Polygala tenuifolia-Acori tatarinowii herbal pair as an inspiration for substituted cinnamic α-asaronol esters: Design, synthesis, anticonvulsant activity, and inhibition of lactate dehydrogenase study

Bai, Yajun; He, Xirui; Bai, Yinjuan; Sun, Ying; Zhao, Zhengyan; Chen, Xufei; Li, Bin; Xie, Jing; Li, Yang; Jia, Ping; Xue, Ming; Zhao, Ye; Ding, Yubin; Xiao, Chaoni; Wang, Shixiang; Yu, Jie; Liao, Sha; Zhang, Yajun; Zhu, Zhiling; Qiang, Zhang; Zhao, Yuhui; Qin, Fanggang; Zhang, Yi; Wei, Xiaoyang; Zhang, Min; Liang, Jing; Cuan, Ye; Shan, Guangzhi; Fan, Tai-Ping; Wu, Biao; Zheng, Xiaohui

doi:10.1016/j.ejmech.2019.111650

Cited by 20 publications

(20 citation statements)

References 73 publications

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“…The fact that α-asarone can be metabolized into α-asaronol was confirmed by liver microsomes of different species and human cytochrome P450 enzymes in other studies. , Our recent study revealed that α-asaronol, against the maximal electroshock seizure (MES), subcutaneous injection pentylenetetrazole (PTZ)-induced seizure, and 3-mercaptopropionic acid (3-MP)-induced seizure, displayed a broad spectrum of antiepileptic activity, better neuroprotective effects, and lower acute toxicity than its metabolic parent compound α-asarone . α-Asaronol and its analogues, when compared with clinical drugs such as stiripentol, lacosamide, carbamazepine, and valproic acid, possessed excellent anticonvulsant activities as well as low neurotoxicity for developing into antiepileptic drugs, especially for the treatment of refractory epilepsies . These encouraging results prompted us to develop further α-asaronol into an efficient and safe antiepileptic drug as a substitute for α-asarone.…”

Section: Introductionmentioning

confidence: 74%

Revealing the Antiepileptic Effect of α-Asaronol on Pentylenetetrazole-Induced Seizure Rats Using NMR-Based Metabolomics

Zhao

Liang

et al. 2022

ACS Omega

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α-Asaronol from Acorus tatarinowii (known as “Shichangpu” in Traditional Chinese medicine) has been proved to possess more efficient antiepileptic activity and lower toxicity than α-asarone (namely “Xixinnaojiaonang” as an antiepileptic drug in China) in our previous study. However, the molecular mechanism of α-asaronol against epilepsy needs to be known if to become a novel antiepileptic medicine. Nuclear magnetic resonance (NMR)-based metabolomics was applied to investigate the metabolic patterns of plasma and the brain tissue extract from pentylenetetrazole (PTZ)-induced seizure rats when treated with α-asaronol or α-asarone. The results showed that α-asaronol can regulate the metabolomic level of epileptic rats to normal to some extent, and four metabolic pathways were associated with the antiepileptic effect of α-asaronol, including alanine, aspartate, and glutamate metabolism; synthesis and degradation of ketone bodies; glutamine and glutamate metabolism; and glycine, serine, and threonine metabolism. It was concluded that α-asaronol plays a vital role in enhancing energy metabolism, regulating the balance of excitatory and inhibitory neurotransmitters, and inhibiting cell membrane damage to prevent the occurrence of epilepsy. These findings are of great significance in developing α-asaronol into a promising antiepileptic drug derived from Traditional Chinese medicine.

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Section: Introductionmentioning

confidence: 74%

Revealing the Antiepileptic Effect of α-Asaronol on Pentylenetetrazole-Induced Seizure Rats Using NMR-Based Metabolomics

Zhao

Liang

et al. 2022

ACS Omega

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“…Although studies have revealed that α-asarone exhibits neuroprotective effects on epilepsy ( Pages et al, 2010 ; Huang et al, 2013 ), Alzheimer’s disease ( Chen et al, 2020 ), and stroke ( Lee et al, 2018 ), the nonnegligible side effects of its carcinogenic and genotoxic potential limit its application ( Chamorro et al, 1993 ; Marczewska et al, 2013 ). With the synthesis of α-asaronol in our lab ( Bai et al, 2019 ), its pharmacokinetics ( Sun et al, 2019 ) and biological activities were gradually evaluated, such as antioxidative stress ( He et al, 2018 ), alleviating neurotoxicity, and anticonvulsant ( Jin et al, 2020 ) and anti-epilepsy by balancing neurotransmitters (data unpublished). However, the effect of α-asaronol on myelination in PWMI neonatal rats and the underlying mechanisms remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Alpha-Asaronol Alleviates Dysmyelination by Enhancing Glutamate Transport Through the Activation of PPARγ-GLT-1 Signaling in Hypoxia-Ischemia Neonatal Rats

Zhen

Liu

et al. 2022

Front. Pharmacol.

