Geniposide attenuates epilepsy symptoms in a mouse model through the PI3K/Akt/GSK‑3β signaling pathway

Abstract

Abstract. Previous reports on the pharmacological actions of geniposide have indicated that it has anti-asthmatic, anti-inflammatory and analgesic effects in the liver and gallbladder, and therapeutic effects in neurological, cardiovascular and cerebrovascular diseases. The results of the current study demonstrate that geniposide attenuates epilepsy in a mouse model through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway. A mouse model of epilepsy was induced by maximal electric shock (50 mA, 50 Hz, 1 sec). Epilepsy mice were intragastrically administered with 0, 5, 10 or 20 mg/kg geniposide. Geniposide significantly reduced the incidence and significantly increased the latency of clonic seizures in epileptic mice compared with non-treated epileptic mice (both P<0.01). Geniposide treatment significantly inhibited cyclooxygenase-2 mRNA expression in epilepsy mice (P<0.01). Furthermore, geniposide significantly suppressed the protein expression of activator protein 1, increased the activation of Akt and increased the protein expression of GSK-3β and PI3K in epilepsy mice (all P<0.01). These results suggest that geniposide attenuates epilepsy in mice through the PI3K/Akt/GSK-3β signaling pathway.

Dynorphin activation of kappa opioid receptor protects against epilepsy and seizure-induced brain injury via PI3K/Akt/Nrf2/HO-1 pathway

“…This study also explored the proteins involved in the PI3K/Akt/Nrf2/HO-1 pathway in the dynorphin-associated protection in epilepsy. Activation of the PI3K/Akt signaling pathway can alter neuronal apoptosis and attenuates the severity of seizures in experimental epilepsy-induced rats [20][21][22]. On the other hand, activation of the antioxidant Nrf2/ ARE pathway confers neuroprotective effects against pentylenetetrazole-or pilocarpine-induced brain damage in vivo and Mg 2+ free-induced seizure-like neuron injury [10,15,16,19].…”

“…The phosphatidylinositol-3-kinase (PI3K)/Akt pathway is a key regulator of cell survival and proliferation that is widely expressed in the central nervous system. Activation of the PI3K/Akt signaling pathway can alter neuronal apoptosis and attenuate the severity of seizures in experimental epilepsy-induced rats [20][21][22]. Interestingly, Tong et al [23] have demonstrated that U50448H, a KOR-selective agonist, protects against heart failure following myocardial ischemia/reperfusion via activation of HO-1 expression through the PI3K/ Akt/Nrf2 pathway.…”

Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study

“…Geniposide, an iridoid glycoside in Gardenia jasminoides , exerts anti-fibrotic, anti-osteoarthritis, and anti-epilepsy actions by modulation of the expression of transforming growth factor-β (TGF-β)/Smad4, p38 mitogen-activated protein kinase (p38 MAPK), and PI3K/Akt/GSK-3beta signaling pathways, respectively [ 55 , 56 , 57 ]. Whereas, geniposide manifested a number of pathological phenomena in the liver of SD rat with the dose greater than 574 mg/kg, such as elevated MDA, liver enzymes (ALT, AST, alkaline phosphatase (ALP), total bilirubin), focal necrosis, and downregulated SOD, leading to the onset of oxidative stress caused hepatotoxicity [ 58 ].…”

Up-Regulation of Trem2 Inhibits Hippocampal Neuronal Apoptosis and Alleviates Oxidative Stress in Epilepsy via the PI3K/Akt Pathway in Mice

“…1C), and this revealed that Trem2 and Tyrobp were in core positions. Interestingly, previous studies have proposed that Trem2 plays an important role in epilepsy [22,23], and the PI3K/ Akt pathway has also been reported to be a crucial regulator in epilepsy [24][25][26]. Moreover, several studies have demonstrated a target relationship between Trem2 and the PI3K/Akt pathway [14,27], indicating that Trem2 could modulate the PI3K/Akt pathway as shown in Fig.…”