Neuroprotective effects of isoliquiritigenin against cognitive impairment via suppression of synaptic dysfunction, neuronal injury, and neuroinflammation in rats with kainic acid-induced seizures

Zhu, Xiaobo; Liu, Jiankun; Huang, Shanying; Zhu, Wenzhen; Wang, Yibiao; Chen, Ou; Xue, Jiang

doi:10.1016/j.intimp.2019.04.028

Cited by 55 publications

(32 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It's well documented that NLRP3 in ammasome is mainly composed of NLRP3, adaptor ASC and effector molecule Caspase1, which can promote IL1β and IL18 to exacerbate neuroin ammation during PD progression [30,58]. It is reported that Isoliquiritigenin inhibits Caspase1 via the regulation of Nrf2, which contributes to its neuroprotective and anti-neuroin ammatory effects [61]. We found that celastrol treatment elevated Nrf2 to inhibit NLRP3 levels in Caspase1-KO mice (Fig.…”

Section: The Effects Of Celastrol Are Mediated By Nrf2-nlrp3-caspase1mentioning

confidence: 73%

The Nrf2-NLRP3-Caspase1 axis mediates the neuroprotective effects of Celastrol in Parkinson's disease

Zhang

Zhao

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), accompanied by chronic neuroinflammation, oxidative stress, and widespread accumulation of α-synuclein. Celastrol (Cel), a potent anti-inflammatory and anti-oxidative pentacyclic triterpene, has emerged as a neuroprotective agent. However, the mechanisms by which celastrol is neuroprotective in PD has not yet been elucidated. Methods: The MPTP and AAV-mediated human wild-type α-syn overexpression within SNc induced PD mouse models were employed in this study. By using multiple genetically modified mice (Nrf2-KO, NLRP3-KO and Caspase1-KO), we identified that celastrol effectively inhibited the NLRP3 inflammasome activation, mitigated motor deficits and nigrostriatal dopaminergic degeneration through Nrf2-NLRP3-Caspase1 pathway. Results: Here we show that celastrol protected against the loss of dopaminergic neurons, mitigated the neuroinflammation and motor deficits in both MPTP-induced PD mouse model and AAV-mediated human α-syn overexpression PD model. Whole-genome deep sequencing analysis reveals that Nrf2, NLRP3 and Caspase1 in SNc may be associated with the neuroprotective actions of celastrol in PD. Conclusions: These findings suggest that Nrf2-NLRP3-Caspase1 axis may be a key target of celastrol in PD treatment, and highlight the favorable properties linked to neuroprotection of celastrol, making celastrol as a promising disease-modifying agent for PD.

show abstract

Section: The Effects Of Celastrol Are Mediated By Nrf2-nlrp3-caspase1mentioning

confidence: 73%

The Nrf2-NLRP3-Caspase1 axis mediates the neuroprotective effects of Celastrol in Parkinson's disease

Zhang

Zhao

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In the past few years, scientists have drawn attention to using a treatment focused on ECS [67,68]. There is already a comprehensive review indicating the roles of ECS dysfunction-induced neuroinflammation in epilepsy [69]. Anticonvulsant-like effects of cannabinoid receptor agonists are dependent on CB 1 R. CB 1 agonists could increase ATP-sensitive K + channel (K ATP ) activation by decreasing mitochondrial ATP levels.…”

Section: Endocannabinoid Systemmentioning

confidence: 99%

The CB2 Receptor as a Novel Therapeutic Target for Epilepsy Treatment

Zeng

2021

IJMS

View full text Add to dashboard Cite

Epilepsy is characterized by repeated spontaneous bursts of neuronal hyperactivity and high synchronization in the central nervous system. It seriously affects the quality of life of epileptic patients, and nearly 30% of individuals are refractory to treatment of antiseizure drugs. Therefore, there is an urgent need to develop new drugs to manage and control refractory epilepsy. Cannabinoid ligands, including selective cannabinoid receptor subtype (CB1 or CB2 receptor) ligands and non-selective cannabinoid (synthetic and endogenous) ligands, may serve as novel candidates for this need. Cannabinoid appears to regulate seizure activity in the brain through the activation of CB1 and CB2 cannabinoid receptors (CB1R and CB2R). An abundant series of cannabinoid analogues have been tested in various animal models, including the rat pilocarpine model of acquired epilepsy, a pentylenetetrazol model of myoclonic seizures in mice, and a penicillin-induced model of epileptiform activity in the rats. The accumulating lines of evidence show that cannabinoid ligands exhibit significant benefits to control seizure activity in different epileptic models. In this review, we summarize the relationship between brain CB2 receptors and seizures and emphasize the potential mechanisms of their therapeutic effects involving the influences of neurons, astrocytes, and microglia cells. The unique features of CB2Rs, such as lower expression levels under physiological conditions and high inducibility under epileptic conditions, make it an important target for future research on drug-resistant epilepsy.

