Secondary metabolites with hypotensive properties: putative mechanisms of action

Objective: Thus, the objective of this review was to survey secondary metabolites with hypotensive action and to highlight possible mechanisms of action. Methodology: The Cochrane Library, Science Direct, Lilacs, Web of Science, and PubMed databases were used with the help of the descriptors: “medicinal plants” OR “herbal medicine”, “volatile oils” OR “alkaloids” OR “diterpene alkaloids” OR “terpenes” OR “sesquiterpenes” OR “monoterpenes” OR “isoprenoids” OR “flavonoids” OR “tannins” OR “phenolic compounds” AND “antihypertensive agents”. The time frame was from 2012 to 2022, and articles were selected in Portuguese, Spanish, and English. The Rayyan platform was used to list references, remove duplicates, screen, and assess eligibility. Results: Of the 6,196 articles retrieved from databases and reference lists, 17 were included. The findings show that various secondary metabolites, such as essential oils, alkaloids, flavonoids, and phenols, present hypotensive activity through various mechanisms, such as blocking calcium channels, increasing the production of nitric oxide via eNOS, decreasing angiotensin-II, and blocking ganglionic receptors. Notably, many metabolites showed antioxidant activity, which may indirectly contribute to the hypotensive effect. The therapeutic potential of the compounds above is relevant since the mentioned effects were found in the main experimental models of AH, among which the following stand out: spontaneously hypertensive rats (SHR), which mimics human essential hypertension; L-NAME model that causes AH by systemic vasoconstriction due to reduction in nitric oxide synthesis; model using deoxycorticosterone (DOCA) which triggers AH due to sodium and water retention; model by administration of nicotine that induces an increase in oxidative stress, resulting in less endothelium-dependent vasodilation due to endothelial dysfunction. Conclusion: It is concluded that secondary metabolites with hypotensive effects can act through different mechanisms of action in different blood pressure control systems, thus becoming potent therapeutic targets, which can contribute to the development of new antihypertensive drugs on the market.