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
Ulceration colitis (UC) is a chronic and recurrent inflammatory disorder in the gastro-intestinal tract. The purpose of our study is to explore the potential mechanisms of ginsenoside Rg1 (GS Rg1) on dextran sulfate sodium (DSS)-induced colitis in mice and lipopolysaccharide (LPS)-induced RAW 264.7 cells. Acute colitis was induced in male C57BL/6 mice. In vitro model of LPS-induced RAW 264.7 cells to simulate enteritis model. The disease activity index (DAI), colon length, body weight and histopathological analysis were performed in vivo. Pro-inflammatory cytokines and markers for oxidative and anti-oxidative stress, MPO level were measured in vivo and in vitro. Nuclear erythroid 2-related factor 2 (Nrf2) and NF-?B p65 protein levels were analyzed using western blotting. Our results indicated that the UC models were established successfully by drinking DSS water. GS Rg1 significantly attenuated UC-related symptoms, including preventing weight loss, decreasing DAI scores, and increasing colon length. GS Rg1 ameliorated the DSS-induced oxidative stress. IL-1beta, IL-6, and TNF-alpha levels were significantly increased in serum and cell supernatant effectively, while treatment with the GS Rg1 significantly reduced these factors. GS Rg1 reduced MPO content in the colon. GS Rg1 treatment increased SOD and decreased MDA levels in the serum, colon, and cell supernatant. GS Rg1 restored the Nrf-2/HO-1/NF-?B pathway in RAW 264.7 cells and UC mice, and these changes were blocked by Nrf-2 siRNA. Overall, GS Rg1 ameliorated inflammation and oxidative stress in colitis via Nrf-2/HO-1/NF-kappaB pathway. Thus, GS Rg1 could serve as a potential therapeutic agent for the treatment of UC.
- MeSH
- dextrany metabolismus farmakologie terapeutické užití MeSH
- ginsenosidy * MeSH
- kolitida * chemicky indukované MeSH
- kolon metabolismus MeSH
- lipopolysacharidy metabolismus MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- NF-kappa B metabolismus MeSH
- síran dextranu toxicita metabolismus MeSH
- sírany * MeSH
- ulcerózní kolitida * chemicky indukované farmakoterapie metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články 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
Platycodin D is an active component isolated from Chinese herb Platycodonis radix with various pharmacological activities, such as antitussive, expectorant, anti-inflammatory, and analgesic effects. Interestingly, platycodin D also exerts anticancer effects against several types of cancer. However, few studies on the anti-tumour effects of platycodin against urinary bladder cancer have been reported. In this study, we explored the anti-tumour effect of platycodin D against human bladder cancer and its mechanisms in vitro and in vivo. We found that platycodin D had significant anti-proliferative effects on four types of cancer cells, especially the 5637 bladder cancer cell line, and exerted these effects by preventing cell cycle progression from G0/G1 to S phase, down-regulating Ki-67 and cyclin D1 protein expression and up-regulating P21 protein expression. Furthermore, platycodin D inhibited 5637 cell migration by decreasing twist-related protein 1 (Twist1) and matrix metallopeptidase 2 (MMP2) expression and exerted significant tumour-suppressive effects in tumour-bearing nude mice. Platycodin D also increased caspase-9, caspase-8, caspase-3, and p53 expression and decreased Bcl-2 expression in tumour tissues. Taken together, our results provide a theoretical basis for application of platycodin D in treating urinary bladder cancer.
In this study, two extracts from Fatsia japonica-FatsiphloginumTM (extract of triterpene glycosides containing 45-50 % of fatsiosides (FS)) and purified triterpene-rich extract of saponins with code name PS-551 (PS) were administered in combination with methotrexate (MTX) and in monotherapy to rats suffering adjuvant arthritis (AA). The anti-inflammatory activities of extracts were evaluated as monotherapies in comparison with untreated AA. PS administered in higher dose showed on day 28 effective decrease of hind paw volume (HPV), decreased activity of gamma-glutamyl transferase (GGT) in joints, and also interleukin-17A was decreased significantly on day 14. The higher dose of PS was more effective than both doses of FS. Further, we evaluated the higher doses of PS and FS in combination with MTX. PS improved the effect of MTX in combination more effective than FS (HPV, body weight and activity of GGT in joint). However, FS was more effective in reducing the level of IL-17A on day 14 and activity of GGT in spleen than PS. In conclusion, our study showed that generally FS has higher anti-arthritic activity comparing to PS. Thus, the novel combination of FatsiphloginumTM and methotrexate could be interesting for future clinical studies in patients suffering auto-immune diseases.
