Alpha-pinene and dizocilpine (MK-801) attenuate kindling development and astrocytosis in an experimental mouse model of epilepsy

Abstract

Understanding the molecular and cellular mechanisms involved during the onset of epilepsy is crucial for elucidating the overall mechanism of epileptogenesis and therapeutic strategies. Previous studies, using a pentylenetetrazole (PTZ)-induced kindling mouse model, showed that astrocyte activation and an increase in perineuronal nets (PNNs) and extracellular matrix (ECM) molecules occurred within the hippocampus. However, the mechanisms of initiation and suppression of these changes, remain unclear. Herein, we analyzed the attenuation of astrocyte activation caused by dizocilpine (MK-801) administration, as well as the anticonvulsant effect of α-pinene on seizures and production of ECM molecules. Our results showed that MK-801 significantly reduced kindling acquisition, while α-pinene treatment prevented an increase in seizures incidences. Both MK-801 and α-pinene administration attenuated astrocyte activation by PTZ and significantly attenuated the increase in ECM molecules. Our results indicate that astrocyte activation and an increase in ECM may contribute to epileptogenesis and suggest that MK-801 and α-pinene may prevent epileptic seizures by suppressing astrocyte activation and ECM molecule production.

Prenatal exposure to α‐pinine improves reflexive motor behaviours in mice offspring

“…Yang et al (2016) reported that the oral administration of the α‐pinene (12.5–200 mg/kg) prior to pentobarbital (45 mg/kg) reduced sleep latency. It is reported that α‐pinene may prevent epileptic seizures by suppressing astrocyte activation and extracellular matrix molecule production (Ueno et al, 2020). α‐pinene has a low molecular weight and high lipophilicity and by high permeability reaches to the brain and induces its physiological effects such as anxiolytic, antioxidant and anti‐seizure by altering GABAergic and NMDA receptors in the hippocampus (Ueno et al, 2019).…”

“…Pinene (C 10 H 16 ) is a bicyclic, double bond, terpenoid hydrocarbon and two isoforms (α and β) found in nature, for example, in pine (coniferous trees) essential oils. α‐pinene is widely used as a food flavouring ingredient and has been approved as a safe food additive by the U.S. Food and Drug Administration (FDA) (Ueno et al, 2020). These two phytochemicals have several biological activities such as fungicidal, antibacterial, anticancer and anti‐nociceptive (Kumar et al, 2019).…”

“…Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are triggered by oxidative imbalance and pretreatment with α‐pinene that prevents the formation of reactive reactive oxygen species (ROS), increased catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase and decreased malondialdehyde (MDA) and apoptosis (Porres‐Martínez et al, 2015b). α‐pinene has neuroprotective activity and an astrocytic response against experimental epilepsy in mice (Ueno et al, 2020).…”

One-pot synthesis of sulfonyl dibenzosuberdiones via In(OTf)3-promoted double Friedel–Crafts reactions of oxygenated arylacetic acids with β-arylvinyl sulfones

“…Simultaneously, water could also be obtained. After In(OTf ) 3mediated tautomerization, the indium-chelated enol moiety of G could react with molecular oxygen (from the air) to lead to H. Finally, the cleavage of the intramolecular oxygen-oxygen bond of the resulting (TfO) 2 In-conjugated peroxide moiety with the six-membered ring was the driving force that triggered the deprotonation of the α-proton, producing 6a via the formation of a carbon-oxygen double bond (red). After the recombination of TfOInvO and two molecules of TfOH, water was generated and In(OTf ) 3 was recovered for the next catalytic cycle under the overall Friedel-Crafts conditions.…”

Recent studies on pinene and its biological and pharmacological activities

“…Herein, we summarize the recent published findings on the biological and pharmacological activities of pinene (Table 1 (Tab. 1) ; References in Table 1: Bouzenna et al, 2017[ 3 ]; Cardoso et al, 2020[ 4 ]; Chen et al, 2015[ 5 ]; de Macêdo et al, 2018[ 6 ]; do Amaral et al, 2020[ 7 ]; Ensaka and Sakamoto, 2020[ 8 ]; Felipe et al, 2019[ 10 ]; Govindarajan et al, 2016[ 11 ]; Hou et al, 2019[ 12 ]; İnce et al, 2018[ 13 ]; Jensen et al, 2020[ 14 ]; Jo et al, 2021[ 15 ]; Karthikeyan et al, 2018[ 17 ], 2019[ 16 ]; Kasuya et al, 2015[ 18 ]; Khoshnazar et al, 2019[ 19 ], 2020[ 20 ]; Kim et al, 2015[ 21 ]; Kovač et al, 2015[ 22 ]; Kusuhara et al, 2019[ 23 ]; Langsi et al, 2020[ 24 ]; Lee et al, 2017[ 25 ]; Li et al, 2016[ 28 ]; Memariani et al, 2017[ 29 ]; Meng et al, 2020[ 30 ]; Min et al, 2020[ 32 ]; Moreira et al, 2016[ 33 ]; Nóbrega et al, 2020[ 34 ]; Pajaro-Castro et al, 2017[ 35 ]; Pinheiro et al, 2015[ 36 ]; Porres-Martínez et al, 2016[ 37 ]; Rodrigues et al, 2015[ 39 ]; Šimunović et al, 2020[ 41 ]; Ueno et al, 2019[ 44 ], 2020[ 43 ]; Wang et al, 2019[ 46 ]; Xu et al, 2018[ 47 ]; Yang et al, 2016[ 48 ]; Zamyad et al, 2019[ 50 ]; Zhang et al, 2015[ 52 ], 202[ 51 ]0; Zhao et al, 2018[ 53 ]).…”