Integrated transcriptomics, proteomics and metabolomics to identify biomarkers of astragaloside IV against cerebral ischemic injury in rats

Wei, Xiaoyu; Wan, Haitong; Yin, Jun-Jun; Lin, Bingying; Ding, Zhongxiang; Yang, Jiehong; Zhou, Huifen

doi:10.1039/d2fo03030f

Cited by 7 publications

(4 citation statements)

References 52 publications

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“…The Proteomic data analysis was performed by Shanghai Luming Biological Technology Co., Ltd. (Shanghai, China). Peptide-labeled proteins were analyzed using an Agilent 1100 high-performance liquid chromatograph and TimsTOF Pro mass spectrometer (Thermo, Bruker, USA) 15 . Chromatographic conditions were set as follows: samples were loaded onto a 25-cm C18 analytical column (RP-C18, IonOpticks) at a flow rate of 300 nL/min, followed by gradient elution.…”

Section: Methodsmentioning

confidence: 99%

Integrated proteomics and metabolomics analysis of sclerosis-related proteins and femoral head necrosis following internal fixation of femoral neck fractures

Liu,

Ma,

Yang

et al. 2024

Sci Rep

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Femoral head necrosis (FHN) is a serious complication after femoral neck fractures (FNF), often linked to sclerosis around screw paths. Our study aimed to uncover the proteomic and metabolomic underpinnings of FHN and sclerosis using integrated proteomics and metabolomics analyses. We identified differentially expressed proteins (DEPs) and metabolites (DEMs) among three groups: patients with FNF (Group A), sclerosis (Group B), and FHN (Group C). Using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we examined the roles of these proteins and metabolites. Our findings highlight the significant differences across the groups, with 218 DEPs and 44 DEMs identified between the sclerosis and FNF groups, 247 DEPs and 31 DEMs between the FHN and sclerosis groups, and a stark 682 DEPs and 94 DEMs between the FHN and FNF groups. Activities related to carbonate dehydratase and hydrolase were similar in the FHN and sclerosis groups, whereas extracellular region and lysosome were prevalent in the FHN and FNF groups. Our study also emphasized the involvement of the PI3K-Akt pathway in sclerosis and FHN. Moreover, the key metabolic pathways were implicated in glycerophospholipid metabolism and retrograde endocannabinoid signaling. Using western blotting, we confirmed the pivotal role of specific genes/proteins such as ITGB5, TNXB, CA II, and CA III in sclerosis and acid phosphatase 5 and cathepsin K in FHN. This comprehensive analyses elucidates the molecular mechanisms behind sclerosis and FHN and suggests potential biomarkers and therapeutic targets, paving the way for improved treatment strategies. Further validation of the findings is necessary to strengthen the robustness and reliability of the results.

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Section: Methodsmentioning

confidence: 99%

Integrated proteomics and metabolomics analysis of sclerosis-related proteins and femoral head necrosis following internal fixation of femoral neck fractures

Liu,

Ma,

Yang

et al. 2024

Sci Rep

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“…The fragmentation and cleavage modes are shown in Figure 2B. The product at m/z 253.1951, which was generated from the quasi-molecular ion m/z 271.2056 ([M + H] + ) of compound 159, was calculated as C 15 H 10 O 5 , corresponding to the cation of galangin [29].…”

Section: Characterization Of Flavonoidsmentioning

confidence: 99%

Comparison of the Metabolomics of Different Dendrobium Species by UPLC-QTOF-MS

Zhang,

Yang,

Wang

et al. 2023

IJMS

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Dendrobium Sw. (family Orchidaceae) is a renowned edible and medicinal plant in China. Although widely cultivated and used, less research has been conducted on differential Dendrobium species. In this study, stems from seven distinct Dendrobium species were subjected to UPLC-QTOF-MS/MS analysis. A total of 242 metabolites were annotated, and multivariate statistical analysis was employed to explore the variance in the extracted metabolites across the various groups. The analysis demonstrated that D. nobile displays conspicuous differences from other species of Dendrobium. Specifically, D. nobile stands out from the remaining six taxa of Dendrobium based on 170 distinct metabolites, mainly terpene and flavonoid components, associated with cysteine and methionine metabolism, flavonoid biosynthesis, and galactose metabolism. It is believed that the variations between D. nobile and other Dendrobium species are mainly attributed to three metabolite synthesis pathways. By comparing the chemical composition of seven species of Dendrobium, this study identified the qualitative components of each species. D. nobile was found to differ significantly from other species, with higher levels of terpenoids, flavonoids, and other compounds that are for the cardiovascular field. By comparing the chemical composition of seven species of Dendrobium, these qualitative components have relevance for establishing quality standards for Dendrobium.

