Integrative pharmacology reveals the mechanisms of Erzhi Pill, a traditional Chinese formulation, against diabetic cardiomyopathy

Peng, Mingming; Xia, Tianyi; Zhong, Yanmei; Zhao, Mantong; Yue, Yimin; Liang, Lanyuan; Zhong, Renxing; Zhang, Han; Li, Chuanqiu; Cao, Xia; Yang, Mengru; Wang, Yi; Shu, Zunpeng

doi:10.1016/j.jep.2022.115474

Cited by 12 publications

(8 citation statements)

References 40 publications

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“…Cell viability may be increased by the activation of Akt kinase with several downstream signaling pathways, including FoxOs, GSK-3β/β-catenin signaling activation, and Bax inactivation [ 23 , 24 ]. Among them, GSK-3β/β-catenin signaling activation is our focus because GSK-3β is one of the key proteins that directs glycogen synthesis in cells and is directly upstream of glycogen synthase (GS); it has a positive effect on regulating glucose in the blood.…”

Section: Discussionmentioning

confidence: 99%

Effect of Black Tea Polysaccharides on Alleviating Type 2 Diabetes Mellitus by Regulating PI3K/Akt/GLUT2 Pathway

Zhang,

Deng,

Chen

et al. 2024

Foods

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The bioactivity of tea polysaccharides (TPs) has been widely reported, but studies to date have focused on green tea. Some human health investigations have implied that black tea may possess potential antidiabetic effects, but less is known about their potential role and related antidiabetic mechanism. The present study was, therefore, conducted to investigate the chemical properties and antidiabetic activity of TPs from black tea. Monosaccharide composition revealed that Alduronic acid (77.8 mol%) considerably predominated in the fraction. TP conformation analysis indicated that three components in TPs were all typical of high-branching structures. Oral administration of TPs could effectively alleviate fasting blood glucose in type 2 diabetes mellitus (T2D) mice, with the values 23.6 ± 1.42, 19.6 ± 2.25, and 16.4 ± 2.07 mmol/L in the 200, 400, and 800 mg/kg·BW groups, respectively. Among these TPs groups, the 800 mg/kg·BW groups significantly decreased by 37.88% when compared with the T2D+water group (p < 0.05). Further studies demonstrated that TP treatment upregulated the expression of p-Akt/p-PI3K (p < 0.001). Additionally, TP treatment significantly promoted glucose transporter protein 2 (GLUT2) translocation in the liver (p < 0.001). These findings suggest that TPs from black tea protect against T2D by activating PI3K/Akt/GLUT2 signaling and might serve as a novel therapeutic candidate for T2D.

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Section: Discussionmentioning

confidence: 99%

Effect of Black Tea Polysaccharides on Alleviating Type 2 Diabetes Mellitus by Regulating PI3K/Akt/GLUT2 Pathway

Zhang,

Deng,

Chen

et al. 2024

Foods

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“…EZW has been demonstrated to inhibit oxidative stress and regulate metabolism in a diabetic cardiomyopathy-related study. 25 Therefore, we hypothesized that the mechanism of action of SEZW in treating AGA may be related to oxidative stress. Experimental research is needed to investigate this further.…”

Section: Discussionmentioning

confidence: 99%

Promotion of Hair Regrowth in Androgenetic Alopecia with Supplemented Erzhi Wan: Exploring Its Mechanism Using Network Pharmacology and Molecular Docking

Ji,

Ma,

Feng

et al. 2023

CCID

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Supplemented Erzhi Wan (SEZW) is a Traditional Chinese Medicine commonly used in the treatment of androgenetic alopecia (AGA). This study aims to verify the effectiveness of SEZW for the treatment of AGA in mice and explore the potential molecular mechanisms underlying its function using network pharmacology and molecular docking. Methods: Forty mice were divided into five groups: Control, AGA-model, AGA-Positive, SEZW Low Dose, and SEZW High Dose. Hair regrowth in mice was evaluated by scoring hair on days 0, 14, and 28 post-treatment and weighing mouse hair on day 28 posttreatment. The targets of the active compounds of SEZW were obtained using the Traditional Chinese Medicine Database. AGArelated targets were downloaded from five databases. Then, the overlapping genes were identified. A protein-protein interaction network was constructed using the STRING database. Hub targets were determined through analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Finally, molecular docking of active compounds and hub targets was performed. Results: Hair regrowth in mice in the SEZW treatment groups was significantly enhanced relative to that in the AGA-model mice. A total of 59 potential drug-disease targets were identified. Based on the GO/KEGG analysis results, oxidative stress and gland development were identified as potential mechanisms of action of SEZW in AGA treatment. The PI3K-Akt and AGE-RAGE signaling pathways and seven hub targets were identified as the potential underlying mechanism of SEZW function. Molecular docking results showed that the most active SEZW compounds bind stably to several of the candidate disease targets. Conclusion: SEZW is effective in the treatment of AGA in a mouse model. Combined with network pharmacological analysis, the potential mechanisms, signaling pathways, and hub targets of SEZW in the treatment of AGA were identified, providing new ideas for further studies.

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“…[15] Additionally, Erzhi Pill, a traditional Chinese formulation, has been shown to improve oxidative stress in DCM, probably by modulating Gln metabolism. [38] Taken together, these studies suggest that Gln can ameliorate oxidative stress injury and thereby improve DCM.…”

Section: Oxidative Stressmentioning

confidence: 90%

The essential role of glutamine metabolism in diabetic cardiomyopathy: A review

Zhang

2023

Medicine

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Diabetic cardiomyopathy (DCM) is a pathophysiological condition caused by diabetes mellitus and is the leading cause of diabetes mellitus-related mortality. The pathophysiology of DCM involves various processes, such as oxidative stress, inflammation, ferroptosis, and abnormal protein modification. New evidence indicates that dysfunction of glutamine (Gln) metabolism contributes to the pathogenesis of DCM by regulating these pathophysiological mechanisms. Gln is a conditionally essential amino acid in the human body, playing a vital role in maintaining cell function. Although the precise molecular mechanisms of Gln in DCM have yet to be fully elucidated, recent studies have shown that supplementing with Gln improves cardiac function in diabetic hearts. However, excessive Gln may worsen myocardial injury in DCM by generating a large amount of glutamates or increasing O-GlcNacylation. To highlight the potential therapeutic method targeting Gln metabolism and its downstream pathophysiological mechanisms, this article aims to review the regulatory function of Gln in the pathophysiological mechanisms of DCM.

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Integrative pharmacology reveals the mechanisms of Erzhi Pill, a traditional Chinese formulation, against diabetic cardiomyopathy

Cited by 12 publications

References 40 publications

Effect of Black Tea Polysaccharides on Alleviating Type 2 Diabetes Mellitus by Regulating PI3K/Akt/GLUT2 Pathway

Effect of Black Tea Polysaccharides on Alleviating Type 2 Diabetes Mellitus by Regulating PI3K/Akt/GLUT2 Pathway

Promotion of Hair Regrowth in Androgenetic Alopecia with Supplemented Erzhi Wan: Exploring Its Mechanism Using Network Pharmacology and Molecular Docking

The essential role of glutamine metabolism in diabetic cardiomyopathy: A review

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