Modified Huang-Lian-Jie-Du Decoction Ameliorates A<i>β</i> Synaptotoxicity in a Murine Model of Alzheimer’s Disease

Liu, Yan; Du, Tao; Zhang, Wenlong; Lu, Weiye; Peng, Zhichao; Huang, Shuqiong; Sun, Xiangdong; Zhu, Xiaodong; Chen, Chaojun; Qian, Lei; Wen, Lei; Xu, Pingyi; Zhang, Yunlong

doi:10.1155/2019/8340192

Cited by 34 publications

(26 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 25 Intriguingly, we and others have suggested the possibility of herbal formulas as being anti-AD drug candidates. 26 , 27 , 28 , 29 In the present study, we investigated the effects of the herbal medicine SST on memory deficiency and neuronal cell changes using an AD-like animal model to corroborate our previous in vitro data. We established an AD-like mouse model by injecting Aβ aggregates into the brain and conducted behavioral tests to explore memory capacity of the mice.…”

Section: Introductionsupporting

confidence: 71%

“… 26 Liu et al reported that the modified Huang-Lian-Jie-Du decoction ameliorates Aβ synaptotoxicity via the regulation of glutamatergic transmission and the adenosine-related signaling pathway in Aβ-induced AD mice. 28 Since donepezil was firstly approved by U.S. FDA as an AD medication in 1996, a number of candidate drugs for AD treatment have been investigated. However, candidates for the treatment of AD had a failure rate of 99% or more.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Korean traditional herbal formula Soshiho-tang attenuates memory impairment and neuronal damage in mice with amyloid-beta-induced Alzheimer's disease

Sohn

Kim

Jeong

2021

Integrative Medicine Research

View full text Add to dashboard Cite

Background Soshiho-tang (SST), also known as Xiaochaihu-tang in China and Sho-saiko-to in Japan, is an Oriental herbal formula traditionally used to treat febrile diseases. Recently, several in vitro and in vivo studies have reported the anti-cancer, anti-liver disease, and anti-inflammatory activities of SST. However, there is little evidence of its effects on neurological diseases. We previously reported the inhibitory effects of SST on in vitro acetylcholinesterase (AChE) activation and amyloid-β (Aβ) aggregation, which are crucial hallmarks of Alzheimer's disease (AD). In the present study, we report that SST has preventive effects on memory impairment and neuronal cell changes in an Aβ-induced AD-like mouse model. Methods Male mice underwent injection of Aβ aggregates and administered SST (500, 1,000, or 2,000 mg/kg/day) for 20 days. Behavioral tests (passive avoidance task [PAT] and Morris water maze [MWM] test) were conducted. Lastly, brain sections were obtained from sacrificed mice for quantitative analysis. Results Intracerebroventricular (ICV) injection of Aβ aggregates significantly decreased the latency time in the PAT and MWM test compared to normal control. In contrast, SST administration markedly reversed the latency caused by Aβ injection. Additionally, our data revealed that SST-mediated improvements in memory impairment are related to its neuroprotective and anti-neuroinflammatory effects. On histological analysis, SST treatment protected neuronal loss and damage as well as microglial activation, and ameliorated amount of Aβ in brain of mouse model of AD. Conclusion Our findings suggest that SST may be a promising candidate for the development of novel drugs for AD.

show abstract

Section: Introductionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Korean traditional herbal formula Soshiho-tang attenuates memory impairment and neuronal damage in mice with amyloid-beta-induced Alzheimer's disease

Sohn

Kim

Jeong

2021

Integrative Medicine Research

View full text Add to dashboard Cite

show abstract

“…Open-field testing was performed as previously described 67 . Mice were placed in the middle of the central area and observed in dim light for 15 min.…”

Section: Methodsmentioning

confidence: 99%

“…Raw data files generated by UHPLC–MS/MS were processed using the Compound Discoverer 3.1 (CD3.1, Thermo Fisher) to perform peak alignment, peak selection, and quantitation for each metabolite. The main parameters were set as previously described 67 . The metabolites were annotated using the KEGG database ( http://www.genome.jp/kegg/ ), HMDB database ( http://www.hmdb.ca/ ), and Lipidmaps database ( http://www.lipidmaps.org/ ).…”

