Chaihu-Longgu-Muli Decoction exerts an antiepileptic effect in rats by improving pyroptosis in hippocampal neurons

Xia, Shuaishuai; Yang, Ping; Li, Feng; Yu, Qian; Kuang, Weiping; Zhu, Yong; Lü, Jun; Wu, Hongyan; Li, Liang; Huang, Huansen

doi:10.1016/j.jep.2021.113794

Cited by 26 publications

(12 citation statements)

References 39 publications

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“…Similarly, Xia et al. recently indicated that inhibiting pyroptosis could suppress the frequency and duration time of epileptic seizures (Xia et al., 2021). In support of our findings, another study noted that inhibition of Stat expression conferred an alleviating effect on NLRP3 inflammasome and pyroptosis (Xu et al., 2021).…”

Section: Discussionmentioning

confidence: 94%

Role of Stat3 in NLRP3/caspase‐1‐mediated hippocampal neuronal pyroptosis in epileptic mice

Jiang

Tang

Zhong

et al. 2021

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Epilepsy, a fairly common neurological disorder, is linked to various sequelae and greatly impairs the quality of life. Meanwhile, there is evidence to suggest an association between pyroptosis and epilepsy. Accordingly, the current study sought to determine the role of signal transduction activator of transcription 3 (Stat3) in pyroptosis in epileptic mice. First, epileptic mouse models were induced by lithium chloride, atropine, and pilocarpine, and HT22 cells were treated with lipopolysaccharide (LPS) to establish in vitro hippocampal neuronal inflammation models. Subsequently, Stat3, NOD‐like receptor protein 3 (NLRP3), cleaved‐caspase‐1, gasdermin D (GSDMD)‐N, activated Stat3 (p‐Stat3), and H3K9Ac levels were detected in the mouse hippocampus and HT22 cells. Morris water maze test was further performed to detect changes in the learning and memory abilities of epileptic mice, and hematoxylin‐eosin staining and Nissl staining were conducted to detect the pathological injury. HT22 cell proliferation and apoptosis were also detected using a cell counting kit‐8 assay and flow cytometry. An enzyme‐linked immunosorbent assay was adopted to detect Interleukin (IL)‐1β and IL‐18 concentrations in the mouse hippocampus and HT22 cells. Furthermore, the enrichment of H3K9Ac and p‐Stat3 in the NLRP3 promoter region was detected with the help of a chromatin immunoprecipitation assay. The obtained findings revealed that Stat3 was highly expressed in the hippocampus of epileptic mice and LPS‐treated HT22 cells. Meanwhile, Stat3 silencing brought about improvements in the learning and memory abilities of the mice, in addition to alleviation of hippocampal neuronal damage and pyroptosis‐related factors in hippocampal tissue and HT22 cells. We also observed that Stat3 bound to the NLRP3 promoter to promote H3K9 acetylation and NLRP3 transcription. Moreover, increasing H3K9Ac in cells annulled the inhibition of silencing Stat3 on neuronal pyroptosis. To conclude, our findings revealed that Stat3 bound to the NLRP3 promoter to augment H3K9 acetylation, NLRP3 transcription, and NLRP3/caspase‐1‐mediated neuronal pyroptosis, resulting in aggravation of neuronal damage in epileptic mice.

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Section: Discussionmentioning

confidence: 94%

Role of Stat3 in NLRP3/caspase‐1‐mediated hippocampal neuronal pyroptosis in epileptic mice

Jiang

Tang

Zhong

et al. 2021

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“…Eokgan-san has been prescribed for restlessness and agitation in children and has been reported to improve the behavioral and psychological symptoms of dementia [ 45 , 46 ] and Tourette’s syndrome symptoms in children and adolescents for a short period of time [ 47 ]. Sihogayonggolmororyeo-tang (written as Chaihu Jia Longgu Muli decoction in Chinese) has been reported to have an antiepileptic effect in an experimental study on rats [ 48 ], and in an SR, it was found to be more effective than conventional medicine in the treatment of post-stroke depression [ 49 ] and insomnia [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

A National Survey on the Clinical Practice Patterns of Korean Medicine Doctors for Attention Deficit Hyperactivity Disorder (ADHD) in Children and Adolescents

