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
There is evidence that a higher serum level of bilirubin (BIL) may be a protective factor for autoimmune diseases. We examined the effect of BIL supplementation in adjuvant-induced arthritis (AIA) where oxidative stress, inflammation and inadequate immune response are present. Male Lewis rats were randomized into groups: CO - control, AIA - untreated adjuvant-induced arthritis, AIA-BIL - adjuvant-induced arthritis administrated BIL (200 mg/kg b.w. daily i.p. during 14 days). Change of hind paw volume in the AIA-BIL group in comparison to the AIA group was significantly decreased after BIL administration. In CO and AIA groups we found almost untraceable levels of BIL. In the AIA-BIL group hyperbilirubinemia was observed. BIL administration significantly decreased plasma levels of C-reactive protein and ceruloplasmin in the AIA-BIL group in comparison to the AIA group. The values of white and red blood cells, hemoglobin and hematocrit were significantly decreased in AIA-BIL after BIL supplementation. Organs like spleen and thymus had a lower weight in AIA-BIL than in AIA. Histological findings showed decreased or even absent damage in hind paw joint of AIA-BIL animals. We observed an immunomodulatory effect of BIL on AIA development, which may also have a novel pharmacological impact.
- MeSH
- artritida experimentální krev patologie MeSH
- bilirubin krev MeSH
- biologické markery krev MeSH
- hyperbilirubinemie krev patologie MeSH
- krysa rodu rattus MeSH
- potkani inbrední LEW MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Ovarian cancer is one of the most common malignancies in women and contributes greatly to cancer-related deaths. Tumor suppressor candidate 3 (TUSC3) is a putative tumor suppressor gene located at chromosomal region 8p22, which is often lost in epithelial cancers. Epigenetic silencing of TUSC3 has been associated with poor prognosis, and hypermethylation of its promoter provides an independent biomarker of overall and disease-free survival in ovarian cancer patients. TUSC3 is localized to the endoplasmic reticulum in an oligosaccharyl tranferase complex responsible for the N-glycosylation of proteins. However, the precise molecular role of TUSC3 in ovarian cancer remains unclear. In this study, we establish TUSC3 as a novel ovarian cancer tumor suppressor using a xenograft mouse model and demonstrate that loss of TUSC3 alters the molecular response to endoplasmic reticulum stress and induces hallmarks of the epithelial-to-mesenchymal transition in ovarian cancer cells. In summary, we have confirmed the tumor-suppressive function of TUSC3 and identified the possible mechanism driving TUSC3-deficient ovarian cancer cells toward a malignant phenotype.
- MeSH
- epitelo-mezenchymální tranzice genetika MeSH
- heterografty MeSH
- lidé MeSH
- membránové proteiny genetika MeSH
- myši inbrední NOD MeSH
- myši SCID MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádorové supresorové proteiny genetika MeSH
- nádory vaječníků genetika MeSH
- stres endoplazmatického retikula genetika MeSH
- tumor supresorové geny fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Klíčová slova
- pinosylvin,
- MeSH
- antioxidancia MeSH
- borovice lesní MeSH
- C-reaktivní protein analýza MeSH
- gama-glutamyltransferasa MeSH
- karnosin * terapeutické užití MeSH
- kombinovaná farmakoterapie * MeSH
- látky reagující s kyselinou thiobarbiturovou MeSH
- methotrexát * terapeutické užití MeSH
- oxidační stres MeSH
- potkani inbrední LEW MeSH
- revmatoidní artritida * farmakoterapie MeSH
- stilbeny * aplikace a dávkování terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- srovnávací studie MeSH