show abstract

“…In previous studies performed in our laboratory and by other authors, an ISL dose of 20 mg/kg/day was most frequently employed to evaluate its pharmacological effects in rats [19,23]. A recent report indicated that 30 mg/kg/day ISL for 28 days effectively attenuated monocrotaline-induced pulmonary hypertension in rats without any evident behavioral changes [28].…”

Section: Effects Of Oral Isl On Nic Withdrawal-induced Anxiety-like Bmentioning

confidence: 99%

“…For example, both were shown to inhibit acute cocaine-induced accumbal dopamine release in the same study [19] and exhibited anxiolytic effects in rats [21,22]. Similar to G. radix, ISL exerts neuroprotective effects via its antioxidant actions [5,23]. Moreover, ISL is an important phytochemical that antagonizes glutamatergic N-methyl-Daspartate (NMDA) receptors, which improved glutamateinduced cell death of primary cultured rat cortical neurons [24,25].…”

Section: Introductionmentioning

confidence: 99%

Isoliquiritigenin Attenuates Anxiety‐Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine

Wang

Kim

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

As important components of positive and negative reinforcement, locomotor sensitization and withdrawal anxiety following repeated exposure to nicotine (NIC) constitute crucial risk factors for relapse to NIC use after abstinence. Glycyrrhiza radix (G. radix), an important tonic used in traditional Oriental medicine, has not only anxiolytic effects but also reduces NIC-induced locomotor sensitization. Isoliquiritigenin (ISL), a bioactive ingredient of G. radix, also exhibits neuropharmacological effects, including anxiolytic action. Previously, we reported that ISL suppressed cocaine-induced extracellular dopamine release in the nucleus accumbens shell (NaccSh) and attenuated methamphetamine-induced neurotoxicity. e present study was performed to evaluate the effects of ISL on both NIC withdrawal anxiety and locomotor sensitization. Adult male rats received subcutaneous administration of NIC hydrogen tartrate (0.4 mg/kg, twice a day) for 7 days followed by 4 days of withdrawal. During the period of NIC withdrawal, the rats received four intragastric treatments with ISL (3, 10, or 30 mg/kg/day). All three doses of ISL significantly inhibited NIC withdrawal-induced anxiety-like behaviors in the elevated plus maze (EPM) test, but only the 10 mg/kg/day and 30 mg/kg/day ISL doses attenuated locomotor sensitization induced by a challenge dose of NIC. Intracerebroventricular ISL also inhibited both NIC-induced withdrawal anxiety and locomotor sensitization, but intra-NaccSh injection of ISL blocked only NIC locomotor sensitization, which was abolished by post-ISL infusion of tert-butyl hydroperoxide (an oxidant) or N-methyl-Daspartate (NMDA) into the NaccSh. Moreover, there was increased protein expression of phosphorylated Erk1/2 in the NICsensitized NaccSh, which was suppressed by ISL. Taken together, these results suggest that ISL can inhibit repeated NIC-induced withdrawal anxiety and locomotor sensitization, and the latter is mediated by antagonizing accumbal reactive oxygen species and NMDA receptor signaling.

show abstract

Neuroprotective effects of isoliquiritigenin against cognitive impairment via suppression of synaptic dysfunction, neuronal injury, and neuroinflammation in rats with kainic acid-induced seizures

Cited by 55 publications

References 51 publications

The Nrf2-NLRP3-Caspase1 axis mediates the neuroprotective effects of Celastrol in Parkinson's disease

The Nrf2-NLRP3-Caspase1 axis mediates the neuroprotective effects of Celastrol in Parkinson's disease

The CB2 Receptor as a Novel Therapeutic Target for Epilepsy Treatment

Isoliquiritigenin Attenuates Anxiety‐Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine

Contact Info

Product

Resources

About