Network pharmacology and metabolomics study on the intervention of traditional Chinese medicine Huanglian Decoction in rats with type 2 diabetes mellitus

Pan, Linlin; Li, Zhuangzhuang; Wang, Yufeng; Zhang, Bingyu; Liu, Guirong; Liu, Juhai

doi:10.1016/j.jep.2020.112842

Cited by 98 publications

(45 citation statements)

References 32 publications

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“…Each herb contained in CXC and HXMMT was searched in the TCMSP database, and all ingredients were obtained. According to most traditional Chinese herbs studies [ 10 – 12 ], an ingredient with an OB of ≥30 and a DL of ≥0.18 was considered an active ingredient, and the targets of these ingredients (CXC and HXMMT targets) were retrieved from the database.…”

Section: Methodsmentioning

confidence: 99%

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Network Pharmacology-Based Approach to Comparatively Predict the Active Ingredients and Molecular Targets of Compound Xueshuantong Capsule and Hexuemingmu Tablet in the Treatment of Proliferative Diabetic Retinopathy

Yao

Xin

Zhan

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Compound Xueshuantong capsule (CXC) and Hexuemingmu tablet (HXMMT) are two important Chinese patent medicines (CPMs) frequently used to treat proliferative diabetic retinopathy (PDR), especially when complicated with vitreous hemorrhage (VH). However, a network pharmacology approach to understand the therapeutic mechanisms of these two CPMs in PDR has not been applied. Objective. To identify differences in the active ingredients between CXC and HXMMT and to comparatively predict and further analyze the molecular targets shared by these CPMs and PDR. Materials and methods. The differentially expressed messenger RNAs (mRNAs) between normal retinal tissues in healthy individuals and active fibrovascular membranes in PDR patients were retrieved from the Gene Expression Omnibus database. The active ingredients of CXC and HXMMT and the targets of these ingredients were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. The intersections of the CPM (CXC and HXMMT) targets and PDR targets were determined. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, and the ingredient-target networks, protein-protein interaction networks, and KEGG-target (KEGG-T) networks were constructed. Results. CXC contains 4 herbs, and HXMMT contains 19. Radix salviae is the only herb common to both. CXC had 34 potential therapeutic targets in PDR, while HXMMT had these 34 and 10 additional targets. Both CPMs shared the following main processes: response to reactive oxygen species and oxidative stress, regulation of blood vessel diameter and size, vasoconstriction, smooth muscle contraction, hemostasis, and blood coagulation. The shared pathways included the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, relaxin signaling pathway, and IL-17 signaling pathway. Conclusions. Both CXC and HXMMT include components effective at treating PDR and affect the following main processes: response to reactive oxygen species and oxidative stress, regulation of blood vessels, and blood coagulation. Radix salviae, the only herb common to both CPMs, contains many useful active ingredients. The PDR-CXC and PDR-HXMMT networks shared 34 common genes (RELA, HSPA8, HSP90AA, HSP90AB1, BRCA, EWSR1, CUL7, HNRNPU, MYC, CTNNB1, MDM2, YWHAZ, CDK2, AR, FN1, HUWE1, TP53, TUBB, EP300, GRB2, VCP, MCM2, EEF1A1, NTRK1, TRAF6, EGFR, PRKDC, SRC, HDAC5, APP, ESR1, AKT1, UBC, and COPS5), and the PDR-HXMMT network has 10 additional genes (RNF2, VNL, RPS27, COPS5, XPO1, PARP1, RACK1, YWHAB, and ITGA4). The top 5 pathways with the highest gene ratio in both networks were the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, relaxin signaling pathway, IL-17 signaling pathway, and focal adhesion. Additional pathways such as neuroactive ligand-receptor interaction, chemokine signaling pathway, and AMPK signaling pathway were enriched with HXMMT targets. Thus, HXMMT has more therapeutic targets shared by different active ingredients and more abundant gene functions than CXC, which may be two major reasons why HXMMT is more strongly recommended than CXC as an auxiliary treatment for new-onset VH secondary to PDR. However, the underlying mechanisms still need to be further explored.

