IMR Press / FBL / Volume 28 / Issue 2 / DOI: 10.31083/j.fbl2802034
Open Access Review
The Investigation of the Molecular Mechanism of Morinda officinalis How in the Treatment of Heart Failure
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1 Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Pharmaceutical, Hainan Medical University, 571199 Haikou, Hainan, China
2 Department of Anesthesiology, Hainan Medical University First Affiliated Hospital, 570102 Haikou, Hainan, China
3 Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, 150086 Harbin, Heilongjiang, China
4 Department of Otolaryngology, Hainan Medical University First Affiliated Hospital, 570102 Haikou, Hainan, China
*Correspondence: (Haiying Zhang); (Yan Liu)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2023, 28(2), 34;
Submitted: 14 October 2022 | Revised: 3 November 2022 | Accepted: 18 November 2022 | Published: 24 February 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Heart failure (HF) is a cardiovascular disease with an extremely high mortality rate. However, Morinda officinalis How (MO) has not been studied for cardiovascular purposes at this time, the aim of this study was to find new mechanism for the MO of treatment of HF through a bioinformatics and experimental validation. The present study also aimed to establish a link between the basic and clinical applications of this medicinal herb. MO compounds and targets were obtained by traditional Chinese medicine systems pharmacology (TCMSP) and Pubchem. Subsequently, HF targets were acquired from DisGeNET and the interactions of all the targets and other human proteins were obtained via String so as to establish a component-target interaction network by Cytoscape 3.7.2. All the targets of clusters were inserted into Database for Annotation, Visualization and Integrated Discovery (DAVID) to perform GO (gene ontology) enrichment analysis. Molecular docking was adopted to predict the targets of MO relevant to the treatment of HF and to further explore the associated pharmacological mechanisms. Subsequently, a series of in vitro experiments, including histopathological staining, immunohistochemical and immunofluorescence analyses were conducted for further verification. Moreover, western blot analysis and in vivo experiments were performed. The results indicated that MO alleviated apoptosis, regulated cholesterol metabolism and transport function, and reduced inflammation, which resulted in the successful treatment of HF. Beta-sitosterol, Asperuloside tetraacetate and americanin A were the key bioactive components of MO. ALB, AKT1, INS, STAT3, IL-6, TNF, CCND1, CTNNB1, CAT, and TP53 were the core potential targets, which were significantly associated with multiple pathways, namely the FoxO signaling pathway, the AMPK signaling pathway, and the HIF-1 signaling pathway. In vivo experiments validated that MO may protect against heart failure or treat this disease by increasing the levels of autophagy via the FoxO3 signaling pathway in rats. The present study suggested that a combination of network pharmacology prediction with experimental validation may offer a useful tool to characterize the molecular mechanism of action of the traditional Chinese medicine (TCM) MO in the treatment of HF.

traditional Chinese medicine
mechanism of action
heart failure
Morinda officinalis How
2019RC376/High Level Talent fund project of Hainan Province
Hnky2022-37/Project supported by the Education Department of Hainan Province
Fig. 1.
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