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Protection of the Geum japonicum Thunb. var. chinense extracts against oxygen-glucose deprivation and re-oxygenation induced astrocytes injury via BDNF/PI3K/Akt/CREB pathway - 30/05/20

Doi : 10.1016/j.biopha.2020.110123 
Lipeng Du a, Zhigang Mei a, b, , Yaguang Huang a, Wei Tao a, Kai Wang a, Weifeng Huang c, Huajun Zhou d, Zhitao Feng a,
a Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, 443002, China 
b Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, 410208, China 
c Institute of Infection and Inflammation, Medical College of China Three Gorges University, Yichang, 443002, China 
d Institute of Neurology, China Three Gorges University, Yichang, 443003, China 

Corresponding authors at: Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, 443002, China.Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese MedicineMedical College of China Three Gorges UniversityYichang443002China

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Graphical abstract

Here we present the flowchart of the related mechanisms underlying the effect of GJ-extracts-containing serum against OGD/R-induced injury in astrocytes. The GJ extracts up-regulate anti-apoptotic gene Bcl-2 expression and down-regulate pro-apoptotic genes Bax, Caspase-3 expression by activating BDNF/PI3K/Akt/CREB signaling pathway, as well as inhibiting the reactivity of astrocytes, leading to the decrease of astrocytes injury caused by OGD/R in vitro.




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Highlights

GJ-extracts-containing serum showed the protective effects against OGD/R-induced astrocytes injury.
The protective effects of GJ extracts may be attributed to inhibiting the astrocytes hyperreactivity and apoptosis.
BDNF/PI3K/Akt/CREB signaling is involved in the protection of GJ extracts against OGD/R-induced astrocytes injury.
5-desgalloylstachyurin, tellimagrandin II and 3,4,5-Trihydroxybenzaldehyde may exert crucial beneficial effects.

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Abstract

Geum japonicum Tunb. var. chinense (GJ) is a traditional Chinese medicine usually used for the alleviation of dizziness and headache. Previous studies have reported that the GJ extracts could alleviate cerebral I/R injury by reducing apoptosis in vivo. To further elucidate the positive role and underlying mechanism of the GJ extracts in cerebral I/R injury, the current study investigated the effects of the GJ extracts on oxygen-glucose deprivation and re-oxygenation (OGD/R)-induced astrocytes injury in light of BDNF/PI3K/Akt/CREB signaling pathway with seropharmacological method. In the present study, the LC–MS profiling of the GJ extracts, obtain by reflux extraction, led to the identification of three possible active components were 5-desgalloylstachyurin, tellimagrandin II (TG II) and 3,4,5-Trihydroxybenzaldehyde (THBA). Drug-containing serum was collected from rats given different doses of the GJ extracts (0, 1.75 g/kg, 7 g/kg). Data indicated that the GJ extracts could increase the cell viability and decrease apoptosis and the expression of glial fibrillary acidic protein (GFAP) in OGD/R-induced astrocytes. In addition, the detection of apoptosis-related factors showed that the GJ extracts could obviously increase the expression of Bcl-2 and reduce the expression of Bax, Caspase-3 and cleaved-Caspase-3. Furthermore, the GJ extracts markedly increased the expression of BDNF, TrkB, PI3K, p-Akt and p-CREB. All these effects of the GJ extracts could be significantly reversed by LY294002, an inhibitor of PI3K. These data indicated that the GJ extracts could protect astrocytes against OGD/R-induced injury by inhibiting astrocytes reactivity and apoptosis, owing to the activation of the BDNF/PI3K/Akt/CREB pathway. The results support the application of the GJ extracts in the treatment of ischemic stroke and other ischemic encephalopathy.

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Keywords : Geum japonicum Tunb. var. chinense (GJ) extracts, Cerebral ischemia/reperfusion (I/R) injury, Oxygen-glucose deprivation and re-oxygenation (OGD/R), Astrocytes, Apoptosis, BDNF/PI3K/Akt/CREB pathway


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