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Trametenolic acid B protects against cerebral ischemia and reperfusion injury through modulation of microRNA-10a and PI3K/Akt/mTOR signaling pathways
- Source :
- Biomedicine & Pharmacotherapy, Vol 112, Iss, Pp-(2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- Trametenolic acid B (TAB) was a lanostane-type triterpenoid isolated from the trametes lactinea (Berk.) Pat. We have previously reported that extract from trametes lactinea (Berk.) Pat and TAB could efficiently improve learning and memory ability of the cerebral ischemia injury rats and suppress mitochondrial-mediated apoptosis in hydrogen peroxide damaged SH-SY5Y cells. However, the potential mechanisms have not been fully understood yet. The current study was to further investigate the protective effect of TAB on oxygen glucose deprivation/reoxygenation (OGD/R)-damaged SH-SY5Y cells and cerebral ischemia/reperfusion (I/R) injury rats, as well as its mechanisms involved. Cell experiments demonstrated that TAB (10, 20 and 40 μg/mL) protected OGD/R-induced SH-SY5Y cell injury by promoting cell proliferation and suppressing LDH leakage; Meanwhile, the results in vivo showed that TAB (20, 40 and 80 mg/kg) might significantly ameliorate the neurological deficit score, cerebral edema, neuronal cell loss and apoptosis, suppress cerebral infarction volume of the cerebral I/R injury rats. Further studies in vitro and in vivo indicated TAB could efficiently reduce OGD/R-damaged SH-SY5Y cell and cerebral I/R rat serum ROS, LDH and MDA levels, elevate SOD, GSH-Px and CAT activities, downregulate miR-10a mRNA and Bax, cytochrome C, cleaved-caspase-3 and cleaved-caspase-9 protein expressions, upregulate p-PIK3CA, p-Akt, p-mTOR, Bcl-2, pro-caspase-9 and pro-caspase-3 protein expressions and p-PIK3CA/PIK3CA, p-Akt/Akt, p-mTOR/mTOR ratios (P
- Subjects :
- Male
0301 basic medicine
Cell
PI3K/Akt/mTOR and mitochondrial apoptotic pathways
RM1-950
Pharmacology
medicine.disease_cause
Brain Ischemia
Cerebral edema
Rats, Sprague-Dawley
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Trametenolic acid B
medicine
Animals
Humans
Cerebral ischemia and reperfusion injury
Protein kinase B
PI3K/AKT/mTOR pathway
Dose-Response Relationship, Drug
Cell growth
Chemistry
TOR Serine-Threonine Kinases
General Medicine
medicine.disease
MicroRNA-10a
Triterpenes
Rats
MicroRNAs
Neuroprotective Agents
030104 developmental biology
medicine.anatomical_structure
Apoptosis
Oxidative stress
Reperfusion Injury
030220 oncology & carcinogenesis
Therapeutics. Pharmacology
Proto-Oncogene Proteins c-akt
Reperfusion injury
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 07533322
- Volume :
- 112
- Database :
- OpenAIRE
- Journal :
- Biomedicine & Pharmacotherapy
- Accession number :
- edsair.doi.dedup.....3e0dbf33b4b2bca32276a88ba8111a20