Lee

2023

Children

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To alleviate the symptoms of attention deficit/hyperactivity disorder (ADHD) in children and reduce the side effects of psychostimulants, parents are opting for complementary and alternative medicine as a therapeutic option. Korean medicine (KM) has been used by Korean medicine doctors (KMDs) to treat ADHD with herbal medication and acupuncture. This study aimed to conduct a cross-sectional survey on the clinical practice patterns of KM for ADHD in children targeting KMDs. The questionnaire included aspects related to patient characteristics, diagnosis, treatment modalities, and perceptions regarding KM. Questionnaires were distributed to all KMDs via e-mail, and the online surveys were conducted from 1 to 15 February 2023. A total 2.1% of KMDs (n = 537/25,574) completed the survey. The predominant diagnostic pattern identification employed was “depressed liver qi transforming into fire” (19.8%). Herbal medicine (HM) was the most common treatment (44.2%). The most frequently used HM prescriptions were Ondam-tang (16.9%), Eokgan-san (15.7%), and Sihogayonggolmoryeo-tang (14.4%). KMDs recognized HM as the most effective among the KM treatments (54.3%). The results of this study elucidate the current clinical practice patterns of KM for ADHD. Based on these findings, a treatment protocol can be developed to provide optimized KM treatment services to patients with ADHD.

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“…The quantitative analysis of the phytochemical compounds of the extract revealed a high concentration of flavonoids and saponins. The antiepileptogenic-like effect of the extract could be related to the presence of these compounds in the extract ( Jiang, 2019 ; Xia et al, 2021 ; Yakubu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Aqueous extract of Parkia biglobosa (Jacq.) R. Br. (Fabaceae) exerts antiepileptogenic, anti-amnesic, and anxiolytic-like effects in mice via mechanisms involving antioxidant and anti-inflammatory pathways

et al. 2022

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Parkia biglobosa (Jacq.) R. Br. (Fabaceae) is a widely distributed tree, used in traditional medicine to treat amebiasis, hookworm infection, ascariasis, asthma, sterility, dental pain, headaches, cardiac disorders, and epilepsy. To date, no study on the effect of an aqueous extract of P. biglobosa on epileptogenesis and associated neuropsychiatric disorders has been undertaken. Therefore, this study aimed to investigate antiepileptogenic-, antiamnesic-, and anxiolytic-like effects of an aqueous extract of P. biglobosa using pentylenetetrazole (PTZ)-induced kindling in mice. Animals were divided into six groups of eight mice each. Thus, a PTZ group received distilled water (10 ml/kg, per os), a positive control group received sodium valproate (300 mg/kg, p.o.), and three test groups received the aqueous extract of P. biglobosa (80, 160, and 320 mg/kg, p.o.).In addition, a control group of eight mice receiving distilled water (10 ml/kg, p.o.) was formed. The treatments were administered to mice, 60 min before administration of PTZ (20 mg/kg, i.p.). These co-administrations were performed once daily, for 22 days. The number and duration of seizures (stages 1, 2, 3, and 4 of seizures) exhibited by each mouse were assessed for 30 min during the treatment period. Twenty-four hours following the last administration of the treatments and PTZ, novel object recognition and T-maze tests were performed to assess working memory impairment in mice, while the open field test was performed to assess anxiety-like behavior. After these tests, the animals were sacrificed, and the hippocampi were collected for biochemical and histological analysis. During the period of PTZ-kindling, the extract at all doses completely (p < 0.001) protected all mice against stages 3 and 4 of seizures when compared to sodium valproate, a standard antiepileptic drug. The extract also significantly (p < 0.001) attenuated working memory impairment and anxiety-like behavior. In post-mortem brain analyses, the extract significantly (p < 0.001) increased γ-aminobutyric acid (GABA) level and reduced oxidative stress and inflammation. Histological analysis showed that the aqueous extract attenuated neuronal degeneration/necrosis in the hippocampus. These results suggest that the extract is endowed with antiepileptogenic-, anti-amnesic-, and anxiolytic-like effects. These effects seem to be mediated in part by GABAergic, antioxidant, and anti-inflammatory mechanisms. These results suggest the merit of further studies to isolate the bioactive molecules responsible for these potentially therapeutically relevant effects of the extract.

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Chaihu-Longgu-Muli Decoction exerts an antiepileptic effect in rats by improving pyroptosis in hippocampal neurons

Cited by 26 publications

References 39 publications

Role of Stat3 in NLRP3/caspase‐1‐mediated hippocampal neuronal pyroptosis in epileptic mice

Role of Stat3 in NLRP3/caspase‐1‐mediated hippocampal neuronal pyroptosis in epileptic mice

A National Survey on the Clinical Practice Patterns of Korean Medicine Doctors for Attention Deficit Hyperactivity Disorder (ADHD) in Children and Adolescents

Aqueous extract of Parkia biglobosa (Jacq.) R. Br. (Fabaceae) exerts antiepileptogenic, anti-amnesic, and anxiolytic-like effects in mice via mechanisms involving antioxidant and anti-inflammatory pathways

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