The antiepileptic effect of Gastrodiae Rhizoma through modulating overexpression of mTOR and attenuating astrogliosis in pilocarpine mice model

Abstract

Objective To investigate the effect of water extract of Gastrodiae Rhizoma (GR) on the development of acquired temporal lobe epilepsy (TLE) and on regulating the expression of the mammalian target of rapamycin (mTOR) and semaphorin 3F (SEMA3F). Methods A pilocarpine‐induced status epilepticus (SE) model was adopted to precipitate injury in the limbic systems. GR and carbamazepine (CBZ) treatments were given to mice for 14 days prior to SE induction to demonstrate the antiepileptic effects and continued for 5 more days to illustrate the effects on histologic studies. Results Our results consolidated that GR treatment (92.1 minutes) could delay the SE onset in comparison with the control group (61.5 minutes, P = .041). Fewer mice had reached SE with GR treatment (41.7%) when compared with the control group (83.3%, P = .044). GR treatment (2.1 hours/mouse) could suppress the number of acute seizures in post‐SE survival mice when compared with the control group (4.5 hours/mouse, P < .001). The effects of GR treatment were elucidated with the mechanism of actions. GR treatment reduced the overexpression of mTOR (0.27 vs 0.67 AU/mg protein, P = .047). GR treatment increased the underexpression of SEMA3F (0.51 vs 0.16 µg/mg protein, P = .034). In the histochemical study of microtubule‐associated protein 2 (MAP2) staining, our results showed that GR prevented neuronal loss in the GR treatment group (64.8% positively stained pixel area) as compared with the control group (59%, P = .014) in the hippocampus. In glial fibrillary acidic protein (GFAP) staining, the severity of astrogliosis was mitigated by the GR treatment (4.1% positively stained pixel area) when compared to the control group (5.6%, P = .047) in the hippocampus. Significance These results provide preclinical evidence to support the use of GR, which could suppress acute seizures and relieve pathological changes in pilocarpine‐induced TLE mice. We demonstrated that the antiepileptic effects of GR could be accompanied by mTOR reduction and astrogliosis attenuation.

A narrative review on traditional Chinese medicine prescriptions and bioactive components in epilepsy treatment

“…Herbs might have variable actions on the metabolism, absorption and transport of AEDs ( 96 ). For example, several studies have reported pharmacokinetic interactions of CBZ with different herbal medicines, such as Rhizoma Gastrodiae ( 98 , 99 ). Pharmacokinetic study in rats indicated that Rhizoma Gastrodiae could reduce the auto-induction of CBZ and increase the plasma concentration of CBZ and its metabolite, demonstrating an herb-drug interaction of Rhizoma Gastrodiae with CBZ which will provide implications for epilepsy treatment in clinic ( 98 ).…”

Dynamic-related protein 1 inhibitor eases epileptic seizures and can regulate equilibrative nucleoside transporter 1 expression

“…SE is a life-threatening emergency that is typically terminated through antiepileptic drug treatment, leading to hippocampus dysfunction typified by neurodegeneration, inflammation, and altered neurogenesis, as well as cognitive and memory deficits. An episode of extended SE is [28][29][30][31]. Neurons are abnormally excited during epileptic seizures, and neuronal excitability depends primarily on energy metabolism [16,32].…”

Temporal Lobe Epilepsy: What do we understand about protein alterations?

“…Due to these changes, a recurrent excitatory circuit formed which causes focal seizures of spontaneous recurrence and epileptic state progression. In rodent epilepsy model, semaphorins have rewiring events (Yip et al., 2020). For mossy fibers, Sema3A acts as a repellent and is delivered to entorhinal cortex neurons from the axons to the molecular layer in the outer part.…”