterations. Additionally, PNS intake resulted in the upregulation of SIRT1, Nrf2, and HO-1 genes and proteins, boosted enzymatic antioxidant activity, and lowered MDA levels, pointing towards a diminution in oxidative stress. The multifaceted antioxidant and neuroprotective properties of PNS underscore its promising role in preserving neuronal function, mitigating oxidative damage, and promoting tissue survival in ischemic conditions. These benefits were associated with the modulation of the SIRT1/Nrf2/HO-1 signaling pathway, emphasizing the therapeutic significance of PNS in addressing cerebral IR injury and related neurological complications. Key words: Ischemia/reperfusion injury, Neuroprotection, Oxidative stress, Panax notoginseng saponins, Stroke.
- MeSH
- faktor 2 související s NF-E2 * metabolismus MeSH
- hemová oxygenasa (decyklizující) MeSH
- infarkt arteria cerebri media farmakoterapie patologie MeSH
- ischemie mozku * metabolismus patologie farmakoterapie MeSH
- krysa rodu Rattus MeSH
- neuroprotektivní látky * farmakologie terapeutické užití MeSH
- Panax notoginseng * chemie MeSH
- potkani Sprague-Dawley MeSH
- reperfuzní poškození * metabolismus prevence a kontrola patologie farmakoterapie MeSH
- saponiny * farmakologie terapeutické užití izolace a purifikace MeSH
- signální transdukce účinky léků MeSH
- sirtuin 1 * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- faktor 2 související s NF-E2 * MeSH
- hemová oxygenasa (decyklizující) MeSH
- Hmox1 protein, rat MeSH Prohlížeč
- neuroprotektivní látky * MeSH
- Nfe2l2 protein, rat MeSH Prohlížeč
- saponiny * MeSH
- Sirt1 protein, rat MeSH Prohlížeč
- sirtuin 1 * MeSH
Salinity stress significantly hinders plant growth by disrupting osmotic balance and inhibiting nutrient uptake, leading to reduced biomass and stunted development. Using saponin (SAP) and boron (B) can effectively overcome this issue. Boron decreases salinity stress by stabilizing cell walls and membranes, regulating ion balance, activating antioxidant enzymes, and enhancing water uptake. SAP are bioactive compounds that have the potential to alleviate salinity stress by improving nutrient uptake, modulating plant hormone levels, promoting root growth, and stimulating antioxidant activity. That's why the current study was planned to use a combination of SAP and boron as amendments to mitigate salinity stress in sweet potatoes. Four levels of SAP (0%, 0.1%, 0.15%, and 0.20%) and B (control, 5, 10, and 20 mg/L B) were applied in 4 replications following a completely randomized design. Results illustrated that 0.15% SAP with 20 mg/L B caused significant enhancement in sweet potato vine length (13.12%), vine weight (12.86%), root weight (8.31%), over control under salinity stress. A significant improvement in sweet potato chlorophyll a (9.84%), chlorophyll b (20.20%), total chlorophyll (13.94%), photosynthetic rate (17.69%), transpiration rate (16.03%), and stomatal conductance (17.59%) contrast to control under salinity stress prove the effectiveness of 0.15% SAP + 20 mg/L B treatment. In conclusion, 0.15% SAP + 20 mg/L B is recommended to mitigate salinity stress in sweet potatoes.
- Klíčová slova
- Antioxidant activity, Boron, Chlorophyll content, Photosynthetic rate, Saponin, Sweet potato,
- MeSH
- bor * farmakologie MeSH
- chlorofyl metabolismus MeSH
- fotosyntéza účinky léků MeSH
- Ipomoea batatas * růst a vývoj MeSH
- kořeny rostlin růst a vývoj účinky léků MeSH
- salinita MeSH
- saponiny * farmakologie MeSH
- solný stres * účinky léků MeSH
- synergismus léků MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bor * MeSH
- chlorofyl MeSH
- saponiny * MeSH
Bioactivity-guided phytochemical fractionation of the methanol extract of Olax subscorpioidea root has led to the isolation of six triterpenes. Three of these compounds are previously undescribed triterpenoid saponins: oleanolic acid 3-O-[α-L-rhamnopyranosyl-(1→3)-β-D-glucopyranosyl-(1 → 2)-6-O-methyl-β-D-glucuronopyranoside]-28-O-β-D-glucopyranosyl ester (2), oleanolic acid 3-O-[β-D-glucopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 3)-β-D-glucopyranoside] (3), and oleanolic acid 3-O-[β-D-glucopyranosyl-(1 → 4)-6-O-methyl-β-D-glucuronopyranoside] ester (5). Other reported known compounds include two triterpene glycosides: oleanolic acid 3-O-[β-D-glucopyranosyl-(1 → 4)-6-O-methyl-β-D-glucuronopyranoside]-28-O-β-D-glucopyranosyl ester (1) and oleanolic acid 3-O-[β-D-glucopyranosyl-(1 → 4)-β-D-glucuronopyranoside] (4); and a triterpene acid, oleanolic acid (6). The structures of these compounds were elucidated by spectroscopic means. The isolated compounds were tested against human cervical cancer (HeLa), colorectal cancer (Caco-2) and breast cancer (MCF-7) cell lines using the in vitro 3-[4,5-dimethylthiazole-2-yl] 3,5-diphenyltetrazolium bromide (MTT) assay, with vincristine as positive control. The cytotoxicity assay showed that compounds 3 and 5 exhibited significant inhibitory effects on the HeLa cell line, with IC50 values of 7.42 ± 0.34 μM and 10.27 ± 1.26 μM; and moderate effects on MCF-7 (IC50 values, 36.67 ± 1.23 μM and 43.83 ± 0.65 μM) and Caco-2 (IC50 values, 35.83 ± 0.55 μM and 39.03 ± 4.38 μM, respectively) cell lines. They were also more selectively cytotoxic than vincristine against the cancer cell lines, when compared with cytotoxicity against the normal lung cell line MRC5.
