Protective role of cinnabar and realgar in Hua-Feng-Dan against LPS plus rotenone-induced neurotoxicity and disturbance of gut microbiota in rats

Chen, Ce; Zhang, Bin-Bin; Hu, Anling; Li, Huan; Liu, Jie; Zhang, Feng

doi:10.1016/j.jep.2019.112299

Cited by 33 publications

(24 citation statements)

References 33 publications

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“…Modern pharmacological studies have shown that HFD has a protective effect on a variety of central nervous system injury and neuroinflammation models. HFD protects mice from bacterial lipopolysaccharide (LPS) plus neurotoxin MPTP toxicity [1] and ameliorates LPS plus pesticide rotenone-induced neuroinflammation and dopaminergic neuron loss in rats [2]. HFD also has modulatory effects on gut microbiota (submitted), which are in line with the clinical experience and theory of traditional Chinese medicines.…”

Section: Introductionmentioning

confidence: 66%

Potential Molecular Target Prediction and Docking Verification of Hua‐Feng‐Dan in Stroke Based on Network Pharmacology

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. Hua-Feng-Dan (HFD) is a Chinese medicine for stroke. This study is to predict and verify potential molecular targets and pathways of HFD against stroke using network pharmacology. Methods. The TCMSP database and TCMID were used to search for the active ingredients of HFD, and GeneCards and DrugBank databases were used to search for stroke-related target genes to construct the “component-target-disease” by Cytoscape 3.7.1, which was further filtered by MCODE to build a core network. The STRING database was used to obtain interrelationships by topology and to construct a protein-protein interaction network. GO and KEGG were carried out through DAVID Bioinformatics. Autodock 4.2 was used for molecular docking. BaseSpace was used to correlate target genes with the GEO database. Results. Based on OB ≥ 30% and DL ≥ 0.18, 42 active ingredients were extracted from HFD, and 107 associated targets were obtained. PPI network and Cytoscape analysis identified 22 key targets. GO analysis suggested 51 cellular biological processes, and KEGG suggested that 60 pathways were related to the antistroke mechanism of HFD, with p53, PI3K-Akt, and apoptosis signaling pathways being most important for HFD effects. Molecular docking verified interactions between the core target (CASP8, CASP9, MDM2, CYCS, RELA, and CCND1) and the active ingredients (beta-sitosterol, luteolin, baicalein, and wogonin). The identified gene targets were highly correlated with the GEO biosets, and the stroke-protection effects of Xuesaitong in the database were verified by identified targets. Conclusion. HFD could regulate the symptoms of stroke through signaling pathways with core targets. This work provided a bioinformatic method to clarify the antistroke mechanism of HFD, and the identified core targets could be valuable to evaluate the antistroke effects of traditional Chinese medicines.

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Section: Introductionmentioning

confidence: 66%

Potential Molecular Target Prediction and Docking Verification of Hua‐Feng‐Dan in Stroke Based on Network Pharmacology

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…Hua-Feng-Dan and its "Guide Drug" Yaomu Hua-Feng-Dan (HFD) and its Guide Drug Yaomu (YM) were provided by Hua-Feng-Dan Pharmaceutical Co. (Guizhou, China). Yaomu is the most important part of the traditional medicine Hua-Feng-Dan [15], and fermented for three months before using as the "Guide Drug" to make Hua-Feng-Dan with other herbs, animal-based products, and minerals as listed in Introduction and reported previously [1,[5][6][7][8].…”

Section: Methodsmentioning

confidence: 99%

“…After acclimatization for one week, mice were randomly divided into four groups: Control group (n = 5),YM-0.1 (n = 5, Yaomu 0.1 g/kg), YM-0.3 (n = 7, Yaomu 0.3 g/kg), HFD (n = 5, Hua-Feng-Dan 1.2 g/kg). Mice received oral gavage daily for 7 consecutive days; the dose of Hua-Feng-Dan selection was based on recent publications [5,6], and Yaomu was estimated from the recipe. Twenty-four hours after the last administration, mice were anesthetized, blood and livers were collected.…”

Section: Animal and Drug Treatmentmentioning

confidence: 99%

“…Hua-Feng-Dan has over 300 years of history in the treatment of stroke and various diseases in China, and is still used today alone or in combination with other medications [1]. Hua-Feng-Dan contains cinnabar (HgS) and realgar (As 4 S 4 ), and our initial research focused on safety evaluation of Hua-Feng-Dan following acute [2], subacute [3,4], and subchronic [5,6] administrations, and demonstrated that the toxicity of Hua-Feng-Dan is different from environmental mercury (Hg) and arsenic (As) compounds [1].…”