- MeSH
- antiflogistika aplikace a dávkování MeSH
- aralkovité chemie MeSH
- artritida experimentální farmakoterapie MeSH
- gama-glutamyltransferasa metabolismus MeSH
- interleukin-17 krev MeSH
- krysa rodu rattus MeSH
- methotrexát aplikace a dávkování MeSH
- potkani inbrední LEW MeSH
- rostlinné extrakty terapeutické užití MeSH
- saponiny aplikace a dávkování MeSH
- triterpeny aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- chronická nemoc MeSH
- diagnostické techniky kardiovaskulární * trendy MeSH
- farmakoterapie * metody normy trendy MeSH
- flavonoidy aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- hodnocení léčiv metody MeSH
- klinický obraz nemoci MeSH
- kožní vředy diagnóza komplikace terapie MeSH
- lidé MeSH
- medicína založená na důkazech metody normy MeSH
- onemocnění periferních arterií * diagnóza farmakoterapie terapie MeSH
- saponiny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- společnosti lékařské normy organizace a řízení trendy MeSH
- varixy patofyziologie prevence a kontrola terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Introduction As a commonly used chemotherapeutic agent, fluorouracil (5-FU) has serious dose-limiting side effects. In this study, we evaluated the synergy between red American ginseng (RAG) and 5-FU on human colorectal cancer cells, and explored the potential mechanisms. Methods Ginsenoside contents of white American ginseng (WAG) and RAG were determined by HPLC. Cell proliferation was evaluated by MTS assay. Combination Index (CI) analysis was executed using CompuSyn software. Paraptotic events were observed after crystal violet staining. Cell cycle distribution, cyclin A expression and apoptotic induction were analyzed using flow cytometry. Results We observed the heat treatment remarkably increased levels of ginsenoside Rg3, 20R-Rg3, Rk1 and Rg5. When the combinations of 5-FU and RAG were applied, cell proliferation inhibition rates were notably increased, indicating that RAG significantly enhanced 5-FU’s effect. Additionally, CI analysis suggested that there was a synergistic action of 5-FU and RAG when combined. The cell cycle data indicated 5-FU induced S phase arrest, and the combination of 5-FU and RAG increased G1 phase. Further, the RAG’s ability to enhance the anti-cancer effects of 5-FU was linked to both paraptosis and apoptosis inductions.
- MeSH
- apoptóza účinky léků MeSH
- fluoruracil aplikace a dávkování farmakologie MeSH
- ginsenosidy aplikace a dávkování farmakologie MeSH
- kolorektální nádory farmakoterapie MeSH
- kombinovaná farmakoterapie MeSH
- nádorové buňky kultivované účinky léků MeSH
- screeningové testy protinádorových léčiv MeSH
- synergismus léků MeSH
- techniky in vitro MeSH
- ženšen chemie MeSH
- Publikační typ
- práce podpořená grantem MeSH
Gymnema sylvestre, známá pod jménem gurmar, je stálezelená liána původem z tropických oblastí Asie, Afriky a Austrálie. Odedávna se používá v tradiční ájurvédské medicíně k léčbě mnoha onemocnění, jako je cukrovka, obezita, malárie, kožní onemocnění, astma, kašel, záněty, infekce a hadí uštknutí. Jako hlavní účinné látky byly identifikovány triterpenické saponiny oleananového a dammaranového typu (gymnemové kyseliny, gymnemasaponiny a gymnemosidy). Antidiabetický a hypolipidemický účinek byl potvrzen v experimentech na zvířatech i v klinických studiích, další výzkum pokračuje.
Gymnema sylvestre, also known as gurmar, is an evergreen climber originated in tropical Asia, Africa and Australia. It has been usedfor centuries in traditional ayurvedic medicine for treatment of many illnesses, such as diabetes, obesity, malaria, skin diseases,asthma, cough, inflammations, infections, and snakebite. The research has identified the main active components as oleanan- anddammarane‑typetriterpenic saponins (gymnemic acids, gymnemasaponins, and gymnemosides). Antidiabetic and hypolipidemiceffects were confirmed in animal studies and clinical trials, further research continues.
- MeSH
- ájurvéda MeSH
- antibakteriální látky terapeutické užití MeSH
- diabetes mellitus * terapie MeSH
- dvojitá slepá metoda MeSH
- fytoterapie * MeSH
- Gymnema sylvestre * chemie MeSH
- hypoglykemika MeSH
- hypolipidemika MeSH
- klinické zkoušky jako téma MeSH
- kombinovaná farmakoterapie MeSH
- léčivé rostliny MeSH
- lidé MeSH
- potravní doplňky MeSH
- saponiny klasifikace škodlivé účinky terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