- Klíčová slova
- Cancer, Olax subscorpioidea, Olacaceae, Triterpene saponins,
- MeSH
- Caco-2 buňky MeSH
- HeLa buňky MeSH
- kyselina olenalová * MeSH
- lidé MeSH
- Olacaceae * MeSH
- protinádorové látky * MeSH
- saponiny * farmakologie chemie MeSH
- triterpeny * farmakologie chemie MeSH
- vinkristin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kyselina olenalová * MeSH
- protinádorové látky * MeSH
- saponiny * MeSH
- triterpeny * MeSH
- vinkristin 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
- Názvy látek
- kaspasa 3 MeSH
- macranthoside B MeSH Prohlížeč
- PARP inhibitory MeSH
- proteiny vázající zesilovač transkripce CCAAT MeSH
- protoonkogenní proteiny c-akt MeSH
- reaktivní formy kyslíku MeSH
- saponiny * MeSH
- ubikvitinligasy MeSH
- UHRF1 protein, human MeSH Prohlížeč
Saponins, a diverse group of natural compounds, offer an interesting pool of derivatives with biomedical application. In this study, three structurally related spirostanol saponins were isolated and identified from the leek flowers of Allium porrum L. (garden leek). Two of them were identical with the already known leek plant constituents: aginoside (1) and 6-deoxyaginoside (2). The third one was identified as new component of A. porrum; however, it was found identical with yayoisaponin A (3) obtained earlier from a mutant of elephant garlic Allium ampeloprasun L. It is a derivative of the aginoside (1) with additional glucose in its glycosidic chain, identified by MS and NMR analysis as (2α, 3β, 6β, 25R)-2,6-dihydroxyspirostan-3-yl β-D-glucopyranosyl-(1 → 3)-β-D-glucopranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl]-(1 → 4)-β-D-galactopyranoside, previously reported also under the name alliporin. The leek native saponins were tested together with other known and structurally related saponins (tomatonin and digitonin) and with their related aglycones (agigenin and diosgenin) for in vitro cytotoxicity and for effects on NO production in mouse peritoneal cells. The highest inhibitory effects were exhibited by 6-deoxyaginoside. The obtained toxicity data, however, closely correlated with the suppression of NO production. Therefore, an unambiguous linking of obtained bioactivities of saponins with their expected immunobiological properties remained uncertain.
- Klíčová slova
- Allium porrum, NO production, aginoside, alliporin, cytotoxicity, leek flowers, steroid saponins,
- MeSH
- Allium chemie MeSH
- buněčné linie MeSH
- květy chemie MeSH
- lipopolysacharidy antagonisté a inhibitory farmakologie MeSH
- molekulární konformace MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- oxid dusnatý antagonisté a inhibitory biosyntéza MeSH
- peritoneální makrofágy účinky léků metabolismus MeSH
- saponiny chemie izolace a purifikace farmakologie MeSH
- spirostany chemie izolace a purifikace farmakologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- lipopolysacharidy MeSH
- oxid dusnatý MeSH
- saponiny MeSH
- spirostany 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
- Názvy látek
- adjuvancia imunologická MeSH
- AS01B adjuvant MeSH Prohlížeč
- glycoprotein E, varicella-zoster virus MeSH Prohlížeč
- lipid A MeSH
- proteiny virového obalu MeSH
- protilátky virové MeSH
- saponiny MeSH
- subjednotkové vakcíny MeSH
- vakcína proti pásovému oparu 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.
- MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- saponiny chemická syntéza chemie farmakologie MeSH
- selen chemie MeSH
- techniky syntetické chemie MeSH
- triterpeny chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- lupane MeSH Prohlížeč
- protinádorové látky MeSH
- saponiny MeSH
- selen MeSH
- triterpeny MeSH
DNA replication in cells takes place in domains scattered throughout the nucleoplasm. We have characterized the dynamics of DNA synthesis in synchronized mid-S-phase HeLa cells. Saponin-permeabilized cells were allowed to elongate nascent DNA chains in presence of biotin-dUTP for 5, 15, and 30 min (a pulse experiment), or for 5 min followed by an incubation with unlabeled precursors for 10 or 25 min (a pulse-and-chase experiment). The replication foci were then identified in ultrathin sections using immunogold labeling of the incorporated biotin. Total number of particles per nucleus, total scanned area of the nucleus, size, shape, and gold particle number of each labeled cluster, and the density of clusters per nucleus were evaluated. We have demonstrated that as replication proceeds, the labeled sites increase in size up to 240 nm (30 min incorporation) while maintaining a broadly round shape. In pulse-and-chase experiments the labeled DNA was shown to spread to occupy DNA foci of approximately 400 nm in diameter. These results demonstrate that DNA replication is compartmentalized within cell nuclei at the level of DNA foci and support the view that the synthetic centers are spatially constrained while the chromatin loops are dynamic during DNA synthesis.
- MeSH
- biotin chemie MeSH
- buněčné jádro metabolismus ultrastruktura MeSH
- časové faktory MeSH
- chromatin chemie MeSH
- DNA chemie ultrastruktura MeSH
- elektronová mikroskopie MeSH
- HeLa buňky MeSH
- kinetika MeSH
- lidé MeSH
- metoda Monte Carlo MeSH
- počítačové zpracování obrazu MeSH
- replikace DNA * MeSH
- saponiny farmakologie MeSH
- vazebná místa MeSH
- zlato chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biotin MeSH
- chromatin MeSH
- DNA MeSH
- saponiny MeSH
- zlato MeSH
Triterpene saponins of ursane and oleane type isolated from the involucral bracts of Cynara cardunculus L. (Asteraceae) were investigated in in vitro assays for their activity on the complement system. The anticomplementary activity of bidesmosidic saponins on the classical pathway activation of the complement was higher than the activity of monodesmosidic saponins, but esterification of the carboxylic group of glucuronic acid in the sugar residue resulted in a significant decrease in anticomplementary activity.
- MeSH
- Cynara * chemie MeSH
- klasická dráha komplementu účinky léků MeSH
- morčata MeSH
- saponiny chemie farmakologie MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- saponiny MeSH
The aim of this study was to evaluate myofibrillar creatine kinase (EC 2.7.3.2) activity on the background of the effect of substrate channeling by myosin ATPase and to compare it with creatine kinase (CK) activity of whole skinned fibers. In order to assess CK activity, skinned fibers were prepared from the rat psoas major muscles defined by light microscopy. The activity in permeabilized fibers after treatment with saponin, Triton X-100 and Ca(2+)-free medium reached 2.80, 6.97 and 3.32 micromol ATP min(-1) mg(-1) protein, respectively, when a coupled enzyme assay system with external hexokinase and glucose-6-phosphate dehydrogenase was used. Transmission electron microscopy (TEM) revealed a possible interference among activities of sarcolemmal, sarcoplasmic, myofibrillar and mitochondrial CK from persisting structures. For evaluation of the myofibrillar CK itself, a pure myofibrillar fraction was prepared. Fraction purity was confirmed by TEM and by enzymatic assays for marker enzymes. Two procedures, i.e. the coupled enzyme assay and the evaluation of phosphocreatine (PCr) concentration before and after the CK reaction, were used for measurement of CK activity in this fraction. The procedures resulted in 3.2 nmol ATP min(-1) mg(-1) protein and 7.6 nmol PCr min(-1) mg(-1) protein, respectively. These alternative approaches revealed a discrepancy between the reacting portions of PCr by more than 50 %, which provides information about the size of the effect, generally described as substrate channeling.
- MeSH
- adenosintrifosfát metabolismus MeSH
- bederní svaly enzymologie MeSH
- elektronová mikroskopie MeSH
- fosfokreatin metabolismus MeSH
- glukosa-6-fosfátdehydrogenasa metabolismus MeSH
- hexokinasa metabolismus MeSH
- kinetika MeSH
- kosterní svalová vlákna účinky léků enzymologie ultrastruktura MeSH
- kreatinkinasa metabolismus MeSH
- krysa rodu Rattus MeSH
- myofibrily enzymologie ultrastruktura MeSH
- oktoxynol farmakologie MeSH
- permeabilita buněčné membrány MeSH
- potkani Wistar MeSH
- saponiny farmakologie MeSH
- vápník aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenosintrifosfát MeSH
- fosfokreatin MeSH
- glukosa-6-fosfátdehydrogenasa MeSH
- hexokinasa MeSH
- kreatinkinasa MeSH
- oktoxynol MeSH
- saponiny MeSH
- vápník MeSH