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“…Astragali Radix (Huangqi) 23 and Chuanxiong Rhizoma (Chuanxiong) 24 are medicinal and food homologous plants in traditional Chinese medicine, which rhizomes are the main edible medicinal parts. Consuming the rhizome with food is a typical therapy to keep healthy.…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV combined with ligustrazine ameliorates abnormal mitochondrial dynamics via Drp1 SUMO/deSUMOylation in cerebral ischemia–reperfusion injury

Chen,

Yang,

Zhou

et al. 2024

CNS Neurosci Ther

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ObjectivesAstragaloside IV (AST IV) and ligustrazine (Lig), the main ingredients of Astragali Radix and Chuanxiong Rhizoma respectively, have demonstrated significant benefits in treatment of cerebral ischemia ‐reperfusion injury (CIRI); however, the mechanisms underlying its benificial effects remain unclear. SUMO‐1ylation and deSUMO‐2/3ylation of dynamin‐related protein 1 (Drp1) results in mitochondrial homeostasis imbalance following CIRI, which subsequently aggravates cell damage. This study investigates the mechanisms by which AST IV combined with Lig protects against CIRI, focusing on the involvement of SUMOylation in mitochondrial dynamics.MethodsRats were administrated AST IV and Lig for 7 days, and middle cerebral artery occlusion was established to mimic CIRI. Neural function, cerebral infarction volume, cerebral blood flow, cognitive function, cortical pathological lesions, and mitochondrial morphology were measured. SH‐SY5Y cells were subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) injury. Mitochondrial membrane potential and lactic dehydrogenase (LDH), reactive oxygen species (ROS), and adenosine triphosphate (ATP) levels were assessed with commercial kits. Moreover, co‐immunoprecipitation (Co‐IP) was used to detect the binding of SUMO1 and SUMO2/3 to Drp1. The protein expressions of Drp1, Fis1, MFF, OPA1, Mfn1, Mfn2, SUMO1, SUMO2/3, SENP1, SENP2, SENP3, SENP5, and SENP6 were measured using western blot.ResultsIn rats with CIRI, AST IV and Lig improved neurological and cognitive functions, restored CBF, reduced brain infarct volume, and alleviated cortical neuron and mitochondrial damage. Moreover, in SH‐SY5Y cells, the combination of AST IV and Lig enhanced cellular viability, decreased release of LDH and ROS, increased ATP content, and improved mitochondrial membrane potential. Furthermore, AST IV combined with Lig reduced the binding of Drp1 with SUMO1, increased the binding of Drp1 with SUMO2/3, suppressed the expressions of Drp1, Fis1, MFF, and SENP3, and increased the expressions of OPA1, Mfn1, Mfn2, SENP1, SENP2, and SENP5. SUMO1 overexpression promoted mitochondrial fission and inhibited mitochondrial fusion, whereas SUMO2/3 overexpression suppressed mitochondrial fission. AST IV combined with Lig could reverse the effects of SUMO1 overexpression while enhancing those of SUMO2/3 overexpression.ConclusionsThis study posits that the combination of AST IV and Lig has the potential to reduce the SUMO‐1ylation of Drp1, augment the SUMO‐2/3ylation of Drp1, and thereby exert a protective effect against CIRI.

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Integrated transcriptomics, proteomics and metabolomics to identify biomarkers of astragaloside IV against cerebral ischemic injury in rats

Abstract: Based on transcriptomic, proteomic, and metabolomic analyses, we developed an strategy to explore the key targets and mechanisms of Astragaloside IV treatment for cerebral ischemia in rats to obtain a compound–reaction–enzyme–gene network.

Cited by 7 publications

References 52 publications

Integrated proteomics and metabolomics analysis of sclerosis-related proteins and femoral head necrosis following internal fixation of femoral neck fractures

Integrated proteomics and metabolomics analysis of sclerosis-related proteins and femoral head necrosis following internal fixation of femoral neck fractures

Comparison of the Metabolomics of Different Dendrobium Species by UPLC-QTOF-MS

Astragaloside IV combined with ligustrazine ameliorates abnormal mitochondrial dynamics via Drp1 SUMO/deSUMOylation in cerebral ischemia–reperfusion injury

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