Integrated transcriptomics and metabolomics analysis reveals that C3 and C5 are vital targets of DuZhi Wan in protecting against cerebral ischemic injury

Hou, Jingyi; Cao, Guangzhao; Tian, Liang-Liang; Zhou, Rui; Zhang, Yi; Xu, He; Wu, Huifeng; Wang, Lifang; Yang, Hongjun; Zhang, Jingjing

doi:10.1016/j.biopha.2022.113703

Cited by 11 publications

(4 citation statements)

References 29 publications

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“…This further suggested that EODF treatment was able to modulate neuroprotective effects related to DEGs, and that its modulation time was mainly focused on the acute and subacute phases after SCI. These included genes that exert beneficial effects on neuroprotection: (1) Socs3 and Arg1 are associated with microglia polarization, with Socs3 potentially inhibiting microglia polarization and thereby exerting a neuroprotective effect (Wu et al, 2016;Aliena-Valero et al, 2021); Arg-1 expression presents an association with the M2 phenotype in microglia, and M2-type microglia are considered a beneficial cell type for recovery from neural injury (Li et al, 2021); (2) Agtr2, Apoe, C3, Cd36, Gabrb2, Il1rn, Nfkbia, and Spp1, which express proteins thought to be involved in exerting anti-inflammatory effects (Marie et al, 2002;Tukhovskaya et al, 2010;Yeung et al, 2018;Huang et al, 2020;Kisucká et al, 2021;Hou et al, 2022;Kaltschmidt et al, 2022;Li and Jakobs, 2022;Shen et al, 2022); (3) Bcl2a1, which exert anti-apoptotic effects (Bedirli et al, 2018); and (4) Cd4 and Serpine1, which are involved in nourishing and promote nerve repair (Calenda et al, 2012;Kofke et al, 2018). (i) The DEGs also included genes involved in nerve injury: (1) Ccl5, Ccl6,Ccr1,Cebpb,Fosl1,Mapk11,Osm,Sphk1,Tnfrsf25,and Trpm2, for which the associated proteins may have been involved in exerting pro-inflammatory effects, including those involved in activating the NF-κB signaling pathway, PI3 kinase/Akt pathway, and CCR1/TPR1/ERK1/2 signaling pathway (Kanno et al, 2005;Li M. et al, 2020;Yan et al, 2020;Komori et al, 2022); (2) Cyba and Sgk1, which promote oxidative stress (Iqbal et al, 2015;Usategui-Martín et al, 2022); (3) Tlr9, which are involved in both pro-inflammatory and induction of oxidative stress, and signal activation, and potentially exacerbate neurodegeneration by ...…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota and transcriptome dynamics in every-other-day fasting are associated with neuroprotection in rats with spinal cord injury

Wang

Zhao

Zhou³

et al. 2023

Front. Microbiol.

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IntroductionEvery-other-day fasting (EODF) is a classical intermittent fasting (IF) mode with neuroprotective effects that promotes motor function recovery after spinal cord injury (SCI) in rats. However, its dynamic effects on the gut microbiota and spinal cord transcriptome remain unknown.MethodsIn this study, 16S rRNA sequencing and RNA-seq analysis were used to investigate the effects of ad libitum (AL) and EODF dietary modes on the structural characteristics of rat gut microbiota in rats and the spinal cord transcriptome at various time points after SCI induction.ResultsOur results showed that both dietary modes affected the bacterial community composition in SCI rats, with EODF treatment inducing and suppressing dynamic changes in the abundances of potentially anti-inflammatory and pro-inflammatory bacteria. Furthermore, the differentially expressed genes (DEGs) enriched after EODF intervention in SCI rats were associated with various biological events, including immune inflammatory response, cell differentiation, protein modification, neural growth, and apoptosis. In particular, significant spatiotemporal differences were apparent in the DEGs associated with neuroprotection between the EODF and AL interventions. These DGEs were mainly focused on days 1, 3, and 7 after SCI. The relative abundance of certain genera was significantly correlated with DEGs associated with neuroprotective effects in the EODF-SCI group.DiscussionOur results showed that EODF treatment may exert neuroprotective effects by modulating the transcriptome expression profile following SCI in rats. Furthermore, gut microbiota may be partially involved in mediating these effects.

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Section: Discussionmentioning

confidence: 99%

Gut microbiota and transcriptome dynamics in every-other-day fasting are associated with neuroprotection in rats with spinal cord injury

Wang

Zhao

Zhou³

et al. 2023

Front. Microbiol.

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“…Hou et al studied the mechanism of Duzhi Wan (DZW), a TCM formula used for IS prevention and treatment [ 153 ]. They identified complement C3 (C3) and C5a complement factor receptor 1 (C5ar1) as core targets of DZW, while also pinpointing key metabolites involved in its neuroprotective effects, such as acetylcholine and inosine 5’-monophosphate.…”

Section: Metabolomic Analysis Of Traditional Chinese Medicine For Ismentioning

confidence: 99%

Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke

Wei,

Chen,

Deng

et al. 2024

Biomark Res

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Ischemic stroke (IS), a devastating cerebrovascular accident, presents with high mortality and morbidity. Following IS onset, a cascade of pathological changes, including excitotoxicity, inflammatory damage, and blood-brain barrier disruption, significantly impacts prognosis. However, current clinical practices struggle with early diagnosis and identifying these alterations. Metabolomics, a powerful tool in systems biology, offers a promising avenue for uncovering early diagnostic biomarkers for IS. By analyzing dynamic metabolic profiles, metabolomics can not only aid in identifying early IS biomarkers but also evaluate Traditional Chinese Medicine (TCM) efficacy and explore its mechanisms of action in IS treatment. Animal studies demonstrate that TCM interventions modulate specific metabolite levels, potentially reflecting their therapeutic effects. Identifying relevant metabolites in cerebral ischemia patients holds immense potential for early diagnosis and improved outcomes. This review focuses on recent metabolomic discoveries of potential early diagnostic biomarkers for IS. We explore variations in metabolites observed across different ages, genders, disease severity, and stages. Additionally, the review examines how specific TCM extracts influence IS development through metabolic changes, potentially revealing their mechanisms of action. Finally, we emphasize the importance of integrating metabolomics with other omics approaches for a comprehensive understanding of IS pathophysiology and TCM efficacy, paving the way for precision medicine in IS management.

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“…In particular, DZP can significantly decrease the infarction size and neurological deficit scores. Moreover, DZP can reduce neuroinflammation and inhibit related metabolic pathways [ 5 ]. In our previous study, a total of 176 DZP components were identified, including 50 flavonoids, 31 phenolic acids, 25 terpenoids, five alkaloids, and 65 other components [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Comparative prototypes and metabolites of Du-zhi pill in normal and cerebral ischemia rats by UHPLC-Q-TOF-MS/MS method

Lai,

Tian,

Pan

et al. 2024

Heliyon

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Integrated transcriptomics and metabolomics analysis reveals that C3 and C5 are vital targets of DuZhi Wan in protecting against cerebral ischemic injury

Cited by 11 publications

References 29 publications

Gut microbiota and transcriptome dynamics in every-other-day fasting are associated with neuroprotection in rats with spinal cord injury

Gut microbiota and transcriptome dynamics in every-other-day fasting are associated with neuroprotection in rats with spinal cord injury

Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke

Comparative prototypes and metabolites of Du-zhi pill in normal and cerebral ischemia rats by UHPLC-Q-TOF-MS/MS method

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