Total Saponins of Panax notoginseng Activate Akt/mTOR Pathway and Exhibit Neuroprotection in vitro and in vivo against Ischemic Damage.
10.1007/s11655-021-3454-y
- Author:
Yu-Wei PAN
1
;
Dong-Ping WU
2
;
Hua-Feng LIANG
2
;
Gen-Yun TANG
1
;
Chun-Lin FAN
2
;
Lei SHI
1
;
Wen-Cai YE
2
;
Man-Mei LI
3
,
4
Author Information
1. JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou, 510632, China.
2. Institute of Traditional Chinese Medicine and Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China.
3. Institute of Traditional Chinese Medicine and Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China. jnulimanmei1209@
4. com.
- Publication Type:Journal Article
- Keywords:
Akt/mTOR pathway;
Chinese medicine;
ischemia-reperfusion;
neuroprotection;
oxygen-glucose deprivation and reoxygenation;
total saponins of Panax notoginseng
- MeSH:
Animals;
Beclin-1;
Brain Ischemia/metabolism*;
Glucose;
Infarction, Middle Cerebral Artery/drug therapy*;
Mammals/metabolism*;
Neuroprotection;
Neuroprotective Agents/therapeutic use*;
Oxygen;
Panax notoginseng;
Proto-Oncogene Proteins c-akt/metabolism*;
Rats;
Reperfusion Injury/metabolism*;
Saponins/therapeutic use*;
TOR Serine-Threonine Kinases/metabolism*
- From:
Chinese journal of integrative medicine
2022;28(5):410-418
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons.
METHODS:The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence. Middle cerebral artery occlusion (MCAO) was developed in rats as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological scoring, tail suspension test, 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl stainings. Western blot analysis, immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin (mTOR) signaling pathway.
RESULTS:MTT showed that TSPN (50, 25 and 12.5 µ g/mL) protected cortical neurons after OGD/R treatment (P<0.01 or P<0.05). Flow cytometry and live/dead cell assays indicated that 25 µ g/mL TSPN decreased neuronal apoptosis (P<0.05), and immunofluorescence showed that 25 µ g/mL TSPN restored the dendritic morphology of damaged neurons (P<0.05). Moreover, 12.5 µ g/mL TSPN downregulated the expression of Beclin-1, Cleaved-caspase 3 and LC3B-II/LC3B-I, and upregulated the levels of phosphorylated (p)-Akt and p-mTOR (P<0.01 or P<0.05). In the MCAO model, 50 µ g/mL TSPN improved defective neurological behavior and reduced infarct volume (P<0.05). Moreover, the expression of Beclin-1 and LC3B in cerebral ischemic penumbra was downregulated after 50 µ g/mL TSPN treatment, whereas the p-mTOR level was upregulated (P<0.05 or P<0.01).
CONCLUSION:TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss. TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage, which may be the mechanism that underlies the neuroprotective activity of TSPN.
