Urine metabolomics study of Bushen Huoxue Prescription on diabetic retinopathy rats by UPLC–Q‐exactive Orbitrap–MS

Wang, Xin; Li, Yang; Xie, Mengjun; Deng, Liping; Zhang, Mei; Xie, Xiaoming

doi:10.1002/bmc.4792

Cited by 14 publications

(6 citation statements)

References 44 publications

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“…Based on the negative impact on the progression of DM and DR, urine metabolomic analysis in diabetic-model Goto-Kakizaki rats showed that metabolites changed by exposure to free CML were matched to carbohydrate metabolism, amino acid metabolism, and the tricarboxylic acid (TCA) cycle ( 90 ). Meanwhile, urine metabolomic research based on UPLC-Q-Exactive Orbitrap-MS was built to explore the metabolic alterations of DR rats and evaluate the therapeutic action of BP on DR, and nine possible biomarkers related to DR were significantly correlated to tryptophan metabolism, lipid metabolism, and gut microbial metabolism in this study ( 91 ).…”

Section: Metabolomics In Diabetic Retinopathymentioning

confidence: 99%

Metabolomics of various samples advancing biomarker discovery and pathogenesis elucidation for diabetic retinopathy

Yang

Kong

et al. 2022

Front. Endocrinol.

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Diabetic retinopathy (DR) is a universal microvascular complication of diabetes mellitus (DM), which is the main reason for global sight damage/loss in middle-aged and/or older people. Current clinical analyses, like hemoglobin A1c, possess some importance as prognostic indicators for DR severity, but no effective circulating biomarkers are used for DR in the clinic currently, and studies on the latent pathophysiology remain lacking. Recent developments in omics, especially metabolomics, continue to disclose novel potential biomarkers in several fields, including but not limited to DR. Therefore, based on the overview of metabolomics, we reviewed progress in analytical technology of metabolomics, the prominent roles and the current status of biomarkers in DR, and the update of potential biomarkers in various DR-related samples via metabolomics, including tear as well as vitreous humor, aqueous humor, retina, plasma, serum, cerebrospinal fluid, urine, and feces. In this review, we underscored the in-depth analysis and elucidation of the common biomarkers in different biological samples based on integrated results, namely, alanine, lactate, and glutamine. Alanine may participate in and regulate glucose metabolism through stimulating N-methyl-D-aspartate receptors and subsequently suppressing insulin secretion, which is the potential pathogenesis of DR. Abnormal lactate could cause extensive oxidative stress and neuroinflammation, eventually leading to retinal hypoxia and metabolic dysfunction; on the other hand, high-level lactate may damage the structure and function of the retinal endothelial cell barrier via the G protein-coupled receptor 81. Abnormal glutamine indicates a disturbance of glutamate recycling, which may affect the activation of Müller cells and proliferation via the PPP1CA–YAP–GS–Gln–mTORC1 pathway.

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Section: Metabolomics In Diabetic Retinopathymentioning

confidence: 99%

Metabolomics of various samples advancing biomarker discovery and pathogenesis elucidation for diabetic retinopathy

Yang

Kong

et al. 2022

Front. Endocrinol.

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“…The imbalance of tryptophan metabolism has a serious effect on DR and reduces the integrity of the retinal neuron unit. Tryptophan is a potential marker of DR progression in T2D patients ( Yun et al, 2020 ) and DR is mainly associated with tryptophan metabolism ( Wang X. et al, 2020 ). Abnormal levels of tryptophan are highly correlated with T2DM and its complications ( Gong et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy

Kong

Sun

et al. 2022

Front. Pharmacol.

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Keluoxin (KLX) is an active agent in the treatment of diabetic retinopathy (DR). However, its mechanism, targets, and effective constituents against DR are still unclear, which seriously restricts its clinical application. Chinmedomics has the promise of explaining the pharmacological effects of herbal medicines and investigating the effective mechanisms. The research results from electroretinography and electron microscope showed that KLX could reduce retinal dysfunction and pathological changes by the DR mouse model. Based on effectiveness, we discovered 64 blood biomarkers of DR by nontargeted metabolomics analysis, 51 of which returned to average levels after KLX treatment including leukotriene D4 and A4, l-tryptophan, 6-hydroxymelatonin, l-phenylalanine, l-tyrosine, and gamma-linolenic acid (GLA). The metabolic pathways involved were phenylalanine metabolism, steroid hormone biosynthesis, sphingolipid metabolism, etc. Adenosine monophosphate-activated protein kinase (AMPK), extracellular signal-regulated protein kinase1/2 (ERK1/2), phosphatidylinositol-3-kinase (PI3K), and protein 70 S6 kinase (p70 S6K) might be potential targets of KLX against DR. This was related to the mammalian target of rapamycin (mTOR) signaling and AMPK signaling pathways. We applied the chinmedomics strategy, integrating serum pharm-chemistry of traditional Chinese medicine (TCM) with metabolomics, to discover astragaloside IV (AS-IV), emodin, rhein, chrysophanol, and other compounds, which were the core effective constituents of KLX when against DR. Our study was the first to apply the chinmedomics strategy to discover the effective constituents of KLX in the treatment of DR, which fills the gap of unclear effective constituents of KLX. In the next step, the research of effective constituents can be used to optimize prescription preparation, improve the quality standard, and develop an innovative drug.

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“…Bushen Huoxue Prescription (BP), comprising Salviae Miltiorrhizae Radix et Rhizoma, Rehmanniae Radix, Puerariae Lobatae Radix, and Ginseng Radix et Rhizoma, has shown promise in DR prevention and treatment. Using urine metabolomics, BP’s anti-DR effect was linked to nine small-molecule metabolites, indicating its potential to regulate gut microbial metabolism, lipid metabolism, and tryptophan metabolism in treating DR. 93 These findings underscore the need for more research to elucidate the molecular effects of TCM on DR’s physiological changes.…”

Section: Metabolomics Studies Of Tcm Treating Diabetic Complicationsmentioning

confidence: 96%

Application of Metabolomics and Traditional Chinese Medicine for Type 2 Diabetes Mellitus Treatment

Li,

Zhu,

Wang

et al. 2023

DMSO

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Diabetes is a major global public health problem with high incidence and case fatality rates. Traditional Chinese medicine (TCM) is used to help manage Type 2 Diabetes Mellitus (T2DM) and has steadily gained international acceptance. Despite being generally accepted in daily practice, the TCM methods and hypotheses for understanding diseases lack applicability in the current scientific characterization systems. To date, there is no systematic evaluation system for TCM in preventing and treating T2DM. Metabonomics is a powerful tool to predict the level of metabolites in vivo, reveal the potential mechanism, and diagnose the physiological state of patients in time to guide the follow-up intervention of T2DM. Notably, metabolomics is also effective in promoting TCM modernization and advancement in personalized medicine. This review provides updated knowledge on applying metabolomics to TCM syndrome differentiation, diagnosis, biomarker discovery, and treatment of T2DM by TCM. Its application in diabetic complications is discussed. The combination of multi-omics and microbiome to fully elucidate the use of TCM to treat T2DM is further envisioned.

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Urine metabolomics study of Bushen Huoxue Prescription on diabetic retinopathy rats by UPLC–Q‐exactive Orbitrap–MS

Cited by 14 publications

References 44 publications

Metabolomics of various samples advancing biomarker discovery and pathogenesis elucidation for diabetic retinopathy

Metabolomics of various samples advancing biomarker discovery and pathogenesis elucidation for diabetic retinopathy

Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy

Application of Metabolomics and Traditional Chinese Medicine for Type 2 Diabetes Mellitus Treatment

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