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Preterm white matter injury (PWMI) is the most common form of brain damage in premature infants caused by hypoxia-ischemia (HI), inflammation, or excitotoxicity. It is characterized by oligodendrocyte precursor cell (OPC) differentiation disorder and dysmyelination. Our previous study confirmed that alpha-asarone (α-asaronol), a major compound isolated from the Chinese medicinal herb Acorus gramineus by our lab, could alleviate neuronal overexcitation and improve the cognitive function of aged rats. In the present study, we investigated the effect and mechanism of α-asaronol on myelination in a rat model of PWMI induced by HI. Notably, α-asaronol promoted OPC differentiation and myelination in the corpus callosum of PWMI rats. Meanwhile, the concentration of glutamate was significantly decreased, and the levels of PPARγ and glutamate transporter 1 (GLT-1) were increased by α-asaronol treatment. In vitro, it was also confirmed that α-asaronol increased GLT-1 expression and recruitment of the PPARγ coactivator PCG-1a in astrocytes under oxygen and glucose deprivation (OGD) conditions. The PPARγ inhibitor GW9662 significantly reversed the effect of α-asaronol on GLT-1 expression and PCG-1a recruitment. Interestingly, the conditioned medium from α-asaronol-treated astrocytes decreased the number of OPCs and increased the number of mature oligodendrocytes. These results suggest that α-asaronol can promote OPC differentiation and relieve dysmyelination by regulating glutamate levels via astrocyte PPARγ-GLT-1 signaling. Although whether α-asaronol binds to PPARγ directly or indirectly is not investigated here, this study still indicates that α-asaronol may be a promising small molecular drug for the treatment of myelin-related diseases.

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“…At present, the major choice for the treatment of epilepsy in the clinic is still mainly drugs (He et al 2018). However, the existing clinical antiepileptic drugs (AEDs) are only about 2/3 of epileptic patients achieve a satisfactory seizure control, and the treatment effect is poor or ineffective for the other 1/3 of epileptic patients (He et al 2018; Kondrat-Wróbel and Łuszczki, 2018; Bai et al 2019). Currently available antiepileptic drugs can also not prevent the development of epilepsy drug resistance, which is considered to be a challenge in epilepsy treatment.…”

Section: Introductionmentioning

confidence: 99%

“…Traditional Chinese medicine has a long history in the treatment of epilepsy, which was recorded in the classical masterpieces Inner Canon of Huangdi ( ) as early as 2200 years ago. In particular, these records revealed the national characteristics and unique advantages of traditional Chinese herbs in the treatment and control seizure in children (Bai et al 2019…”

Section: Introductionmentioning

confidence: 99%

“…3-MP-induced seizures test were carried out according to previously described methods(He et al 2018;Bai et al 2019). Elevated plus mazeThe elevated plus maze (EPM) is a simple method to assess anxiety-like behaviors in mice by estimating contradictory and con icting behavior between the exploring characteristics of animals to new/different environments and the fear of hanging open arms forms (Guillén-Ruiz et al 2021).…”

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Evaluation of the Anticonvulsant Activities of Gastrodia Elata Bl.- Acorus Tatarinowii Decoction on Experimentally Induced Seizures in Mice

Yang

Yuan

et al. 2022

Preprint

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Epilepsy is a serious public health problem in the world. At present, the effect of drug treatment of epilepsy is are not satisfactory. Medicinal plants as pharmaceuticals and for healthcare treatments in the management of epilepsy in China for many centuries. Especially, Gastrodia elata Bl.-Acorus tatarinowii, as a classic and important herb pairs in folk medicine, has been used in folk medicine to control seizures. However, the animal experiment data of its anticonvulsant effect is limited in the literature. The objective of this study was to mainly analyze the anticonvulsant activity of Gastrodia elata-Acorus tatarinowii (GEAT) decoction in maximal electroshock (MES), pentylenetetrazole (PTZ) and trimercaptopropionic acid (3-MP) induced seizures in mice, providing scientific basis for the treatment of convulsive disorders in traditional medicine. In addition, the improvement effect were examined on seizure severity, anxiety, cognitive dysfunction, inflammation and oxidative stress in PTZ kindled mice. The results showed that GEAT decoction dose-dependently protected mice against MES, 3-MP and PTZ induced acute seizures. Meanwhile, GEAT decoction ameliorated seizure severity, decreased the accumulation of inflammatory mediators TNF-α, IL-1β, and IL-6, mitigated oxidative stress, as well as alleviated anxious-like behavior and cognitive deficits in PTZ-kindled mice. Our data evidenced that the anticonvulsant properties attributed to GEAT decoction as adjunctive therapy for epileptic patients in folk medicine.

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Polygala tenuifolia-Acori tatarinowii herbal pair as an inspiration for substituted cinnamic α-asaronol esters: Design, synthesis, anticonvulsant activity, and inhibition of lactate dehydrogenase study

Cited by 20 publications

References 73 publications

Revealing the Antiepileptic Effect of α-Asaronol on Pentylenetetrazole-Induced Seizure Rats Using NMR-Based Metabolomics

Revealing the Antiepileptic Effect of α-Asaronol on Pentylenetetrazole-Induced Seizure Rats Using NMR-Based Metabolomics

Alpha-Asaronol Alleviates Dysmyelination by Enhancing Glutamate Transport Through the Activation of PPARγ-GLT-1 Signaling in Hypoxia-Ischemia Neonatal Rats

Evaluation of the Anticonvulsant Activities of Gastrodia Elata Bl.- Acorus Tatarinowii Decoction on Experimentally Induced Seizures in Mice

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