Bioactive Natural Products against Systemic Arterial Hypertension: A Past 20-Year Systematic and Prospective Review

Abstract

Background: Systemic arterial hypertension is one of the most common cardiovascular risks, corresponding to 45% of deaths involving CVDs. The use of natural products, such as medicinal plants, belongs to a millennial part of human therapeutics history and has been employed as an alternative anti-hypertensive treatment.

Objective: The present review aims to prospect some natural products already experimentally assayed against arterial hypertension through scientific virtual libraries and patent documents over the past 20 years. Search strategy. This is a systematic review of the adoption of the PRISMA protocol and a survey of the scientific literature that synthesizes the results from published articles between 2001 and 2020 concerning the use of medicinal plants in the management of hypertension, including which parts of the plant or organism are used, as well as the mechanisms of action underlying the anti-hypertensive effect. Furthermore, a technological prospection was also carried out in patent offices from different countries in order to check technologies based on natural products claimed for the treatment or prevention of hypertension. Inclusion criteria. Scientific articles where a natural product had been experimentally assayed for anti-hypertensive activity (part of plants, plant extracts, and products derived from other organisms) were included. Data extraction and analysis. The selected abstracts of the articles and patent documents were submitted to a rigorous reading process. Those articles and patents that were not related to anti-hypertensive effects and claimed potential applications were excluded from the search.

Results: Eighty specimens of biological species that showed anti-hypertensive activity were recovered, with 01 representative from the kingdom Fungi and 02 from the kingdom Protista, with emphasis on the families Asteraceae and Lamiaceae, with 6 representatives each. Leaves and aerial parts were the most used parts of the plants for the extraction of anti-hypertensive products, with maceration being the most used extraction method. Regarding phytochemical analyses, the most described classes of biomolecules in the reviewed works were alkaloids, terpenes, coumarins, flavonoids, and peptides, with the reduction of oxidative stress and the release of NO among the mechanisms of action most involved in this process. Regarding the number of patent filings, China was the country that stood out as the main one, with 813 registrations.

Conclusion: The anti-hypertensive activity of natural products is still little explored in Western countries. Besides, China and India have shown more results in this area than other countries, confirming the strong influence of traditional medicine in these countries.

Figure 1

Main mechanisms and signaling pathways involved in blood pressure control.

Figure 2

Process of the research and treatment protocol of scientific production articles about natural products that possess anti-hypertensive activity.

Figure 3

Distribution of the main families used in scientific research on natural products with anti-hypertensive activity published in the virtual libraries portal BVS, CAPES, and SciELO from 2001 to 2020.

Figure 4

Percentages of the main chosen plant parts (a) and the main extractive methods (b) used to obtain the different natural products with anti-hypertensive activity retrieved from the virtual libraries BVS, CAPES, and SciELO over the period between 2001 and 2020.

Figure 5

Distribution of the anti-hypertensive mechanisms elucidated in the scientific research of natural products with anti-hypertensive activity published in the virtual libraries BVS Portal, CAPES, and SciELO in the period of 2001 to 2020.

Figure 6

Distribution of patents deposited in accordance with the depositary office in the INPI (National Institute of Industrial Property, Brazil), the USPTO (European Patent Office), the EPO (European Patent Office), the WIPO (World Intellectual Property Organization), and the LATIPAT.

Figure 7

Patent deposit evolution over the past 20 years on the bases of the INPI (National Institute of Industrial Property, Brazil), the USPTO (United States Patent and Trademark Office), the EPO (European Patent Office), the WIPO (World Intellectual Property Organization), and the LATIPAT.