Section: Methodsmentioning

confidence: 99%

Functional validation of a human GLUD2 variant in a murine model of Parkinson’s disease

et al. 2020

Self Cite

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a common neurodegenerative disease characterized by Lewy body formation and progressive dopaminergic neuron death in the substantia nigra (SN). Genetic susceptibility is a strong risk factor for PD. Previously, a rare gain-of-function variant of GLUD2 glutamate dehydrogenase (T1492G) was reported to be associated with early onset in male PD patients; however, the function and underlying mechanism of this variant remains elusive. In the present study, we generated adeno-associated virus expressing GLUD2 and its mutant under the control of the glial fibrillary acidic protein promotor and injected the virus into the SN pars compacta of either untreated mice or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. Our results demonstrate that GLUD2 mutation in MPTP-induced PD mice exacerbates movement deficits and nigral dopaminergic neuron death and reduces glutamate transporters expression and function. Using GC-Q-TOF/MS-based metabolomics, we determined that GLUD2 mutation damages mitochondrial function by decreasing succinate dehydrogenase activity to impede the tricarboxylic acid cycle in the SN of MPTP-induced PD mice. Accordingly, GLUD2 mutant mice had reduced energy metabolism and increased apoptosis, possibly due to downregulation of brain-derived neurotrophic factor/nuclear factor E2-related factor 2 signaling in in vitro and in vivo PD models. Collectively, our findings verify the function of GLUD2 in PD and unravel a mechanism by which a genetic variant in human GLUD2 may contribute to disease onset.

show abstract

“…HLJDD is used for treatment of symptoms caused by heat toxins ( Yue et al, 2014 ). Several studies report that HLJDD ameliorates multiple central nervous system diseases such as cerebral ischemia, Alzheimer’s disease (AD) and mental disorder ( Liu et al, 2019 ; Okamoto et al, 2013 ; Wang et al, 2013 ). The formula modulates monoamine metabolism and kynureninet metabolism which are both implicated in pathogenesis of depressive syndromes ( Sasaki et al, 2000 ; Yu et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics

Xia

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Depressive disorder is a common mental disorder characterized by depressed mood and loss of interest or pleasure. As the Herbal medicines are mainly used as complementary and alternative therapy for depression. This study aimed at exploring antidepressant activity of Huang-lian Jie-du Decoction (HLJDD), and evaluating active components and potential depression-associated targets. HLJDD was administered on chronic unpredictable mild stress-induced (CUMS) depressive mice. Behavior evaluation was performed through force swimming test (FST), novelty-suppressed feeding test (NSF), and open field test (OFT). Active components of HLJDD, potential targets, and metabolic pathways involved in depression were explored through systemic biology-based network pharmacology assay, molecular docking and metabonomics. FST assay showed that CUMS mice administered with HLJDD had significantly shorter immobility time compared with control mice. Further, HLJDD alleviated feeding latency of CUMS mice in NSFand increased moving distance and duration in OFT. In the following network pharmacology assay, thirty-eight active compounds in HLJDD were identified based on drug-like characteristics, and pharmacokinetics and pharmacodynamics profiles. Moreover, forty-eight molecular targets and ten biochemical pathways were uncovered through molecular docking and metabonomics. GRIN2B, DRD, PRKCA, HTR, MAOA, SLC6A4, GRIN2A, and CACNA1A are implicated in inhibition of depressive symptoms through modulating tryptophan metabolism, serotonergic and dopaminergic synaptic activities, cAMP signaling pathway, and calcium signaling pathway. Further network pharmacology-based analysis showed a correlation between HLJDD and tryptophan metabolism. A total of thirty-seven active compounds, seventy-six targets, and sixteen biochemical pathways were involved in tryptophan metabolism. These findings show that HLJDD acts on potential targets such as SLC6A4, HTR, INS, MAO, CAT, and FoxO, PI3K/Akt, calcium, HIF-1, and mTOR signaling pathways, and modulates serotoninergic and dopaminergic synaptic functions. In addition, metabonomics showed that tryptophan metabolism is the primary target for HLJDD in CUMS mice. The findings of the study show that HLJDD exhibited antidepressant effects. SLC6A4 and MAOA in tryptophan metabolism were modulated by berberine, baicalein, tetrahydroberberine, candicine and may be the main antidepressant targets for HLJDD.

show abstract

Modified Huang-Lian-Jie-Du Decoction Ameliorates Aβ Synaptotoxicity in a Murine Model of Alzheimer’s Disease

Cited by 34 publications

References 82 publications

Korean traditional herbal formula Soshiho-tang attenuates memory impairment and neuronal damage in mice with amyloid-beta-induced Alzheimer's disease

Korean traditional herbal formula Soshiho-tang attenuates memory impairment and neuronal damage in mice with amyloid-beta-induced Alzheimer's disease

Functional validation of a human GLUD2 variant in a murine model of Parkinson’s disease

Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics

Contact Info

Product

Resources

About