Network Pharmacology-Guided Development of a Novel Integrative Regimen to Prevent Acute Graft-vs.-Host Disease

Lyu, Ming; Zhou, Zhengcan; Wang, Xiaoming; Lü, Hong; Wang, Mei; Pan, Guixiang; Wang, Yuefei; Fan, Guanwei; Gao, Xiumei; Feng, Yi; Zhu, Yan

doi:10.3389/fphar.2018.01440

Cited by 22 publications

(22 citation statements)

References 68 publications

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“…C. albicans kills kidney epithelial cells directly, while XBJ partially rescued 293T cell survival upon C. albicans exposures (Figure 6). This is consistent with our previous result that XBJ improved RAW264.7 cells survival upon the insult of LPS (Lyu et al, 2018).…”

Section: Mechanism Of Kidney Failure In Candida Sepsissupporting

confidence: 94%

Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney

Shang

Ren

et al. 2020

Front. Pharmacol.

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Sepsis and septic shock threaten the survival of millions of patients in the intensive care unit. Secondary fungal infections significantly increased the risk of mortality in sepsis patients. Chinese medicine Xuebijing injection (XBJ) has been routinely used as an add-on treatment to sepsis and septic shock in China. Our network pharmacology analysis predicted that XBJ also influences fungal infection, consisting with results of pioneer clinical studies. We conducted in vivo and in vitro experiments to verify this prediction. To our surprise, XBJ rescued mice from lethal Candida sepsis in a disseminated Candida albicans infection model and abolished the colonization of C. albicans in kidneys. Although XBJ did not inhibit the growth and the virulence of C. albicans in vitro, it enhanced the viability of 293T cells upon C. albicans insults. Further RNA-seq analysis revealed that XBJ activated the endoplasmic reticulum (ER) stress pathway upon C. albicans infection. Western blot confirmed that XBJ maintained the expression of GRP78 in the presence of C. albicans. Interestingly, key active ingredients in XBJ (C0127) mirrored the effects of XBJ. C0127 not only rescued mice from lethal Candida sepsis and prevented the colonization of C. albicans in kidneys, but also sustained the survival of kidney epithelial cells partially by maintaining the expression of GRP78. These results suggested that XBJ may prevent fungal infection in sepsis patients. Pre-activation of ER stress pathway is a novel strategy to control C. albicans infection. Network pharmacology may accelerate drug development in the field of infectious diseases.

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Section: Mechanism Of Kidney Failure In Candida Sepsissupporting

confidence: 94%

Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney

Shang

Ren

et al. 2020

Front. Pharmacol.

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“…British pharmacologist Dr. Andrew L. Hopkins established the concept of "network pharmacology", and defined it as a subdivision of pharmacology, which can analyze the overall effects and interactions among the multiple compounds, their targets, and the related pathways [49,50]. With the help of network pharmacology, significant progress has been made in understanding the complicated and complex systems such as the pharmacology of TCM formula and compositions [34,[51][52][53][54].…”

Section: Discussionmentioning

confidence: 99%

A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer’s Disease

Zhang

et al. 2020

IJMS

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Uncaria alkaloids are the major bioactive chemicals found in the Uncaria genus, which have a long history of clinical application in treating cardiovascular and mental diseases in traditional Chinese medicine (TCM). However, there are gaps in understanding the multiple targets, pathways, and biological activities of Uncaria alkaloids. By constructing the interactions among drug-targets-diseases, network pharmacology provides a systemic methodology and a novel perspective to present the intricate connections among drugs, potential targets, and related pathways. It is a valuable tool for studying TCM drugs with multiple indications, and how these multi-indication drugs are affected by complex interactions in the biological system. To better understand the mechanisms and targets of Uncaria alkaloids, we built an integrated analytical platform based on network pharmacology, including target prediction, protein–protein interaction (PPI) network, topology analysis, gene enrichment analysis, and molecular docking. Using this platform, we revealed the underlying mechanisms of Uncaria alkaloids’ anti-hypertensive effects and explored the possible application of Uncaria alkaloids in preventing Alzheimer’s disease. These results were further evaluated and refined using biological experiments. Our study provides a novel strategy for understanding the holistic pharmacology of TCM, as well as for exploring the multi-indication properties of TCM beyond its traditional applications.

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“…DCFH-DA (Jiang et al, 2018) and RHOD2 (Joseph et al, 2017) probes were loaded 12 h later. After incubating at 37°C for 30 min and washing 3 times with PBS, images were taken and analyzed with a PerkinElmer high-content imaging system as described (Lyu et al, 2018b).…”

Section: Cell Culturesmentioning

confidence: 99%

Paeoniflorin and Hydroxysafflor Yellow A in Xuebijing Injection Attenuate Sepsis-Induced Cardiac Dysfunction and Inhibit Proinflammatory Cytokine Production

Wang

Peng

et al. 2021

Front. Pharmacol.

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Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes in vitro culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction in vivo. RNA-seq revealed XBJ attenuated the expression of proinflammatory cytokines and related signalings in the heart which was further confirmed on the mRNA and protein levels. Xuebijing also protected cardiomyocytes from LPS-induced mitochondrial calcium ion overload and reduced the LPS-induced ROS production in cardiomyocytes. The therapeutic effect of XBJ was mediated by the combination of paeoniflorin and hydroxysafflor yellow A (HSYA) (C0127-2). C0127-2 improved the survival of septic mice, protected their cardiac function and cardiomyocytes while balancing gene expression in cytokine-storm-related signalings, such as TNF-α and NF-κB. In summary, Paeoniflorin and HSYA are key active compounds in XBJ for managing sepsis, protecting cardiac function, and controlling inflammation in the cardiac tissue partially by limiting the production of IL-6, IL-1β, and CXCL2.

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Network Pharmacology-Guided Development of a Novel Integrative Regimen to Prevent Acute Graft-vs.-Host Disease

Cited by 22 publications

References 68 publications

Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney

Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney

A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer’s Disease

Paeoniflorin and Hydroxysafflor Yellow A in Xuebijing Injection Attenuate Sepsis-Induced Cardiac Dysfunction and Inhibit Proinflammatory Cytokine Production

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