Network pharmacology-based analysis of the anti-hyperglycemic active ingredients of roselle and experimental validation

doi:10.1016/j.compbiomed.2021.104636

Computers in Biology and Medicine

Volume 141, February 2022, 104636

https://doi.org/10.1016/j.compbiomed.2021.104636 Get rights and content

Highlights

•
Diabetic vasculopathy is one of the major causes of death in patients with diabetes, and hyperglycemia is an important cause of diabetic vascular lesions.
•
Roselle (Hibiscus Sabdariffa L), a traditional herbal medicine, has shown significant clinical efficacy against hyperglycemia.
•
We found that Roselle has a certain protective effect on vascular endothelial cells through this study.
•
The present study made a comprehensive analysis by combining active ingredient screening, target prediction and signaling pathway analysis to elucidate the active ingredients and possible molecular mechanism of roselle for the first time.

Abstract

Diabetes mellitus is one of the top four leading causes of death among noncommunicable diseases worldwide, according to the World Hibiscus sabdariffa 2019. Roselle (Hibiscus sabdariffa L.), a traditional herbal medicine, has shown significant clinical anti-hyperglycemic efficacy. However, the mechanism of the treatment is not yet clear. We found that Roselle has a certain protective effect on vascular endothelial cells through this study. This study was based on network pharmacology and experimental validation. The present study made a comprehensive analysis by combining active ingredient screening, target prediction and signaling pathway analysis to elucidate the active ingredients and possible molecular mechanism of roselle for the first time, which provided theoretical and experimental basis for the development and application of roselle as an antidiabetic drug.

Introduction

Diabetes mellitus is one of the top four leading causes of death among noncommunicable diseases worldwide, according to the World Health Statistics 2019. It is characterized by hyperglycemia due to chronic and/or relative insulin insufficiency. Persistent hyperglycemia is very likely to result in vascular damage, which leads to a series of diabetic complications in the heart, kidneys, peripheral nerves, retina, etc. [[1], [2], [3]]. Currently, the number of patients with diabetes mellitus is increasing at an alarming rate worldwide; thus, there is a global unmet medical need to find therapeutic strategies for the regulation of glucose levels [4,5]. However, no drugs have been found to effectively improve the condition and quality of life of patients with diabetes so far.

Compared with currently used anti-diabetic drugs, traditional Chinese herbal medicines have become attractive as therapeutic agents against diabetes because of their multi-component, multi-target, and multi-pathway characteristics [[6], [7], [8]]. Network pharmacology, first proposed by Hopkins in 2007, is a promising emerging field and an advanced approach to discover active substances and reveal the pharmacological mechanisms of Chinese herbal medicines through the construction of drug-target-disease interaction networks. In previous studies, network pharmacology has been successfully applied to explore the pharmacodynamic basis and mechanisms of Chinese herbal medicines, such as Epimedii Herba for the treatment of Alzheimer's disease [9], icariin for the treatment of ovarian cancer [10], and uncaria alkaloids for the treatment of hypertension [11].

Roselle (Hibiscus sabdariffa L.), a famous traditional Chinese medicine, is widely grown in tropical and subtropical regions, including West Africa, Southeast Asia (e.g., in India, Thailand, and China), and Central America. The flower calyces, buds, seeds, and stems of roselle are traditionally used to prepare food, beverages, and herbal medicines. Evidence has shown that roselle can exert a variety of pharmacological effects, including anti-cancer, anti-bacterial, anti-obesity, anti-hypertensive, and anti-diabetic effects [[12], [13], [14], [15], [16]]. However, the active ingredients and pharmacological mechanisms of roselle associated with its anti-diabetic effects are still poorly known. Therefore, in the present study, we sought to identify the hypoglycemic active ingredients and potential targets of roselle extract through a network pharmacology approach and subsequent experimental validation (Fig. 1).

