Determining antihypertensive herbal formulas based on molecular mechanisms and protein-compound interactions of selected Indonesian medicinal plants using a network pharmacological approach

Abstract

In Indonesia, herbs are used to treat various diseases, including hypertension. A network pharmacology approach can be a breakthrough in research strategy by discovering a new drug using the multicomponent-multitarget concept. The protein-compound mechanism in plants is a potential target for creating new combination formulas that will be developed into new drug discoveries in hypertension therapy. This study aims to determine a new formula from Indonesian medicinal plants using a network pharmacological approach based on molecular mechanisms and protein-compound-plant interactions that have antihypertensive effects. We use graph mining and machine learning to explore compounds and plant-related hypertension target proteins and determine plant formulations based on the molecular mechanisms of hypertension-related target proteins. A search found 78 Indonesian medicinal plants that contain trans zeatin, seselin, sesamin, and other compounds effective as antihypertensive agents. The study obtained a formula with a combination of 2 plants, including 31 formulas bound to 5 target proteins, and a combination of 3 plants, with 85 formulas bound to 6 hypertension target proteins. The plant formula illustrates the involvement of several mechanisms in lowering blood pressure using protein-plant compounds. Some of the plant formula’s constituents, such as antioxidants and anti-inflammatories, have blood pressure-lowering properties. Proteins mitogen-activated protein kinase 3, peroxisome proliferator-activated receptor alpha, estrogen receptor 1, endothelin 1, vascular endothelial growth factor A, and fos proto-oncogene are possible biomarkers that could be used to target hypertension medication in the coming years.