Section: Introductionmentioning

confidence: 99%

“…Network pharmacology has found β-sitosterol, luteolin, baicalein, wogoni and cinnabar are potential active ingredients [7]. In an attempt to examine the pharmacological basis of this traditional medicine, We have used experimental animal models to demonstrate the protective effects of Hua-Feng-Dan against LPS plus MPTP induced Parkinson's disease (PD) mouse model [6], and LPS plus rotenone-induced PD neurodegeneration rat model [5], and identi ed cinnabar and realgar are two active ingredients in the recipe both in LPS-induced neuroin ammation in rat midbrain neuron-glia co-cultures [8] and in LPS plus rotenone induced neuroin ammation and dopaminergic neuron loss in rats [5]. We have also found Hua-Feng-Dan exert bene cial effects on gut microbiota in normal mice [9], in PD mice [6], and in PD rats [5].…”

Section: Introductionmentioning

confidence: 99%

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Transcriptome Analyses Revealed Adaptive-Responses in Livers of Mice Treated With Hua-Feng-Dan and Its “Guide Drug” Yaomu

et al. 2021

Preprint

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BackgroundHua-Feng-Dan is a patent Chinese medicine for stroke recovery and is effective against Parkinson’s disease models with modulatory effects on gut microbiota, but its effects on hepatic gene expression are unknown. This study used RNA-Seq to profile hepatic gene expression by Hua-Feng-Dan and its “Guide Drug” Yaomu.MethodsMice received orally Hua-Feng-Dan 1.2 g/kg, Yaomu 0.1-0.3 g/kg, or vehicle for 7 days. Liver pathology was examined, and total RNA was isolated for RNA-Seq. The bioinformatics, including GO and KEGG pathway enrichment analysis, two-dimensional clustering, Ingenuity Pathways Analysis (IPA), and Illumina BaseSpace Correlation Engine were used to analyze differentially expressed genes (DEGs). qPCR was performed to verify selected genes.ResultsHua-Feng-Dan and Yaomu did not produce liver toxicity as evidenced by histopathology and serum ALT and AST. GO Enrichment revealed Hua-Feng-Dan affected lipid homeostasis, protein folding and cell adhesion. KEGG showed activated cholesterol metabolism, bile secretion and PPAR signaling pathways. DEGs were identified by DESeq2 with p < 0.05 compared to controls. Hua-Feng-Dan produced 806 DEGs, Yaomu-0.1 had 235, and Yaomu-0.3 had 92 DEGs. qPCR on selected genes largely verified RNA-Seq results. IPA upstream regulator analysis revealed activation of MAPK and adaptive responses. Yaomu-0.1 had similar effects, but Yaomu-0.3 had little effects. Hua-Feng-Dan-induced DEGs were highly correlated with the GEO database of chemical-induced adaptive transcriptome changes in the liver. ConclusionHua-Feng-Dan at clinical dose did not produce liver pathological changes but induced metabolic and signaling pathway activations. Low dose of its Guide Drug Yaomu produced similar changes to a lesser extent, but high dose of Yaomu had little effects. The effects of Hua-Feng-Dan on liver transcriptome changes may produce adaptive responses to program the liver to produce beneficial or detrimental (over-dosed) pharmacological effects.

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The microbiota-gut-brain axis: a potential target in the small-molecule compounds and gene therapeutic strategies for Parkinson’s disease

Jiao,

Zhou,

2024

Neurol Sci

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Backgrounds Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by motor symptoms and non-motor symptoms. It has been found that intestinal issues usually precede motor symptoms. Microorganisms in the gastrointestinal tract can affect central nervous system through the microbiota-gut-brain axis. Accumulating evidence has shown that disturbances in the microbiota-gut-brain axis are linked with PD. Thus, this pathway appears to be a promising therapeutic target for treatment of PD. Objectives In this review, we mainly described gut dysbiosis in PD and their underlying mechanisms for mediating neuroinflammation and peripheral immune response in PD pathology and futher discussed the potential small-molecule compounds and genic therapeutic strategies targeting the microbiota-gut-brain axis and their applications in PD. Conclusions Studies have found that some small molecule compounds and alterations of inflammation-related genes can improve the motor and non-motor symptoms of PD by improving the microbiota-gut-brain axis, which may provide potentially beneficial drugs and molecular targets for the therapies of PD.

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Protective role of cinnabar and realgar in Hua-Feng-Dan against LPS plus rotenone-induced neurotoxicity and disturbance of gut microbiota in rats

Cited by 33 publications

References 33 publications

Potential Molecular Target Prediction and Docking Verification of Hua‐Feng‐Dan in Stroke Based on Network Pharmacology

Potential Molecular Target Prediction and Docking Verification of Hua‐Feng‐Dan in Stroke Based on Network Pharmacology

Transcriptome Analyses Revealed Adaptive-Responses in Livers of Mice Treated With Hua-Feng-Dan and Its “Guide Drug” Yaomu

The microbiota-gut-brain axis: a potential target in the small-molecule compounds and gene therapeutic strategies for Parkinson’s disease

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