Section snippets

Software and network databases

The ChemDraw software (Version 15.0, CambridgeSoft Corporation), Open Babel GUI software (Version 2.4.1), Cytoscape software (Version 3.5, the Cytoscape Consortium), PharmMapper database (Version 2018, http://www.lilab-ecust.cn/pharmmapper/), DrugBank database (Version 5.0, https://www.drugbank.ca/), STRING database (Version 10.5, http://www.string-db.org/), UniProtKB database (http://www.uniprot.org/), TCMSP (http://lsp.nwu.edu.cn), TCMID (http://tcm.cmu.edu.tw/), and KEGG database (//www.kegg.jp/

Active ingredients and target information

A total of 119 ingredients of roselle were identified by consulting the literature [17,18]. In this study, we focused on the anti-hyperglycemic effects of roselle. The targets of each compound found in roselle were retrieved from the PharmMapper database by selecting “Homo sapiens” as organism. This database enables to identify potential targets of given drugs or natural products by pharmacophore modeling based on a ligand-based method [[21], [22], [23]]. The parameter matching score (fit

Discussion

In this study, a network pharmacology approach combined with experimental validation was used to study the hypoglycemic active components and possible anti-diabetic pharmacological mechanisms of roselle. According to our network analysis results, there are 50 potential active components and nine targets with anti-hyperglycemic effects in roselle.

The 50 active components were found to be mainly phenols, organic acids, and esters. Roselle calyces are traditionally consumed worldwide for the

Conclusion

In this study, a comprehensive analysis combining active ingredient screening, target prediction, and signaling pathway analysis was performed for the first time to pinpoint the potential active ingredients and elucidate the possible molecular mechanisms of the anti-diabetic activity of roselle. This study provides a theoretical and experimental basis for the development and application of roselle as an anti-diabetic drug. The major limitation of the current study is the lack of animal and cell

Declaration of competing interest

The authors declare that there are no conflicts of interest.

Acknowledgments

This work was supported by a grant from the National Nature Science of China (No. 81673432) and the Natural Science Foundation of Hunan Province, China (No. 2018JJ2543).

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Network pharmacology-based analysis of the anti-hyperglycemic active ingredients of roselle and experimental validation

Highlights

Abstract

Introduction

Section snippets

Software and network databases

Active ingredients and target information

Discussion

Conclusion

Declaration of competing interest

Acknowledgments

Lancet. Diabetes. Endocrinol.

J. Mol. Biol.

J. Pharmaceut. Biomed. Anal.

J. Ethnopharmacol.

Food Chem.

Food Chem.

Food Res. Int.

Eur. J. Pharmaceut. Sci.

Pharmacol. Res.

Brain Res.

Eur. J. Pharmacol.

Food Res. Int.

Biomed. Pharmacother.

Life Sci.

Kidney Int.

J. Biol. Chem.

Cytokine Growth Factor Rev.

Epidemiology of obesity and diabetes and their cardiovascular complications

Circ. Res.

Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus - mechanisms, management, and clinical considerations

Circulation

Diabetes healthcare professionals use multiple continuous glucose monitoring data indicators to assess glucose management

J. Diabetes. Sci. Technol.

Alarm settings of continuous glucose monitoring systems and associations to glucose outcomes in type 1 diabetes

Endocr. J. Soc.

A network pharmacology approach to establish the pharmacological mechanism of JiaWeiXianJiTang on inflammatory bowel disease

Biomed. Rep.

A network pharmacological approach to investigate the mechanism of action of active ingredients of epimedii herba and their potential targets in treatment of Alzheimer's disease

Med. Sci. Mon. Int. Med. J. Exp. Clin. Res.

A network-based approach to explore the mechanisms of uncaria alkaloids in treating hypertension and alleviating Alzheimer's disease

Int. J. Mol. Sci.

Hypolipidemic and antioxidant effects of ethanolic extract from dried calyx of Hibiscus sabdariffa in alloxan-induced diabetic rats

Fundam. Clin. Pharmacol.

In vivo anti-staphylococcal activity of roselle (Hibiscus sabdariffa L.) calyx extract in drosophila model of infection

J. Herbmed. Pharmacol.

Occurrence of root rot and vascular wilt diseases in roselle (Hibiscus sabdariffa L.) in upper Egypt

MYCOBIOLOGY

Antimicrobial effect of roselle (Hibiscus sabdariffa L.) water fraction against pseudomonas aeruginosa using drosophila infection model

Biointerface Res. Appl. Chem.

Study on Furundu, A traditional sudanese fermented roselle (Hibiscus sabdariffa L.) seed: effect on in vitro protein digestibility, chemical composition, and functional properties of the total proteins

J. Agric. Food Chem.

Aqueous extracts of Roselle (Hibiscus sabdariffa Linn.) varieties inhibit α-amylase and α-glucosidase activities in vitro

J. Med. Food

Truly target-focused pharmacophore modeling: a novel tool for mapping intermolecular surfaces

Molecules