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Section: Methodsmentioning

confidence: 99%

“…Network pharmacology analysis is a convenient and systematic approach to identify core targets shared by drugs and diseases [ 10 ]. It can also be performed to identify potential pathways for disease interventions, providing insight into the complex mechanisms of Chinese herbal formulas used to treat diseases.…”

Section: Introductionmentioning

confidence: 99%

Network Pharmacology-Based Approach to Comparatively Predict the Active Ingredients and Molecular Targets of Compound Xueshuantong Capsule and Hexuemingmu Tablet in the Treatment of Proliferative Diabetic Retinopathy

Yao

Xin

Zhan

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Traditional Chinese medicine (TCM) is an important part of complementary and alternative medicine, and it has been widely accepted in China and applied in clinical practice. Recently, a growing body of evidence demonstrated the potential of traditional Chinese medicine as an effective treatment for diabetes mellitus [5–8].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of five alkaloids from Rauvolfia vomitoria in rat plasma by LC‐MS/MS: Application to a comparative pharmacokinetic study in normal and type 2 diabetic rats

Wang

Xie

et al. 2021

J of Separation Science

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Rauvolfia vomitoria is widely distributed in the tropical regions of Africa and Asia, and has been used in traditional folk medicine in China. Indole alkaloids were found to be major bioactive components, while the effects of diabetes mellitus on the pharmacokinetic parameters of the components have not been reflected in vivo. In this study, an efficient and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of five ingredients of R. vomitoria in rats. Detection was implemented in multiple‐reaction‐monitoring mode with an electrospray positive‐ionization source. Validation parameters were all in accordance with the current criterion. The established method was effectively employed to compare the pharmacokinetic behaviors of five alkaloids (reserpine, yohimbine, ajmaline, ajmalicine, and serpentine) between normal and type 2 diabetic rats. The single‐dose pharmacokinetic parameters of the five alkaloids were determined in normal and diabetic rats after oral administration of 100 and 200 mg/kg body weight. The results indicated that diabetes mellitus significantly altered the pharmacokinetic characteristics of yohimbine, ajmaline, and ajmalicine after oral administration in rats. This is an attempt to provide some evidence for clinicians that may serve as a guide for the use of antidiabetic medicine in clinical practice.

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“…Huanglian Decoction is one of the classical Chinese medicine formulas, which has the effect of clearing heat and treating abdominal pain [13][14][15]. This formulation was originally recorded in the classic Chinese medicine book "Treatise on Febrile Diseases" (Chinese name: Shanghan Lun).…”

Section: Introductionmentioning

confidence: 99%

Huanglian Decoction Suppresses the Growth of Hepatocellular Carcinoma Cells by Reducing CCNB1 Expression

Shang

Wang

et al. 2020

Preprint

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Background: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in human populations worldwide. Conversely, Huanglian Decoction is one of the most important Chinese medicine formulas, with the potential to treat cancer. Methods: To identify differentially expressed genes (DEG), we herein downloaded gene expression profile data from the TCGA (TCGA-LIHC) and GEO (GSE45436) databases. We obtained phytochemicals of the four constituent herbs of Huanglian Decoction from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). We also established a regulatory network of DEG and their drug target genes and subsequently analyzed key genes using bioinformatic approaches. Furthermore, we explored the effect of Huanglian Decoction by conducting in vitro experiments so as to verify the prediction. In particular, the CCNB1 gene was knockdown to verify the primary target of this Decoction. Results: Based on the results of network pharmacological analysis, we revealed that there are 5 bioactive compounds in Huanglian Decoction acting on HCC. In addition, our findings confirmed that CCNB1 was the primary key gene, which can be highly expressed in tumors and was significantly associated with a worse prognosis (P = 0.002) according to PPI network analysis of the target genes of these five compounds, as well as expression and prognosis analyses in tumors. We also noted that CCNB1 can be used as an independent prognostic indicator of HCC (P < 0.01). Moreover, in vitro experimental results demonstrate that Huanglian Decoction can significantly inhibit the growth, migration, and invasion of HCC cells. Finally, further analysis showed that this Decoction may inhibit the growth of HCC cells by down-regulating the expression level of CCNB1.

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Network pharmacology and metabolomics study on the intervention of traditional Chinese medicine Huanglian Decoction in rats with type 2 diabetes mellitus

Cited by 98 publications

References 32 publications

Network Pharmacology-Based Approach to Comparatively Predict the Active Ingredients and Molecular Targets of Compound Xueshuantong Capsule and Hexuemingmu Tablet in the Treatment of Proliferative Diabetic Retinopathy

Network Pharmacology-Based Approach to Comparatively Predict the Active Ingredients and Molecular Targets of Compound Xueshuantong Capsule and Hexuemingmu Tablet in the Treatment of Proliferative Diabetic Retinopathy

Simultaneous determination of five alkaloids from Rauvolfia vomitoria in rat plasma by LC‐MS/MS: Application to a comparative pharmacokinetic study in normal and type 2 diabetic rats

Huanglian Decoction Suppresses the Growth of Hepatocellular Carcinoma Cells by Reducing CCNB1 Expression

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